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Javed L, Khakwani A, Khan U, Humphrey MB. Medication-induced fractures: Screening and treatment strategies. Am J Med Sci 2025; 369:1-13. [PMID: 39214248 DOI: 10.1016/j.amjms.2024.08.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/12/2024] [Revised: 08/21/2024] [Accepted: 08/21/2024] [Indexed: 09/04/2024]
Abstract
Medication-induced osteoporosis leads to substantial fracture morbidity. With polypharmacy and the aging population in the United States, significant increases in medication-associated fractures are predicted. The most common medication to cause osteoporosis and increase fractures is glucocorticoids. Many other therapies, including loop diuretics, SGLT2 inhibitors, thiazolidinediones, proton pump inhibitors, selective serotonin reuptake inhibitors, heparin, warfarin, antiepileptics, aromatase inhibitors, anti-androgen therapies, gonadotropin-releasing hormone antagonists, and calcineurin inhibitors are associated with increased fracture risks. Here, we review the latest evidence for fracture risk for these medications and discuss fracture risk screening and management strategies.
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Affiliation(s)
- Laraib Javed
- Department of Medicine, University of Oklahoma, College of Medicine, USA
| | - Aemen Khakwani
- Department of Medicine, University of Oklahoma, College of Medicine, USA
| | - Uzair Khan
- Department of Medicine, University of Oklahoma, College of Medicine, USA
| | - Mary Beth Humphrey
- Department of Medicine, University of Oklahoma, College of Medicine, USA; Oklahoma City Veterans Affairs Medical Center, USA.
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Bektas D, Lanzino G, Smith KM, Flemming KD. Tailored management of cavernous malformations in women: considerations and strategies-a review. Front Neurol 2024; 15:1487808. [PMID: 39512274 PMCID: PMC11542640 DOI: 10.3389/fneur.2024.1487808] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/28/2024] [Accepted: 10/11/2024] [Indexed: 11/15/2024] Open
Abstract
Purpose of reviewCavernous malformations (CM) are vascular lesions in the brain and spinal cord, characterized by clusters of endothelial-lined caverns lacking proper tight junctions. These malformations may be discovered incidentally or present with symptoms such as headaches, focal neurologic deficits, or seizures, with or without hemorrhage. This review focuses on non-surgical management considerations important for women with CM, who face challenges related to pregnancy, exogenous hormone use, anticonvulsive therapy, bone health, and mental health.Recent findingsEmerging evidence suggests that both estrogen and progesterone may influence CM lesion behavior. Exogenous hormones, including those in oral contraceptives and oral hormone replacement therapy, indicate an elevated risk of symptomatic hemorrhage (SH) and may also influence seizure frequency and severity, particularly in women taking antiseizure medications (ASMs). Data suggest that the risk of CM hemorrhage during pregnancy is similar to the risk when not pregnant, although limitations to these studies will be reviewed.SummaryThis review synthesizes the current literature on the interplay between estrogen and progesterone and CM lesion behavior, highlighting the importance of gender- and sex-specific factors in clinical decision-making. Special attention is given to the implications of exogenous hormone use, seizure management, and the psychological well-being of women with CM, underscoring the need for a multidisciplinary approach tailored to the unique needs of this patient population.
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Affiliation(s)
- Delal Bektas
- Department of Neurosurgery, Mayo Clinic, Rochester, MN, United States
- Department of Neurosurgery, University Hospital Zurich, Zurich, Switzerland
| | - Giuseppe Lanzino
- Department of Neurosurgery, Mayo Clinic, Rochester, MN, United States
| | - Kelsey M. Smith
- Department of Neurology, Mayo Clinic, Rochester, MN, United States
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Chassoux F, Navarro V, Quirins M, Laurent A, Gavaret M, Cousyn L, Crépon B, Landré E, Marchi A, Soufflet C, Rusu-Devaux V, Mancusi RL, Piketty ML, Souberbielle JC. Vitamin D deficiency and effect of treatment on seizure frequency and quality of life parameters in patients with drug-resistant epilepsy: A randomized clinical trial. Epilepsia 2024; 65:2612-2625. [PMID: 38980968 DOI: 10.1111/epi.18050] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/09/2024] [Revised: 06/13/2024] [Accepted: 06/13/2024] [Indexed: 07/11/2024]
Abstract
OBJECTIVE This study was undertaken to assess the effect of treatment of vitamin D deficiency in drug-resistant epilepsy. METHODS We conducted a multicenter, double-blind, placebo-controlled, randomized clinical trial, including patients aged ≥15 years with drug-resistant focal or generalized epilepsy. Patients with 25-hydroxyvitamin D (25[OH]D) < 30 ng/mL were randomized to an experimental group (EG) receiving vitamin D3 (cholecalciferol, 100 000 IU, five doses in 3 months) or a control group (CG) receiving matched placebo. During the open-label study, EG patients received 100 000 IU/month for 6 months, whereas CG patients received five doses in 3 months then 1/month for 3 months. Monitoring included seizure frequency (SF), 25(OH)D, calcium, albumin, creatinine assays, and standardized scales for fatigue, anxiety-depression, and quality of life (Modified Fatigue Impact Scale [M-FIS], Hospital Anxiety and Depression Scale, Quality of Life in Epilepsy [QOLIE-31]) at 3, 6, and 12 months. The primary efficacy outcome was the percentage of SF reduction compared to the reference period and CG at 3 months. Secondary outcomes were SF and bilateral tonic-clonic seizure (BTCS) reduction, scale score changes, and correlations with 25(OH)D during the follow-up. RESULTS Eighty-eight patients were enrolled in the study (56 females, aged 17-74 years), with median baseline SF per 3 months = 16.5 and ≥2 antiseizure medications in 88.6%. In 75 patients (85%), 25(OH)D was <30 ng/mL; 40 of them were randomly assigned to EG and 34 to CG. After the 3-month blinded period, SF reduction did not significantly differ between groups. However, during the open-label period, SF significantly decreased (30% median SF reduction, 33% responder rate at 12 months). BTCSs were reduced by 52%. M-FIS and QOLIE-31 scores were significantly improved at the whole group level. SF reduction correlated with 25(OH)D > 30 ng/mL for >6 months. SIGNIFICANCE Despite no proven effect after the 3-month blinded period, the open-label study suggests that long-term vitamin D3 supplementation with optimal 25(OH)D may reduce SF and BTCSs, with a positive effect on fatigue and quality of life. These findings need to be confirmed by further long-term studies. TRIAL REGISTRATION ClinicalTrials.gov identifier: NCT03475225 (03-22-2018).
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Affiliation(s)
- Francine Chassoux
- Department of Neurosurgery, Groupe Hospitalier Universitaire Paris Psychiatry and Neurosciences, Paris, France
| | - Vincent Navarro
- Epilepsy Unit, Pitié-Salpêtrière Hospital and Paris Brain Institute, Assistance Publique Hopitaux de Paris, Sorbonne University, Paris, France
| | - Marion Quirins
- Department of Neurology, Bicêtre Hospital, Le Kremlin-Bicêtre, France
| | - Agathe Laurent
- Department of Neurosurgery, Groupe Hospitalier Universitaire Paris Psychiatry and Neurosciences, Paris, France
| | - Martine Gavaret
- Department of Clinical Neurophysiology, Groupe Hospitalier Universitaire Paris Psychiatry and Neurosciences, Paris, France
- Institute of Psychiatry and Neuroscience of Paris, Université Paris Cité, INSERM UMR 1266, Paris, France
| | - Louis Cousyn
- Epilepsy Unit, Pitié-Salpêtrière Hospital and Paris Brain Institute, Assistance Publique Hopitaux de Paris, Sorbonne University, Paris, France
| | - Benoit Crépon
- Department of Clinical Neurophysiology, Groupe Hospitalier Universitaire Paris Psychiatry and Neurosciences, Paris, France
| | - Elisabeth Landré
- Department of Neurosurgery, Groupe Hospitalier Universitaire Paris Psychiatry and Neurosciences, Paris, France
| | - Angela Marchi
- Department of Clinical Neurophysiology, Groupe Hospitalier Universitaire Paris Psychiatry and Neurosciences, Paris, France
| | - Christine Soufflet
- Department of Clinical Neurophysiology, Groupe Hospitalier Universitaire Paris Psychiatry and Neurosciences, Paris, France
| | - Violeta Rusu-Devaux
- Department of Clinical Neurophysiology, Groupe Hospitalier Universitaire Paris Psychiatry and Neurosciences, Paris, France
| | - Rossella Letizia Mancusi
- Direction of Clinical Research and Innovation, Groupe Hospitalier Universitaire Paris Psychiatry and Neurosciences, Paris, France
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Sourbron J, Auvin S, Cabral-Lim L, Devlin A, Dluglos D, Hosny H, Marson T, Meador KJ, Patel AA, Penell PB, Riney K, Trinka E, Wiebe S, Lagae L. Vitamin D prophylaxis in persons with epilepsy? Epilepsia 2024; 65:2567-2579. [PMID: 39494692 DOI: 10.1111/epi.18046] [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: 02/27/2024] [Revised: 05/24/2024] [Accepted: 06/07/2024] [Indexed: 11/05/2024]
Abstract
Limited guidelines exist regarding osteoporosis prevention in the general population. Despite being a subject of controversy, the majority of research suggests that decreased vitamin D levels correlate with increased bone turnover, that is, an important risk factor for osteoporosis development. In most guidelines, daily vitamin D supplementation is recommended. In persons with epilepsy (PWE), the situation is more complex, as other factors can increase the chance of being vitamin D deficient. Currently, there are no internationally accepted guidelines regarding monitoring bone health in PWE. Our aim was to review the existing evidence in PWE on: (1) risk factors for vitamin D deficiency, (2) the identification of higher risk groups, and (3) the optimal ways to monitor bone health. Our narrative review shows that: (1) anti-seizure medication (ASM) use, especially enzyme-inducing ASM (EIASM) and valproic acid, is identified as an important risk factor for impaired bone health (e.g., increased risk for osteoporosis/fractures and/or vitamin D deficiency); (2) higher risk groups within the PWE population are present: intellectual or physical disability, institutionalized patients, puberty, early onset epilepsy and developmental epileptic encephalopathies, postmenopausal women, and use of multiple ASM/concomitant drugs (e.g. corticosteroids); and (3) a monitoring scheme can be suggested including laboratory tests, bone density measurements, managing of risk factors, and/or vitamin D supplementation. Overall, regular vitamin D measurement in PWE is a cost-effective and practical method for monitoring vitamin D deficiency, whereas in high-risk patients the combination of vitamin D measurement and bone densitometry is recommended. There is not enough evidence to advocate continuous vitamin D supplementation in all PWE. Children with epilepsy should receive the recommended daily intake of vitamin D for age and additional monitoring and supplementation if at higher risk of deficiency. There is a need for prospective trials exploring the potential benefit of vitamin D supplementation in PWE.
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Affiliation(s)
- Jo Sourbron
- Department of Development and Regeneration, Section Pediatric Neurology, University Hospital KU Leuven, Leuven, Belgium
| | - Stéphane Auvin
- A PHP, Service de Neurologie Pédiatrique, Hôpital Robert Debré, Paris, France
- INSERM NeuroDiderot, Université de Paris, Paris, France
- Institut Universitaire de France (IUF), Paris, France
| | - Leonor Cabral-Lim
- Department of Neurosciences, College of Medicine-Philippine General Hospital, the Health Sciences Center, University of the Philippines Manila, Manila, Philippines
| | - Anita Devlin
- Consultant Pediatric Neurologist and Honorary Senior Lecturer, Great North Children's Hospital and Newcastle University, Newcastle-Upon-Tyne, UK
| | - Dennis Dluglos
- Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA
| | - Hassan Hosny
- Department of Neurology, Kasr Al-Ainy Faculty of Medicine, Cairo University, Cairo, Egypt
| | - Tony Marson
- Institute of Translational Medicine, University of Liverpool, Liverpool, UK
| | - Kimford J Meador
- Department of Neurology and Neurological Sciences, Stanford School of Medicine, Stanford University, Palo Alto, California, USA
| | - Archana A Patel
- Department of Neurology, Division of Epilepsy and Clinical Neurophysiology, Boston Children's Hospital, Boston, Massachusetts, USA
| | - Page B Penell
- University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, USA
| | - Kate Riney
- School of Medicine, University of Queensland, Brisbane, Queensland, Australia
- Neurosciences Unit, Queensland Children's Hospital, Brisbane, Queensland, Australia
| | - Eugen Trinka
- Department of Neurology, Kasr Al-Ainy Faculty of Medicine, Cairo University, Cairo, Egypt
- Center for Cognitive Neuroscience, Salzburg, Austria
- Department of Public Health, Health Services Research and Health Technology Assessment, University for Health Sciences, Medical Informatics, and Technology, Hall in Tirol, Austria
| | - Samuel Wiebe
- Department of Clinical Neurosciences, University of Calgary, Calgary, Alberta, Canada
| | - Lieven Lagae
- Department of Development and Regeneration, Section Pediatric Neurology, University Hospital KU Leuven, Leuven, Belgium
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DeShazo SJ, Ozmer GL, Horton KA, Weiss WM. Phenytoin is associated with increased risk of osteoporosis and fragility fractures in adult epileptic patients. J Bone Miner Metab 2024; 42:69-76. [PMID: 38060024 DOI: 10.1007/s00774-023-01475-2] [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: 06/30/2023] [Accepted: 10/23/2023] [Indexed: 12/08/2023]
Abstract
INTRODUCTION Osteoporotic fractures lead to significant decreases in the quality of life with increases in morbidity, mortality, and disability. Treatment with a variety of anti-epileptic drugs, such as phenytoin, has been understood to cause a decrease in bone mineral density. MATERIALS AND METHODS Cohort A was identified as patients that were 18-55 years old that had epilepsy and recurrent seizures that were also prescribed phenytoin. Cohort B was identified as patients that were 18-55 years old that had epilepsy and recurrent seizures but were not prescribed phenytoin or other anti-epileptic medications. Cohorts were matched for relevant confounding pathologies and demographic factors. Outcomes were evaluated from 1 day to 5 years after the indexed event. RESULTS A total of 35,936 patients with epilepsy that were prescribed phenytoin were matched with 109,335 patients with epilepsy that were not prescribed phenytoin. Patients on phenytoin therapy were at significantly higher risk for osteoporosis without pathological fracture, fracture of metatarsal bone, fracture of shoulder and upper arm, fracture of distal radius, fracture of thoracic vertebra, fracture of cervical vertebra, fracture of lumbar vertebra, fracture of femoral head or neck, pertrochanteric fracture, femoral shaft fracture, and distal tibia fracture (all outcomes p < 0.001). CONCLUSION Epileptic patients on phenytoin therapy that were 18-55 years old exhibited higher associated risk of osteoporosis and osteoporotic-fragility fractures of various regions. Patients that undergo phenytoin therapy for epilepsy treatment should be educated on the increased risk of bone fractures and have appropriate lifestyle and diet modifications.
