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Cauley J.A.,University of Pittsburgh | El-Hajj Fuleihan G.,American University of Beirut | Arabi A.,American University of Beirut | Fujiwara S.,Radiation Effects Research Foundation | And 16 more authors.
Journal of Clinical Densitometry | Year: 2011

Osteoporosis is a serious worldwide epidemic. Increased risk of fractures is the hallmark of the disease and is associated with increased morbidity, mortality and economic burden.FRAX® is a web-based tool developed by the Sheffield WHO Collaborating Center team, that integrates clinical risk factors, femoral neck BMD, country specific mortality and fracture data and calculates the 10 year fracture probability in order to help health care professionals identify patients who need treatment. However, only 31 countries have a FRAX® calculator at the time paper was accepted for publication. In the absence of a FRAX® model for a particular country, it has been suggested to use a surrogate country for which the epidemiology of osteoporosis most closely approximates the index country. More specific recommendations for clinicians in these countries are not available.In North America, concerns have also been raised regarding the assumptions used to construct the US ethnic specific FRAX® calculators with respect to the correction factors applied to derive fracture probabilities in Blacks, Asians and Hispanics in comparison to Whites. In addition, questions were raised about calculating fracture risk in other ethnic groups e.g., Native Americans and First Canadians.In order to provide additional guidance to clinicians, a FRAX® International Task Force was formed to address specific questions raised by physicians in countries without FRAX® calculators and seeking to integrate FRAX® into their clinical practice. The main questions that the task force tried to answer were the following:1.What is the evidence supporting ethnic and sex specific adjustments for fracture incidence rates in Blacks, Hispanics and Asians-2.What data exist for other groups, e.g., Native Americans, First Nations Canadians-3.Are there secular changes in fracture rates-4.What are the requirements for the construction of a FRAX® calculator? And what are the desirable/optimal characteristics of the data-5.What do I do if my country does not have a FRAX® calculator? The Task Force members conducted appropriate literature reviews and developed preliminary statements that were discussed and graded by a panel of experts at the ISCD-IOF joint conference. The statements approved by the panel of experts are discussed in the current paper. © 2011.


Rubin M.R.,Metabolic Bone Diseases Unit | Dempster D.W.,Helen Hayes Hospital | Kohler T.,ETH Zurich | Stauber M.,ETH Zurich | And 8 more authors.
Bone | Year: 2010

By conventional 2-dimensional histomorphometric analysis, we have shown that cancellous bone architecture is markedly altered in hypoparathyroidism. We have now extended these observations to a 3-dimensional analysis using microcomputed tomography. Percutaneous iliac crest bone biopsies were analyzed by high-resolution microcomputed tomography from the following 25 subjects with hypoparathyroidism: 5 postmenopausal women, 13 premenopausal women and 7 men. Thirteen living premenopausal healthy controls and 12 cadaver subjects without bone disease served as matched controls. Hypoparathyroid subjects had significantly greater bone surface density (BS/TV: 5.74 ± 4.7 vs. 3.73 ± 1.01 mm2/mm3 [mean ± SD]; p = 0.04), trabecular thickness (Tb.Th: 0.25 ± 0.19 vs. 0.17 ± 0.04 mm; p = 0.04), trabecular number (Tb.N: 2.99 ± 3.4 vs. 1.62 ± 0.39 mm- 1; p = 0.05) and connectivity density (Conn.D: 16.63 ± 18.7 vs. 8.39 ± 5.8 mm3; p = 0.04) in comparison to matched controls. When an additional 8 hypoparathyroid (total n = 33) and 24 cadaver (total cadaver n = 36) subjects were added to the groups for an unmatched analysis, hypoparathyroid subjects had significantly greater cancellous bone volume (BV/TV: 26.98 ± 10 vs. 15.39 ± 4%; p < 0.001), while trabecular separation (Tb.Sp: 0.642 ± 0.10 vs. 0.781 ± 0.13 mm; p < 0.001) and estimation of the plate-rod characteristic (SMI: - 0.457 ± 1.52 vs. 0.742 ± 0.51; p < 0.001) were significantly lower, the latter observation implying a more plate-like trabecular structure. Variables of cancellous bone structure in the hypoparathyroid subjects, as assessed by microcomputed tomography, were highly correlated with those assessed by conventional histomorphometry. We conclude that cancellous bone in hypoparathyroidism is abnormal, suggesting that parathyroid hormone is required to maintain normal trabecular structure. The effect of these structural changes on bone strength remains to be determined. © 2009 Elsevier Inc. All rights reserved.


