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Naik A, Kale AA, Rajwade JM. Sensing the future: A review on emerging technologies for assessing and monitoring bone health. BIOMATERIALS ADVANCES 2024; 165:214008. [PMID: 39213957 DOI: 10.1016/j.bioadv.2024.214008] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 05/24/2024] [Revised: 08/19/2024] [Accepted: 08/25/2024] [Indexed: 09/04/2024]
Abstract
Bone health is crucial at all stages of life. Several medical conditions and changes in lifestyle affect the growth, structure, and functions of bones. This may lead to the development of bone degenerative disorders, such as osteoporosis, osteoarthritis, rheumatoid arthritis, etc., which are major public health concerns worldwide. Accurate and reliable measurement and monitoring of bone health are important aspects for early diagnosis and interventions to prevent such disorders. Significant progress has recently been made in developing new sensing technologies that offer non-invasive, low-cost, and accurate measurements of bone health. In this review, we have described bone remodeling processes and common bone disorders. We have also compiled information on the bone turnover markers for their use as biomarkers in biosensing devices to monitor bone health. Second, this review details biosensing technology for bone health assessment, including the latest developments in various non-invasive techniques, including dual-energy X-ray absorptiometry, magnetic resonance imaging, computed tomography, and biosensors. Further, we have also discussed the potential of emerging technologies, such as biosensors based on nano- and micro-electromechanical systems and application of artificial intelligence in non-invasive techniques for improving bone health assessment. Finally, we have summarized the advantages and limitations of each technology and described clinical applications for detecting bone disorders and monitoring treatment outcomes. Overall, this review highlights the potential of emerging technologies for improving bone health assessment with the potential to revolutionize clinical practice and improve patient outcomes. The review highlights key challenges and future directions for biosensor research that pave the way for continued innovations to improve diagnosis, monitoring, and treatment of bone-related diseases.
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Affiliation(s)
- Amruta Naik
- Department of Biosciences and Technology, School of Science and Environmental Studies, Dr. Vishwanath Karad MIT World Peace University, Pune 411038, Maharashtra, India.
| | - Anup A Kale
- Department of Biosciences and Technology, School of Science and Environmental Studies, Dr. Vishwanath Karad MIT World Peace University, Pune 411038, Maharashtra, India
| | - Jyutika M Rajwade
- Nanobioscience Group, Agharkar Research Institute, Pune 411004, Maharashtra, India.
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Rastogi A, Singh R, Ghosh J, Gupta R. Anti-RANKL Antibody For Active Charcot Foot Neuro-Osteoarthropathy in Patients with Diabetes and Chronic Kidney Disease. Foot Ankle Int 2024; 45:1122-1130. [PMID: 39188121 DOI: 10.1177/10711007241268147] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 08/28/2024]
Abstract
BACKGROUND Charcot neuroosteoarthropathy (CNO) is characterized with increased osteoclastic activity that can be curbed with antiresorptive agents. Chronic kidney disease (CKD) precludes bisphosphonates but anti-receptor activator of nuclear factor-B ligand (anti-RANKL) antibody, denosumab, can be contemplated in CKD. We investigated denosumab for active CNO of foot in CKD for CNO remission. METHODS During the study period, 446 persons of diabetes with unilateral, active CNO of foot and CKD were identified and 78 were finally enrolled. Patients received either 60 mg denosumab (single-dose, subcutaneous) along with standard of care (SoC) as total contact cast (TCC) (group A; n = 26) or SoC (group B; n = 52) only. Patients were followed every 4 weeks until CNO remission and subsequently every 8 weeks until 48 weeks following remission. Remission was defined as temperature difference <2 °C between 2 feet confirmed twice (4 weeks apart) with clinical resolution of signs of inflammation. The primary outcome studied was proportion of patients achieving remission within 48 weeks and the time to remission. RESULTS Median age was 56.5 (48.8-65) and 57 (48.5-61.2) years, P = .57; duration of diabetes 16 (10-25.3) and 14.9 (10-19) years, P = .151; and estimated glomerular filtration rate 44.8 (21.1-65.6) and 45.7 (32.9-55.7) mL/min/1.73 m2, P = .771, in group A and B, respectively. Median temperature difference at presentation between the affected and opposite foot was 3.4 °C (2.7-6.9) and 3.2 °C (2.2-4.0), P = .119, respectively. All patients achieved remission in group A (100%) compared with 42 (80.8%) in group B (P = .006) (hazard ratio 0.52, 95% CI: 0.32-0.87; P = .012). The median time to remission was similar in the 2 groups (15 [11-25] and 17.5 [14-31.5] weeks, P = .229, respectively). 25-Hydroxyvitamin D3 >14 ng/mL was significantly associated (OR 9.5, 95% CI 1.04-87.5, P = .045) with remission. CONCLUSION Anti-RANKL antibody added to SoC (TCC) induces remission of active foot CNO in greater proportions of patients with diabetes and CKD.
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Affiliation(s)
- Ashu Rastogi
- Deptartment of Endocrinology, PGIMER, Chandigarh, India
| | - Raveena Singh
- Deptartment of Endocrinology, PGIMER, Chandigarh, India
| | | | - Rajat Gupta
- Department of Endocrinology, Alchemist Hospitals, Panchkula, India
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Wu J, Niu L, Yang K, Xu J, Zhang D, Ling J, Xia P, Wu Y, Liu X, Liu J, Zhang J, Yu P. The role and mechanism of RNA-binding proteins in bone metabolism and osteoporosis. Ageing Res Rev 2024; 96:102234. [PMID: 38367813 DOI: 10.1016/j.arr.2024.102234] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/11/2023] [Revised: 02/06/2024] [Accepted: 02/13/2024] [Indexed: 02/19/2024]
Abstract
Osteoporosis is a prevalent chronic metabolic bone disease that poses a significant risk of fractures or mortality in elderly individuals. Its pathophysiological basis is often attributed to postmenopausal estrogen deficiency and natural aging, making the progression of primary osteoporosis among elderly people, especially older women, seemingly inevitable. The treatment and prevention of osteoporosis progression have been extensively discussed. Recently, as researchers delve deeper into the molecular biological mechanisms of bone remodeling, they have come to realize the crucial role of posttranscriptional gene control in bone metabolism homeostasis. RNA-binding proteins, as essential actors in posttranscriptional activities, may exert influence on osteoporosis progression by regulating the RNA life cycle. This review compiles recent findings on the involvement of RNA-binding proteins in abnormal bone metabolism in osteoporosis and describes the impact of some key RNA-binding proteins on bone metabolism regulation. Additionally, we explore the potential and rationale for modulating RNA-binding proteins as a means of treating osteoporosis, with an overview of drugs that target these proteins.
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Affiliation(s)
- Jiaqiang Wu
- Jiujiang Clinical Precision Medicine Research Center, Jiujiang, Jiangxi, 332000, China; The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China; Department of General Surgery, First Medical Center of the Chinese PLA General Hospital, Beijing, China
| | - Liyan Niu
- HuanKui College of Nanchang University, Nanchang 330006, China
| | - Kangping Yang
- The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang 330006, China
| | - Jingdong Xu
- Queen Mary College of Nanchang University, Nanchang 330006, China
| | - Deju Zhang
- Food and Nutritional Sciences, School of Biological Sciences, The University of Hong Kong, Pokfulam Road, 999077, Hong Kong, China
| | - Jitao Ling
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1, Minde Road, Donghu District, Nanchang 330006, China; Institute for the Study of Endocrinology and Metabolism in Jiangxi Province, Nanchang 330006, China
| | - Panpan Xia
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1, Minde Road, Donghu District, Nanchang 330006, China; Institute for the Study of Endocrinology and Metabolism in Jiangxi Province, Nanchang 330006, China
| | - Yuting Wu
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1, Minde Road, Donghu District, Nanchang 330006, China; Institute for the Study of Endocrinology and Metabolism in Jiangxi Province, Nanchang 330006, China
| | - Xiao Liu
- Department of Cardiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou 510275, China
| | - Jianping Liu
- Department of Endocrinology and Metabolism, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1, Minde Road, Donghu District, Nanchang 330006, China; Institute for the Study of Endocrinology and Metabolism in Jiangxi Province, Nanchang 330006, China
| | - Jing Zhang
- Jiujiang Clinical Precision Medicine Research Center, Jiujiang, Jiangxi, 332000, China; Department of Anesthesiology, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, China.
| | - Peng Yu
- Jiujiang Clinical Precision Medicine Research Center, Jiujiang, Jiangxi, 332000, China; Department of Endocrinology and Metabolism, The Second Affiliated Hospital, Jiangxi Medical College, Nanchang University, No. 1, Minde Road, Donghu District, Nanchang 330006, China; Institute for the Study of Endocrinology and Metabolism in Jiangxi Province, Nanchang 330006, China.
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Hughes L, Centner C. Idiosyncratic bone responses to blood flow restriction exercise: new insights and future directions. J Appl Physiol (1985) 2024; 136:283-297. [PMID: 37994414 PMCID: PMC11212818 DOI: 10.1152/japplphysiol.00723.2022] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2022] [Revised: 11/14/2023] [Accepted: 11/21/2023] [Indexed: 11/24/2023] Open
Abstract
Applying blood flow restriction (BFR) during low-load exercise induces beneficial adaptations of the myotendinous and neuromuscular systems. Despite the low mechanical tension, BFR exercise facilitates a localized hypoxic environment and increase in metabolic stress, widely regarded as the primary stimulus for tissue adaptations. First evidence indicates that low-load BFR exercise is effective in promoting an osteogenic response in bone, although this has previously been postulated to adapt primarily during high-impact weight-bearing exercise. Besides studies investigating the acute response of bone biomarkers following BFR exercise, first long-term trials demonstrate beneficial adaptations in bone in both healthy and clinical populations. Despite the increasing number of studies, the physiological mechanisms are largely unknown. Moreover, heterogeneity in methodological approaches such as biomarkers of bone metabolism measured, participant and study characteristics, and time course of measurement renders it difficult to formulate accurate conclusions. Furthermore, incongruity in the methods of BFR application (e.g., cuff pressure) limits the comparability of datasets and thus hinders generalizability of study findings. Appropriate use of biomarkers, effective BFR application, and befitting study design have the potential to progress knowledge on the acute and chronic response of bone to BFR exercise and contribute toward the development of a novel strategy to protect or enhance bone health. Therefore, the purpose of the present synthesis review is to 1) evaluate current mechanistic evidence; 2) discuss and offer explanations for similar and contrasting data findings; and 3) create a methodological framework for future mechanistic and applied research.
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Affiliation(s)
- Luke Hughes
- Department of Sport Exercise & Rehabilitation, Northumbria University, Newcastle upon Tyne, United Kingdom
| | - Christoph Centner
- Department of Sport and Sport Science, University of Freiburg, Freiburg, Germany
- Praxisklinik Rennbahn, Muttenz, Switzerland
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Sung J, Barratt KR, Pederson SM, Chenu C, Reichert I, Atkins GJ, Anderson PH, Smitham PJ. Unbiased gene expression analysis of the delayed fracture healing observed in Zucker diabetic fatty rats. Bone Joint Res 2023; 12:657-666. [PMID: 37844909 PMCID: PMC10578971 DOI: 10.1302/2046-3758.1210.bjr-2023-0062.r1] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 10/18/2023] Open
Abstract
Aims Impaired fracture repair in patients with type 2 diabetes mellitus (T2DM) is not fully understood. In this study, we aimed to characterize the local changes in gene expression (GE) associated with diabetic fracture. We used an unbiased approach to compare GE in the fracture callus of Zucker diabetic fatty (ZDF) rats relative to wild-type (WT) littermates at three weeks following femoral osteotomy. Methods Zucker rats, WT and homozygous for leptin receptor mutation (ZDF), were fed a moderately high-fat diet to induce T2DM only in the ZDF animals. At ten weeks of age, open femoral fractures were simulated using a unilateral osteotomy stabilized with an external fixator. At three weeks post-surgery, the fractured femur from each animal was retrieved for analysis. Callus formation and the extent of healing were assessed by radiograph and histology. Bone tissue was processed for total RNA extraction and messenger RNA (mRNA) sequencing (mRNA-Seq). Results Radiographs and histology demonstrated impaired fracture healing in ZDF rats with incomplete bony bridge formation and an influx of intramedullary inflammatory tissue. In comparison, near-complete bridging between cortices was observed in Sham WT animals. Of 13,160 genes, mRNA-Seq analysis identified 13 that were differentially expressed in ZDF rat callus, using a false discovery rate (FDR) threshold of 10%. Seven genes were upregulated with high confidence (FDR = 0.05) in ZDF fracture callus, most with known roles in inflammation. Conclusion These findings suggest that elevated or prolonged inflammation contributes to delayed fracture healing in T2DM. The identified genes may be used as biomarkers to monitor and treat delayed fracture healing in diabetic patients.
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Affiliation(s)
- Jonghoo Sung
- Centre for Orthopaedic and Trauma Research, Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, Australia
| | - Kate R. Barratt
- Clinical and Health Sciences, University of South Australia, Adelaide, Australia
| | - Stephen M. Pederson
- Bioinformatics Hub, School of Biological Sciences, The University of Adelaide, Adelaide, Australia
- Black Ochre Data Labs, Indigenous Genomics, Telethon Kids Institute, Adelaide, Australia
| | | | | | - Gerald J. Atkins
- Centre for Orthopaedic and Trauma Research, Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, Australia
| | - Paul H. Anderson
- Clinical and Health Sciences, University of South Australia, Adelaide, Australia
| | - Peter J. Smitham
- Centre for Orthopaedic and Trauma Research, Adelaide Medical School, Faculty of Health and Medical Sciences, The University of Adelaide, Adelaide, Australia
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Nisha Y, Dubashi B, Bobby Z, Sahoo JP, Kayal S, Ananthakrishnan R, Reddy VB, L C, Ganesan P. Negative impact on bone homeostasis in postmenopausal women with non-metastatic breast cancer during cytotoxic chemotherapy. J Bone Miner Metab 2023; 41:682-692. [PMID: 37410202 DOI: 10.1007/s00774-023-01444-9] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/09/2023] [Accepted: 05/29/2023] [Indexed: 07/07/2023]
Abstract
INTRODUCTION The burden and mechanisms of endocrine therapy-related bone loss are well known, while there are limited data on chemotherapy-induced bone resorption. The study aimed to evaluate the effect of cytotoxic chemotherapy on bone homeostasis among postmenopausal women with non-metastatic breast cancer. MATERIALS AND METHODS Early and locally advanced postmenopausal non-metastatic breast cancer patients aged 45 to 65 planned for three cycles of anthracycline and four cycles of taxane chemotherapy administered along with dexamethasone (cumulative dose-256 mg) as an antiemetic from June 2018 to December 2021 were included. Bone mineral density (BMD), bone turnover markers, calciotropic hormones, pro-inflammatory cytokines, oxidative stress, and total antioxidant levels (TAS) were measured. RESULTS We recruited 109 patients, with early 34 (31.2%) and locally advanced breast cancer 75 (68.8%) with median age 53 (45-65) years. There was a significant decrease in the % BMD at the lumbar spine, neck of the femur, and total hip post-chemotherapy. There was a significant increase in serum C-terminal telopeptide of type I collagen (CTX) and procollagen type I N-terminal propeptide (PINP) levels post-chemotherapy. PINP/CTX ratio significantly decreased post-chemotherapy. Serum 25-OH vitamin D was significantly reduced with a compensatory increase in plasma iPTH levels. The change in CTX, PINP/CTX ratio, 25-OH vitamin D, iPTH, and oxidative stress index was more pronounced during anthracycline as taxane chemotherapy. There were no significant changes in pro-inflammatory cytokine levels. CONCLUSION Chemotherapy and dexamethasone as antiemetic resulted in significant bone loss, as evidenced by bone turnover markers. Further studies are required to understand the mechanism of chemotherapy-induced bone loss and the need for bone-strengthening agents during chemotherapy.