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Affiliation(s)
- Sterling J DeShazo
- John Sealy School of Medicine, The University of Texas Medical Branch, 301 University Blvd, Galveston, TX, 77555, USA.
| | - Garett L Ozmer
- John Sealy School of Medicine, The University of Texas Medical Branch, 301 University Blvd, Galveston, TX, 77555, USA
| | - Kyle A Horton
- John Sealy School of Medicine, The University of Texas Medical Branch, 301 University Blvd, Galveston, TX, 77555, USA
| | - William M Weiss
- Department of Orthopaedic Surgery and Rehabilitation, The University of Texas Medical Branch, 301 University Blvd, Galveston, TX, 77555-0165, USA
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Li Y, Zhang R, Ren M, Liu H, Yang M. Experimental study on the effects of simvastatin in reversing the femoral metaphyseal defects induced by sodium valproate in normal and ovariectomized rats. Heliyon 2022; 8:e10480. [PMID: 36105473 PMCID: PMC9465351 DOI: 10.1016/j.heliyon.2022.e10480] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/16/2022] [Revised: 06/29/2022] [Accepted: 08/24/2022] [Indexed: 11/30/2022] Open
Abstract
Introduction Long-term treatment with antiepileptic drugs may cause secondary osteoporosis. The present study investigated the influence of simvastatin (SIM) in reversing the effects of valproate on bone defect healing in normal and ovariectomized (OVX) rats. Methods Bone defects in femora were established in seven experimental groups of rats: control (vehicle), sodium valproate (SVP; 300 mg/kg/d), SVP plus SIM (25 mg/kg/d), sham control (sham), OVX, OVX SVP and OVX SVP plus SIM. All rats were euthanized at 8 weeks after bone defect creation. Results Micro-CT, biomechanical and histological evaluations demonstrated lower bone strength and delayed bone healing in the SVP therapy group compared with the SVP plus SIM therapy group. Biochemical and immunohistochemical results showed that osteocalcin (OCN), collagen I (Col I) and procollagen type I N-terminal propeptide (P1NP) levels decreased, tartrate-resistant acid phosphatase type 5 precursor (TRACP-5b) expression increased, and Dickkopf-1 (DKK-1) and receptor activator of nuclear factor-κ B ligand (RANKL) expression were upregulated in the SVP therapy rats compared with the SVP plus SIM therapy group. Bone loss was exacerbated by OVX, but the effect of SIM in ameliorating bone loss was also more marked in the OVX rats. Conclusions This study indicated lower bone strength and delayed healing of bone defects in rats given SVP therapy, especially the OVX SVP treatment group. In contrast, treatment with SIM was effective in enhancing bone strength and promoting bone defect repair and showed significant influence on promoting osteogenesis and inhibiting osteoclastogenesis.
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Wagener N, Di Fazio P, Böker KO, Matziolis G. Osteogenic Effect of Pregabalin in Human Primary Mesenchymal Stem Cells, Osteoblasts, and Osteosarcoma Cells. Life (Basel) 2022; 12:496. [PMID: 35454987 PMCID: PMC9032037 DOI: 10.3390/life12040496] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/06/2022] [Revised: 03/06/2022] [Accepted: 03/26/2022] [Indexed: 02/07/2023] Open
Abstract
Seventy million patients worldwide are suffering from epilepsy. The long-term use of antiepileptic drugs causes the alteration of the bone tissue and its metabolism, thus increasing the risk of fractures. Clinical and pre-clinical studies have highlighted conflicting data on the influence of the relatively new antiepileptic drug pregabalin (Lyrica®). The objective of the present study was therefore to investigate its cytotoxicity in primary human osteoblasts (hOB). HOB and human mesenchymal stem cells (hMSC) were isolated from patients. The human osteosarcoma cells MG63 were included as established cell line. Cells were incubated with pregabalin at concentrations ranging from 0 to 40 μg/mL. Time-dependent cell proliferation was measured by automatic cell counting, and metabolism was determined by XTT assay and osseous differentiation by alkaline phosphatase (ALP) activity. Histological examinations of calcium deposit were performed with ALP, Alizarin Red, and von Kossa staining. A concentration-dependent increase in the proliferation of hOB and hMSC was observed after treatment with pregabalin. All cells showed a significant increase in cell metabolism. The osteogenic differentiation, confirmed by the increase of calcium deposit, was promoted by the administration of pregabalin. This effect was already significant at the therapeutic plasma concentration of pregabalin (10 μg/mL). In contrast to the other antiepileptic drugs, pregabalin showed no osteocatabolic effects. Conflicting in-vivo data must therefore be attributed to systemic effects of pregabalin.
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Affiliation(s)
- Nele Wagener
- Department of Trauma Surgery, Orthopedics and Plastic Surgery, University Medical Center Goettingen, Robert-Koch-Str. 40, 37099 Göttingen, Germany;
| | - Pietro Di Fazio
- Department of Visceral Thoracic and Vascular Surgery, Philipps University Marburg, Baldingerstraße, 35043 Marburg, Germany;
| | - Kai Oliver Böker
- Department of Trauma Surgery, Orthopedics and Plastic Surgery, University Medical Center Goettingen, Robert-Koch-Str. 40, 37099 Göttingen, Germany;
| | - Georg Matziolis
- Orthopaedic Professorship of the University Hospital Jena, Orthopaedic Department Waldkliniken Eisenberg, 07607 Eisenberg, Germany;
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de Liyis BG, Tandy SG, Endira JF, Putri KA, Utami DKI. Anti-high mobility group box protein 1 monoclonal antibody downregulating P-glycoprotein as novel epilepsy therapeutics. THE EGYPTIAN JOURNAL OF NEUROLOGY, PSYCHIATRY AND NEUROSURGERY 2022; 58:121. [PMID: 36310854 PMCID: PMC9589779 DOI: 10.1186/s41983-022-00557-8] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2021] [Accepted: 09/29/2022] [Indexed: 11/17/2022] Open
Abstract
Epilepsy, a neurological illness, is characterized by recurrent uncontrolled seizures. There are many treatments of options that can be used as the therapy of epilepsy. However, anti-seizure medications as the primary treatment choice for epilepsy show many possible adverse effects and even pharmacoresistance to the therapy. High Mobility Group Box 1 (HMGB1) as an initiator and amplifier of the neuroinflammation is responsible for the onset and progression of epilepsy by overexpressing P-glycoprotein on the blood brain barrier. HMGB1 proteins then activate TLR4 in neurons and astrocytes, in which proinflammatory cytokines are produced. Anti-HMGB1 mAb works by blocking the HMGB1, reducing inflammatory activity in the brain that may affect epileptogenesis. Through the process, anti-HMGB1 mAb reduces the TLR4 activity and other receptors that may involve in promote signal of epilepsy such as RAGE. Several studies have shown that anti-HMGB1 has the potential to inhibit the increase in serum HMGB1 in plasma and brain tissue. Further research is needed to identify the mechanism of the inhibiting of overexpression of P-glycoprotein through anti-HMGB1 mAb.
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Affiliation(s)
- Bryan Gervais de Liyis
- grid.412828.50000 0001 0692 6937Faculty of Medicine, Udayana University, Bali, Indonesia
| | - Sevinna Geshie Tandy
- grid.412828.50000 0001 0692 6937Faculty of Medicine, Udayana University, Bali, Indonesia
| | - Joana Fourta Endira
- grid.412828.50000 0001 0692 6937Faculty of Medicine, Udayana University, Bali, Indonesia
| | - Komang Andjani Putri
- grid.412828.50000 0001 0692 6937Faculty of Medicine, Udayana University, Bali, Indonesia
| | - Desak Ketut Indrasari Utami
- grid.412828.50000 0001 0692 6937Department of Neurology, Faculty of Medicine, Udayana University, Bali, Indonesia
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Dussault PM, McCarthy D, Davis SA, Thakore-James M, Lazzari AA. High prevalence of vertebral fractures in seizure patients with normal bone density receiving chronic anti-epileptic drugs. Osteoporos Int 2021; 32:2051-2059. [PMID: 33822290 DOI: 10.1007/s00198-021-05926-2] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/04/2020] [Accepted: 03/15/2021] [Indexed: 12/23/2022]
Abstract
UNLABELLED People with epilepsy who take certain medications are at risk for developing osteoporosis and fractures of the vertebrae that commonly go undiagnosed. By using technology available in a bone density scan, we observed at least one fracture in many subjects with bone density in the normal and osteopenic range. PURPOSE/INTRODUCTION Chronic use of antiepileptic drugs (AEDs), both enzyme-inducing (phenytoin, phenobarbital, carbamazepine, and primidone) and non-enzyme-inducing (i.e., valproate), is recognized as a cause of secondary osteoporosis. Vertebral compression fractures (VF) are the most common type of osteoporotic fractures and may confer an increased risk of future hip, wrist, and vertebral fractures. Vertebral compression fractures in the general population are frequently asymptomatic, and under-diagnosed. The purpose of this study is to describe the prevalence of VF in a cohort of male veterans with epilepsy on chronic AEDs. METHODS The cohort for this study consisted of 146 male veterans who carried a diagnosis of epilepsy and were chronic users of AEDs known to cause osteoporosis (phenobarbital, phenytoin, carbamazepine, primidone, and valproate). Chronic AED use was defined as receiving an AED for at least 2 years. Subjects were previously seen in the osteoporosis clinic and had been evaluated by a dual-energy X-Ray absormetry (DXA) instrument including morphometric studies following a standard vertebral fracture assessment (VFA) protocol during the same DXA imaging acquisition session. RESULTS The mean age was 63 years. Low bone mineral density defined as osteoporosis or osteopenia was observed in 29% and 43% respectively. We observed at least one VF in 41 % of the subjects who had normal BMD, 54% in the osteopenic range, and 75% in the osteoporotic range. CONCLUSIONS By performing a VFA in addition to standard bone densitometric studies, we disclosed a large prevalence of compression fractures in individuals with epilepsy chronically treated with AEDs who had BMDs in the normal and osteopenic ranges. The addition of VFA or other imaging methods to evaluate VF should be included in the evaluation of bone health in individuals with epilepsy receiving AEDs since it may modify treatment recommendations to prevent future osteoporotic fractures.
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Affiliation(s)
- P M Dussault
- VA Boston Health Care System, Boston, MA, USA.
- VA Boston Health Care System, Osteoporosis Prevention and Treatment Clinic, Boston, MA, USA.
| | - D McCarthy
- VA Boston Health Care System, Boston, MA, USA
- Boston University School of Medicine, Boston, MA, USA
- Harvard University Medical School, Boston, MA, USA
- Neurology Services, VA Boston HCS, Epilepsy Center of Excellence, Boston, MA, USA
| | - S A Davis
- VA Boston Health Care System, Boston, MA, USA
- VA Boston Health Care System, Osteoporosis Prevention and Treatment Clinic, Boston, MA, USA
| | - M Thakore-James
- VA Boston Health Care System, Boston, MA, USA
- Boston University School of Medicine, Boston, MA, USA
- Neurology Services, VA Boston HCS, Epilepsy Center of Excellence, Boston, MA, USA
| | - A A Lazzari
- VA Boston Health Care System, Boston, MA, USA
- VA Boston Health Care System, Osteoporosis Prevention and Treatment Clinic, Boston, MA, USA
- Boston University School of Medicine, Boston, MA, USA
- Harvard University Medical School, Boston, MA, USA
- Primary Care and Rheumatology Sections, VA Boston Health Care System, Boston, MA, USA
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Whitney DG. Osteoporosis medication is associated with mortality risk reduction among adults with epilepsy: An observational study. Bone 2021; 150:116003. [PMID: 33984552 DOI: 10.1016/j.bone.2021.116003] [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: 11/05/2020] [Revised: 03/31/2021] [Accepted: 05/05/2021] [Indexed: 11/16/2022]
Abstract
BACKGROUND Adults with epilepsy have an increased risk of fragility fractures, which contributes to an accelerated rate of premature morbidity and mortality. In the general population, osteoporosis treatment has shown improvements in health and survival, possibly through improving skeletal robustness; however, the effect of osteoporosis medication on survival among adults with epilepsy has not been investigated. The purpose of this propensity score-matched, observational cohort study was to determine if osteoporosis medication was associated with mortality risk among adults with epilepsy. An exploratory analysis then examined the association between the type of osteoporosis medication with mortality. METHODS Data from 01/01/2012-09/30/2017 was extracted from Optum Clinformatics® Data Mart. Adults ≥50 years of age with epilepsy that were treatment naïve for and initiated osteoporosis medication (EP new users) were the primary group of interest, and were compared to adults with epilepsy that were not prescribed osteoporosis medication (EP no users) and adults without epilepsy that were treatment naïve for and initiated osteoporosis medication (w/o EP new users). Comparison groups were matched 1:4 to EP new users (n = 733; comparison groups, n = 2932) for demographics, glucocorticoid and antiseizure medication, prior 12-month fracture, and the Elixhauser comorbidity index. Crude incidence rate (IR) and IR ratio (IRR and 95% confidence intervals [CI]) was estimated for mortality for up to 3 years of follow-up. For new users, the association between type of osteoporosis medication (bisphosphonates vs. others) and mortality was explored using Cox proportional hazards regression after adjusting for all covariates. RESULTS For new users, the majority of the prescribed osteoporosis medications were bisphosphonates (~83%). The incidence of mortality for EP new users was lower compared to EP no users (IRR = 0.69; 95%CI = 0.52-0.93), but elevated compared to w/o EP new users (IRR = 1.42; 95%CI = 1.04-1.94). Comparing bisphosphonates to other medications for new users (P for EP group interaction = 0.089), EP new users showed a lower fully adjusted hazard ratio for mortality (HR = 0.56; 95%CI = 0.30-1.04), but was marginally insignificant (P = 0.066), while w/o EP new users showed no evidence of an association (HR = 1.09; 95%CI = 0.72-1.65). CONCLUSIONS Osteoporosis medication initiation was associated with a lower 3-year risk of mortality among adults with epilepsy. The exploratory analysis revealed potential evidence of a unique protective effect of bisphosphonates as compared to other osteoporosis medications on 3-year mortality for adults with epilepsy.
