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Effects of a Lifestyle Intervention on Bone Turnover in Persons with Type 2 Diabetes: A Post Hoc Analysis of the U-TURN Trial.
Abildgaard, J, Johansen, MY, Skov-Jeppesen, K, Andersen, LB, Karstoft, K, Hansen, KB, Hartmann, B, Holst, JJ, Pedersen, BK, Ried-Larsen, M
Medicine and science in sports and exercise. 2022;(1):38-46
Abstract
INTRODUCTION/PURPOSE The increased risk of fractures with type 2 diabetes (T2D) is suggested to be caused by decreased bone turnover. Current international guidelines recommend lifestyle modifications, including exercise, as first-line treatment for T2D. The aim of this study was to investigate the effects of an exercise-based lifestyle intervention on bone turnover and bone mineral density (BMD) in persons with T2D. METHODS Persons with T2D were randomized to either a 12-month lifestyle intervention (n = 64) or standard care (n = 34). The lifestyle intervention included five to six weekly aerobic training sessions, half of them combined with resistance training. Serum markers of bone turnover (osteocalcin, N-terminal propeptide of type-I procollagen, reflecting bone formation, and carboxyterminal collagen I crosslinks, reflecting bone resorption) and BMD (by DXA) were measured before the intervention and at follow-up. RESULTS From baseline to follow-up, s-propeptide of type-I procollagen increased by 34% (95% confidence interval [CI], 17%-50%), serum-carboxyterminal collagen I crosslink by 36% (95% CI, 1%-71%), and s-osteocalcin by 31% (95% CI, 11-51%) more in the lifestyle intervention group compared with standard care. Loss of weight and fat mass were the strongest mediators of the increased bone turnover. Bone mineral density was unaffected by the intervention (ΔBMD, 0.1%; 95% CI, -1.1% to 1.2%). CONCLUSIONS A 12-month intensive exercise-based lifestyle intervention led to a substantial but balanced increase in bone turnover in persons with T2D. The increased bone turnover combined with a preserved BMD, despite a considerable weight loss, is likely to reflect improved bone health and warrants further studies addressing the impact of exercise on risk of fractures in persons with T2D.
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Bone Mineral Density Changes in Long-Term Kidney Transplant Recipients: A Real-Life Cohort Study of Native Vitamin D Supplementation.
Battaglia, Y, Bellasi, A, Bortoluzzi, A, Tondolo, F, Esposito, P, Provenzano, M, Russo, D, Andreucci, M, Cianciolo, G, Storari, A
Nutrients. 2022;(2)
Abstract
Vitamin D insufficiency has been associated with reduced bone mineral density (BMD) in kidney transplant patients (KTRs). However, the efficacy of vitamin D supplementation on BMD remains poorly defined, especially for long-term KTRs. We aimed to investigate the effect of native vitamin D supplementation on the BMD of KTRs during a 2-year follow-up. Demographic, clinical, and laboratory data were collected. BMD was evaluated with standard DEXA that was performed at baseline (before vitamin D supplementation) and at the end of study period. BMD was assessed at lumbar vertebral bodies (LV) and right femoral neck (FN) by a single operator. According to WHO criteria, results were expressed as the T-score (standard deviation (SD) relative to young healthy adults) and Z-score (SD relative to age-matched controls). Osteoporosis and osteopenia were defined as a T-score ≤ -2.5 SD and a T-score < -1 and a > -2.5 SD, respectively. Based on plasma levels, 25-OH-vitamin D (25-OH-D) was supplemented as recommended for the general population. Data from 100 KTRs were analyzed. The mean study period was 27.7 ± 3.4 months. At study inception, 25-OH-D insufficiency and deficiency were recorded in 65 and 35 patients. At the basal DEXA, the percentage of osteopenia and osteoporosis was 43.3% and 18.6% at LV and 54.1% and 12.2% at FN, respectively. At the end of the study, no differences in the Z-score and T-score gains were observed. During linear mixed model analysis, native vitamin D supplementation was found to have a negative nitration with Z-score changes at the right femoral neck in KTRs (p < 0.05). The mean dose of administered cholecalciferol was 13.396 ± 7.537 UI per week; increased 25-OH-D levels were found (p < 0.0001). Either low BMD or 25-OH-vitamin D concentration was observed in long-term KTRs. Prolonged supplementation with 25-OH-D did not modify BMD, Z-score, or T-score.
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Endocrinology of bone mineralization: An update.