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Affiliation(s)
- Yadav Nisha
- Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Puducherry, India
| | - Biswajit Dubashi
- Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Puducherry, India.
| | - Zachariah Bobby
- Department of Biochemistry, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Puducherry, India
| | - Jaya Prakash Sahoo
- Department of Endocrinology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Puducherry, India
| | - Smita Kayal
- Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Puducherry, India
| | - Ramesh Ananthakrishnan
- Department of Radiodiagnosis, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Puducherry, India
| | - Vijay Bhaskar Reddy
- Department of Endocrinology, Vijay Diabetes, Thyroid and Endocrine Clinic, Saradambal Nagar, Puducherry, India
| | - Charles L
- Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Puducherry, India
| | - Prasanth Ganesan
- Department of Medical Oncology, Jawaharlal Institute of Postgraduate Medical Education & Research (JIPMER), Puducherry, India
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McGuire BD, Dees A, Hao L, Buckendahl P, Ogilvie AR, Sun H, Rezaee T, Barrett LO, Karim L, Dominguez-Bello MG, Bello NT, Shapses SA. A vitamin D deficient diet increases weight gain and compromises bone biomechanical properties without a reduction in BMD in adult female mice. J Steroid Biochem Mol Biol 2023; 231:106314. [PMID: 37088440 DOI: 10.1016/j.jsbmb.2023.106314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/04/2023] [Revised: 03/27/2023] [Accepted: 04/20/2023] [Indexed: 04/25/2023]
Abstract
Vitamin D contributes to the development and maintenance of bone. Evidence suggests vitamin D status can also alter energy balance and gut health. In young animals, vitamin D deficiency (VDD) negatively affects bone mineral density (BMD) and bone microarchitecture, and these effects may also occur due to chronic ethanol intake. However, evidence is limited in mature models, and addressing this was a goal of the current study. Seven-month-old female C57BL/6 mice (n = 40) were weight-matched and randomized to one of four ad libitum diets: control, alcohol (Alc), vitamin D deficient (0 IU/d), or Alc+VDD for 8 weeks. A purified (AIN-93) diet was provided with water or alcohol (10 %) ad libitum. Body weight and food intake were recorded weekly, and feces were collected at 0, 4, and 8 weeks. At the age of 9 months, intestinal permeability was assessed by oral gavage of fluorescein isothiocyanate-dextran. Thereafter, bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry. The microarchitecture of the distal femur was assessed by micro-computed tomography and biomechanical properties were evaluated by cyclic reference point indentation. VDD did not affect BMD or most bone microarchitecture parameters, however, the polar moment of inertia (p < 0.05) was higher in the VDD groups compared to vitamin D sufficient groups. VDD mice also had lower whole bone water content (p < 0.05) and a greater average unloading slope (p < 0.01), and energy dissipated (p < 0.01), indicating the femur displayed a brittle phenotype. In addition, VDD caused a greater increase in energy intake (p < 0.05), weight gain (p < 0.05), and a trend for higher intestinal permeability (p = 0.08). The gut microbiota of the VDD group had a reduction in alpha diversity (p < 0.05) and a lower abundance of ASVs from Rikenellaceae, Clostridia_UCG-014, Oscillospiraceae, and Lachnospiraceae (p < 0.01). There was little to no effect of alcohol supplementation on outcomes. Overall, these findings suggest that vitamin D deficiency causes excess weight gain and reduces the biomechanical strength of the femur as indicated by the higher average unloading slope and energy dissipated without an effect on BMD in a mature murine model.
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Affiliation(s)
- Brandon D McGuire
- Department of Nutritional Sciences, Rutgers University, New Brunswick, NJ, USA
| | - Azra Dees
- Department of Nutritional Sciences, Rutgers University, New Brunswick, NJ, USA
| | - Lihong Hao
- Department of Animal Sciences, Rutgers University, New Brunswick, NJ, USA
| | | | - Anna R Ogilvie
- Department of Nutritional Sciences, Rutgers University, New Brunswick, NJ, USA
| | - Haipeng Sun
- Department of Microbiology and Biochemistry, New Brunswick, NJ, USA
| | - Taraneh Rezaee
- Department of Bioengineering, University of Massachusetts Dartmouth, Dartmouth, MA 02747, USA
| | - Leland O Barrett
- Department of Bioengineering, University of Massachusetts Dartmouth, Dartmouth, MA 02747, USA
| | - Lamya Karim
- Department of Bioengineering, University of Massachusetts Dartmouth, Dartmouth, MA 02747, USA
| | - Maria Gloria Dominguez-Bello
- Department of Microbiology and Biochemistry, New Brunswick, NJ, USA; NJ Institute of Food, Nutrition and Health, Rutgers University, New Brunswick, NJ, USA
| | - Nicholas T Bello
- Department of Animal Sciences, Rutgers University, New Brunswick, NJ, USA; NJ Institute of Food, Nutrition and Health, Rutgers University, New Brunswick, NJ, USA
| | - Sue A Shapses
- Department of Nutritional Sciences, Rutgers University, New Brunswick, NJ, USA; NJ Institute of Food, Nutrition and Health, Rutgers University, New Brunswick, NJ, USA; Department of Medicine, Rutgers-Robert Wood Johnson Univ. Hospital, New Brunswick, NJ, USA.
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Lu EMC. The role of vitamin D in periodontal health and disease. J Periodontal Res 2023; 58:213-224. [PMID: 36537578 DOI: 10.1111/jre.13083] [Citation(s) in RCA: 22] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/28/2022] [Revised: 11/20/2022] [Accepted: 11/27/2022] [Indexed: 12/24/2022]
Abstract
Vitamin D plays an essential role in calcium and bone metabolism, immune regulation and possesses profound anti-inflammatory effects. Evidence suggests that low serum vitamin D is associated with increased severity of periodontitis, a chronic inflammatory condition characterised by destruction of the supporting tissues surrounding the tooth, which has several shared risk factors with other chronic non-communicable diseases. The biological functions of vitamin D are mediated by its strong anti-microbial, anti-inflammatory, and host modulatory properties. Experimental periodontitis models involving targeted deletion of 1α-hydroxylase, the enzyme responsible for the conversion of inactive substrate to active 1,25(OH)2 D3 (calcitriol), showed augmented alveolar bone loss and gingival inflammation. Vitamin D receptor (VDR) gene polymorphisms have also been associated with increased severity of periodontitis. Thus, the involvement of vitamin D in the pathogenesis of periodontitis is biological plausible. Clinical studies have consistently demonstrated an inverse relationship between serum 25OHD3 and periodontal disease inflammation. However, due to the paucity of well-designed longitudinal studies, there is less support for the impact of vitamin D status on periodontal disease progression and tooth loss. The evidence emphasises the importance of maintaining vitamin D sufficiency in supporting periodontal health. This review aims to first examine the biological mechanisms by which vitamin D might influence the pathogenesis of periodontal disease and second, discuss the clinical evidence which implicate the role of vitamin D in periodontal disease.
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Affiliation(s)
- Emily Ming-Chieh Lu
- Centre for Host-Microbiome Interactions, Faculty of Dentistry, Oral and Craniofacial Sciences, King's College London, Guy's Hospital, London, UK
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Gao X, Sun X, Cheng H, Ruzbarsky JJ, Mullen M, Huard M, Huard J. MRL/MpJ Mice Resist to Age-Related and Long-Term Ovariectomy-Induced Bone Loss: Implications for Bone Regeneration and Repair. Int J Mol Sci 2023; 24:ijms24032396. [PMID: 36768718 PMCID: PMC9916619 DOI: 10.3390/ijms24032396] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2022] [Revised: 01/14/2023] [Accepted: 01/21/2023] [Indexed: 01/27/2023] Open
Abstract
Osteoporosis and age-related bone loss increase bone fracture risk and impair bone healing. The need for identifying new factors to prevent or treat bone loss is critical. Previously, we reported that young MRL/MpJ mice have superior bone microarchitecture and biomechanical properties as compared to wild-type (WT) mice. In this study, MRL/MpJ mice were tested for resistance to age-related and long-term ovariectomy-induced bone loss to uncover potential beneficial factors for bone regeneration and repair. Bone tissues collected from 14-month-old MRL/MpJ and C57BL/6J (WT) mice were analyzed using micro-CT, histology, and immunohistochemistry, and serum protein markers were characterized using ELISAs or multiplex assays. Furthermore, 4-month-old MRL/MpJ and WT mice were subjected to ovariectomy (OV) or sham surgery and bone loss was monitored continuously using micro-CT at 1, 2, 4, and 6 months (M) after surgery with histology and immunohistochemistry performed at 6 M post-surgery. Sera were collected for biomarker detection using ELISA and multiplex assays at 6 M after surgery. Our results indicated that MRL/MpJ mice maintained better bone microarchitecture and higher bone mass than WT mice during aging and long-term ovariectomy. This resistance of bone loss observed in MRL/MpJ mice correlated with the maintenance of higher OSX+ osteoprogenitor cell pools, higher activation of the pSMAD5 signaling pathway, more PCNA+ cells, and a lower number of osteoclasts. Systemically, lower serum RANKL and DKK1 with higher serum IGF1 and OPG in MRL/MpJ mice relative to WT mice may also contribute to the maintenance of higher bone microarchitecture during aging and less severe bone loss after long-term ovariectomy. These findings may be used to develop therapeutic approaches to maintain bone mass and improve bone regeneration and repair due to injury, disease, and aging.
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Affiliation(s)
- Xueqin Gao
- Linda and Mitch Hart Center for Regenerative and Personalized Medicine, Steadman Philippon Research Institute, Vail, CO 81657, USA
- Department of Orthopaedic Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77054, USA
- Correspondence: (X.G.); (J.H.)
| | - Xuying Sun
- Department of Orthopaedic Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77054, USA
| | - Haizi Cheng
- Department of Orthopaedic Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77054, USA
| | - Joseph J. Ruzbarsky
- Linda and Mitch Hart Center for Regenerative and Personalized Medicine, Steadman Philippon Research Institute, Vail, CO 81657, USA
- The Steadman Clinic, Vail, CO 81657, USA
| | - Michael Mullen
- Linda and Mitch Hart Center for Regenerative and Personalized Medicine, Steadman Philippon Research Institute, Vail, CO 81657, USA
| | - Matthieu Huard
- Linda and Mitch Hart Center for Regenerative and Personalized Medicine, Steadman Philippon Research Institute, Vail, CO 81657, USA
| | - Johnny Huard
- Linda and Mitch Hart Center for Regenerative and Personalized Medicine, Steadman Philippon Research Institute, Vail, CO 81657, USA
- Department of Orthopaedic Surgery, McGovern Medical School, University of Texas Health Science Center at Houston, Houston, TX 77054, USA
- Correspondence: (X.G.); (J.H.)
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Berretta M, Quagliariello V, Bignucolo A, Facchini S, Maurea N, Di Francia R, Fiorica F, Sharifi S, Bressan S, Richter SN, Camozzi V, Rinaldi L, Scaroni C, Montopoli M. The Multiple Effects of Vitamin D against Chronic Diseases: From Reduction of Lipid Peroxidation to Updated Evidence from Clinical Studies. Antioxidants (Basel) 2022; 11:1090. [PMID: 35739987 PMCID: PMC9220017 DOI: 10.3390/antiox11061090] [Citation(s) in RCA: 14] [Impact Index Per Article: 4.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/27/2022] [Revised: 05/27/2022] [Accepted: 05/28/2022] [Indexed: 02/01/2023] Open
Abstract
BACKGROUND Vitamin D exerts multiple beneficial effects in humans, including neuronal, immune, and bone homeostasis and the regulation of cardiovascular functions. Recent studies correlate vitamin D with cancer cell growth and survival, but meta-analyses on this topic are often not consistent. METHODS A systematic search of the PubMed database and the Clinical Trial Register was performed to identify all potentially relevant English-language scientific papers containing original research articles on the effects of vitamin D on human health. RESULTS In this review, we analyzed the antioxidant and anti-inflammatory effects of vitamin D against acute and chronic diseases, focusing particularly on cancer, immune-related diseases, cardiomyophaties (including heart failure, cardiac arrhythmias, and atherosclerosis) and infectious diseases. CONCLUSIONS Vitamin D significantly reduces the pro-oxidant systemic and tissue biomarkers involved in the development, progression, and recurrence of chronic cardiometabolic disease and cancer. The overall picture of this review provides the basis for new randomized controlled trials of oral vitamin D supplementation in patients with cancer and infectious, neurodegenerative, and cardiovascular diseases aimed at reducing risk factors for disease recurrence and improving quality of life.
