Bone and Mineral Metabolism Unit

Haifa, Israel

Bone and Mineral Metabolism Unit

Haifa, Israel

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Souberbielle J.-C.,Laboratoire Of Physiologie | Body J.-J.,Free University of Colombia | Lappe J.M.,Creighton University | Plebani M.,University of Padua | And 19 more authors.
Autoimmunity Reviews | Year: 2010

Background: There is increasing evidence that, in addition to the well-known effects on musculoskeletal health, vitamin D status may be related to a number of non-skeletal diseases. An international expert panel formulated recommendations on vitamin D for clinical practice, taking into consideration the best evidence available based on published literature today. In addition, where data were limited to smaller clinical trials or epidemiologic studies, the panel made expert-opinion based recommendations. Methods: Twenty-five experts from various disciplines (classical clinical applications, cardiology, autoimmunity, and cancer) established draft recommendations during a 2-day meeting. Thereafter, representatives of all disciplines refined the recommendations and related texts, subsequently reviewed by all panelists. For all recommendations, panelists expressed the extent of agreement using a 5-point scale. Results and conclusion: Recommendations were restricted to clinical practice and concern adult patients with or at risk for fractures, falls, cardiovascular or autoimmune diseases, and cancer. The panel reached substantial agreement about the need for vitamin D supplementation in specific groups of patients in these clinical areas and the need for assessing their 25-hydroxyvitamin D (25(OH)D) serum levels for optimal clinical care.A target range of at least 30 to 40ng/mL was recommended. As response to treatment varies by environmental factors and starting levels of 25(OH)D, testing may be warranted after at least 3months of supplementation. An assay measuring both 25(OH)D2 and 25(OH)D3 is recommended. Dark-skinned or veiled individuals not exposed much to the sun, elderly and institutionalized individuals may be supplemented (800IU/day) without baseline testing. © 2010 Elsevier B.V.


Ish-Shalom S.,Bone and Mineral Metabolism Unit | Dumitrache C.,Ci Parhon Institute Of Endocrinology | El-Husseini T.F.,Ain Shams University | Hussein A.,Ain Shams University | Barker C.,Lilly Research Laboratories UK
Current Medical Research and Opinion | Year: 2011

Objective: To observe and compare back pain and health-related quality of life (HRQoL) in postmenopausal women with a prior unsatisfactory response to antiresorptive therapy, treated with teriparatide (TPTD) or alternative treatments in normal clinical practice. Research design and methods: Prospective, observational, multicentre, 24-month study of postmenopausal women with osteoporosis. A back pain and HRQoL questionnaire (European Quality of Life Questionnaire, EQ-5D) including visual analogue scale (VAS) was completed at each visit. Results: A total of 153 patients were enrolled, 105 patients started TPTD treatment during the study (TPTD cohort) and 48 patients did not take TPTD treatment at any time during the study (non-TPTD cohort). Four patients did not meet the inclusion criteria for the study. Of the patients in the non-TPTD cohort, 31 (68.9) took antiresorptives during the study. The patients selected by the investigator for teriparatide treatment were distinctly different from those not selected. At baseline, the mean back pain VAS was greater in the TPTD than the non-TPTD cohort, 64mm and 42mm, respectively (p<0.001). During the study, compared with baseline, the mean back pain VAS decreased in the TPTD cohort at all visits (p<0.001). In the non-TPTD cohort, a transitory decrease in the mean after 12 months was observed (-10mm, p0.023) only. After 24 months, the mean back pain VAS improved in the TPTD cohort (-36mm, p<0.001) while no change was observed in the non-TPTD cohort (-4mm, p0.467). At baseline, the mean EQ-VAS was lower in the TPTD than in the non-TPTD cohort, 40.8 and 55.2, respectively (p<0.001). After 24 months, EQ-VAS improved in both cohorts (TPTD 34, p<0.001 and non-TPTD 9, p0.026). Conclusions: TPTD-treated patients had more back pain and lower HRQoL at baseline. In the TPTD cohort the mean value was consistently and significantly improved in back pain and quality of life. In the non-TPTD cohort, the mean improvement in back pain and QoL was inconsistent possibly due to the initially higher QoL and lower back pain leaving less room for improvement. These results should be interpreted in the context of limitations related to a non-randomised observational study. © 2011 Informa UK Ltd All rights reserved.


