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Mao P, Li H, Yu Z. A Review of Skin-Wearable Sensors for Non-Invasive Health Monitoring Applications. SENSORS (BASEL, SWITZERLAND) 2023; 23:3673. [PMID: 37050733 PMCID: PMC10099362 DOI: 10.3390/s23073673] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 02/28/2023] [Revised: 03/24/2023] [Accepted: 03/27/2023] [Indexed: 06/19/2023]
Abstract
The early detection of fatal diseases is crucial for medical diagnostics and treatment, both of which benefit the individual and society. Portable devices, such as thermometers and blood pressure monitors, and large instruments, such as computed tomography (CT) and X-ray scanners, have already been implemented to collect health-related information. However, collecting health information using conventional medical equipment at home or in a hospital can be inefficient and can potentially affect the timeliness of treatment. Therefore, on-time vital signal collection via healthcare monitoring has received increasing attention. As the largest organ of the human body, skin delivers significant signals reflecting our health condition; thus, receiving vital signals directly from the skin offers the opportunity for accessible and versatile non-invasive monitoring. In particular, emerging flexible and stretchable electronics demonstrate the capability of skin-like devices for on-time and continuous long-term health monitoring. Compared to traditional electronic devices, this type of device has better mechanical properties, such as skin conformal attachment, and maintains compatible detectability. This review divides the health information that can be obtained from skin using the sensor aspect's input energy forms into five categories: thermoelectrical signals, neural electrical signals, photoelectrical signals, electrochemical signals, and mechanical pressure signals. We then summarize current skin-wearable health monitoring devices and provide outlooks on future development.
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Affiliation(s)
- Pengsu Mao
- Department of Industrial and Manufacturing Engineering, FAMU-FSU College of Engineering, Florida State University, Tallahassee, FL 32310, USA
- High-Performance Materials Institute, Florida State University, Tallahassee, FL 32310, USA
| | - Haoran Li
- Department of Industrial and Manufacturing Engineering, FAMU-FSU College of Engineering, Florida State University, Tallahassee, FL 32310, USA
- High-Performance Materials Institute, Florida State University, Tallahassee, FL 32310, USA
| | - Zhibin Yu
- Department of Industrial and Manufacturing Engineering, FAMU-FSU College of Engineering, Florida State University, Tallahassee, FL 32310, USA
- High-Performance Materials Institute, Florida State University, Tallahassee, FL 32310, USA
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Pugliese N, Arcari I, Aghemo A, Lania AG, Lleo A, Mazziotti G. Osteosarcopenia in autoimmune cholestatic liver diseases: Causes, management, and challenges. World J Gastroenterol 2022; 28:1430-1443. [PMID: 35582674 PMCID: PMC9048470 DOI: 10.3748/wjg.v28.i14.1430] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2021] [Revised: 12/05/2021] [Accepted: 03/07/2022] [Indexed: 02/06/2023] Open
Abstract
Primary biliary cholangitis and primary sclerosing cholangitis (PSC) are the most common cholestatic liver diseases (CLD) in adults and are both characterized by an immune pathogenesis. While primary biliary cholangitis is a model autoimmune disease, with over 90% of patients presenting very specific autoantibodies against mitochondrial antigens, PSC is considered an immune mediated disease. Osteoporosis is the most common bone disease in CLD, resulting in frequent fractures and leading to significant morbidity. Further, sarcopenia is emerging as a frequent complication of chronic liver diseases with a significant prognostic impact and severe implications on the quality of life of patients. The mechanisms underlying osteoporosis and sarcopenia in CLD are still largely unknown and the association between these clinical conditions remains to be dissected. Although timely diagnosis, prevention, and management of osteosarcopenia are crucial to limit the consequences, there are no specific guidelines for management of osteoporosis and sarcopenia in patients with CLD. International guidelines recommend screening for bone disease at the time of diagnosis of CLD. However, the optimal monitoring strategies and treatments have not been defined yet and vary among centers. We herein aim to comprehensively outline the pathogenic mechanisms and clinical implications of osteosarcopenia in CLD, and to summarize expert recommendations for appropriate diagnostic and therapeutic approaches.
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Affiliation(s)
- Nicola Pugliese
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Milan, Italy
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano 20089, MI, Italy
| | - Ivan Arcari
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Milan, Italy
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano 20089, MI, Italy
| | - Alessio Aghemo
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Milan, Italy
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano 20089, MI, Italy
| | - Andrea G Lania
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Milan, Italy
- Department of Endocrinology, Diabetology and Medical Andrology Unit, IRCCS Humanitas Research Hospital, Rozzano 20089, MI, Italy
| | - Ana Lleo
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Milan, Italy
- Division of Internal Medicine and Hepatology, Department of Gastroenterology, IRCCS Humanitas Research Hospital, Rozzano 20089, MI, Italy
| | - Gherardo Mazziotti
- Department of Biomedical Sciences, Humanitas University, Pieve Emanuele 20090, Milan, Italy
- Department of Endocrinology, Diabetology and Medical Andrology Unit, IRCCS Humanitas Research Hospital, Rozzano 20089, MI, Italy
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Kopic S, Geibel JP. Gastric acid, calcium absorption, and their impact on bone health. Physiol Rev 2013; 93:189-268. [PMID: 23303909 DOI: 10.1152/physrev.00015.2012] [Citation(s) in RCA: 110] [Impact Index Per Article: 9.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022] Open
Abstract
Calcium balance is essential for a multitude of physiological processes, ranging from cell signaling to maintenance of bone health. Adequate intestinal absorption of calcium is a major factor for maintaining systemic calcium homeostasis. Recent observations indicate that a reduction of gastric acidity may impair effective calcium uptake through the intestine. This article reviews the physiology of gastric acid secretion, intestinal calcium absorption, and their respective neuroendocrine regulation and explores the physiological basis of a potential link between these individual systems.
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Affiliation(s)
- Sascha Kopic
- Department of Surgery and Cellular and Molecular Physiology, Yale School of Medicine, New Haven, Connecticut, USA
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Lund B, Sorensen OH, Hilden M, Lund B. The hepatic conversion of vitamin D in alcoholics with varying degrees of liver affection. ACTA MEDICA SCANDINAVICA 2009; 202:221-4. [PMID: 910639 DOI: 10.1111/j.0954-6820.1977.tb16815.x] [Citation(s) in RCA: 46] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
The seasonal variations in circulating 25-hydroxycholecalciferol (25-HCC) were studied in 102 alcoholics with fatty liver disease without histologic signs of cirrhosis and in 35 patients with alcoholic cirrhosis. The mean levels were compared with those of normal persons. Alcoholics had generally lower 25-HCC values than the controls, particularly in the summer. This was primarily explained by insufficient diet and reduced exposure to sunshine. The ability of the liver to hydroxylate in the 25-position was studied in three groups of alcoholics with 1) fatty liver disease without cirrhosis, 2) compensated cirrhosis, 3) severely incompensated liver cirrhosis. All three groups exhibited a significant increase in serum 25-HCC following the peroral administration of cholecalciferol at a dose of 1 200 U daily for 7 days. Similar rises were seen 7 days after a single injection of 10 000 U cholecalciferol. This indicates a normal intestinal absorption of vitamin D, even in advanced alcoholic liver disease, and is inconsistent with a severely damaged 25-hydroxylation capacity in these patients. Osteomalacia due to impaired liver hydroxylation of vitamin D can hardly explain the increased fracture rate and the decreased bone mass, which have been described in alcoholics.