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Affiliation(s)
- Massimiliano Berretta
- Department of Clinical and Experimental Medicine, University of Messina, 98100 Messina, Italy
| | - Vincenzo Quagliariello
- Division of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80121 Naples, Italy; (V.Q.); (N.M.)
| | - Alessia Bignucolo
- Experimental and Clinical Pharmacology, Centro di Riferimento Oncologico di Aviano (CRO) IRCCS, Via Franco Gallini 2, 33081 Aviano, Italy;
| | - Sergio Facchini
- Oncology Operative Unit, Santa Maria delle Grazie Hospital, 80078 Naples, Italy;
| | - Nicola Maurea
- Division of Cardiology, Istituto Nazionale Tumori-IRCCS-Fondazione G. Pascale, 80121 Naples, Italy; (V.Q.); (N.M.)
| | - Raffaele Di Francia
- Gruppo Oncologico Ricercatori Italiani, GORI Onlus, 33170 Pordenone, Italy;
- Italian Association of Pharmacogenomics and Molecular Diagnostics (IAPharmagen), 60126 Ancona, Italy
| | - Francesco Fiorica
- Department of Radiation Oncology and Nuclear Medicine, AULSS 9 Scaligera, 37100 Verona, Italy;
| | - Saman Sharifi
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35122 Padova, Italy; (S.S.); (S.B.); (M.M.)
| | - Silvia Bressan
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35122 Padova, Italy; (S.S.); (S.B.); (M.M.)
- Veneto Institute of Molecular Medicine, 35129 Padova, Italy
| | - Sara N. Richter
- Department of Molecular Medicine, University of Padova, Via A. Gabelli 63, 35121 Padova, Italy; (S.N.R.); (C.S.)
| | - Valentina Camozzi
- Endocrinology Unit, Department of Medicine (DIMED), University of Padua, 35100 Padua, Italy;
| | - Luca Rinaldi
- Department of Advanced Medical and Surgery Sciences, Internal Medicine COVID Center, University of Campania Luigi Vanvitelli, 81100 Naples, Italy;
| | - Carla Scaroni
- Department of Molecular Medicine, University of Padova, Via A. Gabelli 63, 35121 Padova, Italy; (S.N.R.); (C.S.)
| | - Monica Montopoli
- Department of Pharmaceutical and Pharmacological Sciences, University of Padova, 35122 Padova, Italy; (S.S.); (S.B.); (M.M.)
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11
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Barratt KR, Sawyer RK, Atkins GJ, St-Arnaud R, Anderson PH. Vitamin D supplementation improves bone mineralisation independent of dietary phosphate in male X-linked hypophosphatemic (Hyp) mice. Bone 2021; 143:115767. [PMID: 33232838 DOI: 10.1016/j.bone.2020.115767] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/22/2020] [Revised: 11/16/2020] [Accepted: 11/19/2020] [Indexed: 12/21/2022]
Abstract
The disorder of X-linked hypophosphatemia (XLH), results in the supressed renal production of active 1α,25-dihydroxyvitamin D (1,25(OH)2D) due to elevated fibroblast growth factor-23 (FGF23) levels. While adequate 25(OH)D levels are generally associated with improved mineralisation of the skeleton independent of circulating 1,25(OH)2D levels, it is unclear whether raising 25(OH)D to sufficiently high levels through dietary vitamin D3 administration contributes to improving bone mineralisation in the murine homolog for XLH, Hyp mice. Three-week-old male Hyp mice were fed one of four diets containing either 1000 IU (C) or 20,000 IU (D) vitamin D3/kg diet with either 0.35% phosphate or 1.25% phosphate (P) until 12 weeks of age (n = 12/group). When compared to C-fed mice, D-fed mice significantly elevated serum 25(OH)D levels to 72.8 ± 4.9 nmol/L (2-fold, p < 0.001) and increased both cortical bone mineral density (15%, p < 0.01), and vertebral trabecular BV/TV% (80%, p < 0.001), despite persistent hypophosphatemia and normocalcemia. The increase in bone volume was associated with improved Tb.Th (12%, p < 0.01) and Tb.N (63%, p < 0.001). Unlike with D-diet, P-fed mice resulted in increased femoral (15%, p < 0.001) and vertebral (12%, p < 0.001) length, and a 34% increase in vertebral trabecular BV/TV% when compared to control fed animals (p < 0.001). However, the addition of the high P diet to the high D diet did not result in additive effects on bone mineralisation when compared to the effects of D diet alone, despite serum 25(OH)D levels elevated to 118.8 ± 8.6 nmol/L. In D-fed mice, the increase in bone mineral density and volume was associated with reduced osteoid volume, reduced ObS/BS, and a trend for reduced serum PTH levels, suggesting reduced bone turnover in these animals. Thus, elevating serum 25(OH)D levels independently improves bone mineralisation in Hyp mice without causing hypercalcemia, suggesting that further studies are required in XLH patients to establish the role of increasing 25(OH)D levels in improving bone mineralisation.
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Affiliation(s)
- Kate R Barratt
- University of South Australia, Clinical and Health Sciences, Health and Biomedical Innovation, Adelaide, SA 5000, Australia.
| | - Rebecca K Sawyer
- University of South Australia, Clinical and Health Sciences, Health and Biomedical Innovation, Adelaide, SA 5000, Australia.
| | - Gerald J Atkins
- Centre for Orthopaedic & Trauma Research, The University of Adelaide, Adelaide, SA 5000, Australia.
| | - Rene St-Arnaud
- Shriners Hospitals for Children - Canada and McGill University, Montreal, QC H4A 0A9, Canada.
| | - Paul H Anderson
- University of South Australia, Clinical and Health Sciences, Health and Biomedical Innovation, Adelaide, SA 5000, Australia.
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12
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Ribbans WJ, Aujla R, Dalton S, Nunley JA. Vitamin D and the athlete-patient: state of the art. J ISAKOS 2020; 6:46-60. [PMID: 33833045 DOI: 10.1136/jisakos-2020-000435] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/14/2020] [Revised: 07/20/2020] [Accepted: 07/28/2020] [Indexed: 11/04/2022]
Abstract
Vitamin D deficiency is common in athletes. The conventional measurement of vitamin D levels provides a general indicator of body stores. However, there are nuances in its interpretation as values of 25(OH)D do not correlate absolutely with the amount of 'bioavailable' vitamin to the cells. Vitamin D should be regarded as a hormone and influences between 5% and 10% of our total genome. Determining the precise effect of the vitamin, isolated from the actions of other cofactors, is not straightforward and restricts our complete understanding of all of its actions. Deficiency has harmful effects on not only bone and muscle but also wider areas, including immunity and respiratory and neurological activities. More caution should be applied regarding the ability of supranormal vitamin D levels to elevate athletic performance. Hopefully, future research will shed more light on optimal levels of vitamin D and supplementation regimes, and improved understanding of its intracellular control of our genetic mechanisms and how extrinsic influences modify its activity.
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Affiliation(s)
- William J Ribbans
- Faculty of Health, Education and Society, University of Northampton, Northampton, Northamptonshire, UK
| | - Randeep Aujla
- Perth Orthopaedic and Sports Medicine Centre, West Perth, Western Australia, Australia
| | - Seamus Dalton
- North Sydney Sports Medicine, Sydney, New South Wales, Australia
| | - James A Nunley
- Duke Orthopedics, Duke University, Durham, North Carolina, USA
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13
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Prabhakar O, Bhuvaneswari M. Role of diet and lifestyle modification in the management of nonalcoholic fatty liver disease and type 2 diabetes. Tzu Chi Med J 2020; 33:135-145. [PMID: 33912410 PMCID: PMC8059462 DOI: 10.4103/tcmj.tcmj_86_20] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/23/2020] [Revised: 05/11/2020] [Accepted: 06/08/2020] [Indexed: 12/15/2022] Open
Abstract
Nonalcoholic fatty liver disease (NAFLD) is considered as the hepatic evidence of insulin resistance which is the hallmark of type 2 diabetes. NAFLD is considered as the risk factor for developing type 2 diabetes and has a high frequency of occurrence in those with existing type 2 diabetes. Compared with patients with only NAFLD or type 2 diabetes, these patients show a poor metabolic profile and increase mortality. Hence, effective treatment strategies are necessary. Here, we review the role of diet and lifestyle modification in the management of NAFLD and type 2 diabetes. Based on the available studies, it has been shown that the addition of any kind of physical activity or exercise is beneficial for patients with both NAFLD and type 2 diabetes. Proper dietary management leads to weight loss are also effective in improving metabolic parameters in patients with both NAFLD and type 2 diabetes. In conclusion, it is clear that increasing physical activity or exercise is effective in improving metabolic parameters in patients who are suffering with both NAFLD and type 2 diabetes.
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Affiliation(s)
- Orsu Prabhakar
- Department of Pharmacology, GITAM Institute of Pharmacy, Visakhapatnam, Andhra Pradesh, India
| | - Mylipilli Bhuvaneswari
- Department of Pharmacology, GITAM Institute of Pharmacy, Visakhapatnam, Andhra Pradesh, India
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14
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Badger-Emeka LI, AlJaziri ZY, Almulhim CF, Aldrees AS, AlShakhs ZH, AlAithan RI, Alothman FA. Vitamin D Supplementation in Laboratory-Bred Mice: An In Vivo Assay on Gut Microbiome and Body Weight. Microbiol Insights 2020; 13:1178636120945294. [PMID: 32782431 PMCID: PMC7388085 DOI: 10.1177/1178636120945294] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/08/2019] [Accepted: 07/01/2020] [Indexed: 01/11/2023] Open
Abstract
Saudi Arabia is in a tropical geographical region with a population that has
access to adequate diet. There is, however, a high level of vitamin D deficiency
in the Kingdom, comorbid with other disease. There is the postulation of a
correlation between a healthy gut microbiota and balanced levels of serum
vitamin D. This investigation looks into the effect of vitamin D supplementation
on the gut flora of laboratory-bred mice as well as any possible association on
body weight. BALB/C mice weighing between 34 and 35.8 g were divided into 4
groups and placed on daily doses of vitamin D of 3.75 µg (low dose), 7.5 µg
(normal dose), and 15 µg (high dose). The fourth group was the control group
that did not receive any supplementation with vitamin D. Body weights were
monitored on weekly basis, while faecal samples from the rectum were obtained
for microbial culturing and the monitoring of bacterial colony count using the
Vitek 2 Compact automated system (BioMerieux, Marcy-l’Etoile, France) according
to manufacturer’s guidelines. The data presented as mean ± SD, while significant
differences were determined with 2-way analysis of variance in comparing
differences within and between treatment groups. The different doses of vitamin
D showed varying effects on the body weight and gut microbial colonies of the
mice. There was a highly significant difference between the control, 15 µg
(high), and 7.5 µg (normal) dose groups. This is suggestive that supplementation
with vitamin D could a role in the gut microbial flora in the gut which could
reflect in changes in body weight.
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Affiliation(s)
- Lorina Ineta Badger-Emeka
- College of Medicine, King Faisal University, Al-Ahsa, Saudi Arabia.,Department of Biomedical Sciences, Microbiology Division. College of Medicine, King Faisal University, Al-Ahsa. Saudi Arabia
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15
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Is vitamin D deficiency behind the scenes for high incidence of Giant cell tumor amongst the Indian population? Unraveling the vitamin D – RANKL association. Med Hypotheses 2019; 123:67-71. [DOI: 10.1016/j.mehy.2018.12.010] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2018] [Accepted: 12/20/2018] [Indexed: 01/16/2023]
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16
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Itkonen ST, Pajula ET, Dowling KG, Hull GLJ, Cashman KD, Lamberg-Allardt CJE. Poor bioavailability of vitamin D2 from ultraviolet-irradiated D2-rich yeast in rats. Nutr Res 2018; 59:36-43. [DOI: 10.1016/j.nutres.2018.07.008] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/23/2018] [Revised: 07/09/2018] [Accepted: 07/10/2018] [Indexed: 12/19/2022]
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17
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Whitty C, Wardale RJ, Henson FM. The regulation of sclerostin by cathepsin K in periodontal ligament cells. Biochem Biophys Res Commun 2018; 503:550-555. [DOI: 10.1016/j.bbrc.2018.05.160] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2018] [Accepted: 05/23/2018] [Indexed: 12/20/2022]
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18
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Yoon SH, Sugamori KS, Grynpas MD, Mitchell J. Effect of 25-HydroxyVitamin D Deficiency and Its Interaction with Prednisone Treatment on Musculoskeletal Health in Growing Mdx Mice. Calcif Tissue Int 2018; 103:311-323. [PMID: 29691609 DOI: 10.1007/s00223-018-0423-3] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/16/2018] [Accepted: 04/11/2018] [Indexed: 01/28/2023]
Abstract
Duchenne muscular dystrophy (DMD) results from genetic mutations of the gene encoding dystrophin, leading to muscle inflammation and degeneration that is typically treated with glucocorticoids. DMD and its treatment with glucocorticoids result in poor bone health and high risk of fractures. Insufficient levels of 25-hydroxyvitamin D (25-hydroxy D) that may contribute to weakened bone are routinely found in DMD patients. To determine the effect of 25-hydroxy D deficiency, this study examined the effects of low vitamin D dietary intake with and without glucocorticoids on the musculoskeletal system of the Mdx mouse model of DMD. At 10 weeks of age, Mdx mice on control diet had low trabecular bone mineral density of distal femurs and lumbar vertebrae with increased osteoclast numbers compared to wild-type mice. Low vitamin D intake resulted in 25-hydroxy D deficiency but had no effect on trabecular or cortical bone. Cortical bone loss and bone weakness were induced by glucocorticoids while they improved muscle grip strength in Mdx mice. 25-hydroxy D deficiency did not result in any significant effects on growing bone or muscle in the Mdx mice. In combination with glucocorticoid treatment, low 25-hydroxy D resulted in no change in cortical bone mineral density but bone ductility was significantly increased suggesting lower bone mineralization.
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Affiliation(s)
- Sung-Hee Yoon
- Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada
- Lunenfeld-Tanenbaum Research Institute, Mount Sinai Health System, Toronto, ON, Canada
| | - Kim S Sugamori
- Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada
| | - Marc D Grynpas
- Lunenfeld-Tanenbaum Research Institute, Mount Sinai Health System, Toronto, ON, Canada
| | - Jane Mitchell
- Department of Pharmacology and Toxicology, University of Toronto, Toronto, ON, Canada.
- Department of Pharmacology and Toxicology, University of Toronto, 1 King's College Circle, Room 4342, Toronto, ON, M5S 1A8, Canada.