Segal E.,Metabolic Bone Diseases Unit | Segal E.,Technion - Israel Institute of Technology | Felder S.,Sheba Medical Center | Haim N.,Rambam Health Care Campus | And 7 more authors.
Israel Medical Association Journal | Year: 2012

Background: Vitamin D status is not evaluated routinely in cancer patients with bone metastasis who are treated with bisphosphonates. Objectives: To assess the effect of vitamin D status on risk of hypocalcemia and quality of life in these patients. Methods: We performed laboratory tests for routine serum biochemistry, 25(OH)D, plasma parathyroid hormone (PTH) and bone turnover markers (CTX, P1NP) in 54 patients aged 57.5 ± 13 years treated with intravenous bisphosphonates. Results: Most of the patients (n=44, 77.8%) did not receive calcium and vitamin D supplementation. Their mean serum 25(OH)D levels (12.83 ± 6.86 ng/ml) correlated with vitamin D daily intake (P = 0.002). In 53 patients (98.1%) 25(OH) D levels were suboptimal (< 30 ng/ml). Albumin-corrected calcium levels correlated with plasma PTH (P = 0.001). No correlation was observed between daily calcium intake and serum calcium (P = 0.45). Hypocalcemia was observed in one patient. Mean plasma PTH was 88.5 ± 65 ng/L. Plasma PTH correlated negatively with 25(OH)D serum levels (P = 0.003) and positively with P1NP (P = 0.004). Albumincorrected calcium correlated negatively with P1NP (mean 126.9 ± 191 ng/ml) but not with CTX levels (mean 0.265 ± 0.1 ng/ml) (P < 0.001). There was no correlation among quality of life parameters, yearly sun exposure and 25(OH)D levels (P = 0.99). Conclusions: Vitamin D deficiency is frequent in oncology patients with bone metastasis treated with bisphosphonates and might increase bone damage. Our results indicate a minor risk for the development of severe hypocalcemia in vitamin D-deficient patients receiving bisphosphonate therapy. Although vitamin D deficiency might have some effect on the quality of life in these patients, it was not proven significant.


Silva B.C.,Metabolic Bone Diseases Unit | Silva B.C.,Columbia University | Silva B.C.,Federal University of Minas Gerais | Boutroy S.,Metabolic Bone Diseases Unit | And 12 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2013

Context: In the milder form of primary hyperparathyroidism (PHPT), cancellous bone, represented by areal bone mineral density at the lumbar spine by dual-energy x-ray absorptiometry (DXA), is preserved. This finding is in contrast to high-resolution peripheral quantitative computed tomography (HRpQCT) results of abnormal trabecular microstructure and epidemiological evidence for increased overall fracture risk in PHPT. Because DXA does not directly measure trabecular bone and HRpQCT is not widely available, we used trabecular bone score (TBS), a novel gray-level textural analysis applied to spine DXA images, to estimate indirectly trabecular microarchitecture. Objective: The purpose of this study was to assess TBS from spine DXA images in relation to HRpQCT indices and bone stiffness in radius and tibia in PHPT. Design and Setting: This was a cross-sectional study conducted in a referral center. Patients: Participants were 22 postmenopausal women with PHPT. Main Outcome Measures: Outcomes measured were areal bone mineral density by DXA, TBS indices derived from DXA images, HRpQCT standard measures, and bone stiffness assessed by finite element analysis at distal radius and tibia. Results: TBS in PHPT was low at 1.24, representing abnormal trabecular microstructure (normal ≥1.35). TBS was correlated with whole bone stiffness and all HRpQCT indices, except for trabecular thickness and trabecular stiffness at the radius. At the tibia, correlations were observed between TBS and volumetric densities, cortical thickness, trabecular bone volume, and whole bone stiffness. TBS correlated with all indices of trabecular microarchitecture, except trabecular thickness, after adjustment for body weight. Conclusion: TBS, a measurement technology readily available by DXA, shows promise in the clinical assessment of trabecular microstructure in PHPT. Copyright © 2013 by The Endocrine Society.


Segal E.,Metabolic Bone Diseases Unit | Hochberg I.,Institute of Endocrinology | Weisman Y.,Tel Aviv University | Ish-Shalom S.,Metabolic Bone Diseases Unit | Ish-Shalom S.,Technion - Israel Institute of Technology
Osteoporosis International | Year: 2011