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Abstract
This article discusses the clinical importance of hepatic osteopenia, the identification of risk factors for the individual patient, and the selection of patients, timing, and methods for diagnostic screening. General supportive measures to maximize bone health should be used in all patients at risk. In addition, for the patient with established osteoporosis, specific therapeutic measures may be justified, despite the lack of adequate randomized trials of these agents in patients with hepatic osteopenia.
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Affiliation(s)
- J Eileen Hay
- Division of Gastroenterology and Hepatology, Mayo Clinic, 200 First Street, Southwest, Rochester, MN 55905, USA.
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Zein CO, Jorgensen RA, Clarke B, Wenger DE, Keach JC, Angulo P, Lindor KD. Alendronate improves bone mineral density in primary biliary cirrhosis: a randomized placebo-controlled trial. Hepatology 2005; 42:762-71. [PMID: 16175618 DOI: 10.1002/hep.20866] [Citation(s) in RCA: 89] [Impact Index Per Article: 4.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/22/2022]
Abstract
Bone loss is a well-recognized complication of primary biliary cirrhosis (PBC). Although it has been suggested that alendronate might improve bone mineral density (BMD) in PBC, no randomized placebo-controlled trial has been conducted. The primary aim of this study was to compare the effects of alendronate versus placebo on BMD and biochemical measurements of bone turnover in patients with PBC-associated bone loss. We conducted a double-blinded, randomized, placebo-controlled trial. Patients with a PBC and BMD t score of less than -1.5 were randomized to receive 70 mg per week of alendronate or placebo over 1 year. BMD of the lumbar spine and proximal femur were measured at entry and at 1 year. Changes from baseline in BMD and biochemical measurements of bone turnover were assessed. Thirty-four patients were enrolled. Seventeen patients were randomized to each arm. After 1 year, a significantly larger improvement (P = .005) in spine BMD was observed in the alendronate group (0.09 +/- 0.03 g/cm2 SD from baseline) compared with the placebo group (-0.003 +/- 0.02 g/cm2 SD from baseline). A larger improvement (P = .046) was also observed in the femoral BMD of alendronate patients versus placebo. BMD changes were independent of concomitant estrogen therapy. The rate of adverse effects was similar in both groups. In conclusion, in patients with PBC-related bone loss, alendronate significantly improves BMD compared with placebo. Although in this study oral alendronate appears to be well tolerated in patients with PBC, larger studies are needed to formally evaluate safety.
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Affiliation(s)
- Claudia O Zein
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Mayo Clinic and Foundation, Rochester, MN 55905, USA
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Abstract
Primary biliary cirrhosis is predominantly seen in middle-aged women. Typical symptoms are fatigue, pruritus, and abdominal pain. Jaundice develops in the endstage disease. At presentation, about 40% of the patients are asymptomatic, but 30% to 50% already have hepatomegaly, and 15% present with splenomegaly. Even patients with fully developed liver cirrhosis may be free of symptoms. Abnormal physical signs and advanced histological stage are more frequent in symptomatic than in asymptomatic patients. Fatigue, pruritus, and Sjögren's syndrome are more common in women than men, but other signs and symptoms do not differ in the two sexes. PBC is associated with a large variety of other diseases, like arthropathy, CREST syndrome, autoimmune thyroiditis, and so on, which in addition will or will not produce symptoms. Hepatocellular carcinoma is a rare complication in women, but more frequent in men. Diagnosis can be established by the triad antimitochondrial antibodies (AMA), cholestatic indices, and liver histology, diagnostic or compatible with PBC. When AMA are not detected, then antinuclear antibodies (autoantibodies against gp.210 and others) can be detected in 50% of AMA-negative patients. AMA titers do not correlate with the course of the disease nor histological progression. After liver transplantation, AMA recur in nearly 100%. The liver enzyme pattern in PBC patients is cholestatic: alkaline phosphatase and gammaglutamyltransferase increase to 10 or more times the upper limit of normal. The amount of enzymes does not correlate with disease progression or stage of the disease. The only prognostic factor in PBC is serum bilirubin. AMA-negative patients account for about 10% to 15%. Routine biochemical tests are not different from AMA-positive patients, but usually higher ANA, SMA, and IgG concentrations are detected. Histologically, it is PBC. The overlap-syndrome, autoimmune hepatitis-PBC presents with the histological features of autoimmune hepatitis and PBC, with AMA, ANA, or SMA. Imaging procedures are not helpful for the diagnosis of PBC, except for liver histology. Histologically, four different stages can be assessed, ranging from florid bile duct lesions, ductular proliferation, and fibrosis to liver cirrhosis. Liver histology is of interest for the assessment of the diagnosis and for staging of the disease.
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Affiliation(s)
- Ulrich Leuschner
- Johann Wolfgang Goethe University, Medical Clinic II, Theodor Stern Kai 7, Frankfurt am Main, Germany.
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Affiliation(s)
- J Eileen Hay
- Mayo Clinic, 200 First street SW, Rochester, MN 55905, USA.
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Solerio E, Isaia G, Innarella R, Di Stefano M, Farina M, Borghesio E, Framarin L, Rizzetto M, Rosina F. Osteoporosis: still a typical complication of primary biliary cirrhosis? Dig Liver Dis 2003; 35:339-46. [PMID: 12846406 DOI: 10.1016/s1590-8658(03)00078-1] [Citation(s) in RCA: 29] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
BACKGROUND Osteoporosis is a recognized complication of primary biliary cirrhosis but it has been suggested that its prevalence may overlap that observed among postmenopausal women. AIM To evaluate prevalence and risk factors of osteoporosis in primary biliary cirrhosis. PATIENTS A total of 133 female patients (age 53+/-10 years, menopausal status 70%, histological stage I-II 61%, portal hypertension 28%, Mayo Risk Score 4.11+/-0.59) were enrolled. METHODS Dual X-ray absorptiometry of the lumbar spine. RESULTS Mean bone mineral density, T and Z score were 0.861+/-0.160 g/cm2, -1.87+/-1.45 and -0.78+/-2.63, respectively. At multivariate analysis, bone mineral density was inversely correlated with age (p<0.05). Osteoporosis was present in 39/92 (41%) postmenopausal and 8/41 (20%) premenopausal patients. In the premenopausal group, osteoporosis was significantly correlated with serum albumin (p<0.05) and Mayo Risk score (p<0.005). No significant correlation was present in the postmenopausal group. CONCLUSIONS Despite the accepted wisdom that osteoporosis is a common complication of primary biliary cirrhosis, its frequency in post-menopausal patients overlaps that observed in the general population, but is much more frequent in premenopausal patients, where it appears to be related to severity of liver disease and cholestasis.