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Affiliation(s)
- Daniel G Whitney
- Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, MI, USA; Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, MI, USA.
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Berkvens JJL, Wyers CE, Mergler S, Beerhorst K, Verschuure P, Tan IY, Majoie HJM, van den Bergh JPW. Incidence of clinical fractures: A 7-year follow-up study in institutionalized adults with epilepsy and intellectual disability. Seizure 2021; 92:56-61. [PMID: 34438165 DOI: 10.1016/j.seizure.2021.08.009] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/13/2021] [Revised: 08/13/2021] [Accepted: 08/15/2021] [Indexed: 11/29/2022] Open
Abstract
PURPOSE To determine the incidence of clinical fractures over seven years of follow-up, in adults with epilepsy and intellectual disability, residing in a long-stay care facility. METHODS In 2009, all institutionalized adult patients (n = 261) were invited to undergo a Dual-energy X-ray Absorptiometry (DXA) measurement and a Vertebral Fracture Assessment (VFA). Participants were followed over seven years or until date of discharge (in case of moving from the care facility) or date of death. The patients' medical files were screened for radiology reports and staff notes, to identify clinical fractures. Fracture incidence rates (IR) were determined and compared for subgroups, by calculating incidence rate ratios. Hazard ratios were calculated to identify factors associated with fracture risk, using Cox Proportional Hazards analyses. RESULTS A total of 205 patients (124 male, 60.5%) aged between 18 and 88 years (median 48, IQR 34-60) were enrolled. At baseline, 92 patients (44.9%) were diagnosed with osteopenia and 65 (31.7%) with osteoporosis. Between 2009 and 2016, 30 patients (14.6%) deceased and 3 patients (1.5%) left the care facility. During follow-up, 156 clinical fractures were reported in 82 patients (40.0%). Thirty-eight patients (18.5%) had at least one major osteoporotic fracture. Overall, the IR was 11.6 fractures per 100 person-years. Fracture risk was significantly lower in patients who were wheelchair dependent than in patients who were able to walk (p<.001). CONCLUSION This study demonstrated that 40% of institutionalized adults with epilepsy and intellectual disability had at least one clinical fracture during seven years of follow-up, despite adequate anti-osteoporosis treatment.
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Affiliation(s)
- J J L Berkvens
- Department of Residential Care, Epilepsy Center Kempenhaeghe, Heeze, The Netherlands.
| | - C E Wyers
- Department of Internal Medicine, VieCuri Medical Center, Venlo, The Netherlands; NUTRIM School of Nutrition and Translational Research in Metabolism, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
| | - S Mergler
- Medical Department ASVZ, Care and Service Center for People with Intellectual Disabilities, Sliedrecht, The Netherlands; Department of General Practice and Intellectual Disability Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands
| | - K Beerhorst
- Department of Neurology, Zuyderland Medical Center, Heerlen, The Netherlands
| | - P Verschuure
- Laboratory for Clinical Chemistry & Pharmacology, Epilepsy Center Kempenhaeghe, Heeze, The Netherlands
| | - I Y Tan
- Department of Residential Care, Epilepsy Center Kempenhaeghe, Heeze, The Netherlands
| | - H J M Majoie
- Department of Neurology, Academic Center for Epileptology Kempenhaeghe and Maastricht University Medical Center, Heeze and Maastricht, The Netherlands; MHeNs School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Maastricht University Medical Center, Maastricht, The Netherlands; School of Health Professions Education, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands
| | - J P W van den Bergh
- Department of Internal Medicine, VieCuri Medical Center, Venlo, The Netherlands; NUTRIM School of Nutrition and Translational Research in Metabolism, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, The Netherlands
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12
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The effects of antiepileptic drugs on bone health: A systematic review. Epilepsy Res 2021; 173:106619. [PMID: 33774428 DOI: 10.1016/j.eplepsyres.2021.106619] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/01/2020] [Revised: 03/09/2021] [Accepted: 03/18/2021] [Indexed: 11/21/2022]
Abstract
PURPOSE Epilepsy may be treated with antiepileptic drugs (AEDs), which have been reported to decrease bone mineral density (BMD). Current data is conflicting and variable, and little is known with regard to how duration of AED use or specific AEDs, such as CYP-450 enzyme-inducing (EIAEDs) versus non-enzyme inducing (NEIAEDs) drugs affect BMD. We sought to systematically review BMD changes due to AED use to identify trends in reporting. METHODS A literature search via Medline (PubMed), EMBASE, and Cochrane databases was performed. Peer-reviewed articles were identified that reported on BMD measurements in conjunction with AEDs. RESULTS Twenty-six studies met inclusion criteria. Long-term therapy was shown across multiple, well-controlled studies to have the most significant BMD loss. Carbamazepine had the most frequent reporting of unfavorable effects on bone health and Lamotrigine seemed to show the most bone-protective qualities. Serum biochemical markers of bone turnover did not significantly correlate with measured BMD changes. CONCLUSION The present study provides evidence that long-term AED therapy is the most significant risk factor for BMD loss. Furthermore, there was little compelling evidence to support that EIAEDs, as a class, were more harmful to bone than NEIAEDs, which has been previously suggested in multiple studies. Early clinical concern for significant loss of BMD may not be warranted as lower BMD was less likely to be observed during the initial years of AED therapy. Furthermore, serum markers of bone turnover are not clinically reliable in assessing BMD changes in patients taking AEDs.
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Chandrasekaran V, Pasco JA, Stuart AL, Brennan-Olsen SL, Berk M, Hodge JM, Samarasinghe RM, Williams LJ. Anticonvulsant use and bone health in a population-based study of men and women: cross-sectional data from the Geelong Osteoporosis Study. BMC Musculoskelet Disord 2021; 22:172. [PMID: 33573610 PMCID: PMC7879513 DOI: 10.1186/s12891-021-04042-w] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/23/2020] [Accepted: 02/03/2021] [Indexed: 01/10/2023] Open
Abstract
Background Anticonvulsant use has been linked to bone deficits in specific patient populations. We studied the association between anticonvulsant use and bone health in a population-based sample of men and women. Methods Data from 926 men (24-73 yr) and 1070 women (21-94 yr) participating in the Geelong Osteoporosis Study were included. Bone mineral density (BMD, g/cm2) of the PA-spine and total hip was measured using dual-energy X-ray absorptiometry (Lunar). Bone quality was determined using quantitative heel ultrasound (QUS). Anthropometry was conducted and socioeconomic status was determined. Medication and lifestyle information was obtained via questionnaire. Linear regression was used to test associations between anticonvulsant use and bone health before and after adjustment for potential confounders. Results Seventeen (1.8%) men and 20 (1.9%) women reported anticonvulsant use. In men, anticonvulsant users had 9.1% lower adjusted mean BMD at the spine and hip compared to non-users. Body mass index was an effect modifier at the spine. Anticonvulsant users also had 1.8% lower speed of sound (SOS), 10.6% lower broadband ultrasound attenuation (BUA) and 13.7% lower stiffness index (SI) compared to non-users. In women, BMD tended to be lower at the hip compared to non-users as with the bone quality measure, BUA. No significant associations were observed at the spine or the other bone quality measures, SOS and SI. Conclusion Our data suggest that bone quantity and quality, assessed using BMD and QUS, are lower for men and possibly women who use anticonvulsants. While further exploration into potential mechanisms is needed, our findings suggest that monitoring bone health among users of anticonvulsants is warranted.
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Affiliation(s)
- Vinoomika Chandrasekaran
- IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, PO Box 281, Barwon Health, Geelong, Vic, 3220, Australia.
| | - Julie A Pasco
- IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, PO Box 281, Barwon Health, Geelong, Vic, 3220, Australia.,Barwon Health, University Hospital, Geelong, Australia.,Department of Medicine-Western Health, The University of Melbourne, St Albans, Australia.,Department of Epidemiology and Preventive Medicine, Monash University, Prahran, Australia
| | - Amanda L Stuart
- IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, PO Box 281, Barwon Health, Geelong, Vic, 3220, Australia
| | - Sharon L Brennan-Olsen
- Department of Medicine-Western Health, The University of Melbourne, St Albans, Australia.,Australian Institute for Musculoskeletal Science (AIMSS), The University of Melbourne and Western Health, St Albans, Australia.,Deakin University, School of Health and Social Development, Geelong, Waterfront, Australia.,Institute for Health Transformation, Deakin University, Burwood, Australia
| | - Michael Berk
- IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, PO Box 281, Barwon Health, Geelong, Vic, 3220, Australia.,Barwon Health, University Hospital, Geelong, Australia.,Department of Epidemiology and Preventive Medicine, Monash University, Prahran, Australia.,Department of Psychiatry, University of Melbourne, Parkville, Australia.,Florey Institute of Neuroscience and Mental Health, Parkville, Australia.,Orygen the National Centre of Excellence in Youth Mental Health, Parkville, Australia
| | - Jason M Hodge
- IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, PO Box 281, Barwon Health, Geelong, Vic, 3220, Australia.,Barwon Health, University Hospital, Geelong, Australia.,Geelong Centre for Emerging Infectious Diseases, Geelong, Australia
| | - Rasika M Samarasinghe
- IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, PO Box 281, Barwon Health, Geelong, Vic, 3220, Australia
| | - Lana J Williams
- IMPACT, The Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin University, PO Box 281, Barwon Health, Geelong, Vic, 3220, Australia
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Girish M, Mehan A, Venkatesh A. Should children on prolonged antiepileptic drug therapy undergo DEXA scanning to assess bone mineral density? Arch Dis Child 2021; 106:92-95. [PMID: 33032995 DOI: 10.1136/archdischild-2020-319695] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2020] [Revised: 09/10/2020] [Accepted: 09/11/2020] [Indexed: 01/10/2023]
Affiliation(s)
- Milind Girish
- University of Cambridge School of Clinical Medicine, Cambridge, UK
| | - Aman Mehan
- University of Cambridge School of Clinical Medicine, Cambridge, UK
| | - Ashwin Venkatesh
- University of Cambridge School of Clinical Medicine, Cambridge, UK
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15
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Whitney DG. Effectiveness of osteoporosis medication on site-specific fracture-risk attenuation among adults with epilepsy. Epilepsia 2020; 61:2583-2592. [PMID: 33090479 DOI: 10.1111/epi.16700] [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: 06/01/2020] [Revised: 08/31/2020] [Accepted: 08/31/2020] [Indexed: 11/28/2022]
Abstract
OBJECTIVE The objective of this propensity score-matched, observational cohort study was to determine the effectiveness of osteoporosis medication on reducing the risk of non-trauma fracture (NTFx) among adults with epilepsy. METHODS Data from 01/01/2012 to 09/30/2015 was extracted from Optum Clinformatics Data Mart. NTFx risk attenuation from 12 months prior to 12 months after the individual's index date was examined for each group of adults ≥50 years of age as risk ratios (RRs with 95% confidence intervals [CIs]). Groups were stratified based on: (1) epilepsy status, as with vs without epilepsy (EP); and (2) if and when osteoporosis medication was first prescribed, as new users (treatment naive), consistent users (osteoporosis medication prescribed in pre-index period), and no users. Comparison groups were matched 1:1 to EP new users (n = 828/group) for demographics, glucocorticoid and antiseizure medication, and the Elixhauser comorbidity index. Difference-in-difference analysis compared the change in pre- to post-index NTFx risk among groups as the ratio of the RR (RRR). RESULTS The pre- to post-index NTFx risk at any site was reduced for EP new users (RR = 0.49; 95% CI = 0.40-0.61) and EP consistent users (RR = 0.70; 95% CI = 0.38-0.98), but nonsignificantly elevated for EP no users (RR = 1.39; 95% CI = 0.93-2.07)-findings were consistent for most sites (eg, vertebral column). EP new users had a larger NTFx risk attenuation at any site compared to EP no users (RRR = 0.35; 95% CI = 0.23-0.54) and EP consistent users (RRR = 0.70; 95% CI = 0.51-0.97). EP consistent users had a larger NTFx risk attenuation at any site compared to EP no users (RRR = 0.50; 95% CI = 0.32-0.79). The extent of NTFx risk attenuation at any site was similar for new users with vs without epilepsy (RRR = 0.99; 95% CI = 0.73-1.34) and consistent users with vs without epilepsy (RRR = 0.81; 95% CI = 0.55-1.17). There was evidence of site-specific effects (eg, hip). CONCLUSION Osteoporosis medication is associated with a clinically meaningful 12-month NTFx risk attenuation for adults with epilepsy, especially for those just starting osteoporosis medication.