Constantini N.W.,Hebrew University of Jerusalem | Dubnov-Raz G.,Safra Childrens Hospital | Chodick G.,Tel Aviv University | Rozen G.S.,Rambam Health Care Campus | And 2 more authors.
Medicine and Science in Sports and Exercise | Year: 2010

Introduction: Studies have shown that physical activity (PA) is superior to many other environmental factors in determining bone mineral density (BMD), but none has examined the independent relationship between PA and vitamin D status. Purpose: The aim of this study was to assess the relationship among amount of PA, vitamin D (25(OH)D), and BMD. Methods: A total of 166 female ballet dancers and sedentary adolescents were divided by tertiles of serum levels of 25(OH)D (<11.3, 11.3-14.9, and >15 ng·mL-1). Diet, PA, and menstruation were assessed by questionnaires; BMD was measured in three sites by dual-energy x-ray absorptiometry. Results: Across 25(OH)D tertiles, there were no differences in mean participant age, weight, height, PA, calcium and energy intake, BMD, or parathyroid hormone. PA was positively associated with BMD in participants with vitamin D deficiency. Multivariable regression analysis, controlling for age, body mass index, parathyroid hormone, and bone turnover markers, showed that total body, femoral neck, and lumbar spine BMD were all positively related to PA, with regression coefficients increasing as vitamin D levels dropped across tertiles. Conclusions: PA is positively related to BMD in vitamin D - deficient female adolescents and with increasing magnitude as serum vitamin D levels drop. These findings suggest that PA may counteract the detrimental effect of marked vitamin D deficiency on bone mass. Copyright © 2010 by the American College of Sports Medicine.


Ma Y.L.,Lilly Research Laboratories | Marin F.,Lilly Research Center | Stepan J.,Charles University | Ish-Shalom S.,Bone and Mineral Metabolism Unit | And 10 more authors.
Bone | Year: 2011

The periosteum contains osteogenic cells that regulate the outer shape of bone and contribute to determine its cortical thickness, size and position. We assessed the effects of subcutaneous injections of teriparatide (TPTD, 20μg/day) or oral strontium ranelate (SrR, 2g/day) in postmenopausal women with osteoporosis on new bone formation activity at the periosteal and endosteal bone surfaces using dynamic histomorphometric measurements. Evaluable tetracycline-labeled transiliac crest bone biopsies were analyzed from 27 patients in the TPTD group, and 22 in the SrR group after six months of treatment. Measurements were conducted on the thicker and thinner cortices separately, and comparisons between the thicker, thinner and combined cortices were carried out. At the combined periosteal cortex, the mineralization surface as a percent of bone surface (MS/BS%) was greater for TPTD (mean±SE: 8.08±1.22%) than SrR (3.22±1.05%) (p<0.005). The difference in mineral apposition rate (MAR) between TPTD (0.35±0.06μm/day) and SrR (0.14±0.06μm/day) was also significant (p<0.05), while that of bone formation rate per bone surface (BFR/BS) between TPTD (0.014plusmn;0.004 mm 3/mm 2/year) and SrR (0.004plusmn;0.003 mm 3/mm 2/year) was not (p=0.057). Statistically significant differences between the two treatments were also observed for MS/BS%, BFR/BS, MAR and the double-labeled perimeter in the periosteum of the thicker, but not thinner, iliac crest cortices. The comparison between the thicker and thinner cortices of both periosteal and endosteal surfaces showed statistically significant differences for MAR and the double-labeled perimeter for TPTD treated women. There were no statistically significant differences in any bone formation dynamic measurements between the two cortices in the SrR group.In conclusion, most of the bone formation and mineralization variables were significantly higher for TPTD- than SrR-treated women at both the periosteal and endosteal combined cortices. The response to TPTD for dynamic bone formation measurements in the periosteal surface was greater for the thicker than thinner cortex, but this difference was not significant in SrR treated patients. This may reflect a greater ability of TPTD to enhance responsiveness of bone to the mechanical loading environment. These effects on bone formation may underlie the improvement in bone quality in patients with osteoporosis treated with TPTD. © 2011 Elsevier Inc.