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Affiliation(s)
- E Solerio
- Division of Gastroenterology and Hepatology, Gradenigo Hospital, C.so Regina Margherita 10, 10153 Turin, Italy
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Shiomi S, Nishiguchi S, Kubo S, Tamori A, Habu D, Takeda T, Ochi H. Vitamin K2 (menatetrenone) for bone loss in patients with cirrhosis of the liver. Am J Gastroenterol 2002; 97:978-81. [PMID: 12003435 DOI: 10.1111/j.1572-0241.2002.05618.x] [Citation(s) in RCA: 35] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
OBJECTIVE Bone loss frequently appears in the natural history of liver disease. The effects of therapy for osteoporosis associated with cirrhosis of the liver are still controversial. We evaluated the effects of vitamin K2 on osteopenia in women with cirrhosis. METHODS The subjects were 50 women with cirrhosis who had underlying hepatitis viral infections. Half of the patients were randomly assigned to receive vitamin K2 (menatetrenone). The bone mineral density (BMD) of the lumbar vertebrae was measured by dual-energy X-ray absorptiometry at entry and at 1-yr intervals for 2 yr. RESULTS The percentages of change from the initial BMD at 1 and 2 yr after initiation of the study were, respectively, +0.1 +/- 2.6% and -0.5 +/- 3.5% for the vitamin K2-treated group and -2.2 +/- 2.4% and -4.6 +/- 3.9% for the control group. The changes in BMD at each timepoint differed significantly between the control and treated groups (p = 0.008 for 1 yr and p = 0.002 for 2 yr). In the vitamin K2-treated group, the ratio of osteocalcin to undercarboxylated osteocalcin in those patients with increases in BMD after 1 yr of treatment was significantly lower than that in patients showing decreases in BMD (p = 0.017). No adverse effects of vitamin K2 were noted. CONCLUSIONS Vitamin K2 can prevent bone loss and may therefore be useful in the management of bone disease in women with cirrhosis of the liver.
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Affiliation(s)
- Susumu Shiomi
- Third Department of Internal Medicine, Osaka City University Medical School, Osaka, Japan
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11
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Menon KV, Angulo P, Weston S, Dickson ER, Lindor KD. Bone disease in primary biliary cirrhosis: independent indicators and rate of progression. J Hepatol 2001; 35:316-23. [PMID: 11592591 DOI: 10.1016/s0168-8278(01)00144-1] [Citation(s) in RCA: 130] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND/AIMS To identify indicators of osteoporosis and to determine the rate of bone loss in patients with primary biliary cirrhosis (PBC). METHODS Bone mineral density of the lumbar spine and hip was measured at annual intervals over 7 years of follow-up in 176 patients with PBC. RESULTS Osteoporosis (t-score below -2.5) was found in 20% of patients and occurred 32.1 times more frequently in patients with PBC than expected. Patients with histologic stage 3 or 4 disease had a 5.4-fold increased risk of osteoporosis compared to patients with stage 1 or 2. Age, body mass index, advanced stage (3 or 4), and history of fractures were the only independent indicators of osteoporosis. After 3 years of follow up, the rate of bone loss in patients with stage 1 or 2 increased and equaled that seen in patients with stage 3 or 4. Serum bilirubin level was the only variable independently associated with the rate of bone loss over time. CONCLUSIONS Severity of the liver disease contributes significantly to the severity of bone disease in PBC. PBC patients who are older, thinner and have more advanced liver disease may have the most benefit from bone density measurements and treatment for their osteoporosis.
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Affiliation(s)
- K V Menon
- Division of Gastroenterology and Hepatology, Mayo Clinic and Foundation, Rochester, MN, USA
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Newton J, Francis R, Prince M, James O, Bassendine M, Rawlings D, Jones D. Osteoporosis in primary biliary cirrhosis revisited. Gut 2001; 49:282-7. [PMID: 11454807 PMCID: PMC1728382 DOI: 10.1136/gut.49.2.282] [Citation(s) in RCA: 71] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
Abstract
BACKGROUND Primary biliary cirrhosis (PBC) is increasingly being diagnosed in the earlier non-cholestatic stages of disease. Accepted wisdom has been that PBC is frequently complicated by osteoporosis. Whether this association holds true for the broader spectrum of PBC patients now recognised has not as yet been studied. AIMS To examine the extent to which osteoporosis occurs more commonly in PBC patients than in normal individuals of the same age and sex. DESIGN Retrospective review of a large cohort of well characterised PBC patients. PATIENTS A total of 272 PBC patients with definite or probable PBC followed up for a mean of 10.1 years (total follow up 2726 patient years) who had at least one bone mineral density measurement (BMD). RESULTS In this unselected group of PBC patients, mean Z scores (number of SDs from age and sex matched normal mean values) at the neck of femur (NOF) and lumbar spine (LS) at first BMD measurement (7 (6) years after PBC diagnosis) were -0.1 (1.4) and 0.1 (1.4), respectively. At first BMD measurement, 18 PBC patients had Z scores less than -2.0 and 85 had T scores less than -2.5. No factors predictive of osteoporosis were found in affected patients. A total of 957 BMD measurements were performed (0.35 per patient year of follow up); 220 patients had two or more measurements. No patient went on to develop de novo osteoporosis during follow up. In the 51 patients (who were clinically representative of the whole group) who received no PBC or bone related treatment during follow up, %BMD changes per year at the NOF and LS were -1.6 (3.2) and 0.1 (2.2), respectively. No variance in this "natural" rate of BMD measurement was seen in patients receiving PBC modulating agents (including prednisolone and UDCA) or osteoporosis prophylaxis/therapy. Significant improvement at the LS was seen in patients undergoing liver transplantation. CONCLUSIONS Osteoporosis is not a specific complication of PBC.
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Affiliation(s)
- J Newton
- Centre for Liver Research, University of Newcastle, Newcastle upon Tyne, UK
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Abstract
Osteopenia, in the form of osteoporosis, is a common complication of chronic cholestatic liver diseases and, although its cause is poorly understood, it appears to be intimately related to the cholestasis itself. With more patients surviving longer with successful liver transplantation, the clinical significance of such osteopenia has increased, and a traumatic fracturing has become a major cause of morbidity in this patient population. Noninvasive diagnosis is easy, and serial measurements allow assessment of disease progression. Although no effective therapy can treat or prevent this complication, supportive measures can improve skeletal well-being, especially in high-risk individuals who are candidates for liver transplantation.
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Affiliation(s)
- J E Hay
- Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, Minnesota 55905, USA
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Nakano A, Kanda T, Abe H. Bone changes and mineral metabolism disorders in rats with experimental liver cirrhosis. J Gastroenterol Hepatol 1996; 11:1143-54. [PMID: 9034934 DOI: 10.1111/j.1440-1746.1996.tb01843.x] [Citation(s) in RCA: 18] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/03/2023]
Abstract
To investigate the pathogenesis of hepatic osteodystrophy (HOD) in parenchymal liver disease, we developed a laboratory model in animals using carbon tetrachloride (CCl4) and thioacetamide. Biochemical and histological parameters in the model were measured. In rats with both chronic non-cirrhotic liver injury and CCl4-induced cirrhosis, tibial bone volume was significantly lower than in controls. In CCl4-treated cirrhotic rats, the osteoid volume decreased while the urinary calcium/creatinine ratio increased. In all CCl4-treated rats, bone volume was significantly correlated with both the serum albumin concentration and the number of goblet cells reflecting intestinal villous atrophy. The serum concentration of vitamin D metabolites was not correlated with bone volume. Whole body retention of 47Ca was significantly lower in CCl4-treated cirrhotic rats than in controls. Furthermore, the bone volume in thioacetamide-treated cirrhotic rats was significantly lower than in controls. These data demonstrate that chronic parenchymal liver injury itself causes osteoporosis (i.e. HOD) due to a combination of low bone formation rates and high resorption rates, that HOD begins at the stage of chronic non-cirrhotic liver injury, that bone volume in HOD parallels liver damage and that the principal pathogenesis of HOD seems to be intestinal Ca malabsorption due to lower serum albumin and villous atrophy, while serum levels of vitamin D metabolites have little influence on the pathogenesis of HOD.