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Affiliation(s)
- Daniel G Whitney
- Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, MI, USA.,Institute for Healthcare Policy and Innovation, University of Michigan, Ann Arbor, MI, USA
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16
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Manousaki D, Forgetta V, Keller-Baruch J, Zhao K, Greenwood CM, Mooser V, Bassett JD, Leslie WD, Richards JB. A Polygenic Risk Score as a Risk Factor for Medication-Associated Fractures. J Bone Miner Res 2020; 35:1935-1941. [PMID: 32511779 DOI: 10.1002/jbmr.4104] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/11/2019] [Revised: 03/17/2020] [Accepted: 04/13/2020] [Indexed: 12/11/2022]
Abstract
Some commonly prescribed drugs are associated with increased risk of osteoporotic fractures. However, fracture risk stratification using skeletal measures is not often performed to identify those at risk before these medications are prescribed. We tested whether a genomically predicted skeletal measure, speed of sound (gSOS) from heel ultrasound, which was developed in 341,449 individuals from UK Biobank and tested in a separate subset consisting of 80,027 individuals, is an independent risk factor for fracture in users of fracture-related drugs (FRDs). To do this, we first assessed 80,014 UK Biobank participants (including 12,678 FRD users) for incident major osteoporotic fracture (MOF, n = 1189) and incident hip fracture (n = 209). Effects of gSOS on incident fracture were adjusted for baseline clinical fracture risk factors. We found that each standard deviation decrease in gSOS increased the adjusted odds of MOF by 42% (95% confidence interval [CI] 1.34-1.51, p < 2 × 10-16 ) and of hip fracture by 31% (95% CI 1.15-1.50, p = 9 × 10-5 ). gSOS below versus above the mean increased the adjusted odds of MOF by 79% (95% CI 1.58-2.01, p < 2 × 10-16 ) and of hip fracture by 42% (95% CI 1.08-1.88, p = 1.3 × 10-2 ). Among FRD users, each standard deviation decrease in gSOS increased the adjusted odds of MOF by 29% (nMOF = 256, 95% CI 1.14-1.46, p = 7 × 10-5 ) and of hip fracture by 30% (nhip fracture = 68, 95% CI 1.02-1.65, p = 0.0335). FRD users with gSOS below versus above the mean had a 54% increased adjusted odds of MOF (95% 1.19-1.99, p = 8.95 × 10-4 ) and a twofold increased adjusted odds of hip fracture (95% 1.19-3.31, p = 8.5 × 10-3 ). We therefore showed that genomically predicted heel SOS is independently associated with incident fracture among FRD users. © 2020 American Society for Bone and Mineral Research.
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Affiliation(s)
- Despoina Manousaki
- Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montréal, Canada.,Department of Human Genetics, McGill University, Montréal, Canada
| | - Vincenzo Forgetta
- Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montréal, Canada
| | - Julyan Keller-Baruch
- Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montréal, Canada.,Department of Human Genetics, McGill University, Montréal, Canada
| | - Kaiqiong Zhao
- Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montréal, Canada.,Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montréal, Canada
| | - Celia Mt Greenwood
- Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montréal, Canada.,Department of Human Genetics, McGill University, Montréal, Canada.,Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montréal, Canada.,Gerald Bronfman Department of Oncology, McGill University, Montréal, Canada
| | - Vincent Mooser
- Department of Human Genetics, McGill University, Montréal, Canada
| | - Jh Duncan Bassett
- Molecular Endocrinology Laboratory, Department of Medicine, Imperial College London, London, UK
| | - William D Leslie
- Department of Medicine, University of Manitoba, Winnipeg, Canada
| | - J Brent Richards
- Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montréal, Canada.,Department of Human Genetics, McGill University, Montréal, Canada.,Department of Epidemiology, Biostatistics, and Occupational Health, McGill University, Montréal, Canada.,Department of Medicine, McGill University, Montréal, Canada.,Department of Twin Research and Genetic Epidemiology, King's College London, London, UK
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17
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Berkvens J, Majoie M, Mergler S, Beerhorst K, Verschuure P, Tan I, den Bergh JV. Prevalence and incidence of vertebral fractures: a 7-year follow-up study in institutionalized adults with refractory epilepsy and intellectual disability. Epilepsy Res 2020; 167:106461. [PMID: 32949979 DOI: 10.1016/j.eplepsyres.2020.106461] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/29/2020] [Revised: 09/04/2020] [Accepted: 09/04/2020] [Indexed: 11/29/2022]
Abstract
OBJECTIVE The main objective of this cohort study is to determine the prevalence and incidence of morphometric vertebral fractures (VFs) over 7 years follow-up, in institutionalized adults with refractory epilepsy and intellectual disability (ID). METHODS Dual-energy X-ray Absorptiometry (DXA) and Vertebral Fracture Assessment (VFA) were performed in 2009 and 2016. Vertebrae T4-L4 were assessed using quantitative morphometry. Severity of VFs was graded as 1 (mild; 20-25% reduction in height), 2 (moderate; 25-40% reduction) or 3 (severe; >40% reduction) according to the method described by Genant. Prevalent VFs were analyzed at baseline. VFs (grade 1, 2 or 3) present at follow-up, but not at baseline, were considered new VFs. Worsening VFs were defined as VFs with at least one grade deterioration at follow-up, compared to baseline (grade 1 to 2 or 3, or grade 2 to 3). Patients were treated with anti-osteoporosis treatment according to the Dutch guideline. RESULTS Baseline and follow-up DXA and VFA could be obtained in 141 patients (87 male) aged between 18-79 years old (mean 44.8 ± 15.7). At baseline, 56 patients had at least one prevalent VF. Patients with a prevalent VF were significantly older than patients without (49.2 ± 13.7 vs 41.9 ± 16.4, p < .01). After 7 years follow-up, 38 new VFs occurred in 27 patients and 15 patients had a worsening VF, leading to an overall cumulative incidence of 27.0%. VF incidence was significantly higher in patients with at least one prevalent VF at baseline (48.2% vs 12.9%, respectively, p < .01) compared to no VF. SIGNIFICANCE In adults with refractory epilepsy VFA is challenging, due to physical and behavioral aspects, resulting in a substantial proportion of unevaluable vertebrae and scans. Nevertheless, 40% of the patients had a VF at baseline and after 7 years follow-up, 27% had at least one new and/or worsening VF despite adequate anti-osteoporosis treatment.
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Affiliation(s)
- Jessica Berkvens
- Department of Residential Care, Epilepsy Center Kempenhaeghe, Heeze, the Netherlands.
| | - Marian Majoie
- Department of Neurology, Academic Center for Epileptology Kempenhaeghe, Maastricht University Medical Center, Heeze and Maastricht, the Netherlands; MHeNs School for Mental Health and Neuroscience, Department of Psychiatry and Neuropsychology, Maastricht University Medical Center, Maastricht, the Netherlands; School of Health Professions Education, Faculty of Health, Medicine and Life Sciences, Maastricht University, Maastricht, the Netherlands
| | - Sandra Mergler
- Medical Department ASVZ, Care and Service Center for People with Intellectual Disabilities, Sliedrecht, the Netherlands; Department of General Practice and Intellectual Disability Medicine, Erasmus University Medical Center, Rotterdam, the Netherlands
| | - Kim Beerhorst
- Department of Neurology, Zuyderland Medical Center, Heerlen, the Netherlands
| | - Pauline Verschuure
- Laboratory for Clinical Chemistry & Pharmacology, Epilepsy Center Kempenhaeghe, Heeze, the Netherlands
| | - In Tan
- Department of Residential Care, Epilepsy Center Kempenhaeghe, Heeze, the Netherlands
| | - Joop van den Bergh
- Department of Internal Medicine, Subdivision of Endocrinology, VieCuri Medical Center, Venlo, the Netherlands; NUTRIM School of Nutrition and Translational Research in Metabolism, Department of Internal Medicine, Maastricht University Medical Center, Maastricht, the Netherlands; Faculty of Medicine and Life Sciences, Hasselt University, Hasselt, Belgium
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18
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Moreira CA, Ferreira CEDS, Madeira M, Silva BCC, Maeda SS, Batista MC, Bandeira F, Borba VZC, Lazaretti-Castro M. Reference values of 25-hydroxyvitamin D revisited: a position statement from the Brazilian Society of Endocrinology and Metabolism (SBEM) and the Brazilian Society of Clinical Pathology/Laboratory Medicine (SBPC). ARCHIVES OF ENDOCRINOLOGY AND METABOLISM 2020; 64:462-478. [PMID: 32813765 PMCID: PMC10522078 DOI: 10.20945/2359-3997000000258] [Citation(s) in RCA: 12] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 06/02/2019] [Accepted: 03/01/2020] [Indexed: 11/23/2022]
Abstract
Hypovitaminosis D is a common condition with a negative impact on health. This statement, prepared by experts from the Brazilian Society of Endocrinology and Metabolism and the Brazilian Society of Clinical Pathology/Laboratory Medicine, includes methodological aspects and limitations of the measurement of 25-hydroxyvitamin D [25(OH)D] for identification of vitamin D status, and identifies individuals at increased risk for deficiency of this vitamin in whom 25(OH)D measurement is recommended. For the general population, 25(OH)D levels between 20 and 60 ng/mL are considered normal, while individuals with levels below 20 ng/mL are considered to be vitamin D deficient. This statement identifies potential benefits of maintaining 25(OH)D levels > 30 ng/mL in specific conditions, including patients aged > 65 years or pregnant, those with recurrent falls, fragility fractures, osteoporosis, secondary hyperparathyroidism, chronic kidney disease, or cancer, and individuals using drugs with the potential to affect the vitamin D metabolism. This statement also calls attention to the risk of vitamin D intoxication, a life-threatening condition that occurs at 25(OH)D levels above 100 ng/mL.
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Affiliation(s)
- Carolina Aguiar Moreira
- Departamento de Metabolismo Ósseo, Sociedade Brasileira de Endocrinologia e Metabologia, Brasil
| | | | - Miguel Madeira
- Departamento de Metabolismo Ósseo, Sociedade Brasileira de Endocrinologia e Metabologia, Brasil
| | | | - Sergio Setsuo Maeda
- Departamento de Metabolismo Ósseo, Sociedade Brasileira de Endocrinologia e Metabologia, Brasil
| | | | - Francisco Bandeira
- Departamento de Metabolismo Ósseo, Sociedade Brasileira de Endocrinologia e Metabologia, Brasil
| | | | - Marise Lazaretti-Castro
- Departamento de Metabolismo Ósseo, Sociedade Brasileira de Endocrinologia e Metabologia, Brasil
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Siniscalchi A, Murphy S, Cione E, Piro L, Sarro GD, Gallelli L. Antiepileptic Drugs and Bone Health: Current Concepts. PSYCHOPHARMACOLOGY BULLETIN 2020; 50:36-44. [PMID: 32508365 PMCID: PMC7255839] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Indexed: 06/11/2023]
Abstract
Chronic use of antiepileptic drugs (AEDs) can induce the development of adverse effects on bone metabolism. In epileptic patients treated with AED, the monitoring of biochemical markers of bone turnover, such as the measurement of serum 25 (OH) vitamin D, bone mineral density, before the beginning of the treatment and during the follow-up is not routinely required. In the future, monitoring of biochemical markers in epileptic patients treated with AED may help us for adequate prevention therapy.