We present a 27-year-old woman with hypoparathyroidism following total thyroidectomy for papillary carcinoma, who presented postpartum during lactation with several vertebral osteoporotic fractures, increase in bone turnover markers, and measurable parathyroid hormone-related protein (PTHrP) levels. Cessations of lactation led to gradual decrease in bone turnover markers and PTHrP and improvement in bone mineral density. Pregnancy- and postpartum-associated osteoporosis is an uncommon condition characterized by the occurrence of fractures during late pregnancy or the puerperium. The patient presented postpartum with severe back pain and multiple vertebral fractures. Metabolic evaluation performed at presentation revealed hypercalcemia, hypercalciuria, increased alkaline phosphatase, vitamin D insufficiency, normal serum protein immunoelectrophoresis, and a detectable level of PTHrP. Serum levels of bone turnover markers were markedly increased. Bone mineral density at the lumbar spine was severely reduced. After cessation of lactation, the PTHrP level became undetectable. Bone turnover markers gradually decreased to normal and bone mineral density improved. Several factors contributed to the reduced bone mass in this patient, including amenorrhea treated with oral contraceptives, suppressive levothyroxine treatment, and lactation of twins with increased PTHrP. Patients with severely reduced bone mass need surveillance during pregnancy and lactation and should possibly consider avoiding breastfeeding. Patients with hypoparathyroidism should temporarily reduce their alphacalcidiol dose while lactating. © 2011 International Osteoporosis Foundation and National Osteoporosis Foundation.


Dodiuk-Gad R.P.,University of Toronto | Dodiuk-Gad R.P.,Haemek Medical Center | Ish-Shalom S.,Metabolic Bone Diseases Unit | Ish-Shalom S.,Technion - Israel Institute of Technology | Shear N.H.,University of Toronto
International Journal of Dermatology | Year: 2015

Background: The potent anti-inflammatory and immunosuppressive effects of systemic glucocorticoids have led to their wide use in the treatment of dermatologic diseases. However, glucocorticoids have been designated the "archetypal double-edged sword of medicine" as a result of their various potential adverse side effects. Dermatologists face major challenges in their usage and require knowledge of both the risks related to their usage and strategies with which to manage them. Objectives: This brief review includes an evidence-based, strategic approach to the general risk management of systemic glucocorticoids with a focus on preventing glucocorticoid-induced osteoporosis (GIOP). Methods: We assess which classes of corticosteroid are most likely to provoke allergic cross-reactions and outline the mechanism for glucocorticoid resistance. We examine how glucocorticoids both help and impair normal physiology. Results: Five reactivity groups are defined, based on the structural and clinical characteristics of glucocorticoids. Tests for allergy reactions and mechanisms for glucocorticoid resistance are described. Guidelines for the prevention and treatment of GIOP are introduced. Conclusion: Glucocorticoids play an important teleologic role in maintaining blood glucose levels adequate for brain function by inducing a catabolic state through the production of carbohydrates at the expense of proteins and fat stores. It is hoped that the various recommendations for the protection of patients treated with systemic glucocorticoids will provide physicians with practical guidelines for prescribing. © 2015 The International Society of Dermatology.


Ruiz-Gaspa S.,Research Center Biomedica en Red en Enfermedades Hepaticas y Digestivas | Ruiz-Gaspa S.,Metabolic Bone Diseases Unit | Guanabens N.,Research Center Biomedica en Red en Enfermedades Hepaticas y Digestivas | Guanabens N.,Metabolic Bone Diseases Unit | And 17 more authors.
European Journal of Clinical Investigation | Year: 2010

Background Osteoporosis is a common complication in chronic cholestasis. It has been proposed that retained substances such as bile acids may produce a damaging effect on bone cells. This study analyses the effects of lithocholic acid (LCA) on cell survival and vitamin D metabolism in human osteoblasts (hOB). Materials and methods Human osteoblasts cultures were performed with or without foetal bovine serum (FBS) or human albumin (HA) at different LCA concentrations and times with or without vitamin D. Results Lithocholic acid at concentrations higher than 10 -5M decreased cell survival. This effect was partially prevented by the presence of FBS or HA. Vitamin D stimulated CYP24A, BGLAP and TNFSF11 expression in hOB and these effects were modified by nontoxic LCA concentrations. LCA significantly decreased vitamin D stimulation of CYP24A, BGLAP and TNFSF11 gene expression at 72%, 79% and 56% (respectively). LCA alone has an agonistic effect, as has vitamin D, thus partially increasing CYP24A and BGLAP expression, but with no changes on TNFRSF11B expression. Equivalent effects of the LCA were observed by performing gene reporter assays using MG-63 cells transfected with constructs containing CYP24A1 promoter regions. Conclusions Lithocholic acid decreases the stimulatory effect of vitamin D on CYP24A, BGLAP and TNFSF11 expression in hOB. This effect is produced through vitamin D response elements (VDREs), located in the promoter regions of these genes, suggesting that LCA acts as a mild analogous of vitamin D, interacting with the vitamin D receptor. These results may explain the potential deleterious effects of retained bile acids on hOB. © 2009 Stichting European Society for Clinical Investigation Journal Foundation.