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Affiliation(s)
- A Nakano
- Department of Pharmacology, Kinki University, School of Medicine, Osaka, Japan
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15
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Tsuneoka K, Tameda Y, Takase K, Nakano T. Osteodystrophy in patients with chronic hepatitis and liver cirrhosis. J Gastroenterol 1996; 31:669-78. [PMID: 8887033 DOI: 10.1007/bf02347615] [Citation(s) in RCA: 54] [Impact Index Per Article: 1.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Bone mineral density (BMD) of the lumber vertebrae and factors related to bone metabolism were determined in patients with chronic viral hepatitis and patients with liver cirrhosis to clarify correlations between hepatic dysfunction, considered to be one of the causes of hepatic osteodystrophy, and decrease in bone mass. BMD of the second to fourth lumbar vertebrae was determined with a Lunar (Madison, WI, USA) DPX, a dual-energy X-ray absorptiometry diagnostic system. BMD was significantly lowest in patients with liver cirrhosis, followed by patients with chronic hepatitis, and healthy subjects, in this order. There was a significantly positive but weak correlation between albumin and BMD. Levels of 25(OH)D and 1,25(OH)2D were significantly lower in patients with liver cirrhosis than in those with chronic hepatitis. BMD and vitamin D were decreased in all patients whose cholinesterase (ChE) was below 0.3 delta pH. Urinary pyridinoline (Upyr) was significantly higher in the patients with liver cirrhosis, in whom bone mass was decreased, than in the patients with chronic hepatitis, whereas serum osteocalcin levels were distributed in the upper normal range in patients with chronic hepatitis and those with liver cirrhosis. There was a positive correlation between 25(OH)D and serum osteocalcin levels in patients with liver cirrhosis. These results indicate that osteogenesis is decreased and suggest that the decrease in BMD which occurs in viral liver cirrhosis, probably related to decreased, bone formation and slight promotion of bone resorption, reflects deranged hepatic function. This is the first report of Upyr and urinary deoxypyridinoline (UDpyr) determination in patients with liver cirrhosis and patients with chronic hepatitis. The negative correlation of Upyr and UDpyr with ChE is a novel finding.
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Affiliation(s)
- K Tsuneoka
- First Department of Internal Medicine, Mie University School of Medicine, Japan
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16
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Abstract
Osteopenia in the form of osteoporosis is a common clinical problem associated with chronic cholestatic liver disease, and clinical morbidity from atraumatic fractures is increasing as more patients with PBC and PSC undergo successful liver transplantation. In the absence of symptomatic fractures, the clinical diagnosis may not be evident and must be sought by specific means to assess bone mineral density. The clinical problem has now been defined, but much remains unknown, from etiologic mechanisms to effective therapies. At present, it seems reasonable to provide aggressive supportive therapy in an attempt to maximize skeletal well-being until more effective therapies for osteopenia become available.
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Affiliation(s)
- J E Hay
- Mayo Clinic, Rochester, Minnesota
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Shiomi S, Kuroki T, Masaki K, Takeda T, Nishiguchi S, Nakajima S, Seki S, Kobayashi K, Okamura T, Ochi H. Osteopenia in primary biliary cirrhosis and cirrhosis of the liver in women, evaluated by dual-energy X-ray absorptiometry. J Gastroenterol 1994; 29:605-9. [PMID: 8000509 DOI: 10.1007/bf02365443] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
To study bone involvement in primary biliary cirrhosis (PBC), we used dual-energy X-ray absorptiometry to measure bone mineral density (BMD) in Japanese women with PBC and with cirrhosis of the liver. In both groups, in each decade up to 60 years of age, the mean BMD of the lumbar spine was not significantly different from that in healthy Japanese women; however, in patients aged 60 years or more, the level was significantly lower both in the patients with PBC (P < 0.001) and in those with cirrhosis of the liver (P < 0.01). Patients with PBC were also examined by single-photon absorptiometry. The BMD of the radius in the patients with PBC was less changed than that of the lumbar vertebrae; thus, the bone changes in PBC seem to be greater in spongy than in cortical bone.
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Affiliation(s)
- S Shiomi
- Third Department of Internal Medicine, Osaka City University Medical School, Japan
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18
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Hay JE, Lindor KD, Wiesner RH, Dickson ER, Krom RA, LaRusso NF. The metabolic bone disease of primary sclerosing cholangitis. Hepatology 1991. [PMID: 1860683 DOI: 10.1002/hep.1840140209] [Citation(s) in RCA: 67] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/16/2022]
Abstract
The incidence and severity of osteopenic bone disease in primary sclerosing cholangitis is poorly defined. Clinical, biochemical and radiographic assessment and bone mineral density measurements of the lumbar spine were carried out in two groups of patients. Group 1 consisted of 30 patients with advanced primary sclerosing cholangitis; group 2 consisted of 18 patients with newly diagnosed primary sclerosing cholangitis. Only one patient had bone pain. All patients were normocalcemic; two had elevated serum parathormone levels. Fourteen patients (47%) from group 1 but no patients from group 2 had low serum 25-hydroxyvitamin D levels. Mean bone mineral density was significantly reduced in group 1 patients (0.97 +/- 0.04 gm/cm2) compared with age-matched and sex-matched controls (1.25 +/- 0.01 gm/cm2, p less than 0.0001), and in 15 patients (50%) bone mineral density was below the fracture threshold (0.98 gm/cm2). The bone mineral density in group 2 was not significantly different from controls, and no patient was below the fracture threshold. In neither group did bone mineral density correlate with serum bilirubin, 25-hydroxyvitamin D, fecal fat excretion, previous drug therapy or the presence of chronic ulcerative colitis. Histomorphometrical examination of bone from four group 1 patients showed increased bone resorption, reduced bone formation, moderate-to-severe osteopenia and no osteomalacia. In conclusion, severe osteopenic bone disease is common in advanced primary sclerosing cholangitis and, like that seen in other cholestatis diseases, is consistent with osteoporosis.
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Affiliation(s)
- J E Hay
- Division of Gastroenterology, Mayo Clinic, Rochester, Minnesota 55905
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19
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Affiliation(s)
- T H Diamond
- Department of Endocrinology, Royal North Shore Hospital, St Leonards, New South Wales, Australia
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20
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Mitchison HC, Malcolm AJ, Bassendine MF, James OF. Metabolic bone disease in primary biliary cirrhosis at presentation. Gastroenterology 1988; 94:463-70. [PMID: 3335317 DOI: 10.1016/0016-5085(88)90438-6] [Citation(s) in RCA: 66] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
Metabolic bone disease, particularly osteoporosis, is a complication of advanced primary biliary cirrhosis, but the extent of the problem is unclear. We present 33 patients who were investigated for bone disease at the time of diagnosis of their liver disease and who had received no prior treatment likely to influence their bones. Iliac crest bone biopsy showed no patient with osteoporosis, and mild osteomalacic changes in 1 patient. Slight elevations in appositional rate, osteoid volume, and resorption surface were compatible with a state of high bone turnover. Photon absorptiometry revealed a low forearm bone mineral content in 3 of 25 patients, calcium absorption was below normal in 14 of 24 patients, and there was evidence of fat malabsorption in 11 of 25 patients. Five patients also had low serum levels of 25-hydroxyvitamin D and 1,25-dihydroxyvitamin D. Thus, little evidence of significant metabolic bone disease was found in this group by these methods, but abnormalities were seen, such as poor calcium absorption, that may predispose to its later development.