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19
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Pieralice S, Vigevano F, Del Toro R, Napoli N, Maddaloni E. Lifestyle Management of Diabetes: Implications for the Bone-Vascular Axis. Curr Diab Rep 2018; 18:84. [PMID: 30121859 DOI: 10.1007/s11892-018-1060-y] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/15/2022]
Abstract
PURPOSE OF REVIEW To describe the main pathways involved in the interplay between bone and cardiovascular disease and to highlight the possible impact of physical activity and medical nutrition therapy on the bone-vascular axis. RECENT FINDINGS Diabetes increases the risk of both cardiovascular disease and bone fragility fractures, sharing common pathogenic pathways, including OPG/RANK/RANKL, the FGF23/Klotho axis, calciotropic hormones, and circulating osteogenic cells. This may offer new therapeutic targets for future treatment strategies. As lifestyle intervention is the cornerstone of diabetes treatment, there is potential for an impact on the bone-vascular axis. Evidence published suggests the bone-vascular axis encompasses key pathways for cardiovascular disease. This, along with studies showing physical activity plays a crucial role in the prevention of both bone fragility and cardiovascular disease, suggests that lifestyle intervention incorporating exercise and diet may be helpful in managing skeletal health decline in diabetes. Studies investigating the controversial role of high-fiber diet and dietary vitamin D/calcium on bone and cardiovascular health suggest an overall benefit, but further investigations are needed in this regard.
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Affiliation(s)
- Silvia Pieralice
- Department of Medicine, Unit of Endocrinology and Diabetes, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 21, 00128, Rome, Italy
| | - Francesca Vigevano
- Department of Medicine, Unit of Endocrinology and Diabetes, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 21, 00128, Rome, Italy
| | - Rossella Del Toro
- Department of Medicine, Unit of Endocrinology and Diabetes, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 21, 00128, Rome, Italy
| | - Nicola Napoli
- Department of Medicine, Unit of Endocrinology and Diabetes, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 21, 00128, Rome, Italy
| | - Ernesto Maddaloni
- Department of Medicine, Unit of Endocrinology and Diabetes, Campus Bio-Medico University of Rome, Via Alvaro del Portillo 21, 00128, Rome, Italy.
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20
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Effect of the dietary delivery matrix on vitamin D3 bioavailability and bone mineralisation in vitamin-D3-deficient growing male rats. Br J Nutr 2017; 119:143-152. [PMID: 29268806 DOI: 10.1017/s0007114517003518] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/05/2022]
Abstract
This study assessed bioavailability and utilisation of vitamin D3 in two feeding trials using young, growing Sprague-Dawley male rats. Trial one fed animals standard AIN-93G diet (casein protein) containing no vitamin D3 and goat or cow skimmed milk supplemented with vitamin D3. Trial two fed animals modified dairy-free AIN-93G diet (egg albumin) containing no vitamin D3 and goat or cow skimmed or full-fat milk supplemented with vitamin D3. Control groups received AIN-93G diets with or without vitamin D, and water. At 8 weeks of age, blood samples were collected for vitamin and mineral analysis, and femurs and spines were collected for assessment of bone mineralisation and strength. In both trials, analyses showed differences in bioavailability of vitamin D3, with ratios of serum 25-hydroxyvitamin D3 to vitamin D3 intake more than 2-fold higher in groups drinking supplemented milk compared with groups fed supplemented solid food. Bone mineralisation was higher in groups drinking supplemented milk compared with groups fed supplemented solid food, for both trials (P<0·05). There was no difference in the parameters tested between skimmed milk and full-fat milk or between cow milk and goat milk. Comparison of the two trials suggested that dietary protein source promoted bone mineralisation in a growing rat model: modified AIN-93G with egg albumin produced lower bone mineralisation compared with standard AIN-93G with casein. Overall, this study showed that effects of vitamin D3 deficiency in solid diets were reversed by offering milk supplemented with vitamin D3, and suggests that using milk as a vehicle to deliver vitamin D is advantageous.
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21
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Luo Z, Liu Y, Liu Y, Chen H, Shi S, Liu Y. Cellular and molecular mechanisms of alcohol-induced osteopenia. Cell Mol Life Sci 2017; 74:4443-4453. [PMID: 28674727 PMCID: PMC11107754 DOI: 10.1007/s00018-017-2585-y] [Citation(s) in RCA: 62] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/22/2017] [Revised: 05/24/2017] [Accepted: 06/27/2017] [Indexed: 02/07/2023]
Abstract
Alcoholic beverages are widely consumed, resulting in a staggering economic cost in different social and cultural settings. Types of alcohol consumption vary from light occasional to heavy, binge drinking, and chronic alcohol abuse at all ages. In general, heavy alcohol consumption is widely recognized as a major epidemiological risk factor for chronic diseases and is detrimental to many organs and tissues, including bones. Indeed, recent findings demonstrate that alcohol has a dose-dependent toxic effect in promoting imbalanced bone remodeling. This imbalance eventually results in osteopenia, an established risk factor for osteoporosis. Decreased bone mass and strength are major hallmarks of osteopenia, which is predominantly attributed not only to inhibition of bone synthesis but also to increased bone resorption through direct and indirect pathways. In this review, we present knowledge to elucidate the epidemiology, potential pathogenesis, and major molecular mechanisms and cellular effects that underlie alcoholism-induced bone loss in osteopenia. Novel therapeutic targets for correcting alcohol-induced osteopenia are also reviewed, such as modulation of proinflammatory cytokines and Wnt and mTOR signaling and the application of new drugs.
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Affiliation(s)
- Zhenhua Luo
- Laboratory of Tissue Regeneration and Immunology, Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Tian Tan Xi Li No. 4, Beijing, 100050, People's Republic of China
| | - Yao Liu
- Liaoning Province Key Laboratory of Oral Disease, 117 Nanjing North Street, Shenyang, 110002, People's Republic of China
| | - Yitong Liu
- Laboratory of Tissue Regeneration and Immunology, Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Tian Tan Xi Li No. 4, Beijing, 100050, People's Republic of China
| | - Hui Chen
- Liaoning Province Key Laboratory of Oral Disease, 117 Nanjing North Street, Shenyang, 110002, People's Republic of China
| | - Songtao Shi
- Department of Anatomy and Cell Biology, University of Pennsylvania, School of Dental Medicine, Philadelphia, PA, USA
| | - Yi Liu
- Laboratory of Tissue Regeneration and Immunology, Department of Periodontics, Beijing Key Laboratory of Tooth Regeneration and Function Reconstruction, School of Stomatology, Capital Medical University, Tian Tan Xi Li No. 4, Beijing, 100050, People's Republic of China.
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Abstract
PURPOSE OF REVIEW In addition to the actions of the endocrine hormone, 1alpha,25-dihydroxyvitamin D (1,25(OH)2D) in stimulating intestinal calcium absorption, the regulation of bone mineral metabolism by 1,25(OH)2D is also considered an important contributor to calcium homeostasis. However, recent evidence suggest that 1,25(OH)2D acting either via endocrine or autocrine pathways plays varied roles in bone, which suggests that vitamin D contributes to the maintenance of bone mineral in addition to its catabolic roles. This review highlights the contrasting evidence for the direct action for vitamin D metabolism and activity in bone. RECENT FINDINGS Numerous cells within bone express vitamin D receptor (VDR), synthesise and catabolise 1,25(OH)2D via 25-hydroxyvitamin D 1alpha-hydroxylase (CYP27B1), and 25-hydroxyvitamin D 24-hydroxylase (CYP24A1) enzymes, respectively. Recent evidence suggests that all three genes are required to regulate processes of bone resorption, mineralization and fracture repair. The actions of vitamin D in bone appear to negatively or positively regulate bone mineral depending on the physiological and pathological circumstances, suggesting that vitamin D plays pleiotropic roles in bone.
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Affiliation(s)
- Paul H Anderson
- Musculoskeletal Biology Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, 5001, Australia.
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23
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Poggiogalle E, Donini LM, Lenzi A, Chiesa C, Pacifico L. Non-alcoholic fatty liver disease connections with fat-free tissues: A focus on bone and skeletal muscle. World J Gastroenterol 2017; 23:1747-1757. [PMID: 28348479 PMCID: PMC5352914 DOI: 10.3748/wjg.v23.i10.1747] [Citation(s) in RCA: 36] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2016] [Revised: 01/30/2017] [Accepted: 02/17/2017] [Indexed: 02/06/2023] Open
Abstract
The estimates of global incidence and prevalence of non-alcoholic fatty liver disease (NAFLD) are worrisome, due to the parallel burden of obesity and its metabolic complications. Indeed, excess adiposity and insulin resistance represent two of the major risk factors for NAFLD; interestingly, in the last years a growing body of evidence tended to support a novel mechanistic perspective, in which the liver is at the center of a complex interplay involving organs and systems, other than adipose tissue and glucose homeostasis. Bone and the skeletal muscle are fat- free tissues which appeared to be independently associated with NAFLD in several cross-sectional studies. The deterioration of bone mineral density and lean body mass, leading to osteoporosis and sarcopenia, respectively, are age-related processes. The prevalence of NAFLD also increases with age. Beyond physiological aging, the three conditions share some common underlying mechanisms, and their elucidations could be of paramount importance to design more effective treatment strategies for the management of NAFLD. In this review, we provide an overview on epidemiological data as well as on potential contributors to the connections of NAFLD with bone and skeletal muscle.
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24
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Seldeen KL, Pang M, Rodríguez-Gonzalez M, Hernandez M, Sheridan Z, Yu P, Troen BR. A mouse model of vitamin D insufficiency: is there a relationship between 25(OH) vitamin D levels and obesity? Nutr Metab (Lond) 2017; 14:26. [PMID: 28293271 PMCID: PMC5346213 DOI: 10.1186/s12986-017-0174-6] [Citation(s) in RCA: 27] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2016] [Accepted: 02/13/2017] [Indexed: 01/08/2023] Open
Abstract
Background Vitamin D insufficiency (serum 25-OH vitamin D > 10 ng/ml and < 30 ng/ml) is prevalent in the obese (body mass index (BMI) > 30 kg/m2), yet relationships between the two are poorly understood. Objectives of this study include identification of the impact of obesity on reducing serum 25-OH vitamin D concentration, particularly in response to altered vitamin D3 supplementation, and to elucidate the longitudinal impact of serum 25-OH vitamin D on body mass index. Methods Twenty four-week-old lean and obese male C57BL/6 J mice were fed low, standard, or high levels of cholecalciferol supplementation and followed for 24 weeks. Longitudinal measurements include serum 25-OH and 1,25-(OH)2 vitamin D, intact PTH, and calcium concentrations, as well as BMI, bone density and body fat/lean mass. Results Baseline serum 25-OH concentrations were not different in lean and obese mice (lean 32.8 ± 4.4 ng/ml versus obese 30.9 ± 1.6 ng/ml p = 0.09). Lean mice receiving low supplementation exhibited rapid declines in serum 25-OH vitamin D concentrations, falling from 33.4 ± 5.4 ng/ml to 14.5 ± 3.4 ng/ml after 2 weeks, while obese mice declined at a lower rate, falling from 30.9 ± 1.5 to 19.0 ± 0.9 ng/ml within the same time period. Surprisingly, high vitamin D3 supplementation did not substantially increase serum vitamin D concentrations above standard supplementation, in either lean or obese mice. No differences in serum 1,25-(OH)2 vitamin D, intact parathyroid hormone (PTH) or serum calcium were observed between lean and obese mice within the same vitamin D supplementation group. Yet obese mice exhibited lower serum calcitriol, higher serum PTH, and lower bone mineral density (BMD) than did lean mice. Additionally, neither body mass index nor body fat % was significantly correlated with vitamin D concentrations. Interestingly, lean mice with high vitamin D supplementation consumed significantly more food than did lean mice with standard or low supplementation (14.6 ± 1.7 kcal/mouse/day versus 11.8 ± 1.4 and 12.3 ± 1.7 respectively, p < 0.0001 for both). Conclusions Low cholecalciferol supplementation in both lean and obese mice significantly and sustainably reduces serum 25-OH vitamin D concentrations. Interestingly, obesity slowed the rate of decline. Over the period of the study, vitamin D insufficiency was not subsequently correlated with greater BMI/body fat, although lean mice with high supplementation consumed greater calories with no apparent BMI increase.
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Affiliation(s)
- Kenneth L Seldeen
- Division of Geriatrics and Palliative Medicine, Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo and Research Service, Veterans Affairs Western New York Healthcare System, Buffalo, NY USA
| | - Manhui Pang
- Division of Geriatrics and Palliative Medicine, Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo and Research Service, Veterans Affairs Western New York Healthcare System, Buffalo, NY USA
| | - Maria Rodríguez-Gonzalez
- Division of Geriatrics and Palliative Medicine, Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo and Research Service, Veterans Affairs Western New York Healthcare System, Buffalo, NY USA
| | - Mireya Hernandez
- Division of Geriatrics and Palliative Medicine, Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo and Research Service, Veterans Affairs Western New York Healthcare System, Buffalo, NY USA
| | - Zachary Sheridan
- Division of Geriatrics and Palliative Medicine, Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo and Research Service, Veterans Affairs Western New York Healthcare System, Buffalo, NY USA
| | - Ping Yu
- Division of Geriatrics and Palliative Medicine, Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo and Research Service, Veterans Affairs Western New York Healthcare System, Buffalo, NY USA
| | - Bruce R Troen
- Division of Geriatrics and Palliative Medicine, Department of Medicine, Jacobs School of Medicine and Biomedical Sciences, University at Buffalo and Research Service, Veterans Affairs Western New York Healthcare System, Buffalo, NY USA
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25
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Siddiqui JA, Partridge NC. Physiological Bone Remodeling: Systemic Regulation and Growth Factor Involvement. Physiology (Bethesda) 2017; 31:233-45. [PMID: 27053737 DOI: 10.1152/physiol.00061.2014] [Citation(s) in RCA: 275] [Impact Index Per Article: 34.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/06/2023] Open
Abstract
Bone remodeling is essential for adult bone homeostasis. It comprises two phases: bone formation and resorption. The balance between the two phases is crucial for sustaining bone mass and systemic mineral homeostasis. This review highlights recent work on physiological bone remodeling and discusses our knowledge of how systemic and growth factors regulate this process.