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Affiliation(s)
- Antonio Siniscalchi
- Siniscalchi, Department of Neurology and Stroke Unit, Annunziata Hospital of Cosenza, Cosenza, Italy. Murphy, General Medicine, Stroke Unit, Mater Misericordiae University Hospital, Dublin, Ireland. Cione, Department of Pharmacy, Health and Nutritional Sciences, Department of Excellence 2018-2022, University of Calabria, Rende (CS), Italy. Piro, Orthopedic Unit, Corigliano-Rossano Hospital, ASP Cosenza, Italy. De Sarro and Gallelli, Chair of Pharmacology, Department of Health Science, School of Medicine, University of Catanzaro, Clinical Pharmacology Unit, Mater Domini University Hospital, Catanzaro, Italy
| | - Sean Murphy
- Siniscalchi, Department of Neurology and Stroke Unit, Annunziata Hospital of Cosenza, Cosenza, Italy. Murphy, General Medicine, Stroke Unit, Mater Misericordiae University Hospital, Dublin, Ireland. Cione, Department of Pharmacy, Health and Nutritional Sciences, Department of Excellence 2018-2022, University of Calabria, Rende (CS), Italy. Piro, Orthopedic Unit, Corigliano-Rossano Hospital, ASP Cosenza, Italy. De Sarro and Gallelli, Chair of Pharmacology, Department of Health Science, School of Medicine, University of Catanzaro, Clinical Pharmacology Unit, Mater Domini University Hospital, Catanzaro, Italy
| | - Erika Cione
- Siniscalchi, Department of Neurology and Stroke Unit, Annunziata Hospital of Cosenza, Cosenza, Italy. Murphy, General Medicine, Stroke Unit, Mater Misericordiae University Hospital, Dublin, Ireland. Cione, Department of Pharmacy, Health and Nutritional Sciences, Department of Excellence 2018-2022, University of Calabria, Rende (CS), Italy. Piro, Orthopedic Unit, Corigliano-Rossano Hospital, ASP Cosenza, Italy. De Sarro and Gallelli, Chair of Pharmacology, Department of Health Science, School of Medicine, University of Catanzaro, Clinical Pharmacology Unit, Mater Domini University Hospital, Catanzaro, Italy
| | - Leonardo Piro
- Siniscalchi, Department of Neurology and Stroke Unit, Annunziata Hospital of Cosenza, Cosenza, Italy. Murphy, General Medicine, Stroke Unit, Mater Misericordiae University Hospital, Dublin, Ireland. Cione, Department of Pharmacy, Health and Nutritional Sciences, Department of Excellence 2018-2022, University of Calabria, Rende (CS), Italy. Piro, Orthopedic Unit, Corigliano-Rossano Hospital, ASP Cosenza, Italy. De Sarro and Gallelli, Chair of Pharmacology, Department of Health Science, School of Medicine, University of Catanzaro, Clinical Pharmacology Unit, Mater Domini University Hospital, Catanzaro, Italy
| | - Giovambattista De Sarro
- Siniscalchi, Department of Neurology and Stroke Unit, Annunziata Hospital of Cosenza, Cosenza, Italy. Murphy, General Medicine, Stroke Unit, Mater Misericordiae University Hospital, Dublin, Ireland. Cione, Department of Pharmacy, Health and Nutritional Sciences, Department of Excellence 2018-2022, University of Calabria, Rende (CS), Italy. Piro, Orthopedic Unit, Corigliano-Rossano Hospital, ASP Cosenza, Italy. De Sarro and Gallelli, Chair of Pharmacology, Department of Health Science, School of Medicine, University of Catanzaro, Clinical Pharmacology Unit, Mater Domini University Hospital, Catanzaro, Italy
| | - Luca Gallelli
- Siniscalchi, Department of Neurology and Stroke Unit, Annunziata Hospital of Cosenza, Cosenza, Italy. Murphy, General Medicine, Stroke Unit, Mater Misericordiae University Hospital, Dublin, Ireland. Cione, Department of Pharmacy, Health and Nutritional Sciences, Department of Excellence 2018-2022, University of Calabria, Rende (CS), Italy. Piro, Orthopedic Unit, Corigliano-Rossano Hospital, ASP Cosenza, Italy. De Sarro and Gallelli, Chair of Pharmacology, Department of Health Science, School of Medicine, University of Catanzaro, Clinical Pharmacology Unit, Mater Domini University Hospital, Catanzaro, Italy
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Early N, Fairman K, Ma J, Hong K. Changes in Psychotropic Prescribing for Patients With Dementia, 2014-2016: Potential implications for Pharmacists. Sr Care Pharm 2020; 35:207-219. [PMID: 32340657 DOI: 10.4140/tcp.n.2020.207] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/22/2022]
Abstract
OBJECTIVE To assess changes in psychotropic pharmacotherapy for patients with dementia over a three-year period.<br/> SETTING: National Ambulatory Medical Care Survey, physician office visits from 2014 to 2016.<br/> PRACTICE DESCRIPTION: Retrospective analysis of publicly available, nationally representative data on patient characteristics; diagnoses, including comorbidities; and treatments, including medications. Included were patients with a diagnosis of Alzheimer's disease or dementia who were 18 years of age or older. No sample exclusions were applied.<br/> INTERVENTION: Time period, comparing calendar year (CY) 2014 versus the calendar years 2015 and 2016 using Pearson chi-square tests.<br/> MAIN OUTCOME MEASURE(S): Prescribing rates of psychotropic medications, grouped by therapy class.<br/> RESULTS: The sample included 647 patients (337 in 2014 and 310 in 2015-2016). A majority (69.5%) of the patients were 75 years of age or older; 62.4% were female. Prescribing rates remained relatively stable for antipsychotics (15.1% in 2014 to 12.9% in 2015-16; P = 0.607); antidepressants (35.0% to 27.7%; P = 0.263); acetylcholinesterase inhibitors (38.6% to 33.9%; P = 0.446); and memantine (19.4% to 16.8%; P = 0.551). Significant increases were noted for sedatives (11.9% to 21.7%; P = 0.037) and anticonvulsants (10.0% to 27.6%, P = 0.001).<br/> CONCLUSION: Clinically significant increases in the prescribing of anticonvulsants and sedatives suggest the possibility that these agents are used to combat behavioral and psychological symptoms of dementia in patients with dementia. Further research is required to assess the rationale, efficacy, and safety of these uses.
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Ko A, Kong J, Samadov F, Mukhamedov A, Kim YM, Lee YJ, Nam SO. Bone health in pediatric patients with neurological disorders. Ann Pediatr Endocrinol Metab 2020; 25:15-23. [PMID: 32252212 PMCID: PMC7136510 DOI: 10.6065/apem.2020.25.1.15] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/13/2020] [Revised: 03/02/2020] [Accepted: 03/10/2020] [Indexed: 12/17/2022] Open
Abstract
Patients with neurological disorders are at high risk of developing osteoporosis, as they possess multiple risk factors leading to low bone mineral density. Such factors include inactivity, decreased exposure to sunlight, poor nutrition, and the use of medication or treatment that can cause lower bone mineral density such as antiepileptic drugs, ketogenic diet, and glucocorticoids. In this article, mechanisms involved in altered bone health in children with neurological disorders and management for patients with epilepsy, cerebral palsy, and Duchenne muscular dystrophy regarding bone health are reviewed.
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Affiliation(s)
- Ara Ko
- Division of Pediatric Neurology, Department of Pediatrics, Pusan National University Children's Hospital, Pusan National University School of Medicine, Yangsan, Korea
- Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Juhyun Kong
- Division of Pediatric Neurology, Department of Pediatrics, Pusan National University Children's Hospital, Pusan National University School of Medicine, Yangsan, Korea
- Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Furkat Samadov
- Division of Pediatric Neurology, Department of Pediatrics, Pusan National University Children's Hospital, Pusan National University School of Medicine, Yangsan, Korea
- Neuroscience Center, National Children's Medical Center, Tashkent, Uzbekistan
| | - Akmal Mukhamedov
- Division of Pediatric Neurology, Department of Pediatrics, Pusan National University Children's Hospital, Pusan National University School of Medicine, Yangsan, Korea
- Neuroscience Center, National Children's Medical Center, Tashkent, Uzbekistan
| | - Young Mi Kim
- Department of Pediatrics, Pusan National University Hospital, Pusan National University School of Medicine, Busan, Korea
| | - Yun-Jin Lee
- Division of Pediatric Neurology, Department of Pediatrics, Pusan National University Children's Hospital, Pusan National University School of Medicine, Yangsan, Korea
- Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea
| | - Sang Ook Nam
- Division of Pediatric Neurology, Department of Pediatrics, Pusan National University Children's Hospital, Pusan National University School of Medicine, Yangsan, Korea
- Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan Hospital, Yangsan, Korea
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Menninga N, Koukounas Y, Margolis A, Breslow R, Gidal B. Effects of enzyme-inducing antiseizure medication on vitamin D dosing in adult veterans with epilepsy. Epilepsy Res 2020; 161:106287. [PMID: 32088519 DOI: 10.1016/j.eplepsyres.2020.106287] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/31/2019] [Revised: 01/28/2020] [Accepted: 02/04/2020] [Indexed: 11/15/2022]
Abstract
BACKGROUND The association of antiseizure medication (ASM) and bone density abnormalities has long been recognized; however, there remains a lack of consensus on efficacy and optimal vitamin D dosing in patients receiving enzyme inducing and non-inducing ASMs. The objective was to explore the relationship between ASMs and vitamin D supplementation requirements in a population of adult patients with epilepsy. METHODS Patients with a diagnosis of epilepsy receiving supplemental vitamin D were included in this retrospective chart review. All instances of 25-hydroxyvitamin D3 (25-OHD) measured among those patients were compared between patients taking an enzyme inducing antiseizure medication (EIASM) to patients receiving ASM regimens only containing non-enzyme inducing antiseizure medications (NIASM). ASM use, prescription and over the counter (OTC) vitamin D use, 25-OHD plasma concentration, presence of chronic kidney disease (CKD), age, gender, and ethnicity were collected. Multiple linear regression was used to adjust for potentially confounding variables; the model included a cluster by participant term to account for repeated patients in the dataset. RESULTS There were 542 vitamin D levels evaluated from 172 unique patients. There was an 11.5 % higher absolute percent increase in patients who achieved a 25-OHD level over 30 ng/mL in the NIASM (p = 0.012). Patients on EIASMs were supplemented with an additional 508 units of vitamin D daily (95 %CI 136-878, p = 0.007). When adjusted for CKD, OTC vitamin D use, OTC multivitamin use, age, gender, and ethnicity, patients on EIASMs were supplemented with an additional 445 units of vitamin D (95 %CI -69 to 960, p = 0.089) compared to NIASM use. CONCLUSIONS Patients taking EIASMs had an increase in vitamin D deficiency and vitamin D supplementation suggesting that EIASMs impact vitamin D metabolism. Closer monitoring of vitamin D status in patients with epilepsy, especially those on EIASMs, is warranted. This evaluation suggests that for patients taking ASM, use of a lower dose OTC requires closer monitoring of vitamin D status in patients with epilepsy, especially those on EIASMs, is warranted. vitamin D agent may not be adequate.
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Affiliation(s)
- Nathan Menninga
- William S. Middleton Memorial Veterans Hospital, Madison, WI, United States
| | - Yannis Koukounas
- University of Wisconsin-Madison School of Pharmacy, Madison, WI, United States; Penn State Health Milton S. Hershey Medical Center, Hershey, PA, United States
| | - Amanda Margolis
- University of Wisconsin-Madison School of Pharmacy, Madison, WI, United States.
| | - Robert Breslow
- University of Wisconsin-Madison School of Pharmacy, Madison, WI, United States
| | - Barry Gidal
- University of Wisconsin-Madison School of Pharmacy, Madison, WI, United States
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Cheng HH, Kung PT, Wang BR, Chiu LT, Tsai WC. Cost-benefit analysis, cost-effectiveness analysis, and impact of antiepileptic drugs on the risk of fracture in patients with epilepsy: A nationwide cohort study. Epilepsy Behav 2020; 103:106851. [PMID: 31889639 DOI: 10.1016/j.yebeh.2019.106851] [Citation(s) in RCA: 4] [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: 09/29/2019] [Revised: 12/08/2019] [Accepted: 12/08/2019] [Indexed: 11/16/2022]
Abstract
PURPOSE Although nonenzyme-inducing antiepileptic drugs (nEIAEDs) are accepted for the treatment of epilepsy, few studies have examined the costs, benefits, and cost-effectiveness of nEIAEDs in relation to the incidence of fracture among patients with epilepsy. In the present study, we performed cost-benefit and cost-effectiveness analyses comparing the influence of enzyme-inducing AEDs (EIAEDs) and nEIAEDs on the risk of fracture in this population. METHODS A total of 4864 patients with epilepsy were classified into EIAED and nEIAED groups. Propensity score matching was applied to reduce the influence of selection bias. Clinical outcomes were measured in relation to AED fee, medical expenses associated with epilepsy and fracture, and the total number of fractures. Cost-benefit and cost-effectiveness analyses were performed for all patients. RESULTS Patients in the unmatched EIAED cohort (n = 3686) were older and had more comorbidities. After matching, the cohorts exhibited similar features (n = 2432 each). Fracture risk was lower in the nEIAED group than in the EIAED group (HR = 0.70). The additional medical expense of nEIAEDs in fractures and epilepsy for 2 years per person was 107,731 New Taiwan dollars (NT$). The additional cost for nEIAEDs to reduce one event of fracture was $14,789,421 NT$. CONCLUSIONS Patients with epilepsy using nEIAEDs had a lower risk of fracture than those using EIAEDs. However, the cost-benefit ratio and cost-effectiveness of such treatment were lower in the nEIAED group than in the EIAED group.
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Affiliation(s)
- Hsin-Hsuan Cheng
- Department of Pharmacy, Taichung Veterans' General Hospital, Taichung 40705, Taiwan, ROC
| | - Pei-Tseng Kung
- Department of Health Administration, Asia University, No. 500, Lioufeng Rd., Wufeng, Taichung 41354, Taiwan, ROC; Department of Medical Research, China Medical University Hospital, China Medical University, No. 91 Hsueh-Shih Road, Taichung 40402, Taiwan, ROC
| | - Bo-Ren Wang
- Division of Urology, Department of Surgery, Taichung Armed Forces General Hospital, No. 348, Sec. 2, Chungshan Rd., Taiping Dist., Taichung 41152, Taiwan, ROC
| | - Li-Ting Chiu
- Department of Health Services Administration, China Medical University, No. 91 Hsueh-Shih Road, Taichung 40402, Taiwan, ROC
| | - Wen-Chen Tsai
- Department of Health Services Administration, China Medical University, No. 91 Hsueh-Shih Road, Taichung 40402, Taiwan, ROC.
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Abstract
PURPOSE OF REVIEW For patients living with epilepsy, quality of life is determined not only by seizure control but by mood, antiepileptic drug adverse effects, relationships, and access to education, employment, and transportation. This article reviews some of the most commonly encountered concerns associated with epilepsy, including mood disorders, driving, injuries, mortality, bone health, genetic burden, and impact on relationships. RECENT FINDINGS People with epilepsy are at increased risk for anxiety, depression, and suicide. Depression is underrecognized in patients with epilepsy, but effective validated screening tools are available for use. Mortality rates for people with epilepsy are 2 times higher than those of the general population, but much of this is attributable to underlying conditions rather than seizures. Sudden unexpected death in epilepsy (SUDEP) occurs in an estimated 1:1000 adults with epilepsy per year, and the risk can be reduced by improved observation and seizure control. An increased risk of injury, including fractures, is also present in patients with epilepsy. Reduced bone health leading to increased fracture risk is an important negative consequence of long-term use of antiepileptic medication. Seizures while driving can also cause accidents and injury. Despite the importance of driving for people with epilepsy, physicians are underperforming in providing counsel about driving. SUMMARY Optimal care of the patient with epilepsy includes addressing risks to emotional health, physical health including fractures and SUDEP, social health, and an independent lifestyle. Identification of and treatments to reduce these risks can do more to improve quality of life than a narrow clinical focus on seizure control alone.