Jannin, A, Kerlan, V, Desailloud, R
Annales d'endocrinologie. 2022;(1):46-53
Abstract
Throughout the world, millions of people suffer from fragilizing osteopathies such as osteomalacia and osteoporosis. Osteomalacia is a rare disorder, corresponding to mineralization abnormalities in adult bone, as opposed to rickets in children. Renal phosphate loss and hypophosphatasia are the main causes of vitamin-resistant osteomalacia. Diagnosis is based on clinical history, phosphocalcic metabolism assessment and, if necessary, molecular characterization, and must be rapid in order to initiate the most appropriate treatment and consider new treatments such as burosumab if necessary. Osteoporosis is characterized by reduced bone mass and strength, which increases the risk of fragility fracture. Fracture-related burden is expected to increase over the coming decades linked to the aging of population and a treatment gap. In order to reduce this treatment gap, it is important to develop two strategies: improvement of screening and of treatment. Systematic screening using the FRAX® fracture risk assessment tool could be useful to increase anti-osteoporosis medical treatment and reduce fracture rates. The question of treatment sequencing in osteoporosis is another challenge, notably after denosumab cessation, complicated by a decrease in bone mineral density and increased risk of fracture. New treatments are also available, including romosozumab, a humanized monoclonal antibody, which promotes bone formation and inhibits bone resorption by inhibiting sclerostin. Romosozumab is approved in several countries, including France, for treating severe osteoporosis in postmenopausal women at high risk of fracture and free of cardiovascular comorbidity. Endocrinologists need to be aware of these fragilizing osteopathies in order to improve both diagnosis and treatment.
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The Efficacy of Nitrates for Bone Health: A Systematic Review and Meta-Analysis of Observational and Randomized Controlled Studies.
Liu, W, Meng, Z, Wang, G
Frontiers in endocrinology. 2022;:833932
Abstract
BACKGROUND Although some studies have found that nitrates were beneficial for bone health, the findings are inconsistent. To assess the efficacy of nitrates for bone health, we conducted a meta-analysis. METHODS PubMed, EMBASE databases, Cochrane Library for relevant articles published before December 2021 were searched. All observational and randomized controlled studies that reporting bone mineral density (BMD), fractures with nitrates use were included. A meta-analysis was performed to calculate risk ratios (RRs) for fractures, change differences for bone mineral density. RESULTS Four cohort studies and two case-control studies examining the association between nitrates use and fractures were identified. The nitrates use was not associated with any fracture risk (RR = 0.97; 95% CI, 0.94-1.01; I2 = 31.5%) and hip fracture (RR = 0.88; 95% CI, 0.76-1.02; I2 = 74.5%). Subgroup analyses revealed no differences in fracture risk, whereas two cohort studies revealed a reduced risk of hip fracture (RR = 0.71, 95% CI, 0.58-0.86, I2 = 0.0%). There were no statistically significant differences in BMD percent changes at lumbar spine (WMD = -0.07, 95% CI,-0.78-0.65; I2 = 0.0%), total hip (WMD = -0.42, 95% CI,-0.88-0.04; I2 = 0.0%), femoral neck (WMD = -0.38, 95% CI,-1.02-0.25; I2 = 0.0%), or total body (WMD = -0.17, 95% CI,-0.51-0.17; I2 = 0.0%) in two randomized controlled trials (RCTs) compared with a placebo. Another two RCTs compared nitrates with alendronate. Nitrates were comparable to alendronate in increasing bone mineral density at lumbar spine (WMD = 0.00, 95% CI,-0.01-0.02; I2 = 0.0%). Besides, the most common adverse effect was headache, contributing to low adherence to therapy. CONCLUSION Our meta-analysis showed no association between nitrates use and fractures in observational studies. The results of RCTs on the usage of nitrates and their effects on BMD were inconsistent. High-quality, long-term studies are needed to clarify the efficacy of nitrates for bone health.
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Rationale and Design for a Higher (Dairy) Protein Weight Loss Intervention That Promotes Muscle Quality and Bone Health in Older Adults with Obesity: A Randomized, Controlled Pilot Study.
Miller, MG, Porter Starr, KN, Rincker, J, Orenduff, MC, McDonald, SR, Pieper, CF, Fruik, AR, Lyles, KW, Bales, CW
Journal of nutrition in gerontology and geriatrics. 2021;(2-3):150-170
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Abstract
In contrast to recommendations for young and middle-aged adults, intentional weight loss among older adults remains controversial and is inconsistently advised. Recent research suggests that a higher protein diet can mitigate loss of lean mass during periods of intentional weight loss among older adults with obesity; however, the effects of intentional weight loss on skeletal muscle and bone are not fully understood. The Dairy in the Diet Yields New Approaches for Muscle Optimization (DDYNAMO) trial is a 6-month, randomized, controlled pilot study assessing the effects of combining regular, generous intakes of high quality protein (30 g/meal; primarily from dairy) with caloric restriction (-500kcal/d) and low-intensity resistance exercise (30 min/3 times per week) on muscle quality, muscle composition, bone mineral density in men and women aged ≥60 years with obesity and mild to moderate functional impairment (Short Physical Performance Battery [SPPB] score ≥4 to ≤10). Participants will be re-assessed at 18 months to evaluate weight maintenance, bone mineral density, physical function, and other secondary measures. ClinicalTrials.gov Identifier: NCT02437643.