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Affiliation(s)
- Jawed A Siddiqui
- Department of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, New York
| | - Nicola C Partridge
- Department of Basic Science and Craniofacial Biology, New York University College of Dentistry, New York, New York
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26
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Mallya SM, Corrado KR, Saria EA, Yuan FNF, Tran HQ, Saucier K, Atti E, Tetradis S, Arnold A. Modeling vitamin D insufficiency and moderate deficiency in adult mice via dietary cholecalciferol restriction. Endocr Res 2016; 41:290-299. [PMID: 26906176 PMCID: PMC4995161 DOI: 10.3109/07435800.2016.1141937] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022]
Abstract
PURPOSE We sought to develop and characterize a model of human vitamin D nutritional insufficiency/deficiency in the adult mouse, which could have broad utility in examining health consequences of this common condition. METHODS Adult mice were fed diets containing cholecalciferol contents of 0.05 IU/g, 0.25 IU/g, 0.5 IU/g or 1.5 IU/g for four months. We studied induction of steady-state vitamin D insufficiency, and its consequences on primary cholecalciferol metabolite levels, calcium homeostasis, parathyroid physiology, and bone morphology. RESULTS All diets were well tolerated, without adverse effects on body weight. Diets containing 0.05 IU/g and 0.25 IU/g cholecalciferol significantly lowered serum 25-hydroxyvitamin D levels (median 25OHD, 10.5 ng/ml, and 21.6 ng/ml, respectively), starting as early as one month following initiation of the diets, maintained through the four-month experimental period. The 0.05 IU/g diet significantly decreased 1,25-dihydroxyvitamin D (1,25OH2D) levels (median, 78 pg/ml). Despite these decreased 25OHD and 1,25OH2D levels, the diets did not alter parathyroid gland morphology or parathyroid cell proliferation. There were no statistical differences in the serum total calcium and serum PTH levels among the various dietary groups. Furthermore, the 0.05 IU/g diet did not cause any alterations in the cortical and trabecular bone morphology, as determined by microCT. CONCLUSIONS The dietary manipulations yielded states of vitamin D insufficiency or modest deficiency in adult mice, with no overtly detectable impact on parathyroid and bone physiology, and calcium homeostasis. This model system may be of value to study health effects of vitamin D insufficiency/deficiency especially on extraskeletal phenotypes such as cancer susceptibility or immune function.
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Affiliation(s)
- Sanjay M. Mallya
- Section of Oral & Maxillofacial Radiology, UCLA School of Dentistry, Los Angeles, CA
- Co-corresponding authors: Sanjay M. Mallya, BDS, MDS, PhD, 10833 Le Conte Avenue, Los Angeles, CA 90095-1668, Tel: 310 825 1689 Fax: 310 825 7232, , Andrew Arnold, MD, 263 Farmington Avenue, Farmington, CT 06030-3101, Tel: 860 679 7640 Fax: 860 679 7640,
| | - Kristin R. Corrado
- Center for Molecular Medicine, University of Connecticut School of Medicine, Farmington, CT
| | - Elizabeth A. Saria
- Center for Molecular Medicine, University of Connecticut School of Medicine, Farmington, CT
| | - Feng-ning Frank Yuan
- Section of Oral & Maxillofacial Radiology, UCLA School of Dentistry, Los Angeles, CA
| | - Huy Q. Tran
- Section of Oral & Maxillofacial Radiology, UCLA School of Dentistry, Los Angeles, CA
| | - Kirsten Saucier
- Center for Molecular Medicine, University of Connecticut School of Medicine, Farmington, CT
| | - Elisa Atti
- Section of Oral & Maxillofacial Radiology, UCLA School of Dentistry, Los Angeles, CA
| | - Sotirios Tetradis
- Section of Oral & Maxillofacial Radiology, UCLA School of Dentistry, Los Angeles, CA
| | - Andrew Arnold
- Center for Molecular Medicine, University of Connecticut School of Medicine, Farmington, CT
- Co-corresponding authors: Sanjay M. Mallya, BDS, MDS, PhD, 10833 Le Conte Avenue, Los Angeles, CA 90095-1668, Tel: 310 825 1689 Fax: 310 825 7232, , Andrew Arnold, MD, 263 Farmington Avenue, Farmington, CT 06030-3101, Tel: 860 679 7640 Fax: 860 679 7640,
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Ryan JW, Starczak Y, Tsangari H, Sawyer RK, Davey RA, Atkins GJ, Morris HA, Anderson PH. Sex-related differences in the skeletal phenotype of aged vitamin D receptor global knockout mice. J Steroid Biochem Mol Biol 2016; 164:361-368. [PMID: 26690785 DOI: 10.1016/j.jsbmb.2015.12.005] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/11/2015] [Revised: 11/09/2015] [Accepted: 12/06/2015] [Indexed: 10/22/2022]
Abstract
The role of the vitamin D receptor (VDR) in maintaining skeletal health appears to be complex and dependent on the physiological context. Global Vdr deletion in a mouse model (Vdr-/-) results in hypocalcemia, secondary hyperparathyroidism and bone features typical of vitamin D-dependent rickets type II. When weanling Vdr-/- mice are fed a diet containing high levels of calcium, phosphorus and lactose, termed the rescue diet, normalisation of serum calcium, phosphate and parathyroid hormone levels results in prevention of rickets at 10 weeks of age. However, 17 week old male Vdr-/- mice, fed the rescue diet, have been reported as osteopenic due to a decrease in bone formation when compared to wild type mice. We now report confirmation of this finding with further data on the effect of the rescue diet on appendicular and axial skeletal structures in male and female Vdr-/- mice at 26 weeks of age compared to Vdr+/- controls. All Vdr-/- mice were normocalcemic with no evidence of any mineralization defect. However, male Vdr-/- mice exhibited significantly reduced mineral in femoral and vertebral bones when compared to control littermate Vdr+/- mice, consistent with the previously reported data. In contrast, 26-week-old female Vdr-/- mice demonstrated significantly increased femoral trabecular bone volume although there was decreased vertebral trabecular bone volume, similar to males, and femoral cortical bone volume was unchanged. Thus, the Vdr-/- mouse model displays sex- and site-specific differences in skeletal structures with long-term feeding of a rescue diet. Although the global Vdr-/- ablation does not permit the determination of skeletal mechanisms producing these differences, these data confirm skeletal changes even when fed the rescue diet.
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Affiliation(s)
- Jackson W Ryan
- School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, SA 5001, Australia; Department of Medicine, Austin Health, University of Melbourne, Heidelberg, VIC, Australia; Centre for Orthopaedic and Trauma Research, School of Medicine, University of Adelaide, Adelaide, SA 5001, Australia
| | - Yolandi Starczak
- School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, SA 5001, Australia; Department of Medicine, Austin Health, University of Melbourne, Heidelberg, VIC, Australia; Centre for Orthopaedic and Trauma Research, School of Medicine, University of Adelaide, Adelaide, SA 5001, Australia
| | - Helen Tsangari
- School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, SA 5001, Australia; Department of Medicine, Austin Health, University of Melbourne, Heidelberg, VIC, Australia; Centre for Orthopaedic and Trauma Research, School of Medicine, University of Adelaide, Adelaide, SA 5001, Australia
| | - Rebecca K Sawyer
- School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, SA 5001, Australia; Department of Medicine, Austin Health, University of Melbourne, Heidelberg, VIC, Australia; Centre for Orthopaedic and Trauma Research, School of Medicine, University of Adelaide, Adelaide, SA 5001, Australia
| | - Rachel A Davey
- School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, SA 5001, Australia; Department of Medicine, Austin Health, University of Melbourne, Heidelberg, VIC, Australia; Centre for Orthopaedic and Trauma Research, School of Medicine, University of Adelaide, Adelaide, SA 5001, Australia
| | - Gerald J Atkins
- School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, SA 5001, Australia; Department of Medicine, Austin Health, University of Melbourne, Heidelberg, VIC, Australia; Centre for Orthopaedic and Trauma Research, School of Medicine, University of Adelaide, Adelaide, SA 5001, Australia
| | - Howard A Morris
- School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, SA 5001, Australia; Department of Medicine, Austin Health, University of Melbourne, Heidelberg, VIC, Australia; Centre for Orthopaedic and Trauma Research, School of Medicine, University of Adelaide, Adelaide, SA 5001, Australia,.
| | - Paul H Anderson
- School of Pharmacy and Medical Sciences, Sansom Institute, University of South Australia, Adelaide, SA 5001, Australia; Department of Medicine, Austin Health, University of Melbourne, Heidelberg, VIC, Australia; Centre for Orthopaedic and Trauma Research, School of Medicine, University of Adelaide, Adelaide, SA 5001, Australia
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28
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Triliana R, Lam NN, Sawyer RK, Atkins GJ, Morris HA, Anderson PH. Skeletal characterization of an osteoblast-specific vitamin D receptor transgenic (ObVDR-B6) mouse model. J Steroid Biochem Mol Biol 2016; 164:331-336. [PMID: 26343450 DOI: 10.1016/j.jsbmb.2015.08.009] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/15/2015] [Revised: 08/05/2015] [Accepted: 08/11/2015] [Indexed: 11/25/2022]
Abstract
BACKGROUND Overexpression of the human vitamin D receptor (hVDR) transgene under control of the human osteocalcin promoter in FVB/N mice (OSVDR) was previously demonstrated to exhibit increased cortical and trabecular bone volume and strength due to decreased bone resorption and increased bone formation. An important question to address is whether the OSVDR bone phenotype persists on an alternative genetic background such as C57Bl6/J. METHODS OSVDR mice (OSV3 line) were backcrossed onto the C57Bl6/J genetic background for at least 6 generations to produce OSVDR mice with 98.4% C57Bl6/J congenicity (ObVDR-B6 mice). Hemizygous male and female ObVDR-B6 and littermate wild-type (WT) mice were fed a standard laboratory chow diet and killed at 3, 9 and 20 weeks of age for analyses of biochemical and structural variables and dynamic indices of bone histomorphometry. RESULTS At 9 weeks of age, both cortical and trabecular femoral bone volumes were increased in both male and female ObVDR-B6 mice, when compared to WT levels (P<0.05), without systemic changes to calciotropic parameters. The increase in femoral trabecular bone volume was associated with increase in MAR (P<0.01) and reduced osteoclast size (P<0.05). However, in female mice trabecular bone volume was unchanged in femoral metaphysis of 20 weeks mice and in vertebra both at 9 and 20 weeks of age. Increased cortical bone in both male and female ObVDR-B6 mice was due largely to increased periosteal expansion and was associated with increased cortical strength at 20 weeks of age. CONCLUSION Overexpression of the human VDR gene in mature osteoblasts of C57Bl6/J mice increases cortical and trabecular bone volumes and confirms the previous reports of increased bone in OSVDR mice on the FVB/N background. However, site-specific and gender-related differences in bone volume suggest that the effects of osteoblast-specific VDR overexpression are more complex than hitherto recognised.
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Affiliation(s)
- Rahma Triliana
- Faculty of Medicine, Islamic University of Malang, Malang, East Java 65144 Indonesia; School of Medicine, Faculty of Health Science, The University of Adelaide, Adelaide, 5000 SA, Australia
| | - Nga N Lam
- School of Medicine, Faculty of Health Science, The University of Adelaide, Adelaide, 5000 SA, Australia
| | - Rebecca K Sawyer
- School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, 5001 SA, Australia
| | - Gerald J Atkins
- Centre for Orthopaedics and Trauma Research, The University of Adelaide, Adelaide, 5000 SA, Australia
| | - Howard A Morris
- School of Medicine, Faculty of Health Science, The University of Adelaide, Adelaide, 5000 SA, Australia; School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, 5001 SA, Australia
| | - Paul H Anderson
- School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, 5001 SA, Australia.
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van der Meijden K, Buskermolen J, van Essen HW, Schuurman T, Steegenga WT, Brouwer-Brolsma EM, Langenbach GEJ, van Ruijven LJ, den Heijer M, Lips P, Bravenboer N. Long-term vitamin D deficiency in older adult C57BL/6 mice does not affect bone structure, remodeling and mineralization. J Steroid Biochem Mol Biol 2016; 164:344-352. [PMID: 26361014 DOI: 10.1016/j.jsbmb.2015.09.004] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2015] [Accepted: 09/03/2015] [Indexed: 12/22/2022]
Abstract
Animal models show that vitamin D deficiency may have severe consequences for skeletal health. However, most studies have been performed in young rodents for a relatively short period, while in older adult rodents the effects of long-term vitamin D deficiency on skeletal health have not been extensively studied. Therefore, the first aim of this study was to determine the effects of long-term vitamin D deficiency on bone structure, remodeling and mineralization in bones from older adult mice. The second aim was to determine the effects of long-term vitamin D deficiency on mRNA levels of genes involved in vitamin D metabolism in bones from older adult mice. Ten months old male C57BL/6 mice were fed a diet containing 0.5% calcium, 0.2% phosphate and 0 (n=8) or 1 (n=9) IU vitamin D3/gram for 14 months. At an age of 24 months, mice were sacrificed for histomorphometric and micro-computed tomography (micro-CT) analysis of humeri as well as analysis of CYP27B1, CYP24 and VDR mRNA levels in tibiae and kidneys using RT-qPCR. Plasma samples, obtained at 17 and 24 months of age, were used for measurements of 25-hydroxyvitamin D (25(OH)D) (all samples), phosphate and parathyroid hormone (PTH) (terminal samples) concentrations. At the age of 17 and 24 months, mean plasma 25(OH)D concentrations were below the detection limit (<4nmol/L) in mice receiving vitamin D deficient diets. Plasma phosphate and PTH concentrations did not differ between both groups. Micro-CT and histomorphometric analysis of bone mineral density, structure and remodeling did not reveal differences between control and vitamin D deficient mice. Long-term vitamin D deficiency did also not affect CYP27B1 mRNA levels in tibiae, while CYP24 mRNA levels in tibiae were below the detection threshold in both groups. VDR mRNA levels in tibiae from vitamin D deficient mice were 0.7 fold lower than those in control mice. In conclusion, long-term vitamin D deficiency in older adult C57BL/6 mice, accompanied by normal plasma PTH and phosphate concentrations, does not affect bone structure, remodeling and mineralization. In bone, expression levels of CYP27B1 are also not affected by long-term vitamin D deficiency in older adult C57BL/6 mice. Our results suggest that mice at old age have a low or absent response to vitamin D deficiency probably due to factors such as a decreased bone formation rate or a reduced response of bone cells to 25(OH)D and 1,25(OH)2D. Older adult mice may therefore be less useful for the study of the effects of vitamin D deficiency on bone health in older people.