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Miziak B, Chrościńska-Krawczyk M, Czuczwar SJ. An update on the problem of osteoporosis in people with epilepsy taking antiepileptic drugs. Expert Opin Drug Saf 2019; 18:679-689. [PMID: 31159612 DOI: 10.1080/14740338.2019.1625887] [Citation(s) in RCA: 30] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
INTRODUCTION Antiepileptic drugs (AEDs) have been associated with a negative impact on bone health. Comorbid disorders in patients with epilepsy may require drugs exerting a pro-osteoporotic effect, so a possibility of untoward interactions with AEDs is probable. AREAS COVERED This review discusses evidence related to the deteriorating influence of AEDs on bone, demonstrating generally stronger negative effects of conventional AEDs. Lamotrigine seems to be a safer AED in this regard. Further, literature data indicate that generally AEDs can lower the serum concentration of vitamin D. Importantly, pediatric patients are of greater risk of bone problems during therapy with AEDs, which is probably due to their effects on bone-forming processes. EXPERT OPINION Supplementation with vitamin D and calcium is frequently recommended in patients taking AEDs chronically. Whether to add a bisphosphonate remains an open question due to the limited data on this issue. A possibility of negative interactions exists between AEDs and other pro-osteoporotic drugs: glucocorticoids, proton pump inhibitors and aromatase inhibitors. Depression is a frequent comorbidity in patients with epilepsy. Clinical data indicate that antidepressant drugs may also increase the risk of fractures. Again, patients with epilepsy and depression may be exposed to a greater risk of osteoporosis.
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Affiliation(s)
- Barbara Miziak
- a Department of Pathophysiology, Medical University of Lublin , Lublin , Poland
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26
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Rocha S, Ferraz R, Prudêncio C, Fernandes MH, Costa-Rodrigues J. Differential effects of antiepileptic drugs on human bone cells. J Cell Physiol 2019; 234:19691-19701. [PMID: 30941778 DOI: 10.1002/jcp.28569] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2018] [Revised: 02/19/2019] [Accepted: 02/20/2019] [Indexed: 01/10/2023]
Abstract
Antiepileptic drugs (AED) have been associated to in vivo deleterious consequences in bone tissue. The present work aimed to characterize the cellular and molecular effects of five different AED on human osteoclastogenesis and osteblastogenesis. It was observed that the different drugs had the ability to differentially modulate both processes, in a way dependent on the identity and dose of the AED. Shortly, valproic acid stimulated either osteoclastogenesis and osteoblastogenesis, whereas carbamazepine, gabapentin, and lamotrigine revealed an opposite behavior; topiramate elicited a decrease of osteoclast development and an increase in osteoblast differentiation. This is the first report describing the direct effects of different AED on human primary bone cells, which is a very important issue, because these drugs are usually consumed in long-term therapeutics, with acknowledged in vivo effects in bone tissue.
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Affiliation(s)
- Sara Rocha
- Laboratory for Bone Metabolism and Regeneration, Faculty of Dental Medicine, U. Porto, Portugal.,Ciências Químicas e das Biomoléculas (CQB) e Centro de Investigação em Saúde e Ambiente (CISA), Escola Superior de Saúde do Instituto Politécnico do Porto, Portugal
| | - Ricardo Ferraz
- Ciências Químicas e das Biomoléculas (CQB) e Centro de Investigação em Saúde e Ambiente (CISA), Escola Superior de Saúde do Instituto Politécnico do Porto, Portugal.,REQUIMTE/LAQV, U. Porto, Portugal
| | - Cristina Prudêncio
- Ciências Químicas e das Biomoléculas (CQB) e Centro de Investigação em Saúde e Ambiente (CISA), Escola Superior de Saúde do Instituto Politécnico do Porto, Portugal.,i3S, Instituto de Inovação e Investigação em Saúde, Universidade do Porto, Portugal
| | - Maria Helena Fernandes
- Laboratory for Bone Metabolism and Regeneration, Faculty of Dental Medicine, U. Porto, Portugal.,REQUIMTE/LAQV, U. Porto, Portugal
| | - João Costa-Rodrigues
- Laboratory for Bone Metabolism and Regeneration, Faculty of Dental Medicine, U. Porto, Portugal.,ESS - Escola Superior de Saúde, P. Porto, Portugal.,Instituto Politécnico de Viana do Castelo, Escola Superior de Saúde, Portugal.,i3S, Instituto de Inovação e Investigação em Saúde, Universidade do Porto, Portugal
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Prevalence, risk factors and therapeutic aspects of injuries and accidents in women with epilepsy. Eur J Trauma Emerg Surg 2018; 45:375-381. [DOI: 10.1007/s00068-018-1030-8] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2018] [Accepted: 10/08/2018] [Indexed: 11/26/2022]
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Zhang P, Zhong ZH, Yu HT, Zhou W, Li J. Therapeutic effects of new-type hydraulic delivery vertebroplasty, balloon kyphoplasty and conventional pusher-type vertebroplasty on single segmental osteoporotic vertebral compression fracture. Exp Ther Med 2018; 16:3553-3561. [PMID: 30233708 PMCID: PMC6143827 DOI: 10.3892/etm.2018.6624] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/11/2018] [Accepted: 07/31/2018] [Indexed: 12/28/2022] Open
Abstract
This study aims to evaluate safety and practicality in clinical application for better guidance of single segmental osteoporotic vertebral compression fractures treatment. From May 2012 to September 2013, a total of 188 cases of patients with fractures, who received different treatment, were incorporated in the study and then divided into: group A (n=59), conventional pusher-type vertebroplasty; group B (n=54), balloon kyphoplasty; group C (n=60), new-type hydraulic delivery vertebroplasty treatment. The overall follow-up rate was 92.02%. Postoperative visual analogue scale (VAS) and Oswestry disability index (ODI) scores were significantly improved more than those of the preoperative scores in the three groups. Bone cement injection volumes in group A were significantly lower than those in group B and group C. Vertebral height recovery rates among groups were obviously different, showing statistical significance. After a year of follow-up, the vertebral height recovery outcome in group A was obviously poorer than that in group B and group C. A poorer outcome in group B was also found when compared with group C. In addition, the vertebral height restoration had a certain degree of loss, with the loss rate of 20.5, 14.0 and 7.5% in the three groups, respectively. Three operation methods have equivalent effects in the improvement of symptoms and functional recovery. Therefore, the new-type hydraulic delivery vertebroplasty provides a relatively more concise operation and shorter operation time, displaying more outstanding performance of clinical efficacy in spinal reconstruction and reduction of complications risks by evaluating the diffusion of the bone cement, vertebral height restoration rate and postoperative complications.
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Affiliation(s)
- Ping Zhang
- Department of Orthopaedic, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510000, P.R. China
| | - Zhi-Hong Zhong
- Department of Orthopaedic, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510000, P.R. China
| | - Hao-Tao Yu
- Department of Orthopaedic, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510000, P.R. China
| | - Wei Zhou
- Department of Orthopaedic, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510000, P.R. China
| | - Jian Li
- Department of Orthopaedic, The Third Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510000, P.R. China
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Fricke-Galindo I, LLerena A, Jung-Cook H, López-López M. Carbamazepine adverse drug reactions. Expert Rev Clin Pharmacol 2018; 11:705-718. [PMID: 29898616 DOI: 10.1080/17512433.2018.1486707] [Citation(s) in RCA: 28] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/08/2023]
Abstract
INTRODUCTION Carbamazepine (CBZ) is used for the treatment of epilepsy and other neurological and psychiatric disorders. The occurrence of adverse reactions (ADRs) to CBZ can negatively impact the quality of life of patients, as well as increase health-care costs. Thus, knowledge of CBZ-induced ADRs is important to achieve safer treatment outcomes. Areas covered: This review describes the clinical features, known mechanisms, and clinical management of the main CBZ-induced ADRs. In addition, pharmacogenetic studies focused on ADRs induced by CBZ are cited. Expert commentary: CBZ-induced ADRs are well known in the literature. The metabolite CBZ-10,11-epoxide plays an important role in the mechanism that underlies the ADRs induced by CBZ. Several factors should be considered for a safer use of CBZ, such as monotherapy prescription when possible, an adequate dose titration, knowledge of previous ADRs in the patient, and routine monitoring of CBZ plasma concentrations in symptomatic patients. Pharmacogenetics is a potential tool for CBZ therapy improvement, and the design of multicenter studies focused on the identification of biomarkers for CBZ-induced ADRs could provide useful information for a safer CBZ therapy.
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Affiliation(s)
- Ingrid Fricke-Galindo
- a Doctorate in Biological and Health Sciences , Metropolitan Autonomous University , Coyoacán, Mexico City , Mexico
| | - Adrián LLerena
- b CICAB Clinical Research Centre , Extremadura University Hospital and Medical School , Badajoz , Spain
| | - Helgi Jung-Cook
- c Department of Pharmacy, Chemistry Faculty , National Autonomous University of Mexico , Mexico City , Mexico.,d Department of Neuropharmacology , National Institute of Neurology and Neurosurgery Manuel Velasco Suárez , Mexico City , Mexico
| | - Marisol López-López
- e Department of Biological Systems , Metropolitan Autonomous University , Coyoacán, Mexico City , Mexico
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Duan W, Chen Y, Wang XR. MicroRNA‑155 contributes to the occurrence of epilepsy through the PI3K/Akt/mTOR signaling pathway. Int J Mol Med 2018; 42:1577-1584. [PMID: 29901097 DOI: 10.3892/ijmm.2018.3711] [Citation(s) in RCA: 21] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/05/2016] [Accepted: 03/15/2018] [Indexed: 11/05/2022] Open
Abstract
Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to measure the expression of microRNA-155 in patients with temporal lobe epilepsy. Commercial kit and western blot analysis were used to measure gap-associated protein expression. The aim of the present study was to investigate the effect of microRNA‑155 (miRNA‑155) in the occurrence of epilepsy and the molecular mechanism involved. In patients with temporal lobe epilepsy, miRNA‑155 expression was evidently higher than that in patients of the normal volunteers group. Overexpression of miRNA‑155 resulted in decreased brain‑derived neurotrophic factor (BDNF) and tropomyosin receptor kinase B (TrkB) protein expression, increased caspase‑3 activity, tumor protein p53 (p53) and apoptosis regulator BAX (Bax) protein expression, and inhibited phosphoinositide 3‑kinase (PI3K), phosphorylated (p‑)protein kinase B (Akt) and p‑mechanistic target of rapamycin (mTOR) protein expression in epilepsy cells. PI3K inhibitor accelerated the effect of miRNA‑155 on the inhibition of BDNF and TrkB protein expression, the promotion of caspase‑3 activity, p53 and Bax protein expression, and the inhibition of PI3K, p‑Akt and p‑mTOR protein expression in epilepsy cells. The present findings indicate that miRNA‑155 contributes to the occurrence of epilepsy through the PI3K/Akt/mTOR signaling pathway.
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Affiliation(s)
- Wei Duan
- Department of Neurology, The Fifth Affiliated Hospital, Harbin Medical University, Harbin, Heilongjiang 150001, P.R. China
| | - Yan Chen
- Department of Neurophysiology, Oilfields General Hospital in Daqing, Daqing, Heilongjiang 163001, P.R. China
| | - Xiao-Rong Wang
- Department of Neurology, Ya'an Hospital, Ya'an, Sichuan 625000, P.R. China
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Fernandez H, Mohammed HT, Patel T. Vitamin D supplementation for bone health in adults with epilepsy: A systematic review. Epilepsia 2018; 59:885-896. [PMID: 29399794 DOI: 10.1111/epi.14015] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 01/09/2017] [Indexed: 12/24/2022]
Abstract
OBJECTIVE Several antiepileptic drugs (AEDs) have been associated with a detrimental effect on bone health through a reduction in serum vitamin D. Subsequently, several studies have investigated the effect of vitamin D supplementation in persons with epilepsy being treated with AEDs. The present systematic review of published literature was conducted to determine the effect of vitamin D intervention on bone health in adults with epilepsy. METHODS The following databases were searched using keywords including but not limited to epilepsy, bone, and vitamin D: PubMed, Medline, Embase, Scopus, Cochrane Clinical Trials, International Pharmaceutical Abstracts, Health Canada Clinical Trials Database, ClinicalTrials.gov, EU Clinical Trials, and Google. Studies were eligible if there was an epilepsy diagnosis, participants were adults (18+ years old), and vitamin D treatment and bone outcome were provided. Articles were screened independently by 2 reviewers. Methodological quality was assessed using the Cochrane Collaboration's tool and a modified Newcastle Ottawa Scale for nonrandomized studies. RESULTS Nine studies were found to be eligible for this review. After vitamin D treatment, there appeared to be positive changes in bone turnover markers; 3 of 8 studies found the increase in serum calcium to be significant, 6 of 8 studies found the decrease in alkaline phosphatase to be significant, and 2 of 4 studies found the decrease in parathyroid hormone to be significant. All 6 studies that investigated bone mineralization had significant findings; however, due to varying methodologies, the impact of vitamin D on bone mineralization was inconclusive. SIGNIFICANCE Vitamin D does appear to have some benefit to bone health in adults with epilepsy, and therefore supplementation could potentially be a requisite to using some AEDs. To clarify the role of vitamin D supplementation to manage the adverse effect of AEDs on bone health in adults with epilepsy, long-term trials that use higher doses (>1800 IU) and measure bone mineral density are necessary.