Devogelaer J.-P.,Catholic University of Leuven | Sambrook P.,University of Sydney | Reid D.M.,University of Aberdeen | Goemaere S.,Universitair Ziekenhuis Gent | And 6 more authors.
Rheumatology (United Kingdom) | Year: 2013

Objective: Long-term glucocorticoid use is accompanied by rapid bone loss; however, early treatment with bisphosphonates prevents bone loss and reduces fracture risk. The aim of this study was to examine the effects of two bisphosphonates, i.v. zoledronic acid (ZOL) versus oral risedronate (RIS), on bone turnover markers (BTMs) in subjects with glucocorticoid-induced osteoporosis (GIO). Methods: Patients were randomly stratified according to the duration of pre-study glucocorticoid therapy [prevention subpopulation (ZOL, n = 144; RIS, n = 144) ≤3 months, treatment subpopulation (ZOL, n = 272; RIS, n = 273) >3 months]. Changes in β-C-terminal telopeptides of type 1 collagen (b-CTx), N-terminal telopeptide of type I collagen (NTx), procollagen type 1 N-terminal propeptide (P1NP) and bone-specific alkaline phosphatase (BSAP) from baseline were measured on day 10 and months 3, 6 and 12. Results: At most time points, there were significantly greater reductions (P<0.05) in the concentrations of serum β-CTx, P1NP and BSAP and urine NTx in subjects on ZOL compared with RIS in both males and females of the treatment and prevention subpopulations. In pre- and post-menopausal women, there were significantly greater reductions in the concentrations of BTMs with ZOL compared with RIS. At 12 months, ZOL had significantly greater reductions compared with RIS (P<0.05) for β-CTx, P1NP, BSAP and NTx levels, independent of glucocorticoid dose. Conclusions: Once-yearly i.v. infusion of ZOL 5mg was well tolerated in different subgroups of GIO patients. ZOL was non-inferior to RIS and even superior to RIS in the response of BTMs in GIO patients. © The Author 2013. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved.


Dubnov-Raz G.,Edmond and Lily Safra Childrens Hospital | Ish-Shalom S.,Bone and Mineral Metabolism Unit | Chodick G.,Tel Aviv University | Rozen G.S.,Rambam Health Care Campus | And 2 more authors.
Pediatric Obesity | Year: 2012

Objective: Osteocalcin is a bone-related protein, recently found to correlate with body mass index (BMI), waist circumference, fat percentage and metabolic syndrome in adults. The aim of this study was to determine the relationship between osteocalcin and BMI in adolescence, a time of significant bone accrual, while considering possible confounders related to bone and body composition. Methods: We analyzed data from 160 female adolescents (mean age 15.1 ± 0.7 years), which were divided into tertiles by osteocalcin levels. Across these three groups, we examined the differences in BMI with relation to age, total daily energy intake, calcium intake, physical activity (PA), total body bone mineral density, parathyroid hormone (PTH), 25(OH)-vitamin D, bone alkaline phosphatase and body fat percentage. Results: Mean BMI values differed significantly between participants in the three osteocalcin tertiles, including after adjustment for age, PA, PTH, energy and calcium intakes. Post-hoc analysis revealed that girls in the highest osteocalcin tertile, had a significantly lower BMI than those in the two lower ones (19.3 ± 2.2 vs. 20.6 ± 3.0 and 20.7 ± 2.9 kg m-2, respectively, P = 0.018). There was no significant difference in energy and calcium intakes, bone mineral density, 25(OH)-vitamin D levels and PTH between study groups. Conclusions: In female adolescents, BMI is inversely related to osteocalcin, even after consideration of several factors that may affect bone and fat mass. As bone mineral density, 25(OH)D and PTH did not differ between groups, it is possible that the relation between osteocalcin and BMI could be unrelated to bone tissue itself. © 2012 The Author.