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Affiliation(s)
- K van der Meijden
- Department of Endocrinology/Internal Medicine, VU University Medical Center, MOVE Research Institute, Amsterdam, The Netherlands
| | - J Buskermolen
- Department of Clinical Chemistry, VU University Medical Center, Research Institute MOVE, Amsterdam, The Netherlands
| | - H W van Essen
- Department of Clinical Chemistry, VU University Medical Center, Research Institute MOVE, Amsterdam, The Netherlands
| | - T Schuurman
- Department of Animal Sciences, Animal Nutrition Group, Wageningen University, Wageningen, The Netherlands
| | - W T Steegenga
- Division of Human Nutrition, Nutrition and Health Group/Nutrition and Epidemiology Group/Nutrition, Metabolism and Genomics Group, Wageningen University, Wageningen, The Netherlands
| | - E M Brouwer-Brolsma
- Division of Human Nutrition, Nutrition and Health Group/Nutrition and Epidemiology Group/Nutrition, Metabolism and Genomics Group, Wageningen University, Wageningen, The Netherlands
| | - G E J Langenbach
- Department of Oral Cell Biology and Functional Anatomy, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, MOVE Research Institute, Amsterdam, The Netherlands
| | - L J van Ruijven
- Department of Oral Cell Biology and Functional Anatomy, Academic Centre for Dentistry Amsterdam (ACTA), University of Amsterdam and VU University Amsterdam, MOVE Research Institute, Amsterdam, The Netherlands
| | - M den Heijer
- Department of Endocrinology/Internal Medicine, VU University Medical Center, MOVE Research Institute, Amsterdam, The Netherlands
| | - P Lips
- Department of Endocrinology/Internal Medicine, VU University Medical Center, MOVE Research Institute, Amsterdam, The Netherlands
| | - N Bravenboer
- Department of Clinical Chemistry, VU University Medical Center, Research Institute MOVE, Amsterdam, The Netherlands.
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Bone health and vitamin D status in alcoholic liver disease. Indian J Gastroenterol 2016; 35:253-9. [PMID: 27246833 DOI: 10.1007/s12664-016-0652-1] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/02/2015] [Accepted: 03/26/2016] [Indexed: 02/07/2023]
Abstract
Alcohol consumption is harmful to many organs and tissues, including bones, and it leads to osteoporosis. Hepatic osteodystrophy is abnormal bone metabolism that has been defined in patients with chronic liver disease (CLD), including osteopenia, osteoporosis, and osteomalacia. Decreased bone density in patients with CLD results from decreased bone formation or increased bone resorption. The prevalence of osteopenia in alcoholic liver disease (ALD) patients is between 34 % and 48 %, and the prevalence of osteoporosis is between 11 % and 36 %. Cirrhosis is also a risk factor for osteoporosis. The liver has an important role in vitamin D metabolism. Ninety percent of patients with alcoholic liver cirrhosis have vitamin D inadequacy (<80 nmol/L). The lowest serum vitamin D levels were observed in patients with Child-Pugh class C. Bone densitometry is used for the definitive diagnosis of osteoporosis in ALD. There are no specific controlled clinical studies on the treatment of osteoporosis in patients with ALD. Alcohol cessation and abstinence are principal for the prevention and treatment of osteoporosis in ALD patients, and the progression of osteopenia can be stopped in this way. Calcium and vitamin D supplementation is recommended, and associated nutritional deficiencies should also be corrected. The treatment recommendations of osteoporosis in CLD tend to be extended to ALD. Bisphosphonates have been proven to be effective in increasing bone mineral density (BMD) in chronic cholestatic disease and post-transplant patients, and they can be used in ALD patients. Randomized studies assessing the management of CLD-associated osteoporosis and the development of new drugs for osteoporosis may change the future. Here, we will discuss bone quality, vitamin D status, mechanism of bone effects, and diagnosis and treatment of osteoporosis in ALD.
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Yang D, Turner AG, Wijenayaka AR, Anderson PH, Morris HA, Atkins GJ. 1,25-Dihydroxyvitamin D3 and extracellular calcium promote mineral deposition via NPP1 activity in a mature osteoblast cell line MLO-A5. Mol Cell Endocrinol 2015; 412:140-7. [PMID: 26054750 DOI: 10.1016/j.mce.2015.06.005] [Citation(s) in RCA: 19] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/10/2015] [Revised: 06/01/2015] [Accepted: 06/03/2015] [Indexed: 10/23/2022]
Abstract
While vitamin D supplementation is common, the anabolic mechanisms that improve bone status are poorly understood. Under standard mineralising conditions including media ionised calcium of 1.1 mM, 1,25-dihydroxyvitamin D3 (1,25D) enhanced differentiation and mineral deposition by the mature osteoblast/pre-osteocyte cell line, MLO-A5. This effect was markedly increased with a higher ionised calcium level (1.5 mM). Gene expression analyses revealed that 1,25D-induced mineral deposition was associated with induction of Enpp1 mRNA, coding for nucleotide pyrophosphatase phosphodiesterase 1 (NPP1) and NPP1 protein levels. Since MLO-A5 cells express abundant alkaline phosphatase that was not further modified by 1,25D treatment or exposure to increased calcium, this finding suggested that the NPP1 production of pyrophosphate (PPi) may provide alkaline phosphatase with substrate for the generation of inorganic phosphate (Pi). Consistent with this, co-treatment with Enpp1 siRNA or a NPP1 inhibitor, PPADS, abrogated 1,25D-induced mineral deposition. These data demonstrate that 1,25D stimulates osteoblast differentiation and mineral deposition, and interacts with the extracellular calcium concentration. 1,25D regulates Enpp1 expression, which presumably, in the context of adequate tissue non-specific alkaline phosphatase activity, provides Pi to stimulate mineralisation. Our findings suggest a mechanism by which vitamin D with adequate dietary calcium can improve bone mineral status.
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Affiliation(s)
- Dongqing Yang
- Bone Cell Biology Group, Centre for Orthopaedic and Trauma Research, University of Adelaide, Adelaide, SA 5005, Australia; Discipline of Medicine, University of Adelaide, Adelaide, SA 5005, Australia
| | - Andrew G Turner
- Discipline of Medicine, University of Adelaide, Adelaide, SA 5005, Australia; Musculoskeletal Biology Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5000, Australia
| | - Asiri R Wijenayaka
- Bone Cell Biology Group, Centre for Orthopaedic and Trauma Research, University of Adelaide, Adelaide, SA 5005, Australia
| | - Paul H Anderson
- Discipline of Medicine, University of Adelaide, Adelaide, SA 5005, Australia; Musculoskeletal Biology Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5000, Australia
| | - Howard A Morris
- Discipline of Medicine, University of Adelaide, Adelaide, SA 5005, Australia; Musculoskeletal Biology Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA 5000, Australia; Endocrine Bone Research, Chemical Pathology, SA Pathology, Adelaide, SA 5000, Australia
| | - Gerald J Atkins
- Bone Cell Biology Group, Centre for Orthopaedic and Trauma Research, University of Adelaide, Adelaide, SA 5005, Australia.
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Schulze-Späte U, Dietrich T, Wu C, Wang K, Hasturk H, Dibart S. Systemic vitamin D supplementation and local bone formation after maxillary sinus augmentation - a randomized, double-blind, placebo-controlled clinical investigation. Clin Oral Implants Res 2015; 27:701-6. [DOI: 10.1111/clr.12641] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 05/18/2015] [Indexed: 11/29/2022]
Affiliation(s)
- Ulrike Schulze-Späte
- Division of Periodontics; Section of Oral and Diagnostic Sciences; College of Dental Medicine; Columbia University; New York NY USA
| | - Thomas Dietrich
- Department of Oral Surgery; The School of Dentistry; University of Birmingham; Birmingham UK
| | - Christina Wu
- Department of Medicine; Division of Cardiology; Columbia University Medical Center; New York NY USA
| | - Kun Wang
- Division of Periodontics; Section of Oral and Diagnostic Sciences; College of Dental Medicine; Columbia University; New York NY USA
| | - Hatice Hasturk
- Department of Applied Oral Sciences; The Forsyth Institute; Cambridge MA USA
| | - Serge Dibart
- Department of Periodontology; Goldman School of Dental Medicine; Boston University; Boston MA USA
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Perayil J, Menon KS, Kurup S, Thomas AE, Fenol A, Vyloppillil R, Bhaskar A, Megha S. Influence of Vitamin D & Calcium Supplementation in the Management of Periodontitis. J Clin Diagn Res 2015; 9:ZC35-8. [PMID: 26266214 DOI: 10.7860/jcdr/2015/12292.6091] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2014] [Accepted: 04/21/2015] [Indexed: 11/24/2022]
Abstract
INTRODUCTION It has long been recognized that vitamin D is a hormone and were many studies reporting that patients in periodontal maintenance programs taking vitamin D and calcium supplementation had a trend for better periodontal health compared to patients not taking supplementation. AIM To evaluate the effect of vitamin D and calcium supplementation in reducing gingival inflammation, using clinical parameters like gingival index (GI), oral hygiene index-simplified (OHIS), probing pocket depth (PPD), clinical attachment level (CAL) and bone density (BD). Also, to assess whether calcium and vitamin D oral supplementation influences alveolar Bone Density (BD). DESIGN AND SETTINGS A nonrandomised clinical trial done in Amrita School of dentistry, Kochi, India. MATERIALS AND METHODS Group A taking vitamin D (250IU/day) and calcium (500 mg/day) supplementation, and Group B were not taking oral supplementation. All subjects had at least one or more teeth with chronic moderate periodontitis. Digital Orthopantomogram images were taken to assess bone density. Data were collected at baseline and three months. STATISTICAL ANALYSIS USED OHI-S, GI, PPD, CAL, and Bone Densities (BD) were calculated per group. Karl Pearson Coefficient of correlation was used to test correlation of bone density with GI and OHI -S. Intergroup comparison of parameters were done using Independent two Sample t-test. Intragroup comparison of parameters at recall interval was done using Paired sample t-test. The results were considered statistically significant when p-value was <0.05. RESULTS Both Groups showed significant change in the periodontal parameters and bone density after three months and intragroup comparison showed highly significant results for vitamin D group in relation to GI, OHI S and bone density. CONCLUSION Calcium and vitamin D supplementation has got a positive effect on periodontal health and it can be used as an adjunct to non surgical periodontal therapy.
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Affiliation(s)
- Jayachandran Perayil
- Professor and HOD, Department of Periodontics, Amrita School of Dentistry , Ponekkara, Kochi, India
| | - Keerthy S Menon
- Post Graduate Trainee, Department of Periodontics, Amrita School of Dentistry , Ponekkara, Kochi, India
| | - Seema Kurup
- Professor and HOD, Department of Oral Medicine and Radiology, Amrita School of Dentistry , Ponekkara, Kochi, India
| | - Anju Elizebath Thomas
- Post Graduate Trainee, Department of Oral Medicine and Radiology, Amrita School of Dentistry , Ponekkara, Kochi, India
| | - Angel Fenol
- Professor, Department of Periodontics, Amrita School of Dentistry , Ponekkara, Kochi, India
| | - Rajesh Vyloppillil
- Professor, Department of Periodontics, Amrita School of Dentistry , Ponekkara, Kochi, India
| | - Anuradha Bhaskar
- Reader, Department of Periodontics, Amrita School of Dentistry , Ponekkara, Kochi, India
| | - Sai Megha
- Assistant Professor, Department of Periodontics, Amrita School of Dentistry , Ponekkara, Kochi, India
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Bianchini C, Lavery P, Agellon S, Weiler HA. The generation of C-3α epimer of 25-hydroxyvitamin D and its biological effects on bone mineral density in adult rodents. Calcif Tissue Int 2015; 96:453-64. [PMID: 25712257 DOI: 10.1007/s00223-015-9973-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/25/2014] [Accepted: 02/13/2015] [Indexed: 11/26/2022]
Abstract
The source and function of C-3α epimer of 25(OH)D (C-3 epimer) is unknown. The objectives were to (1) establish if increasing doses of vitamin D (VD) results in a proportionate dose-response in C-3 epimer; and (2) determine the biological response of bone to C-3 epimer treatment. Sprague Dawley rats (12 weeks, n = 36 female, n = 36 male) were randomized to control AIN93-M diet (1 IU VD3/g diet) or an experimental diet for 8 weeks containing VD3 at 2 or 4 IU/g diet, C-3 epimer at 0.5 or 1 IU/g diet or 25(OH)D (0.5 IU/g diet). BW and food consumption were measured weekly. Blood was sampled at week 0, 4, and 8 for assessment of VD metabolites and bone metabolism biomarkers. DXA (week 0, 4, and 8) and in vivo micro CT (μCT) (week 0 and 8) were performed in vivo plus ex vivo μCT imaging and bone biomechanics. Dietary intake and anthropometry did not differ among diet groups. The dose-response of VD generated significantly elevated C-3 epimer only in females with concentrations of 4 IU VD diet group [mean 84.6 (62.5) nmol/L] exceeding control [mean 21.4 (18.5) nmol/L, p = 0.005]. Both sexes in the 25(OH)D group did not show significant increases in C-3 epimer, whereas 0.5 and 1 IU epimer groups exceeded 100 nmol/L of C-3 epimer by 8 weeks. These data suggest C-3 epimer is endogenously generated with higher intakes of VD. Endogenous and exogenous C-3 epimer accumulates in serum without impact upon bone health outcomes in a healthy young adult model over 8 weeks.
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Affiliation(s)
- Christina Bianchini
- Dietetics and Human Nutrition, McGill University, Macdonald-Stewart Building, Macdonald Campus, 21111 Lakeshore Road, Ste-Anne-de-Bellevue, Montréal, QC, H9X 3V9, Canada
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Lee AMC, Sawyer RK, Moore AJ, Morris HA, O'Loughlin PD, Anderson PH. Adequate dietary vitamin D and calcium are both required to reduce bone turnover and increased bone mineral volume. J Steroid Biochem Mol Biol 2014; 144 Pt A:159-62. [PMID: 24309068 DOI: 10.1016/j.jsbmb.2013.11.009] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2013] [Revised: 11/11/2013] [Accepted: 11/13/2013] [Indexed: 11/28/2022]
Abstract
Clinical studies indicate that the combination of vitamin D and dietary calcium supplementation is more effective for reducing fracture risk than either supplement alone. Our previous dietary studies demonstrated that an adequate serum 25-hydroxyvitamin D3 (25D) of 80nmol/L or more reduces bone RANKL expression, osteoclastogenesis and maintains the optimal levels of trabecular bone volume (BV/TV%) in young rats. The important clinical question of the interaction between vitamin D status, dietary calcium intake and age remains unclear. Hence, 9 month-old female Sprague-Dawley rats (n=5-6/group) were pair-fed a semi-synthetic diet containing varying levels of vitamin D (0, 2, 12 or 20IU/day) and dietary calcium (0.1% or 1%) for 6 months. At 15 months of age, animals were killed, for biochemical and skeletal analyses. While changes to serum 25D were determined by both dietary vitamin D and calcium levels, changes to serum 1,25-dihydroxyvitamin D3 (1,25D) were consistently raised in animals fed 0.1% Ca regardless of dietary vitamin D or vitamin D status. Importantly, serum cross-laps levels were significantly increased in animals fed 0.1% Ca only when combined with 0 or 2 IUD/day of vitamin D, suggesting a contribution of both dietary calcium and vitamin D in determining bone resorption activity. Serum 25(OH)D3 levels were positively correlated with both femoral mid-diaphyseal cortical bone volume (R(2)=0.24, P<0.01) and metaphyseal BV/TV% (R(2)=0.23, P<0.01, data not shown). In multiple linear regressions, serum 1,25(OH)2D3 levels were a negative determinant of CBV (R(2)=0.24, P<0.01) and were not a determinant of metaphyseal BV/TV% levels. These data support clinical data that reduced bone resorption and increased bone volume can only be achieved with adequate 25D levels in combination with high dietary calcium and low serum 1,25D levels. This article is part of a Special Issue entitled '16th Vitamin D Workshop'.