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Affiliation(s)
- H C Mitchison
- Department of Medicine, University of Newcastle Upon Tyne, United Kingdom
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21
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Abstract
This is a report of six patients with cirrhosis of the liver in whom primary hyperparathyroidism occurred due to a solitary parathyroid adenoma 3 months to 9 years after undergoing emergency portacaval shunt for hemorrhage from esophageal varices. The presenting symptoms in all six patients were weakness and bone pain. Three patients had a bone fracture after insignificant trauma, one and probably two passed kidney stones, and a duodenal ulcer developed in two. Bone x-ray films showed generalized osteoporosis in all patients. Renal function and arterial blood pH were within normal limits in every patient. The diagnosis of primary hyperparathyroidism in each patient was based on repeated demonstrations of hypercalcemia, hypophosphatemia, and markedly elevated serum immunoreactive parathyroid hormone concentrations. In all six patients, removal of the parathyroid adenoma resulted in disappearance of symptoms; normalization of serum calcium, phosphorus, and immunoreactive parathyroid hormone levels; and in four of the six, improvement in radiographic evidence of osteoporosis during follow-up of from 1 to 6 years. The association of cirrhosis, portacaval shunt, and primary hyperparathyroidism has not been documented previously. Our six patients with primary hyperparathyroidism constitute 3.4 percent of 174 survivors of emergency portacaval shunt in a series of 264 unselected, consecutive patients with cirrhosis and bleeding esophageal varices. Hepatic osteodystrophy is known to have occurred in only 11 of these 174 survivors. Primary hyperparathyroidism may be a more common cause of hepatic osteodystrophy than has been previously recognized, and should be considered in patients with cirrhosis in whom weakness, bone pain, and bone demineralization develop, particularly if they have a portacaval anastomosis.
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Affiliation(s)
- M J Orloff
- Department of Surgery, University of California, San Diego Medical Center 92103
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Abstract
To determine whether bone loss in patients with chronic cholestatic liver disease is the consequence of a high or low bone turnover state, 30 female patients with biopsy-proven primary biliary cirrhosis underwent iliac crest biopsy following double tetracycline labeling. The mean trabecular bone volume was decreased as a result of trabecular plate thinning in both the premenopausal (p less than 0.02) and postmenopausal (p less than 0.05) patients, compared to age- and sex-matched controls. Indications that osteoblastic function was impaired included a significantly lower mean wall thickness (p less than 0.01) and mean osteoid seam width (p less than 0.05), and this in association with a decreased mineral appositional rate and prolonged mineralization lag time was suggestive of a defect in matrix synthesis. Further evidence of impaired osteoblastic activity was the significantly lower bone formation rate at both tissue (p less than 0.001) and basic multicellular unit levels (p less than 0.05) in the postmenopausal patients. Total resorption surfaces and fasting urinary calcium/creatinine ratios were significantly increased (p less than 0.005 and 0.05, respectively) in the premenopausal patients and mean interstitial bone thickness reduced in both pre- and postmenopausal patients, suggesting that increased resorption may also contribute to bone loss in primary biliary cirrhosis.
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24
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Kishan T, Lal H, Sehgal RK. Skeletal changes in Indian childhood cirrhosis. Indian J Pediatr 1986; 53:415-8. [PMID: 3759220 DOI: 10.1007/bf02760429] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/07/2023]
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25
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Bengoa JM, Sitrin MD, Meredith S, Kelly SE, Shah N, Baker AL, Rosenberg IH. Intestinal calcium absorption and vitamin D status in chronic cholestatic liver disease. Hepatology 1984; 4:261-5. [PMID: 6706300 DOI: 10.1002/hep.1840040215] [Citation(s) in RCA: 49] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
Metabolic bone disease is common in patients with cholestatic liver disease. The importance of vitamin D status and calcium malabsorption in the pathogenesis of bone disease in these patients remains undefined. We have measured intestinal calcium absorption in relation to vitamin D status in 14 patients with chronic cholestatic liver disease including 11 with primary biliary cirrhosis. Fractional calcium absorption was determined from radioactive counts in the right forearm after separate oral and intravenous doses of 47CaCl2 in the fasting state. Eight of 14 patients (57%) had a decreased calcium absorption compared to controls. A significant correlation was observed between serum 25-hydroxyvitamin D levels and fractional calcium absorption (r = 0.623, p less than 0.02). Treatment with oral 25-hydroxyvitamin D3 in three patients with low serum 25-hydroxyvitamin D levels resulted in correction of serum 25-hydroxyvitamin D levels and improvement in fractional calcium absorption. No correlation was found between serum 1,25-dihydroxyvitamin D levels and fractional calcium absorption (r = 0.221). Calcium malabsorption was common in this series of patients, and serum 25-hydroxyvitamin D levels were useful in predicting fractional calcium absorption. Treatment with oral 25-hydroxyvitamin D3 was accompanied by improved calcium absorption.
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27
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Mobarhan SA, Russell RM, Recker RR, Posner DB, Iber FL, Miller P. Metabolic bone disease in alcoholic cirrhosis: a comparison of the effect of vitamin D2, 25-hydroxyvitamin D, or supportive treatment. Hepatology 1984; 4:266-73. [PMID: 6608483 DOI: 10.1002/hep.1840040216] [Citation(s) in RCA: 58] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
In a study of 56 alcoholics with liver cirrhosis, 18 (32%) had decreased bone density and low levels of serum 25-hydroxyvitamin D (25-OH-D) (less than 20 ng per ml). To compare the efficacy of vitamin D2 and 25-OH-D treatment in correcting the metabolic bone disease in alcoholic cirrhosis, the 18 patients were randomized in the following manner, in groups of six patients each: Group 1, control (received no supplemental vitamin D treatment); Group 2, given vitamin D2 (50,000 IU p.o.) two to three times weekly, and Group 3, treated with 25-OH-D (20 to 50 mg p.o.) daily as required to attain normal serum 25-OH-D levels. The study period lasted 6 to 12 months (mean, 10.7 months). Initial histomorphometric study of transiliac bone biopsy with double tetracycline labeling in nine patients in whom biopsy was feasible showed only osteoporosis without evidence of osteomalacia. By the end of the study, serum 25-OH-D levels in the control group (Group 1) raised slightly while showing marked improvement in Groups 2 and 3. Bone density results remained unchanged in control patients but demonstrated a significant increase in both treatment groups. Vitamin D2 and 25-OH-D were equally effective in increasing bone density measurements. Posttreatment biopsies were performed in three patients of Group 2 and two patients of Group 3. While the histomorphometric results in Group 3 were not conclusive, in Group 2 improvement in static measures of bone remodeling was noted. Osteoporosis is the usual form of bone disease in alcoholic cirrhosis and a response to either vitamin D2 or 25-OH-D treatment is suggested.