Haham M.,Technion - Israel Institute of Technology | Ish-Shalom S.,Bone and Mineral Metabolism Unit | Ish-Shalom S.,Technion - Israel Institute of Technology | Nodelman M.,Bone and Mineral Metabolism Unit | And 4 more authors.
Food and Function | Year: 2012

We have previously introduced the potential of casein micelles (CM) as natural nanovehicles for hydrophobic nutraceuticals, e.g. vitamin D (VD) (E. Semo, E. Kesselman, D. Danino and Y. D. Livney, Food Hydrocolloids, 2007, 21, 936-942). The aims of the current study were to improve performance by adding an ultra-high-pressure homogenization step, and to evaluate the protection conferred by re-assembled CM (rCM) against VD thermal and oxidative degradation, and the bioavailability of VD3 in rCM, by a clinical trial. Dynamic-light-scattering showed that VD3-rCM had a diameter of 91 ± 8 nm (average ± standard error). When VD3 was encapsulated in rCM and subjected to thermal treatment (80°C, 1 min), no significant loss was observed (P > 0.05), compared to 13 and 14% loss of VD3 emulsified with Tween-80 (a synthetic emulsifier typically used for VD solubilization) and of unencapsulated VD3 respectively (P < 0.05). VD3 in rCM was also more stable during 28 d cold storage (∼40% loss) compared to Tween-80 emulsified (∼50% loss) or to un-encapsulated (∼70% loss) VD3. Ultra-high-pressure homogenization of VD3-rCM (∼155 MPa) significantly enhanced vitamin stability, resulting in only ∼10% loss after 28 d of storage. Bioavailability of a single-dose of 50000 international-units (IU) VD 3 encapsulated in rCM, in 1% fat milk, investigated in a randomized double blinded placebo controlled clinical study with 87 human volunteers, was at least as high as that using an aqueous Tween-80-emulsified VD3 supplement. We conclude that ultra-high-pressure homogenization treated rCM protect VD3 against heat- and storage-induced degradation, and VD3 encapsulated in rCM is highly bioavailable. © 2012 The Royal Society of Chemistry.


Levinson Y.,Technion - Israel Institute of Technology | Ish-Shalom S.,Bone and Mineral Metabolism Unit | Ish-Shalom S.,Technion - Israel Institute of Technology | Segal E.,Bone and Mineral Metabolism Unit | Livney Y.D.,Technion - Israel Institute of Technology
Food and Function | Year: 2016

Vitamin D3 (VD3) deficiency is a global problem. Better ways are needed to enrich foods with this important nutraceutical. VD3 is fat-soluble, hence requiring a suitable vehicle for enriching nonfat foods. Our objectives were to assess the bioavailability of VD3, from fat-free yogurt, in re-assembled casein micelles (rCMs) compared to that in polysorbate-80 (PS80/Tween-80) a commonly used synthetic emulsifier, and to assess and compare their rheology and palatability. We enriched fat-free yogurt with VD3 loaded into either rCM (VD3-rCMs) or PS80 (VD3-PS80). In vivo VD3 bioavailability was evaluated by a large randomized, double blind, placebo-controlled clinical trial, measuring serum 25(OH)D increase in subjects who consumed fat-free yogurt with 50 000 IU of either VD3-rCM, VD3-PS80, or VD3-free placebo yogurt. Both VD3-rCM and VD3-PS80 increased the serum 25(OH)D levels by ∼8 ng ml-1 and no significant differences in mean 25(OH)D levels were observed, evidencing the fact that VD3 bioavailability in rCM was as high as that in the synthetic emulsifier. VD3-rCM yogurt had a higher viscosity than VD3-PS80 yogurt. In sensory evaluations, panelists were able to discern between VD3-rCM and VD3-PS80 yogurt, and showed a dislike for PS80 yogurt, compared to rCM or the unenriched control. These results complement our past results showing higher protection against thermal treatment, UV irradiation, and deterioration during shelf life, conferred to hydrophobic nutraceuticals by rCM compared to that by the synthetic surfactant or to the unprotected bioactive, in showing the advantageous use of rCM over the synthetic emulsifier as a delivery system for the enrichment of food with VD3 and other hydrophobic nutraceuticals. © The Royal Society of Chemistry 2016.