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Does Vitamin D affects changes in volumetric bone mineral density and architecture in postmenopausal women after conservatively treated distal radius fractures?
Raptis, K, Makris, K, Trovas, G, Galanos, A, Koutserimpas, C, Papaioannou, N, Vlamis, I, Vlasis, K, Tournis, S
Journal of musculoskeletal & neuronal interactions. 2021;(1):93-103
Abstract
OBJECTIVE We examined the role of vitamin D on volumetric bone mineral density (vBMD) and architecture during the first week's post-fracture in postmenopausal women (PMW) with distal radial fractures (DRF) treated conservatively using peripheral Quantitative Computed Tomography (pQCT). METHODS Patients were classified into 2 groups according to initial median 25(OH)D level; Group A (25(OH)D ≥15 ng/ml) and group B (25(OH)D <15 ng/ml). All patients were followed for 12 weeks at three visits: baseline, 6 weeks and 12 weeks post fracture. pQCT was performed at baseline in fractured and contralateral non-fractured radius and at 6th and 12th week on the fractured side. RESULTS 39 patients completed the protocol. Mean 25(OH)D levels were 15.60±7.35 ng/ml (3.5-41.7). Trabecular (trab) bone mineral content (BMC) and trabvBMD increased at 6 wk. vs. baseline (p<0.001). Cortical BMC, cortvBMD and cross- sectional area (CSA) progressively decreased (p<0.001) during the 12 weeks. There was no interaction between baseline 25(OH)D levels and changes in trabecular and cortical BMC, vBMD and CSA. Advanced age and higher CTX and P1NP were associated with higher cortical bone loss. CONCLUSION Vitamin D deficiency does not affect the early architectural changes after a DRF. Advanced age and higher bone remodeling were associated with higher cortical bone loss, probably related to immobilization and independent of vitamin D levels.
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The impact of preoperative vitamin administration on skeletal status following sleeve gastrectomy in young and middle-aged women: a randomized controlled trial.
Ben-Porat, T, Weiss, R, Khalaileh, A, Abu Gazala, M, Kaluti, D, Mintz, Y, Sherf-Dagan, S, Yackobovitch-Gavan, M, Rottenstreich, A, Brodie, R, et al
International journal of obesity (2005). 2021;(9):1925-1936
Abstract
BACKGROUND The appropriate strategies to minimize skeletal deterioration following bariatric surgeries are inconclusive. This randomized controlled trial evaluated the effect of preoperative vitamin supplementation on bone mineral density (BMD) and biochemical parameters in females post-sleeve gastrectomy (SG). METHODS Participants were randomized to a 2-month preoperative treatment with a multivitamin and vitamin D 4000 IU/d (intervention arm) or 1200 IU/d (control arm). Preoperative and 12-month postoperative follow-up evaluations included anthropometrics, biochemical parameters, and dual energy X-ray absorptiometry (DEXA). RESULTS Sixty-two females (median age 29.7 years and median BMI 43.4 kg/m2) were recruited, 87% completed the 12-month follow-up. For the intervention and control arms, significant and similar reductions at 12-months post-surgery were observed in BMD of the hip (-6.8 ± 3.7% vs. -6.0 ± 3.6%; P = 0.646) and of the femoral neck (-7.1 ± 5.8% vs. -7.2 ± 5.5%; P = 0.973). For the intervention compared to the control arm, the 25 hydroxyvitamin D (25(OH)D) increment was greater after 2 months treatment, and vitamin D deficiency rates were lower at 3 and 6-months follow-up (P < 0.016). However, at 12-months postoperative, 25(OH)D values and vitamin D deficiency were comparable between the arms (P > 0.339). Predictors for BMD decline in the total hip were the percentage of excess weight-loss, age>50 years, and lower initial BMI (P ≤ 0.003). CONCLUSIONS SG was associated with a significant decline in BMD of the hip and femoral neck in young and middle-aged women, and was unaffected by preoperative vitamin D supplementation. Females who are peri-menopausal or with greater postoperative weight-loss should be particularly followed for BMD decline.
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Efficacy of Creatine Supplementation and Resistance Training on Area and Density of Bone and Muscle in Older Adults.