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Cuthbert JA, Pak CY, Zerwekh JE, Glass KD, Combes B. Bone disease in primary biliary cirrhosis: increased bone resorption and turnover in the absence of osteoporosis or osteomalacia. Hepatology 1984; 4:1-8. [PMID: 6693061 DOI: 10.1002/hep.1840040101] [Citation(s) in RCA: 83] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/21/2023]
Abstract
The role of vitamin D in hepatic osteodystrophy was examined. Eleven unselected patients with primary biliary cirrhosis (PBC) were assessed for disorders of mineral and vitamin D metabolism. Six were not receiving supplementary vitamin D, and five were being treated with oral vitamin D (50,000 IU daily). Serum levels of 25-hydroxyvitamin D were normal in all patients receiving oral therapy and in 4 of 6 untreated patients. Levels of serum 1,25-dihydroxyvitamin D and 24,25-dihydroxyvitamin D were normal or near normal in all patients. Studies were repeated after 6 months of therapy with parenteral vitamin D2 (100,000 IU i.m. monthly) in 7 patients. Initial bone histomorphometry revealed no evidence of osteomalacia or osteoporosis. However, the bone resorption surface of trabecular bone was increased. This abnormality was no longer present on repeat bone biopsies obtained after parenteral vitamin D therapy, and bone formation had decreased. In addition, trabecular bone volume remained normal in the face of the lower rate of bone formation. Increased bone resorption surface in the absence of osteoporosis or osteomalacia has not been previously described in PBC. Improvement in this bone parameter, associated with the finding of a decrease in the formation of bone and in hydroxyproline excretion in urine after parenteral vitamin D, suggests that increased turnover may be an early feature of the bone disease which complicates PBC and that parenteral vitamin D may retard the rate at which hepatic osteodystrophy develops in chronic cholestatic liver disease.
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29
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Atkinson MJ, Vido I, Keck E, Hesch RD. Hepatic osteodystrophy in primary biliary cirrhosis: a possible defect in Kupffer cell mediated cleavage of parathyroid hormone. Clin Endocrinol (Oxf) 1983; 19:21-8. [PMID: 6311459 DOI: 10.1111/j.1365-2265.1983.tb00738.x] [Citation(s) in RCA: 16] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Twelve of fourteen female patients with primary biliary cirrhosis, receiving vitamin D supplementation, exhibited unequivocal signs of osteoporosis but not of osteomalacia. Vitamin D treatment reproduced normal 25-hydroxyvitamin D levels in all but two patients and the 1,25 and 24,25-dihydroxyvitamin D metabolic pathways appeared to be unimpaired. A possible mechanism for the vitamin D resistant osteoporosis has been identified following the observation that, in those patients with severe cirrhosis, the circulating concentration of intact PTH was elevated. The increase in intact hormone appears to be at the expense of the carboxyl-regional PTH produced by hepatic Kupffer cell mediated cleavage of intact PTH. As a defect in Kupffer cell function is documented in primary biliary cirrhosis we postulate that the increased intact PTH/decreased carboxyl-regional PTH concentrations arise as a result of diminished Kupffer cell mediated cleavage. The reduced generation of cleaved PTH, due to this loss of Kupffer cell activity, would thus contribute to the development of osteoporosis in primary biliary cirrhosis.
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30
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Davies M, Mawer EB, Klass HJ, Lumb GA, Berry JL, Warnes TW. Vitamin D deficiency, osteomalacia, and primary biliary cirrhosis. Response to orally administered vitamin D3. Dig Dis Sci 1983; 28:145-53. [PMID: 6297863 DOI: 10.1007/bf01315144] [Citation(s) in RCA: 25] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Five patients with primary biliary cirrhosis and vitamin D deficiency (serum 25-hydroxyvitamin D less than 6 ng/ml) are presented. All patients had low serum 24,25-dihydroxyvitamin D3 concentrations. Three patients had histological osteomalacia, negative calcium balance, and subnormal serum 1,25-dihydroxyvitamin D3. Malabsorption of a standard dose of [3H]vitamin D3 was found in three of four patients with steatorrhea, enabling the effective dose of vitamin D3 given to be calculated. Oral vitamin D3 400-4000 IU/day (effectively 400-1860 IU/day) resulted in a return to normal of the serum vitamin D metabolites, correction of the impaired intestinal calcium absorption and healing of the osteomalacia. Increases in serum calcium, phosphate, and the renal tubular reabsorption of phosphate occurred with a concomitant decrease in serum parathyroid hormone. It is suggested that osteomalacia in primary biliary cirrhosis is the end result of vitamin D deficiency; the hepatic and renal hydroxylations of vitamin D are normal and target tissues are responsive to endogenously produced metabolites of vitamin D.
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31
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32
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Kato Y, Epstein O, Dick R, Sherlock S. Radiological patterns of cortical bone modelling in women with chronic liver disease. Clin Radiol 1982; 33:313-7. [PMID: 7075137 DOI: 10.1016/s0009-9260(82)80276-6] [Citation(s) in RCA: 11] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/23/2023]
Abstract
The pattern of cortical bone modelling in healthy and diseased populations can be derived from simple measurements taken from radiographs of tubular bones. To determine the pattern of bone modelling in women with chronic cholestatic and parenchymal liver diseases, these parameters have been measured in 83 women with primary biliary cirrhosis (PBC), 34 with steroid-treated chronic active hepatitis (CAH) and 27 with parenchymal liver disease (PLD) not treated with corticosteroids. Bone modelling profiles have been compared in these groups with expected pattern in healthy females. Abnormal bone modelling occurs in all three groups. In PBC, cortical thinning is progressive from the fourth decade onwards. In steroid-treated CAH, an initial increase in cortical thickness is observed in the third and fourth decades, after which cortical thinning occurs. In the PLD group, progressive loss of bone cortex is present from the fourth decade onwards. In all forms of liver disease, cortical thinning results from widening of the medullary cavity rather than resorption of the cortical surface.
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Abstract
We evaluated D-penicillamine in the treatment of primary biliary cirrhosis. In a prospective double-blind trial, 26 patients received D-penicillamine (250 mg four times a day), and 26 received an identical placebo. Although the desired urinary excretion of copper was achieved in patients taking D-penicillamine, there was no improvement in survival or symptoms after 28 months. Serum bilirubin and alkaline phosphatase increased equally in both groups. Alanine and aspartate aminotransferases were lower in the D-penicillamine group, but serum albumin was also lower in this group. Liver histology worsened equally in both groups. Major side effects, some appearing more than 24 months after the start of treatment, occurred in 31 per cent of the patients receiving D-penicillamine. Less serious side effects occurred in an additional 46 per cent. We conclude that D-penicillamine at the dosage we used is not effective in the treatment of primary biliary cirrhosis and is associated with a high incidence of serious side effects.