Tepper S.,Ben - Gurion University of the Negev | Shahar D.R.,Ben - Gurion University of the Negev | Geva D.,Ben - Gurion University of the Negev | Ish-Shalom S.,Bone and Mineral Metabolism Unit
Journal of Steroid Biochemistry and Molecular Biology | Year: 2014

Vitamin D replenishment therapy typically entails standard dosages, but related increases in serum 25(OH)D levels vary between individuals. This study was aimed to identify factors that affect the efficacy of vitamin D supplementation. Subjects and methods 79 healthy men aged 25-65 with 25(OH)D < 20 ng/ml participated in a vitamin D supplementation study. All participants received 100,000 IU vitamin D bimonthly, e.g., 1666 IU/day. Personal and demographic information, physical activity and sun-exposure questionnaires were completed by the participants. Weight, height, and waist circumference were recorded. Serum calcium, creatinine, 25(OH)D, PTH, lipid profile, and liver-enzyme levels were assessed. All measurements were repeated after 6 and 12 months. The difference between baseline serum 25(OH)D and 12-month measurements was calculated (delta). Linear regression was performed to identify predictors for increases in 25(OH)D levels. Results Mean serum 25(OH)D level increases according to BMI were 12.6 ± 5.29 ng/ml for BMI ≠25, 10.12 ± 4.95 ng/ml for 25 < BMI 30, and only 6.39 ;plusmn 5.33 ng/ml for BMI 30, which differed significantly from the other BMI categories (p = 0.003). In a regression model to predict 25(OH)D increase, BMI was the main predictor (p ;< 0.001), explaining 21.6% of the variance in serum 25(OH)D (inverse association). Age, sun-exposure, serum cholesterol, physical-activity, baseline 25(OH)D levels and seasonality were insignificant. The full model explained 27.9% of the variance in serum 25(OH)D. Conclusion This study's main findings are that BMI affect vitamin D response in healthy men. Quantitative supplementation adjustments may be warranted in obese men, for whom the dose may need to be doubled. This article is part of a special issue entitled '16th Vitamin D Workshop'.© 2013 Elsevier Ltd.


PubMed | Ben - Gurion University of the Negev and Bone and Mineral Metabolism Unit
Type: | Journal: The Journal of steroid biochemistry and molecular biology | Year: 2014

Vitamin D replenishment therapy typically entails standard dosages, but related increases in serum 25(OH)D levels vary between individuals. This study was aimed to identify factors that affect the efficacy of vitamin D supplementation.79 healthy men aged 25-65 with 25(OH)D<20ng/ml participated in a vitamin D supplementation study. All participants received 100,000IU vitamin D bimonthly, e.g., 1666IU/day. Personal and demographic information, physical activity and sun-exposure questionnaires were completed by the participants. Weight, height, and waist circumference were recorded. Serum calcium, creatinine, 25(OH)D, PTH, lipid profile, and liver-enzyme levels were assessed. All measurements were repeated after 6 and 12 months. The difference between baseline serum 25(OH)D and 12-month measurements was calculated (delta). Linear regression was performed to identify predictors for increases in 25(OH)D levels.Mean serum 25(OH)D level increases according to BMI were 12.65.29ng/ml for BMI25, 10.124.95ng/ml for 2530, which differed significantly from the other BMI categories (p=0.003). In a regression model to predict 25(OH)D increase, BMI was the main predictor (p<0.001), explaining 21.6% of the variance in serum 25(OH)D (inverse association). Age, sun-exposure, serum cholesterol, physical-activity, baseline 25(OH)D levels and seasonality were insignificant. The full model explained 27.9% of the variance in serum 25(OH)D.This studys main findings are that BMI affect vitamin D response in healthy men. Quantitative supplementation adjustments may be warranted in obese men, for whom the dose may need to be doubled. This article is part of a special issue entitled 16th Vitamin D Workshop.

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