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Affiliation(s)
- Alice M C Lee
- Centre for Musculoskeletal Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia; Chemical Pathology, SA Pathology, Adelaide, SA, Australia
| | - Rebecca K Sawyer
- Centre for Musculoskeletal Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia; Chemical Pathology, SA Pathology, Adelaide, SA, Australia
| | - Alison J Moore
- Centre for Musculoskeletal Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia; Chemical Pathology, SA Pathology, Adelaide, SA, Australia
| | - Howard A Morris
- Centre for Musculoskeletal Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia; Chemical Pathology, SA Pathology, Adelaide, SA, Australia
| | - Peter D O'Loughlin
- Centre for Musculoskeletal Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia; Chemical Pathology, SA Pathology, Adelaide, SA, Australia
| | - Paul H Anderson
- Centre for Musculoskeletal Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, SA, Australia; Chemical Pathology, SA Pathology, Adelaide, SA, Australia.
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Lam NN, Triliana R, Sawyer RK, Atkins GJ, Morris HA, O'Loughlin PD, Anderson PH. Vitamin D receptor overexpression in osteoblasts and osteocytes prevents bone loss during vitamin D-deficiency. J Steroid Biochem Mol Biol 2014; 144 Pt A:128-31. [PMID: 24434283 DOI: 10.1016/j.jsbmb.2014.01.002] [Citation(s) in RCA: 27] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/01/2013] [Revised: 12/17/2013] [Accepted: 01/02/2014] [Indexed: 10/25/2022]
Abstract
There are several lines of evidence that demonstrate the ability of 1,25-dihydroxyvitamin D (1,25(OH)2D3), acting via the vitamin D receptor (VDR) to mediate negative or positive effects in bone. Transgenic over-expression of VDR in osteoblasts and osteocytes in a mouse model (OSVDR) has been previously shown to inhibit processes of bone resorption and enhance bone formation, under conditions of adequate calcium intake. While these findings suggest that vitamin D signalling in osteoblasts and osteocytes promotes bone mineral accrual, the vitamin D requirement for this action is not well understood. In this study, 4 week old female OSVDR and wild-type (WT) mice were fed either a vitamin D-replete (1000IU/kg diet, D+) or vitamin D-deficient (D-) diet for 4 months to observe changes to bone mineral homeostasis. Tibial bone mineral volume was analysed by micro-CT and changes to bone cell activities were measured using standard dynamic histomorphometric techniques. While vitamin D-deplete WT mice demonstrated a reduction in periosteal bone accrual and overall bone mineral volume, OSVDR mice, however, displayed increased cortical and cancellous bone volume in mice which remained higher during vitamin D-depletion due to a reduced osteoclast number and increased bone formation rate. These data suggest that increased VDR-mediated activity in osteoblast and osteocytes prevents bone loss due to vitamin D-deficiency. This article is part of a Special Issue entitled '16th Vitamin D Workshop'.
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Affiliation(s)
- Nga N Lam
- School of Health Sciences, University of Adelaide, Adelaide, South Australia, Australia
| | - Rahma Triliana
- School of Health Sciences, University of Adelaide, Adelaide, South Australia, Australia
| | - Rebecca K Sawyer
- Centre for Musculoskeletal Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia
| | - Gerald J Atkins
- Bone Cell Biology Group, Centre for Orthopaedic & Trauma Research, The University of Adelaide, SA 5005, Australia
| | - Howard A Morris
- School of Health Sciences, University of Adelaide, Adelaide, South Australia, Australia; Centre for Musculoskeletal Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia; Chemical Pathology, SA Pathology, Adelaide, South Australia, Australia
| | - Peter D O'Loughlin
- School of Health Sciences, University of Adelaide, Adelaide, South Australia, Australia; Chemical Pathology, SA Pathology, Adelaide, South Australia, Australia
| | - Paul H Anderson
- School of Health Sciences, University of Adelaide, Adelaide, South Australia, Australia; Centre for Musculoskeletal Health Research, School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia.
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Park CY, Lee WH, Fleet JC, Allen MR, McCabe GP, Walsh DM, Weaver CM. Calcium and vitamin D intake maintained from preovariectomy independently affect calcium metabolism and bone properties in Sprague Dawley rats. Osteoporos Int 2014; 25:1905-15. [PMID: 24740476 DOI: 10.1007/s00198-014-2709-2] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/12/2013] [Accepted: 04/03/2014] [Indexed: 10/25/2022]
Abstract
UNLABELLED The interaction of habitual Ca and vitamin D intake from preovariectomy to 4 months postovariectomy on bone and Ca metabolism was assessed. Higher Ca intake suppressed net bone turnover, and both nutrients independently benefitted trabecular structure. Habitual intake of adequate Ca and ~50 nmol/L vitamin D status is most beneficial. INTRODUCTION Dietary strategies to benefit bone are typically tested prior to or after menopause but not through menopause transition. We investigated the interaction of Ca and vitamin D status on Ca absorption, bone remodeling, Ca kinetics, and bone strength as rats transitioned through estrogen deficiency. METHODS Sprague Dawley rats were randomized at 8 weeks to 0.2 or 1.0 % Ca and 50, 100, or 1,000 IU (1.25, 2.5, or 25 μg) vitamin D/kg diet (2 × 3 factorial design) and ovariectomized at 12 weeks. Urinary (45)Ca excretion from deep-labeled bone was used to assess net bone turnover weekly. Ca kinetics was performed between 25 and 28 weeks. Rats were killed at 29 weeks. Femoral and tibiae structure (by μCT), dynamic histomorphometry, and bone Ca content were assessed. RESULTS Mean 25(OH)D for rats on the 50, 100, 1,000 IU vitamin D/kg diet were 32, 54, and 175 nmol/L, respectively. Higher Ca intake ameliorated net bone turnover, reduced fractional Ca absorption and bone resorption, and increased net Ca absorption. Tibial and femoral trabecular structures were enhanced independently by higher Ca and vitamin D intake. Tibial bone width and fracture resistance were enhanced by higher vitamin D intake. Dynamic histomorphometry in the tibia was not affected by either nutrient. A Ca × vitamin D interaction existed in femur length, tibial Ca content, and mass of the soft tissue/extracellular fluid compartment. CONCLUSIONS Adequate Ca intake and serum 25(OH)D level of 50 nmol/L provided the most benefit for bone health, mostly through independent effects of Ca and vitamin D.
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Affiliation(s)
- C Y Park
- Department of Nutrition Science, Purdue University, 700 W State St, West Lafayette, IN, 47907, USA
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Morris HA. Vitamin D activities for health outcomes. Ann Lab Med 2014; 34:181-6. [PMID: 24790904 PMCID: PMC3999315 DOI: 10.3343/alm.2014.34.3.181] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/09/2014] [Accepted: 03/10/2014] [Indexed: 12/14/2022] Open
Abstract
Reports describing significant health risks due to inadequate vitamin D status continue to generate considerable interest amongst the medical and lay communities alike. Recent research on the various molecular activities of the vitamin D system, including the nuclear vitamin D receptor and other receptors for 1,25-dihydroxyvitamin D and vitamin D metabolism, provides evidence that the vitamin D system carries out biological activities across a wide range of tissues similar to other nuclear receptor hormones. This knowledge provides physiological plausibility of the various health benefits claimed to be provided by vitamin D and supports the proposals for conducting clinical trials. The vitamin D system plays critical roles in the maintenance of plasma calcium and phosphate and bone mineral homeostasis. Recent evidence confirms that plasma calcium homeostasis is the critical factor modulating vitamin D activity. Vitamin D activities in the skeleton include stimulation or inhibition of bone resorption and inhibition or stimulation of bone formation. The three major bone cell types, which are osteoblasts, osteocytes and osteoclasts, can all respond to vitamin D via the classical nuclear vitamin D receptor and metabolize 25-hydroxyvitamin D to 1,25-dihydroxyvitamin D to activate the vitamin D receptor and modulate gene expression. Dietary calcium intake interacts with vitamin D metabolism at both the renal and bone tissue levels to direct either a catabolic action on the bone through the endocrine system when calcium intake is inadequate or an anabolic action through a bone autocrine or paracrine system when calcium intake is sufficient.
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Affiliation(s)
- Howard A Morris
- School of Pharmacy and Medical Sciences, University of South Australia, Chemical Pathology Directorate and Hanson Institute, SA Pathology, Adelaide, Australia
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Darling AL, Hart KH, Gibbs MA, Gossiel F, Kantermann T, Horton K, Johnsen S, Berry JL, Skene DJ, Eastell R, Vieth R, Lanham-New SA. Greater seasonal cycling of 25-hydroxyvitamin D is associated with increased parathyroid hormone and bone resorption. Osteoporos Int 2014; 25:933-41. [PMID: 23982802 DOI: 10.1007/s00198-013-2493-4] [Citation(s) in RCA: 31] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/19/2012] [Accepted: 08/07/2013] [Indexed: 11/28/2022]
Abstract
SUMMARY This analysis assessed whether seasonal change in 25-hydroxyvitamin D concentration was associated with bone resorption, as evidenced by serum parathyroid hormone and C-terminal telopeptide concentrations. The main finding was that increased seasonal fluctuation in 25-hydroxyvitamin D was associated with increased levels of parathyroid hormone and C-terminal telopeptide. INTRODUCTION It is established that adequate 25-hydroxyvitamin D (25(OH)D, vitamin D) concentration is required for healthy bone mineralisation. It is unknown whether seasonal fluctuations in 25(OH)D also impact on bone health. If large seasonal fluctuations in 25(OH)D were associated with increased bone resorption, this would suggest a detriment to bone health. Therefore, this analysis assessed whether there is an association between seasonal variation in 25(OH)D and bone resorption. METHODS The participants were (n = 279) Caucasian and (n = 88) South Asian women (mean (±SD); age 48.2 years (14.4)) who participated in the longitudinal Diet, Food Intake, Nutrition and Exposure to the Sun in Southern England study (2006-2007). The main outcomes were serum 25(OH)D, serum parathyroid hormone (sPTH) and serum C-terminal telopeptide of collagen (sCTX), sampled once per season for each participant. RESULTS Non-linear mixed modelling showed the (amplitude/mesor) ratio for seasonal change in log 25(OH)D to be predictive of log sPTH (estimate = 0.057, 95 % CI (0.051, 0.063), p < 0.0001). Therefore, individuals with a higher seasonal change in log 25(OH)D, adjusted for overall log 25(OH)D concentration, showed increased levels of log sPTH. There was a corresponding significant ability to predict the range of seasonal change in log 25(OH)D through the level of sCTX. Here, the corresponding parameter statistics were estimate = 0.528, 95 % CI (0.418, 0.638) and p ≤ 0.0001. CONCLUSIONS These findings suggest a possible detriment to bone health via increased levels of sPTH and sCTX in individuals with a larger seasonal change in 25(OH)D concentration. Further larger cohort studies are required to further investigate these preliminary findings.
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Affiliation(s)
- A L Darling
- Department of Nutritional Sciences, School of Biosciences and Medicine, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey, GU2 7XH, UK,
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Rana T, Chakrabarti A, Freeman M, Biswas S. Doxorubicin-mediated bone loss in breast cancer bone metastases is driven by an interplay between oxidative stress and induction of TGFβ. PLoS One 2013; 8:e78043. [PMID: 24205081 PMCID: PMC3813496 DOI: 10.1371/journal.pone.0078043] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/05/2013] [Accepted: 09/07/2013] [Indexed: 12/29/2022] Open
Abstract
Breast cancer patients, who are already at increased risk of developing bone metastases and osteolytic bone damage, are often treated with doxorubicin. Unfortunately, doxorubicin has been reported to induce damage to bone. Moreover, we have previously reported that doxorubicin treatment increases circulating levels of TGFβ in murine pre-clinical models. TGFβ has been implicated in promoting osteolytic bone damage, a consequence of increased osteoclast-mediated resorption and suppression of osteoblast differentiation. Therefore, we hypothesized that in a preclinical breast cancer bone metastasis model, administration of doxorubicin would accelerate bone loss in a TGFβ-mediated manner. Administration of doxorubicin to 4T1 tumor-bearing mice produced an eightfold increase in osteolytic lesion areas compared untreated tumor-bearing mice (P = 0.002) and an almost 50% decrease in trabecular bone volume expressed in BV/TV (P = 0.0005), both of which were rescued by anti-TGFβ antibody (1D11). Doxorubicin, which is a known inducer of oxidative stress, decreased osteoblast survival and differentiation, which was rescued by N-acetyl cysteine (NAC). Furthermore, doxorubicin treatment decreased Cu-ZnSOD (SOD1) expression and enzyme activity in vitro, and treatment with anti-TGFβ antibody was able to rescue both. In conclusion, a combination therapy using doxorubicin and anti-TGFβ antibody might be beneficial for preventing therapy-related bone loss in cancer patients.