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34
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Dibble JB, Sheridan P, Hampshire R, Hardy GJ, Losowsky MS. Evidence for secondary hyperparathyroidism in the osteomalacia associated with chronic liver disease. Clin Endocrinol (Oxf) 1981; 15:373-83. [PMID: 6274546 DOI: 10.1111/j.1365-2265.1981.tb00677.x] [Citation(s) in RCA: 27] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/19/2023]
Abstract
Previous reports have suggested that secondary hyperparathyroidism is extremely uncommon in hepatic osteomalacia. This, together with other findings, has led to suggestions that in chronic liver disease there may be selective resistance of bone to vitamin D or a specific bone mineralization defect unrelated to Vitamin D. To examine these possibilities, twenty-five patients with chronic liver disease have been studied by bone biopsy, serum calcium and inorganic phosphate, plasma 25-hydroxyvitamin D, plasma immunoreactive parathormone (iPTH), fasting urine cAMP, fasting renal tubular maximal reabsorptive capacity for phosphate (TmP/GFR) and fine grain hand x-rays. Nine of the patients had osteomalacia on bone biopsy, eight of these had subnormal levels of plasma 25-hydroxyvitamin D and the other had a borderline result. Based on the consensus of all the tests, five of these had evidence of secondary hyperparathyroidism. Plasma iPTH was higher in patients with osteomalacia than in patients without osteomalacia (P less than 0.01) or controls (P less than 0.01). Urine cAMP was higher in patients with osteomalacia than in patients without osteomalacia (P less than 0.001) or controls (P less than 0.01). TmP/GFR was significantly lower in patients with osteomalacia than in controls (P less than 0.05) but not significantly different from patients without osteomalacia. The findings of this study indicate that hyperparathyroidism occurs in a substantial proportion of patients with the osteomalacia of chronic liver disease. Moreover, osteomalacia in chronic liver disease is clearly related to reduced levels of plasma 25-hydroxyvitamin D. We conclude that hepatic osteomalacia is a vitamin D deficiency state and there is no need to suggest an unusual aetiology.
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35
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36
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Compston JE, Crowe JP, Wells IP, Horton LW, Hirst D, Merrett AL, Woodhead JS, Williams R. Vitamin D prophylaxis and osteomalacia in chronic cholestatic liver disease. Dig Dis Sci 1980; 25:28-32. [PMID: 7353448 DOI: 10.1007/bf01312729] [Citation(s) in RCA: 36] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/24/2023]
Abstract
Bone histology was examined in 32 patients with chronic cholestatic liver disease, of whom just over one half were receiving high-dose parenteral vitamin D therapy. Four patients had histological evidence of osteomalacia; two of these were receiving vitamin D therapy, and showed only very mild osteomalacia, while the remaining two untreated patients had more severe bone disease. Plasma 25-hydroxyvitamin D levels were normal in all vitamin D-treated patients, and serum calcium concentrations were significantly higher in the treated group. Clinical symptoms and biochemical and radiological findings were unreliable in predicting osteomalacia. It is concluded that osteomalacia is uncommon in patients with chronic cholestatic liver disease irrespective of whether or not they are receiving vitamin D therapy. However, high-dose parenteral vitamin D prophylaxis protects against vitamin D deficiency and may also prevent the development of severe bone disease.
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37
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Whelton MJ. Perspective in liver disease: An Irish experience. Ir J Med Sci 1979; 148:161-7. [PMID: 27517411 DOI: 10.1007/bf02938073] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 10/21/2022]
Abstract
CONCLUSIONS Graves travelled extensively and on one trip to Italy in 1819 he was joined by a man he describes as of rough exterior and being more "like a ship's mate" (Widdess, 1963). This man sketched extensively and was in fact the famous English painter - J. M. W. Turner. Graves, who was also sketching, was under no illusion as to who was the master and remarked later to Stokes - "When we compared drawings, the effect was strange. Not a single stroke in Turner's drawing was like nature … and yet my work was worthless in comparison to his. The whole glory of the scene was there". Graves acknowledged Turner's mastery in the field of sketching. No one can deny that this extra-ordinary man, with his clinical observations, deserves his eminent place in Irish medicine. Indeed continued studies of his writings can still prove beneficial to the present day scholar.
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Affiliation(s)
- M J Whelton
- Department of Medicine, Regional Hospital, Cork
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38
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Smart RC, Holdsworth CD. Uptake of 47Ca into the forearm in normal subjects and in patients with osteomalacia, primary biliary cirrhosis, and hyperparathyroidism. Calcif Tissue Int 1979; 27:3-11. [PMID: 111784 DOI: 10.1007/bf02441154] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
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39
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Long RG, Varghese Z, Meinhard EA, Skinner RK, Wills MR, Sherlock S. Parenteral 1,25-dihydroxycholecalciferol in hepatic osteomalacia. BRITISH MEDICAL JOURNAL 1978; 1:75-7. [PMID: 620204 PMCID: PMC1602652 DOI: 10.1136/bmj.1.6105.75] [Citation(s) in RCA: 40] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/23/2022]
Abstract
Despite regular long-term parenteral vitamin D2 treatment, four patients with biliary cirrhosis had multiple symptoms of bone disease and bone biopsy specimens showed osteomalacia without osteoporosis. Three patients also had a proximal myopathy. Plasma calcium values (after correction for albumin), phosphorus, magnesium, and serum 25-hydroxy-vitamin D were within normal limits. Treatment with 1,25-dihydroxy-cholecalciferol (1,25-(OH)2D3) relieved symptoms in three of the four patients and improved those in the fourth. Histological examination of bone showed improvement in all four patients, but serum and urinary biochemical changes were not pronounced. We conclude that 1,25-(0H)2D3 treatment has a beneficial effect on bone and muscle in hepatic osteomalacia, either because vitamin D 1-hydroxylation fails in biliary cirrhosis or because hepatic osteomalacia is resistant to vitamin D2 metabolites.
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40
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Danö P, Christiansen C. Calcium malabsorption and absence of bone decalcination following intestinal shunt operation for obesity. A comparison of two types of operation. Scand J Gastroenterol 1978; 13:81-5. [PMID: 635450 DOI: 10.3109/00365527809179810] [Citation(s) in RCA: 15] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
Abstract
Calcium absorption was studied in 23 patients before and one year after intestinal shunt operation for obesity. It decreased from 23 to 12% (p less than 0.02) after surgery, when the jejunum/ileum ratio was 36cm/12cm [type I], and only from 19 to 16% (p greater than 0.05), when the ratio was 12cm/36cm [type III]. It is suggested that the difference is due to variation in absorptive surface in the distal half of the small intestine and to a minor degree to change in external pancreatic function, bile acid metabolism, and fat digestion. Bone mineral content was lower in 37 obese than in normal subjects and underwent only minor changes (p greater than 0.01) 3 and 12 months after surgery, possible because of postoperative daily calcium and vitamin-D substitution.
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41
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Abstract
Oral vitamin D3 was poorly absorbed by 4 out of 6 patients with primary biliary cirrhosis; absorption was negatively correlated with faecal fat excretion. 25-hydroxylation of vitamin D3 given by mouth or intravenously was not impaired in the patients compared with controls of similar vitamin-D nutritional status. Urinary radioactivity derived from the intravenous dose of vitamin D3 was significantly greater in patients than in controls and was positively correlated with the serum-bilirubin concentration. Excretion in the urine may lead to loss of administered and endogenous vitamin D and thus contribute to vitamin-D deficiency in patients with primary biliary cirrhosis.
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42
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Abstract
Bone histology and intestinal absorption of 25-hydroxyvitamin D3 (25-OHD) were investigated in 11 patients with primary biliary cirrhosis (P.B.C.). 4 patients had osteomalacia, and all these had received long-term cholestyramine. Plasma-25-hydroxyvitamin-D (25-OHD) concentrations after an oral dose of 25-OHD3 were significantly lower in the patients with P.B.C. (especially those with osteomalacia) than in normal controls. Serum calcium and urinary calcium excretion were lower, and serum-alkaline-phosphatase higher, in patients with osteomalacia. It is suggested that absorption of 25-OHD undergoing enterohepatic circulation and of dietary vitamin D is reduced in patients with P.B.C. Absorption of 25-OHD is further decreased by cholestyramine and the development of osteomalacia is thus hastened.