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Affiliation(s)
- Haya Fernandez
- School of Pharmacy, University of Waterloo, Waterloo, Ontario, Canada
| | - Heba Tallah Mohammed
- School of Pharmacy, University of Waterloo, Waterloo, Ontario, Canada
- Department of Community Medicine, Aim Shams University, Cairo, Egypt
| | - Tejal Patel
- School of Pharmacy, University of Waterloo, Waterloo, Ontario, Canada
- Michael G. DeGroote School of Medicine, McMaster University, Hamilton, Ontario, Canada
- Centre for Family Medicine Family Health Team, Kitchener, Ontario, Canada
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Abstract
PURPOSE OF REVIEW It is well-recognized that individuals with epilepsy have an increased risk of vertebral and nonvertebral fractures; this increased risk has been described to be secondary to an increased bone fragility and to an increased risk of falls. Osteoporosis is the most common bone disease which has been characterized by microarchitectural deterioration of trabecula and cortical bone mass with a decrease in bone mineral density and bone strength. Specific side effects of antiepileptic drugs (AEDs) on bone metabolism have been identified; recent research publications further characterized some of the specific side effects of AEDs on bone metabolism. It is the purpose of this review to describe recent advances on the knowledge of the effects of AEDs on bone metabolism and the cause of osteoporosis in the field of epilepsy. RECENT FINDINGS Recent literature demonstrates that the increased risk of fractures in the epileptic patient population is likely multifactorial and includes seizure activity, injuries from falls, decreased bone strength, adverse effects from AEDs. Reviewed publications suggest that the mechanism of adverse effects on bone metabolism may differ among different AEDs. The impact of vitamin D deficiency or its metabolism in the epileptic population has also been a concern of several reviewed publications. SUMMARY This is a review is of the recent epilepsy and osteoporosis literature published over the past 18 months, highlighting reports and studies concerning the cause, pathogenesis, and possible preventive measures and effects of AEDs on changes of bone metabolism, bone loss, and development of osteoporosis. In addition, we also reviewed articles focusing on issues of prevention and treatment of osteoporosis in individuals with epilepsy. We utilized the search engines of PubMed and Cochrane Reviews from January 2016 to June 2017.
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Affiliation(s)
- Philip M Dussault
- aVA Boston Healthcare System bVA Boston Health Care System and Boston University School of Medicine and Harvard Medical School, Boston, Massachusetts, USA
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McNamara NA, Romanowski EMF, Olson DP, Shellhaas RA. Bone Health and Endocrine Comorbidities in Pediatric Epilepsy. Semin Pediatr Neurol 2017; 24:301-309. [PMID: 29249510 DOI: 10.1016/j.spen.2017.10.005] [Citation(s) in RCA: 17] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/08/2022]
Abstract
Antiseizure medications and dietary therapies have associated effects on the endocrine system. We provided an overview of the relationship between epilepsy treatment and bone health in children with epilepsy. Additionally, we discussed the effects of epilepsy treatment on other endocrine systems including thyroid function, growth, reproduction, and weight. The effect of epilepsy on bone health is multifactorial; there are direct and indirect effects of medication and dietary treatments as well as a decrease in physical activity, decreased sunlight exposure, decreased vitamin D levels, and additional comorbidities. Some medications have a greater effect on vitamin D and bone health than others, however all antiseizure medical treatments are associated with lower vitamin D levels in pediatric patients. We have provided practical suggestions for vitamin D surveillance in children with epilepsy as well as replacement strategies. Children with epilepsy have an increased likelihood of additional endocrine disorders including subclinical hypothyroidism, decreased growth, weight abnormalities, reproductive and sexual dysfunction. To a great extent, this is medication specific. Though more studies are needed to elucidate optimal treatment and monitoring of bone health and other endocrinopathies in children with epilepsy, it is critical that caregivers pay close attention to these issues to provide optimal comprehensive care to their patients.
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Affiliation(s)
- Nancy A McNamara
- Divisions of Pediatric Neurology, Department of Pediatrics, University of Michigan, Ann Arbor, MI.
| | | | - David P Olson
- Pediatric Endocrinology, Department of Pediatrics, University of Michigan, Ann Arbor, MI
| | - Renee A Shellhaas
- Divisions of Pediatric Neurology, Department of Pediatrics, University of Michigan, Ann Arbor, MI
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Wang Q, Verrall I, Walker R, Tetsworth K, Drobetz H. U-type bilateral sacral fracture with spino-pelvic dissociation caused by epileptic seizure. J Surg Case Rep 2017; 2017:rjx043. [PMID: 28458849 PMCID: PMC5400439 DOI: 10.1093/jscr/rjx043] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/20/2016] [Accepted: 02/17/2017] [Indexed: 12/02/2022] Open
Abstract
Sacral fracture with spino-pelvic dissociation is a rare and unstable injury caused by high-energy trauma, often with serious haemodynamic and neurological implications. Diagnosis is easily delayed or missed as it is often masked by severe associated injuries. Here, we present an unusual case of spino-pelvic dissociation sustained during a seizure episode in a young epileptic patient on long-term anticonvulsant therapy with previous thoracolumbar spinal arthrodesis. This unique case brings to light the need for clinicians to consider sacral fractures in patients presenting with low back pain with no preceding trauma who otherwise may have risk factors for pathological fractures.
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Affiliation(s)
- Qian Wang
- Department of Surgery, Austin Health, Heidelberg, Australia
| | - Ian Verrall
- Department of Orthopaedic Surgery, Mackay Base Hospital, Mackay, Australia
| | - Rowan Walker
- Department of Orthopaedic Surgery, Mackay Base Hospital, Mackay, Australia
| | - Kevin Tetsworth
- Department of Orthopaedic Surgery, Royal Brisbane and Women's Hospital, Herston, Australia.,University of Queensland School of Medicine, St Lucia, Australia.,Queensland University of Technology Science and Engineering Faculty, Brisbane, Australia.,Orthopaedic Research Centre of Australia, Brisbane, Australia
| | - Herwig Drobetz
- Department of Orthopaedic Surgery, Mackay Base Hospital, Mackay, Australia.,James Cook University School of Medicine and Dentistry Mackay Campus, Mackay, Australia
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Fan HC, Lee HS, Chang KP, Lee YY, Lai HC, Hung PL, Lee HF, Chi CS. The Impact of Anti-Epileptic Drugs on Growth and Bone Metabolism. Int J Mol Sci 2016; 17:E1242. [PMID: 27490534 PMCID: PMC5000640 DOI: 10.3390/ijms17081242] [Citation(s) in RCA: 65] [Impact Index Per Article: 7.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/13/2016] [Revised: 07/20/2016] [Accepted: 07/28/2016] [Indexed: 12/13/2022] Open
Abstract
Epilepsy is a common neurological disorder worldwide and anti-epileptic drugs (AEDs) are always the first choice for treatment. However, more than 50% of patients with epilepsy who take AEDs have reported bone abnormalities. Cytochrome P450 (CYP450) isoenzymes are induced by AEDs, especially the classical AEDs, such as benzodiazepines (BZDs), carbamazepine (CBZ), phenytoin (PT), phenobarbital (PB), and valproic acid (VPA). The induction of CYP450 isoenzymes may cause vitamin D deficiency, hypocalcemia, increased fracture risks, and altered bone turnover, leading to impaired bone mineral density (BMD). Newer AEDs, such as levetiracetam (LEV), oxcarbazepine (OXC), lamotrigine (LTG), topiramate (TPM), gabapentin (GP), and vigabatrin (VB) have broader spectra, and are safer and better tolerated than the classical AEDs. The effects of AEDs on bone health are controversial. This review focuses on the impact of AEDs on growth and bone metabolism and emphasizes the need for caution and timely withdrawal of these medications to avoid serious disabilities.
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Affiliation(s)
- Hueng-Chuen Fan
- Department of Pediatrics, Tungs' Taichung Metroharbor Hospital, Wuchi, 435 Taichung, Taiwan.
- Department of Nursing, Jen-Teh Junior College of Medicine, Nursing and Management, 356 Miaoli, Taiwan.
| | - Herng-Shen Lee
- Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, 813 Kaohsiung, Taiwan.
| | - Kai-Ping Chang
- Department of Pediatrics, Taipei Veterans General Hospital, 112 Taipei, Taiwan.
| | - Yi-Yen Lee
- Division of Pediatric Neurosurgery, Neurological Institute, Taipei Veterans General Hospital, 112 Taipei, Taiwan.
- Faculty of Medicine, National Yang-Ming University, 112 Taipei, Taiwan.
| | - Hsin-Chuan Lai
- Department of Pediatrics, Tungs' Taichung Metroharbor Hospital, Wuchi, 435 Taichung, Taiwan.
- Department of Nursing, Jen-Teh Junior College of Medicine, Nursing and Management, 356 Miaoli, Taiwan.
| | - Pi-Lien Hung
- Department of Pediatrics, Kaohsiung Chang Gung Medical Center, 833 Kaohsiung, Taiwan.
| | - Hsiu-Fen Lee
- Department of Pediatrics, Taichung Veterans General Hospital, 407 Taichung, Taiwan.
| | - Ching-Shiang Chi
- Department of Pediatrics, Tungs' Taichung Metroharbor Hospital, Wuchi, 435 Taichung, Taiwan.
- Department of Nursing, Jen-Teh Junior College of Medicine, Nursing and Management, 356 Miaoli, Taiwan.
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Huo K, Hashim SI, Yong KLY, Su H, Qu QM. Impact and risk factors of post-stroke bone fracture. World J Exp Med 2016; 6:1-8. [PMID: 26929915 PMCID: PMC4759351 DOI: 10.5493/wjem.v6.i1.1] [Citation(s) in RCA: 19] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/23/2015] [Revised: 11/27/2015] [Accepted: 01/22/2016] [Indexed: 02/06/2023] Open
Abstract
Bone fracture occurs in stroke patients at different times during the recovery phase, prolonging recovery time and increasing medical costs. In this review, we discuss the potential risk factors for post-stroke bone fracture and preventive methods. Most post-stroke bone fractures occur in the lower extremities, indicating fragile bones are a risk factor. Motor changes, including posture, mobility, and balance post-stroke contribute to bone loss and thus increase risk of bone fracture. Bone mineral density is a useful indicator for bone resorption, useful to identify patients at risk of post-stroke bone fracture. Calcium supplementation was previously regarded as a useful treatment during physical rehabilitation. However, recent data suggests calcium supplementation has a negative impact on atherosclerotic conditions. Vitamin D intake may prevent osteoporosis and fractures in patients with stroke. Although drugs such as teriparatide show some benefits in preventing osteoporosis, additional clinical trials are needed to determine the most effective conditions for post-stroke applications.
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Arora E, Singh H, Gupta YK. Impact of antiepileptic drugs on bone health: Need for monitoring, treatment, and prevention strategies. J Family Med Prim Care 2016; 5:248-253. [PMID: 27843822 PMCID: PMC5084542 DOI: 10.4103/2249-4863.192338] [Citation(s) in RCA: 50] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/10/2023] Open
Abstract
Epilepsy is the most common neurological disorder affecting approximately 50 million people worldwide. In India, overall prevalence of epilepsy is reported to be 5.59/1000 population. Antiepileptic drugs (AEDs) constitute the main-stay of treatment with a large number of AEDs available in the market. High incidence of adverse effects is a major limitation with AEDs. One of the major concerns is significant metabolic effects on the bone. However, little attention has been paid to this issue because most of the bone effects remain subclinical for a long time and may take years to manifest clinically. The main effects include hypocalcemia, hypophosphatemia, reduced serum levels of Vitamin D, increase in parathormone (PTH) levels, and alterations in bone turnover markers. The CYP450 enzyme-inducing AEDs such as phenytoin, phenobarbital, carbamazepine, and primidone are the most common AEDs associated with bone disorders while the data regarding the effect of valproate and newer AEDs such as lamotrigine, gabapentin, vigabatrin, levetiracetam, and topiramate on bone metabolism and bone density are scanty and controversial. Deficiency of Vitamin D is commonly described as a cause for the bone loss in epileptic patients while others being decreased absorption of calcium, increased PTH levels, and inhibition of calcitonin secretion, etc. However, there are no formal practical guidelines for the management of bone disease among those taking AEDs. Evidence-based strategies regarding monitoring, prevention, and treatment of bone diseases in patients on AED therapy are needed.
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Affiliation(s)
- Ekta Arora
- Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India
| | - Harmanjit Singh
- Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India
| | - Yogendra Kumar Gupta
- Department of Pharmacology, All India Institute of Medical Sciences, New Delhi, India
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Karlov VA, Guekht AB, Guzeva VI, Lipatova LV, Bazilevich SN, Mkrtchyan VR, Vlasov PN, Zhidkova IA, Mukhin KY, Petrukhin AS, Lebedeva AV. [Algorithms of mono- and polytherapy in clinical epileptology]. Zh Nevrol Psikhiatr Im S S Korsakova 2016. [PMID: 28635941 DOI: 10.17116/jnevro201611671120-129] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/11/2023]
Abstract
The large number of antiepileptic drugs (AEDs) at the physician's disposal provides not only a broad therapeutic potential in the treatment of epilepsy (EP), but creates difficulties in the adequate choice of AED. The sufficient experience in the management of patients with epilepsy has been gained so far in the world, based on which the International League Against Epilepsy (ILAE), updated classification, adopted the basic definition of efficiency, remission, resistance, evidence of research on the effectiveness of AED therapy, and introduced the concept of "resolved" epilepsy. In this article, a group of Russian experts suggest recommendations on the main steps in the choice of therapy in epilepsy. Possible drug interactions between different AEDs and other drugs as well as main characteristics of mono- and polytherapy of epilepsy are described. Some features of the use of AEDs in the elderly, characteristics of the "female" epilepsy related to the reproductive function and basic requirements for the therapy of epilepsy in children are presented.