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Affiliation(s)
- Tapasi Rana
- Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America
| | - Anwesa Chakrabarti
- College of Pharmacy, University of Tennessee Health Science Center, Memphis, Tennessee, United States of America
| | - Michael Freeman
- Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America
- Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America
| | - Swati Biswas
- Department of Radiation Oncology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America
- Department of Cancer Biology, Vanderbilt University School of Medicine, Nashville, Tennessee, United States of America
- * E-mail:
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41
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Vitamin D activities and metabolic bone disease. Clin Chim Acta 2013; 425:148-52. [DOI: 10.1016/j.cca.2013.07.024] [Citation(s) in RCA: 29] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2013] [Accepted: 07/23/2013] [Indexed: 12/16/2022]
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Anderson PH, Lam NN, Turner AG, Davey RA, Kogawa M, Atkins GJ, Morris HA. The pleiotropic effects of vitamin D in bone. J Steroid Biochem Mol Biol 2013; 136:190-4. [PMID: 22981997 DOI: 10.1016/j.jsbmb.2012.08.008] [Citation(s) in RCA: 40] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/06/2012] [Revised: 08/09/2012] [Accepted: 08/14/2012] [Indexed: 01/01/2023]
Abstract
A current controversial question related to vitamin D supplementation is what level of serum 25-hydroxyvitamin D3 (25(OH)D3) is required to reduce the incidence of osteoporotic fractures. The reasoning behind vitamin D supplementation has been mostly derived from the role of vitamin D to promote intestinal calcium absorption and reduce bone resorption. While minimum 25(OH)D3 levels of 20nmol/L are required for sufficient intestinal calcium absorption to prevent osteomalacia, the mechanistic details of how higher 25(OH)D3 levels, well beyond that required for optimal calcium absorption, are able to prevent fractures and increase bone mineral density is unclear. Substantial evidence has arisen over the past decade that conversion of 25(OH)D3 to 1,25(OH)2D3via the 1-alpha hydroxylase (CYP27B1) enzyme in osteoblasts, osteocytes, chondrocytes and osteoclasts regulates processes such as cell proliferation, maturation and mineralization as well as bone resorption, which are all dependent on the presence the of the vitamin D receptor (VDR). We and others have also shown that increased vitamin D activity in mature osteoblasts by increasing levels of VDR or CYP27B1 leads to improved bone mineral volume using two separate transgenic mouse models. While questions remain regarding activities of vitamin D in bone to influence the anabolic and catabolic processes, the biological importance of vitamin D activity within the bone is unquestioned. However, a clearer understanding of the varied mechanisms by which vitamin D directly and indirectly influences mineral bone status are required to support evidence-based recommendations for vitamin D supplementation to reduce the risk of fractures. This article is part of a Special Issue entitled 'Vitamin D workshop'.
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Affiliation(s)
- Paul H Anderson
- School of Pharmacy and Medical Sciences, University of South Australia, Adelaide 5000, Australia.
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Wang Y, Inger M, Jiang H, Tenenbaum H, Glogauer M. CD109 plays a role in osteoclastogenesis. PLoS One 2013; 8:e61213. [PMID: 23593435 PMCID: PMC3625217 DOI: 10.1371/journal.pone.0061213] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/18/2012] [Accepted: 03/07/2013] [Indexed: 11/18/2022] Open
Abstract
Osteoclasts are large multinucleated cells that arise from the fusion of cells from the monocyte/macrophage lineage. Osteoclastogenesis is mediated by macrophage colony-stimulating factor (M-CSF) and receptor activator of nuclear factor-kB ligand (RANKL) and involves a complex multistep process that requires numerous other elements, many of which remain undefined. The primary aim of this project was to identify novel factors which regulate osteoclastogenesis. To carry out this investigation, microarray analysis was performed comparing two pre-osteoclast cell lines generated from RAW264.7 macrophages: one that has the capacity to fuse forming large multinucleated cells and one that does not fuse. It was found that CD109 was up-regulated by>17-fold in the osteoclast forming cell line when compared to the cell line that does not fuse, at day 2 of the differentiation process. Results obtained with microarray were confirmed by RT-qPCR and Western blot analyses in the two cell lines, in the parental RAW264.7 cell line, as well as primary murine monocytes from bone marrow. A significant increase of CD109 mRNA and protein expression during osteoclastogenesis occurred in all tested cell types. In order to characterize the role of CD109 in osteoclastogenesis, CD109 stable knockdown cell lines were established and fusion of osteoclast precursors into osteoclasts was assessed. It was found that CD109 knockdown cell lines were less capable of forming large multinucleated osteoclasts. It has been shown here that CD109 is expressed in monocytes undergoing RANKL-induced osteoclastogenesis. Moreover, when CD109 expression is suppressed in vitro, osteoclast formation decreases. This suggests that CD109 might be an important regulator of osteoclastogenesis. Further research is needed in order to characterize the role played by CD109 in regulation of osteoclast differentiation.
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Affiliation(s)
- Yongqiang Wang
- Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada
| | - Maayan Inger
- Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada
| | - Hongwei Jiang
- Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada
| | - Howard Tenenbaum
- Department of Periodontology, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada
| | - Michael Glogauer
- Matrix Dynamics Group, Faculty of Dentistry, University of Toronto, Toronto, Ontario, Canada
- * E-mail:
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Park CY, Weaver CM. Vitamin D interactions with soy isoflavones on bone after menopause: a review. Nutrients 2012; 4:1610-21. [PMID: 23201836 PMCID: PMC3509509 DOI: 10.3390/nu4111610] [Citation(s) in RCA: 21] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/17/2012] [Revised: 10/26/2012] [Accepted: 10/30/2012] [Indexed: 12/13/2022] Open
Abstract
Vitamin D is known to increase Ca absorption in adults. However, the threshold vitamin D status to benefit Ca absorption is lower than the target vitamin D status for higher bone mineral density and lower fracture risk, pointing to another pathway for vitamin D to benefit bone. One possibility is by affecting osteoblast and osteoclasts directly. Vitamin D-related bone metabolism may also be affected by soy isoflavones, which selectively bind to the estrogen receptor β and may reduce bone loss in postmenopausal women. We discuss a possible synergistic effect of soy isoflavones and vitamin D on bone by affecting osteoblast and osteoclast formation and activity in postmenopausal women.
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Affiliation(s)
- Clara Y Park
- Department of Nutrition Science, Purdue University, 700 W State St, West Lafayette, IN 47907, USA.
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Mercer KE, Wynne RA, Lazarenko OP, Lumpkin CK, Hogue WR, Suva LJ, Chen JR, Mason AZ, Badger TM, Ronis MJJ. Vitamin D supplementation protects against bone loss associated with chronic alcohol administration in female mice. J Pharmacol Exp Ther 2012; 343:401-12. [PMID: 22892342 PMCID: PMC3477212 DOI: 10.1124/jpet.112.197038] [Citation(s) in RCA: 35] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2012] [Accepted: 08/13/2012] [Indexed: 12/13/2022] Open
Abstract
Chronic alcohol abuse results in decreased bone mineral density (BMD), which can lead to increased fracture risk. In contrast, low levels of alcohol have been associated with increased BMD in epidemiological studies. Alcohol's toxic skeletal effects have been suggested to involve impaired vitamin D/calcium homeostasis. Therefore, dietary vitamin D supplementation may be beneficial in reducing bone loss associated with chronic alcohol consumption. Six-week-old female C57BL/6J mice were pair-fed ethanol (EtOH)-containing liquid diets (10 or 36% total calories) for 78 days. EtOH exposure at 10% calories had no effects on any measured bone or serum parameter. EtOH consumption at 36% of calories reduced BMD and bone strength (P<0.05), decreased osteoblastogenesis, increased osteoclastogenesis, suppressed 1,25-hydroxyvitamin D3 [1,25(OH)2D3] serum concentrations (P<0.05), and increased apoptosis in bone cells compared with pair-fed controls. In a second study, female mice were pair-fed 30% EtOH diets with or without dietary supplementation with vitamin D3 (cholecalciferol; VitD) for 40 days. VitD supplementation in the EtOH diet protected against cortical bone loss, normalized alcohol-induced hypocalcaemia, and suppressed EtOH-induced expression of receptor of nuclear factor-κB ligand mRNA in bone. In vitro, pretreatment of 1,25(OH)2D3 in osteoblastic cells inhibited EtOH-induced apoptosis. In EtOH/VitD mice circulating 1,25(OH)2D3 was lower compared with mice receiving EtOH alone (P<0.05), suggesting increased sensitivity to feedback control of VitD metabolism in the kidney. These findings suggest dietary VitD supplementation may prevent skeletal toxicity in chronic drinkers by normalizing calcium homeostasis, preventing apoptosis, and suppressing EtOH-induced increases in bone resorption.
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Affiliation(s)
- Kelly E Mercer
- Department of Pharmacology and Toxicology, University of Arkansas for Medical Sciences, Arkansas Children's Nutrition Center, 15 Children's Way, Little Rock, AR 72202, USA
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Anderson PH, Turner AG, Morris HA. Vitamin D actions to regulate calcium and skeletal homeostasis. Clin Biochem 2012; 45:880-6. [PMID: 22414785 DOI: 10.1016/j.clinbiochem.2012.02.020] [Citation(s) in RCA: 51] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/30/2011] [Revised: 02/22/2012] [Accepted: 02/24/2012] [Indexed: 12/22/2022]
Abstract
The endocrine action of plasma 1,25-dihydroxyvitamin D plays a key role in the regulation of plasma calcium and phosphate homeostasis with activities on the intestine, kidney and bone. A current, controversial question is whether vitamin D exerts direct actions on bone cells to regulate bone mineral homeostasis. Results from clinical, rodent model and in vitro studies on human bone cells provide an impressive body of data to support this proposal particularly at the level of serum 25-hydroxyvitamin D status. Each of the major bone cell types is capable of metabolising vitamin D to the active metabolite, 1,25-dihydroxyvitamin D. Thus under conditions when bone tissue synthesis of 1,25-dihydroxyvitamin D is optimal, vitamin D activity enhances bone mineral status. Dietary calcium and phosphate intakes are the critical environmental cues together with vitamin D status to determine whether 1,25-dihydroxyvitamin D exerts an anabolic or catabolic action on bone mineral status.
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Affiliation(s)
- Paul H Anderson
- School of Pharmacy and Medical Sciences, University of South Australia, and Chemical Pathology Directorate, SA Pathology, Frome Road, Adelaide 5000 SA, Australia
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Anderson PH, Atkins GJ, Turner AG, Kogawa M, Findlay DM, Morris HA. Vitamin D metabolism within bone cells: effects on bone structure and strength. Mol Cell Endocrinol 2011; 347:42-7. [PMID: 21664230 DOI: 10.1016/j.mce.2011.05.024] [Citation(s) in RCA: 46] [Impact Index Per Article: 3.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/15/2011] [Revised: 05/04/2011] [Accepted: 05/09/2011] [Indexed: 11/16/2022]
Abstract
The endocrine activity of 1,25-dihydroxyvitamin D (1,25(OH)(2)D(3)) contributes to maintaining plasma calcium and phosphate homeostasis through actions on the intestine, kidney and bone. A significant body of evidence has been published over the last 10 years indicating that all major bone cells have the capacity to metabolise 25-hydroxyvitamin D (25(OH)D(3)) to 1,25(OH)(2)D(3), which in turn exerts autocrine/paracrine actions to regulate bone cell proliferation and maturation as well as bone mineralisation and resorption. In vivo and in vitro studies indicate that these autocrine/paracrine activities of 1,25(OH)(2)D(3) in bone tissue contribute to maintaining bone mineral homeostasis and enhancing skeletal health.
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Affiliation(s)
- Paul H Anderson
- Endocrine Bone Research Laboratory, Chemical Pathology, SA Pathology, Adelaide, SA 5000, Australia
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Findlay DM, Atkins GJ. Relationship between serum RANKL and RANKL in bone. Osteoporos Int 2011; 22:2597-602. [PMID: 21850548 DOI: 10.1007/s00198-011-1740-9] [Citation(s) in RCA: 53] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/09/2011] [Accepted: 07/25/2011] [Indexed: 11/25/2022]
Abstract
It is now well accepted that the molecule receptor activator of NFκB ligand (RANKL) and osteoprotegerin play key roles in regulating physiological and pathological bone turnover. There are a large number of published reports of circulating RANKL levels in both health and pathology. However, interpretation of these data has been elusive, and the relationship between circulating RANKL and RANKL levels in bone is still not clear. This review explores this subject, documenting the possible origins of circulating RANKL and suggesting additional information that is required before serum RANKL levels can provide useful diagnostic or research information.
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Affiliation(s)
- D M Findlay
- Discipline of Orthopaedics and Trauma, University of Adelaide, Level 4 Bice Building, Royal Adelaide Hospital, Adelaide 5000, SA, Australia.
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Hohman EE, Martin BR, Lachcik PJ, Gordon DT, Fleet JC, Weaver CM. Bioavailability and efficacy of vitamin D2 from UV-irradiated yeast in growing, vitamin D-deficient rats. JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY 2011; 59:2341-6. [PMID: 21332187 PMCID: PMC3235799 DOI: 10.1021/jf104679c] [Citation(s) in RCA: 33] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 05/08/2023]
Abstract
New food sources are needed to bridge the gap between vitamin D intake and recommended intake. We assessed the bioavailability and efficacy of vitamin D in an 8 week dose-response study of bread made with vitamin D2-rich yeast compared to vitamin D3 in growing, vitamin D-deficient rats. Plasma 25-hydroxyvitamin D (25OHD) levels increased in a curvilinear, dose-dependent manner with both forms of vitamin D, but rats fed vitamin D2-rich yeast achieved lower levels than rats fed vitamin D3. Rats fed the highest doses of vitamin D had significantly greater (p<0.05) trabecular BMC, BMD, bone volume, and connectivity density, and greater midshaft total cross-sectional area, compared to rats on the vitamin D-deficient diets, with no significant difference due to vitamin D source. Vitamin D2-rich yeast baked into bread is bioavailable and improves bone quality in vitamin D-deficient animals.
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Affiliation(s)
- Emily E. Hohman
- Department of Foods & Nutrition, 700 W. State Street, Purdue University, West Lafayette, Indiana 47907, United States
| | - Berdine R. Martin
- Department of Foods & Nutrition, 700 W. State Street, Purdue University, West Lafayette, Indiana 47907, United States
| | - Pamela J. Lachcik
- Department of Foods & Nutrition, 700 W. State Street, Purdue University, West Lafayette, Indiana 47907, United States
| | - Dennis T. Gordon
- North Dakota State University, Fargo, North Dakota 58102, United States
| | - James C. Fleet
- Department of Foods & Nutrition, 700 W. State Street, Purdue University, West Lafayette, Indiana 47907, United States
| | - Connie M. Weaver
- Department of Foods & Nutrition, 700 W. State Street, Purdue University, West Lafayette, Indiana 47907, United States
- Phone: (765) 494-8237. Fax: (765) 494-0674.
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Symposium Abstracts. Clin Chem Lab Med 2011. [DOI: 10.1515/cclm.2011.500] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022]
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