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43
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Rochman J, Chaimovitz C, Eidelman S, Better OS. Renal handling of sodium, water and divalent ions in patients with primary biliary cirrhosis. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 1977; 81:121-9. [PMID: 899921 DOI: 10.1007/978-1-4613-4217-5_14] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
1) Fluid retention and ascites are rarely seen in patients with primary biliary cirrhosis (PBC). In an attempt to clarify this clinical observation, renal handling of sodium, water and divalent ions was studied during extracellular volume expansion (ECVE) and maximal suppression of antidiuretic hormone (ADH) secretion in 5 patients with PBC and 9 normal subjects. 2) Mean fractional excretion of sodium, water, phosphate and calculated fractional distal delivery of sodium were significantly greater in patients with PBC as compared with normal controls. Fractional CH20 for given fractional urine flow was similar in patients with PBC and normals. 3) The data suggest that patients with PBC have a greater diminution of proximal tubular reabsorption of sodium in response to ECVE than controls. This augmented elimination of salt during ECVE in patients with PBC may explain the rarity of ascites and edema in this type of cirrhosis.
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44
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Wagonfeld JB, Nemchausky BA, Bolt M, Horst JV, Boyer JL, Rosenberg IH. Comparison of vitamin D and 25-hydroxy-vitamin-D in the therapy of primary biliary cirrhosis. Lancet 1976; 2:391-4. [PMID: 73853 DOI: 10.1016/s0140-6736(76)92407-7] [Citation(s) in RCA: 61] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Skeletal demineralisation and low serum concentrations of 25-hydroxy-vitamin-D were observed in patients with primary biliary cirrhosis. Neither oral nor parenteral vitamin-D increased 25-hydroxy-vitamin-D in serum or prevented further skeletal demineralisation. In contrast, oral 25-hydroxy-vitamin-D increased serum-25-hydroxy-vitamin D concentrations in all patients, and bone mineral content either improved or stabilised in all but one, 25-hydroxy-vitamin-D may be the preferred form of vitamin-D therapy in primary biliary cirrhosis.
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45
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Hepner GW, Roginsky M, Moo HF. Abnormal vitamin D metabolism in patients with cirrhosis. THE AMERICAN JOURNAL OF DIGESTIVE DISEASES 1976; 21:527-32. [PMID: 181983 DOI: 10.1007/bf01464758] [Citation(s) in RCA: 66] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/13/2022]
Abstract
To assess the role of hepatic function and alcohol on vitamin D metabolism, serum 25-hydroxyvitamin D (25-OHD) levels were measured in 20 healthy nonalcoholic control subjects, 31 "inactive" cirrhotics whose alcoholism was in remission, 8 alcoholic cirrhotics, and 15 alcoholics with normal liver function. Cirrhosis but not alcoholism, was assoicated with low serum 25-OHD levels. The aminopyrine breath test (ABT) was performed because aminopyrine, like vitamin D3, is metabolized by hepatic microsomes; the ABT correlated highly (r = 0.74, rho less than 0.01) with serum 25-OHD in the inactive cirrhotics. After an intravenous injection of 120 mug vitamin D3, serum 25-OHD rose significantly within 24 hr in 6 healthy controls and 2 patients with celiac disease but not in 6 inactive cirrhotics. The data suggest impaired 25-hydroxylation of vitamin-D impaired in patients with cirrhosis, related predominantly to the degree of hepatic dysfunction.
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46
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Abstract
Metabolism of calcium and magnesium may be disturbed in hepatobiliary disease because of deficient or absent bile flow into the gut, since bile is important for the intestinal absorption of these elements. In the present paper the tubular reabsorption of phosphate (TRP), calcium (TRCa), and magnesium (TRMg) were determined in an attempt to evaluate the parathyroid function of infants and children with hepatobiliary disease. In unrepaired biliary atresia TRP was conspicuously reduced (mean 49.8%, SD 15.1). In successfully repaired biliary atresia the value was increased near the normal range (mean 80.7%, SD 8.1). In neonatal hepatitis the value was variable in individual cases, but significantly lower than the normal (mean 47.6%, SD 19.9). TRCa was reduced in one third of the patients with unrepaired biliary atresia and in one fifth of the cases of neonatal hepatitis. The value was within the normal range in repaired biliary atresia. TRMg was decreased in both unrepaired and repaired biliary atresia and in neonatal hepatitis. The effect of intravenous calcium infusion on TRP, TRCa and TRMg was evaluated in 3 patients with unrepaired biliary atresia. TRP was conspicuously enhanced after infusion. TRCa was decreased in 3 to a variable extent. TRMg was moderately increased in 2 and greatly decreased in 1. These results indicate that infants with hepatobiliary disease are in a state of secondary hyperparathyroidism because of deficient or absent bile flow into the intestines.
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47
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Abstract
A permature male infant required intravenous alimentation for six weeks following extensive surgery for ileal and cecal necrosis. At 3 months he developed evidence of hepatitis. Subsequently osteoporosis and the Fanconi syndrome appeared. Urine phosphate clearance was 83 percent of creatinine clearance at a serum phosphate concentration of 1.6 mg/dl. Concentration of plasma immunoreactive parathyroid hormone was elevated at 550 pg/ml. 25-Hydroxycholecalciferol was given at 240 mug/day. Aminoaciduria disappeared and bone healing occurred. Serum phosphate rose to 6.5 mg/dl and phosphate clearance fell to 2 percent of creatinine clearance. Upon cessation of 25-OHCC therapy, the Fanconi syndrome recurred despite administration of vitamin D2. 25-OHCC was then administered at 40 mug/day, and the urine abnormalities were reversed. The patient probably developed hyperparathyroidism, secondary malabsorption, and hepatitis. The Fanconi syndrome was the consequence of the hyperparathyroidism. 25-OHCC therapy was more effective than vitamin D in reversing the disordered state, possibly because of impaired hepatic metabolism of vitamin D2.
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49
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Abstract
Radiological studies of bone were performed in infants and children with hepatobiliary disease. Rickets was found in 23 out of 39 patients (59%) with surgically unrepaired biliary atresia, in 4 out of 15 (27%) with surgically repaired biliary atresia, in 11 out of 21 (52%) with neonatal hepatitis, and in 2 out of 4 (50%) with intrahepatic cholestasis. Osteoporosis was found in 23 out of 39 (59%) with unrepaired biliary atresia, in 3 out of 15 (20%) with repaired biliary atresia, in 5 out of 21 (24%) with neonatal hepatitis, and in 1 out of 4 (25%) with intrahepatic cholestasis. 2 girls with Byler disease and 1 infant with choledochal cyst showed no radiological evidence of bone disease. In unrepaired biliary atresia comparative studies of biochemical data in the groups with and without bone disease showed the following. Serum calcium levels were reduced in the patients with bone disease compared with those in the group without it. Serum magnesium levels were markedly reduced in the groups with and without bone disease. The product of serum calcium and phosphorus was reduced in the group with osteoporosis compared with that in the group without it. The raised levels of serum alkaline phosphatase were unrelated to the presence or absence of bone disease.
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50
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Whelton MJ. Metabolic bone diseases and chronic liver disease. Ir J Med Sci 1974; 0:suppl:64-71. [PMID: 4853170 DOI: 10.1007/bf02938128] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/12/2023]
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