PubMed | Metabolic Bone Diseases Unit
Type: Case Reports | Journal: Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA | Year: 2011

We present a 27-year-old woman with hypoparathyroidism following total thyroidectomy for papillary carcinoma, who presented postpartum during lactation with several vertebral osteoporotic fractures, increase in bone turnover markers, and measurable parathyroid hormone-related protein (PTHrP) levels. Cessations of lactation led to gradual decrease in bone turnover markers and PTHrP and improvement in bone mineral density. Pregnancy- and postpartum-associated osteoporosis is an uncommon condition characterized by the occurrence of fractures during late pregnancy or the puerperium. The patient presented postpartum with severe back pain and multiple vertebral fractures. Metabolic evaluation performed at presentation revealed hypercalcemia, hypercalciuria, increased alkaline phosphatase, vitamin D insufficiency, normal serum protein immunoelectrophoresis, and a detectable level of PTHrP. Serum levels of bone turnover markers were markedly increased. Bone mineral density at the lumbar spine was severely reduced. After cessation of lactation, the PTHrP level became undetectable. Bone turnover markers gradually decreased to normal and bone mineral density improved. Several factors contributed to the reduced bone mass in this patient, including amenorrhea treated with oral contraceptives, suppressive levothyroxine treatment, and lactation of twins with increased PTHrP. Patients with severely reduced bone mass need surveillance during pregnancy and lactation and should possibly consider avoiding breastfeeding. Patients with hypoparathyroidism should temporarily reduce their alphacalcidiol dose while lactating.


PubMed | University of Toronto and Metabolic Bone Diseases Unit
Type: Journal Article | Journal: International journal of dermatology | Year: 2015

The potent anti-inflammatory and immunosuppressive effects of systemic glucocorticoids have led to their wide use in the treatment of dermatologic diseases. However, glucocorticoids have been designated the archetypal double-edged sword of medicine as a result of their various potential adverse side effects. Dermatologists face major challenges in their usage and require knowledge of both the risks related to their usage and strategies with which to manage them.This brief review includes an evidence-based, strategic approach to the general risk management of systemic glucocorticoids with a focus on preventing glucocorticoid-induced osteoporosis (GIOP).We assess which classes of corticosteroid are most likely to provoke allergic cross-reactions and outline the mechanism for glucocorticoid resistance. We examine how glucocorticoids both help and impair normal physiology.Five reactivity groups are defined, based on the structural and clinical characteristics of glucocorticoids. Tests for allergy reactions and mechanisms for glucocorticoid resistance are described. Guidelines for the prevention and treatment of GIOP are introduced.Glucocorticoids play an important teleologic role in maintaining blood glucose levels adequate for brain function by inducing a catabolic state through the production of carbohydrates at the expense of proteins and fat stores. It is hoped that the various recommendations for the protection of patients treated with systemic glucocorticoids will provide physicians with practical guidelines for prescribing.


Hernandez M.V.,Metabolic Bone Diseases Unit | Peris P.,Metabolic Bone Diseases Unit | Peris P.,University of Barcelona | Monegal A.,Metabolic Bone Diseases Unit | And 4 more authors.
American Journal of the Medical Sciences | Year: 2010

Introduction: To analyze the effects of intravenous pamidronate (APD) on bone remodelling, bone mineral density (BMD), fractures and bone mineral metabolism parameters, and the rate of adverse events, with special attention to renal function, in patients with osteoporosis with intolerance and/or any contraindication to oral bisphosphonates. Methods: We analyzed prospectively 17 osteoporotic patients (age, 66.8 ± 9.4 years): 65% women, 82% with prevalent vertebral fractures. All patients received APD therapy (30 mg intravenously every 3 months) and were followed up for 1 year. We analyzed serum amino-terminal propeptide of type I procollagen and urinary N-terminal cross-linked telopeptide of type I collagen (as markers of bone turnover), serum calcium, phosphate, parathormone, 25OH-vitamin D, creatinine, and the creatinine clearance: at baseline, 1 week after starting APD treatment, and thereafter for every 3 months (before infusion) during 1 year. We also analyzed lumbar and femoral BMD at baseline and after 1 year, the incidence of new fractures, and the treatment-related adverse events. Results: One week after starting APD treatment, a significant decrease of N-terminal cross-linked telopeptide of type I collagen (32%) (P < 0.05) and an increase of parathormone values (72%) (P < 0.01) were observed, without significant differences found thereafter. No significant differences were observed in BMD evolution and in the other parameters analyzed throughout the study, nor in impairment of renal function. Sixty-four percent of patients suffered new skeletal fractures, 41% of patients showed flu-like syndrome after APD infusion, and 1 patient was withdrawn from treatment because of adverse events. Conclusion: Patients with severe osteoporosis receiving APD infusions had a high rate of fractures without significant changes in bone mass or in bone markers; nevertheless, such a therapeutic regimen showed a good renal safety profile, suggesting that APD at this dosage is safe but ineffective for treating severe osteoporosis. © Copyright 2010 Southern Society for Clinical Investigation.

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