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Affiliation(s)
- V A Karlov
- Evdokimov Moscow State Medical and Dentistry University, Moscow, Russia
| | - A B Guekht
- Pirogov Russian National Research Medical University, Moscow, Russia
| | - V I Guzeva
- Saint-Petersburg State Medical Academy, St. Petersburg, Russia
| | - L V Lipatova
- Bekhterev Saint-Petersburg Research Psychoneurological Institute, St. Petersburg, Russia
| | | | - V R Mkrtchyan
- Soloviev Scientific-Practical Psycho-Neurological Сenter, Moscow, Russia
| | - P N Vlasov
- Evdokimov Moscow State Medical and Dentistry University, Moscow, Russia
| | - I A Zhidkova
- Evdokimov Moscow State Medical and Dentistry University, Moscow, Russia
| | - K Yu Mukhin
- Svt. Luka's Institute of Child Neurology and Epilepsy, Moscow, Russia
| | - A S Petrukhin
- Pirogov Russian National Research Medical University, Moscow, Russia
| | - A V Lebedeva
- Pirogov Russian National Research Medical University, Moscow, Russia
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McClafferty HH, Kemper KJ. Integrative Medicine. HEALTH CARE FOR PEOPLE WITH INTELLECTUAL AND DEVELOPMENTAL DISABILITIES ACROSS THE LIFESPAN 2016:1943-1965. [DOI: 10.1007/978-3-319-18096-0_149] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/03/2025]
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Hamed SA. Markers of bone turnover in patients with epilepsy and their relationship to management of bone diseases induced by antiepileptic drugs. Expert Rev Clin Pharmacol 2015; 9:267-286. [PMID: 26589104 DOI: 10.1586/17512433.2016.1123617] [Citation(s) in RCA: 18] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2025]
Abstract
Data from cross-sectional and prospective studies revealed that patients with epilepsy and on long-term treatment with antiepileptic drugs (AEDs) are at increased risk for metabolic bone diseases. Bone diseases were reported in about 50% of patients on AEDs. Low bone mineral density, osteopenia/osteoporosis, osteomalacia, rickets, altered concentration of bone turnover markers and fractures were reported with phenobarbital, phenytoin, carbamazepine, valproate, oxcarbazepine and lamotrigine. The mechanisms for AEDs-induced bone diseases are heterogeneous and include hypovitaminosis D, hypocalcemia and direct acceleration of bone loss and/or reduction of bone formation. This article reviews the evidence, predictors and mechanisms of AEDs-induced bone abnormalities and its clinical implications. For patients on AEDs, regular monitoring of bone health is recommended. Prophylactic administration of calcium and vitamin D is recommended for all patients. Treatment doses of calcium and vitamin D and even anti-resorptive drug therapy are reserved for patients at high risk of pathological fracture.
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Affiliation(s)
- Sherifa A Hamed
- a Department of Neurology and Psychiatry , Assiut University Hospital , Assiut , Egypt
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Hamed SA. Markers of bone turnover in patients with epilepsy and their relationship to management of bone diseases induced by antiepileptic drugs. Expert Rev Clin Pharmacol 2015; 9:267-286. [PMID: 26589104 DOI: org/10.1586/17512433.2016.1123617] [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] [Indexed: 11/08/2022]
Abstract
Data from cross-sectional and prospective studies revealed that patients with epilepsy and on long-term treatment with antiepileptic drugs (AEDs) are at increased risk for metabolic bone diseases. Bone diseases were reported in about 50% of patients on AEDs. Low bone mineral density, osteopenia/osteoporosis, osteomalacia, rickets, altered concentration of bone turnover markers and fractures were reported with phenobarbital, phenytoin, carbamazepine, valproate, oxcarbazepine and lamotrigine. The mechanisms for AEDs-induced bone diseases are heterogeneous and include hypovitaminosis D, hypocalcemia and direct acceleration of bone loss and/or reduction of bone formation. This article reviews the evidence, predictors and mechanisms of AEDs-induced bone abnormalities and its clinical implications. For patients on AEDs, regular monitoring of bone health is recommended. Prophylactic administration of calcium and vitamin D is recommended for all patients. Treatment doses of calcium and vitamin D and even anti-resorptive drug therapy are reserved for patients at high risk of pathological fracture.
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Affiliation(s)
- Sherifa A Hamed
- a Department of Neurology and Psychiatry , Assiut University Hospital , Assiut , Egypt
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Mirza F, Canalis E. Management of endocrine disease: Secondary osteoporosis: pathophysiology and management. Eur J Endocrinol 2015; 173:R131-51. [PMID: 25971649 PMCID: PMC4534332 DOI: 10.1530/eje-15-0118] [Citation(s) in RCA: 202] [Impact Index Per Article: 20.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/30/2015] [Accepted: 05/12/2015] [Indexed: 12/14/2022]
Abstract
Osteoporosis is a skeletal disorder characterized by decreased mass and compromised bone strength predisposing to an increased risk of fractures. Although idiopathic osteoporosis is the most common form of osteoporosis, secondary factors may contribute to the bone loss and increased fracture risk in patients presenting with fragility fractures or osteoporosis. Several medical conditions and medications significantly increase the risk for bone loss and skeletal fragility. This review focuses on some of the common causes of osteoporosis, addressing the underlying mechanisms, diagnostic approach and treatment of low bone mass in the presence of these conditions.
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Affiliation(s)
- Faryal Mirza
- Division of Endocrinology and MetabolismDepartments of MedicineOrthopaedic SurgeryUConn Musculoskeletal Institute, UConn Health, 263 Farmington Avenue, Farmington, Connecticut 06030-5456, USA
| | - Ernesto Canalis
- Division of Endocrinology and MetabolismDepartments of MedicineOrthopaedic SurgeryUConn Musculoskeletal Institute, UConn Health, 263 Farmington Avenue, Farmington, Connecticut 06030-5456, USA Division of Endocrinology and MetabolismDepartments of MedicineOrthopaedic SurgeryUConn Musculoskeletal Institute, UConn Health, 263 Farmington Avenue, Farmington, Connecticut 06030-5456, USA
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Mula M, Cock HR. More than seizures: improving the lives of people with refractory epilepsy. Eur J Neurol 2014; 22:24-30. [DOI: 10.1111/ene.12603] [Citation(s) in RCA: 53] [Impact Index Per Article: 4.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/29/2014] [Accepted: 09/29/2014] [Indexed: 11/30/2022]
Affiliation(s)
- M. Mula
- Atkinson Morley Epilepsy Group; St Georges NHS Trust; London UK
- St George's University of London; London UK
| | - H. R. Cock
- Atkinson Morley Epilepsy Group; St Georges NHS Trust; London UK
- St George's University of London; London UK
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Panday K, Gona A, Humphrey MB. Medication-induced osteoporosis: screening and treatment strategies. Ther Adv Musculoskelet Dis 2014; 6:185-202. [PMID: 25342997 DOI: 10.1177/1759720x14546350] [Citation(s) in RCA: 101] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/18/2022] Open
Abstract
Drug-induced osteoporosis is a significant health problem and many physicians are unaware that many commonly prescribed medications contribute to significant bone loss and fractures. In addition to glucocorticoids, proton pump inhibitors, selective serotonin receptor inhibitors, thiazolidinediones, anticonvulsants, medroxyprogesterone acetate, aromatase inhibitors, androgen deprivation therapy, heparin, calcineurin inhibitors, and some chemotherapies have deleterious effects on bone health. Furthermore, many patients are treated with combinations of these medications, possibly compounding the harmful effects of these drugs. Increasing physician awareness of these side effects will allow for monitoring of bone health and therapeutic interventions to prevent or treat drug-induced osteoporosis.
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Affiliation(s)
- Keshav Panday
- Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - Amitha Gona
- Department of Medicine, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA
| | - Mary Beth Humphrey
- Department of Medicine, University of Oklahoma Health Sciences Center, and Veterans Affairs Medical Center, 975 NE 10th St, BRC209, Oklahoma City, OK 73104, USA
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Anwar MJ, Radhakrishna KV, Sharma A, Vohora D. Raloxifene preserves phenytoin and sodium valproate induced bone loss by modulating serum estradiol and TGF-β3 content in bone of female mice. Eur J Pharm Sci 2014; 62:219-226. [PMID: 24880111 DOI: 10.1016/j.ejps.2014.05.018] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/06/2014] [Revised: 04/21/2014] [Accepted: 05/21/2014] [Indexed: 11/25/2022]
Abstract
Antiepileptic drugs (AEDs)-induced adverse consequences on bone are now well recognized. Despite this, there is limited data on the effect of anti-osteoporotic therapies on AEDs-induced bone loss. We hypothesize that estrogen deprivation following phenytoin (PHT) and sodium valproate (SVP) therapy could lead to adverse bony effects. Both PHT and SVP inhibit human aromatase enzyme and stimulate microsomal catabolism of oestrogens. Estrogen deficiency states are known to reduce the deposition of transforming growth factor-β (TGF-β3), a bone matrix protein, having anti-osteoclastic property. Thus, an attempt was made to investigate the effect of raloxifene, a selective oestrogen receptor modulator, in comparison with calcium and vitamin D3 (CVD) supplementation, on PHT and SVP-induced alterations in bone in mice and to unravel the role of estradiol and TGF-β3 in mediation of bony effects by either AEDs or raloxifene. Further, the effect of raloxifene on seizures and on the antiepileptic efficacy of PHT and SVP was investigated. Swiss strains of female mice were treated with PHT (35 mg/kg, p.o.) and SVP (300 mg/kg, p.o.) for 120 days to induce bone loss as evidenced by reduced bone mineral density (BMD) and altered bone turnover markers (BTMs) in lumbar bones (alkaline phosphatase, tartarate resistant acid phosphatase, hydroxyproline) and urine (calcium). The bone loss was accompanied by reduced serum estradiol levels and bone TGF-β3 content. Preventive and therapeutic treatment with raloxifene ameliorated bony alterations and was more effective than CVD. It also significantly restored estradiol and TGF-β3 levels. Deprived estrogen levels (that in turn reduced lumbar TGF-β3 content) following PHT and SVP, thus, might represent one of the various mechanisms of AEDs-induced bone loss. Raloxifene preserved the bony changes without interfering with antiepileptic efficacy of these drugs, and hence raloxifene could be a potential therapeutic option in the management of PHT and SVP-induced bone disease if clinically approved.
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Affiliation(s)
- Md Jamir Anwar
- Neurobehavioral Pharmacology Laboratory, Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, Hamdard University, New Delhi 110062, India
| | - K V Radhakrishna
- Department of Clinical Research, National Institute of Nutrition (NIN), Tarnaka, Hyderabad 500007, India
| | - Abhay Sharma
- Institute of Genomics and Integrative Biology, Sukhdev Vihar, Mathura Road, New Delhi 110025, India
| | - Divya Vohora
- Neurobehavioral Pharmacology Laboratory, Department of Pharmacology, Faculty of Pharmacy, Jamia Hamdard, Hamdard University, New Delhi 110062, India.
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Low vitamin D levels are common in patients with epilepsy. Epilepsy Res 2014; 108:1352-6. [PMID: 25060996 DOI: 10.1016/j.eplepsyres.2014.06.008] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/06/2013] [Revised: 05/24/2014] [Accepted: 06/13/2014] [Indexed: 01/22/2023]
Abstract
PURPOSE Vitamin D is important for bone health, and vitamin D deficiency may contribute to other disorders (e.g., autoimmune, infections, cancer, degenerative, diabetic, and vascular). Enzyme-inducing antiepileptic drugs have been particularly implicated for osteoporosis risk given their effects on vitamin D. We examined the prevalence of vitamin D deficiency in adult epilepsy patients. METHODS We conducted an observational study of consecutive epilepsy patients treated by two clinicians at the Emory University Epilepsy Center from 2008 to 2011 in order to determine the frequency of low vitamin D levels and possible differential antiepileptic drug risks. Vitamin D 25-OH levels were categorized as low (<20 ng/ml), borderline (20-29 ng/ml), or normal (≥30 ng/ml). Antiepileptic drugs were categorized based on their enzyme inducing properties. Descriptive and inferential statistics were employed. RESULTS Vitamin D levels were obtained on 596 patients with epilepsy. Mean age was 41 years (SD=14; range=18-81); 56% were women. Race/ethnicity was 55% Caucasian, 34% Black, 2% Asian, and 7% Unknown. The mean vitamin D level was 22.5 (SD=11.9; range = <4 to 98), and 45% had level <20 ng/ml. Mean vitamin D levels (F=6.48, p=.002) and frequencies of vitamin D categories (p=.002, Chi square test) differed across the antiepileptic drug groups. Vitamin D deficiency was present in 54% of enzyme-inducing and 37% of non-enzyme-inducing antiepileptic drugs groups. CONCLUSIONS Vitamin D deficiency is common in patients with epilepsy on antiepileptic drugs. Monitoring of vitamin D should be considered as part of the routine management of patients with epilepsy.
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Management of Seizures in the Elderly. CURRENT GERIATRICS REPORTS 2014. [DOI: 10.1007/s13670-014-0078-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/25/2022]
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Miziak B, Błaszczyk B, Chrościńska-Krawczyk M, Danilkiewicz G, Jagiełło-Wójtowicz E, Czuczwar SJ. The problem of osteoporosis in epileptic patients taking antiepileptic drugs. Expert Opin Drug Saf 2014; 13:935-46. [PMID: 24821596 DOI: 10.1517/14740338.2014.919255] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
INTRODUCTION Epilepsy is a common neurological disorder associated with recurrent seizures. Therapy with antiepileptic drugs (AEDs) helps achieve seizure remission in approximately 70% of epileptic patients. Treatment with AEDs is frequently lifelong and there are reports suggesting its negative influence on bone health. This is especially important in terms of general occurrence of osteoporosis, affecting over 50 million people worldwide. AREAS COVERED This study refers to two main groups of AEDs: hepatic enzyme inducers (carbamazepine, oxcarbazepine, phenobarbital, phenytoin, primidone and topiramate) and non-inducers (clobazam, clonazepam, ethosuximide, gabapentin, lacosamide, lamotrigine, levetiracetam, pregabalin, tiagabine, valproate, vigabatrin and zonisamide). Some reports indicate that enzyme inducers may exert a more negative influence on bone mineral density (BMD) compared to non-inducers. Bone problems may appear in both sexes during AED therapy, although women are additionally burdened with postmenopausal osteoporosis. Supplementation of vitamin D and calcium in patients on AEDs is recommended. EXPERT OPINION Apart from enzyme inducers, valproate (an even enzyme inhibitor) may also negatively affect BMD. However, the untoward effects of AEDs may depend upon their doses and duration of treatment. Although the problem of supplementation of vitamin D and calcium in epileptic patients on AEDs is controversial, there are recommendations to do so.
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Affiliation(s)
- Barbara Miziak
- Medical University, Department of Pathophysiology , Jaczewskiego 8, PL 20-090 Lublin , Poland
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