Candow, DG, Chilibeck, PD, Gordon, JJ, Kontulainen, S
Medicine and science in sports and exercise. 2021;(11):2388-2395
Abstract
PURPOSE To examine the efficacy of creatine (Cr) supplementation and any sex differences during supervised whole-body resistance training (RT) on properties of bone and muscle in older adults. METHODS Seventy participants (39 men, 31 women; mean age ± standard deviation: 58 ± 6 yr) were randomized to supplement with Cr (0.1 g·kg-1·d-1) or placebo (Pl) during RT (3 d·wk-1 for 1 yr). Bone geometry (radius and tibia) and muscle area and density (forearm and lower leg) were assessed using peripheral quantitative computed tomography. RESULTS Compared with Pl, Cr increased or maintained total bone area in the distal tibia (Cr, Δ +17 ± 27 mm2; Pl, Δ -1 ± 22 mm2; P = 0.031) and tibial shaft (Cr, Δ 0 ± 9 mm2; Pl, Δ -5 ± 7 mm2; P = 0.032). Men on Cr increased trabecular (Δ +28 ± 31 mm2; P < 0.001) and cortical bone areas in the tibia (Δ +4 ± 4 mm2; P < 0.05), whereas men on Pl increased trabecular bone density (Δ +2 ± 2 mg·cm-3; P < 0.01). There were no bone changes in the radius (P > 0.05). Cr increased lower leg muscle density (Δ +0.83 ± 1.15 mg·cm-3; P = 0.016) compared with Pl (Δ -0.16 ± 1.56 mg·cm-3), with no changes in the forearm muscle. CONCLUSIONS One year of Cr supplementation and RT had some favorable effects on measures of bone area and muscle density in older adults.
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Nutritional Supplements and Skeletal Health.
Tabatabai, LS, Sellmeyer, DE
Current osteoporosis reports. 2021;(1):23-33
Abstract
PURPOSE OF REVIEW Nutrition influences skeletal health throughout the lifespan, from the impact of maternal intakes during development, through the development of peak bone mass, to the rate of bone loss during aging. However, there are limited data available on the effects of nutritional supplements on bone density, let alone fracture risk. This review will assess the current literature, focusing on human studies, and emphasizing nutrients where bone density or fracture data are available. RECENT FINDINGS Calcium and vitamin D supplements, in combination, reduce fracture risk, particularly in populations with low intakes. Extensive recent analyses have supported the safety of these interventions at recommended intakes. There is growing evidence that specific isoflavones may improve bone density although fracture data are lacking. Multiple other nutrient supplements may benefit skeletal health, but data are limited. The effect size of nutrient interventions are relatively small, requiring large sample sizes for trials with bone outcomes, may be difficult to blind, and the impact of supplementation may depend on baseline intake. However, nutrition is the only intervention that can be implemented life long and on a population wide basis. Further investigation is needed into the potential benefits of nutritional supplements to determine in which settings supplements may add benefit in addition to dietary intakes.
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Correlational analysis of bone health status and vitamin D-related biomarkers in women working in agriculture.
Cho, MC, Park, KS, Shin, JK, Lee, SA, Cho, IA, Jo, HC, Kim, SC, Choi, WJ
Medicine. 2021;(34):e27071
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Abstract
The purpose of this study was to investigate the status of bone health in women working in agriculture and analyze the associations between bone health and various vitamin D-related biomarkers.This observational study enrolled women working in agriculture (n = 210) and control occupations (n = 180). The concentration of serum total 25-hydroxy vitamin D [25(OH)D] was measured using the Elecsys Vitamin D Total Kit, and serum vitamin D-binding protein (VDBP) was measured by enzyme-linked immunosorbent assay. Along with albumin, 25(OH)D and VDBP were used to calculate the concentrations of bioavailable and free 25(OH)D. Bone mineral density (BMD) and T-score were measured at lumbar 1 to 4 and the femur neck using dual-energy X-ray absorptiometry. To identify factors affecting BMD, log-linear model and linear regression analysis were performed for statistical analysis.Agricultural women workers showed higher serum concentrations of bioavailable 25(OH)D (12.8 ± 3.7 vs 8.7 ± 5.1 ng/mL) and lower VDBP concentrations (201.8 ± 45.0 vs 216.0 ± 68.2 μg/mL) than control women. The association between these 2 vitamin D related-biomarkers and femur neck BMD were confirmed through univariable and multivariable linear model analysis. Although lumbar BMD did not differ between groups, the agricultural group displayed a lower femur BMD and a 4.3-fold increase in the risk of osteoporosis compared with the control group.Women working in agriculture showed lower femur BMD than the control group. Of the vitamin D-related biomarkers tested, bioavailable 25(OH)D and VDBP were associated with BMD. As bioavailable 25(OH)D levels are affected mainly by VDBP levels, VDBP may play a role in the lower femur neck BMD values observed in the agricultural group. Thus, the measurement of VDBP concentration might be considered a simple and non-invasive method for measuring bone health status.