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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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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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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.
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Genetically determined SCFA concentration modifies the association of dietary fiber intake with changes in bone mineral density during weight loss: The Preventing Overweight Using Novel Dietary Strategies (POUNDS LOST) trial.
Zhou, T, Sun, D, Li, X, Heianza, Y, LeBoff, MS, Bray, GA, Sacks, FM, Qi, L
The American journal of clinical nutrition. 2021;(1):42-48
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BACKGROUND SCFAs are involved in regulation of body weight and bone health. OBJECTIVES We aimed to examine whether genetic variations related to butyrate modified the relation between dietary fiber intake and changes in bone mineral density (BMD) in response to weight-loss dietary interventions. METHODS In the 2-y Preventing Overweight Using Novel Dietary Strategies trial, 424 participants with BMD measured by DXA scan were randomly assigned to 1 of 4 diets varying in macronutrient intakes. A polygenic score (PGS) was calculated based on 7 genetic variants related to the production of butyrate for 370 of the 424 participants. RESULTS SCFA PGS significantly modified the association between baseline dietary fiber intake and sex on 2-y changes in whole-body BMD (P-interaction = 0.049 and 0.008). In participants with the highest tertile of SCFA PGS, higher dietary fiber intake was related to a greater increase in BMD (β: 0.0022; 95% CI: 0.0009, 0.0035; P = 0.002), whereas no such association was found for participants in the lower tertiles. In the lowest tertiles of SCFA PGS, men showed a significant increase in whole-body BMD (β: 0.0280; 95% CI: 0.0112, 0.0447; P = 0.002) compared with women. In the highest tertile, no significant difference was found for the change in BMD between men and women. CONCLUSIONS Our data indicate that genetic variants related to butyrate modify the relations of dietary fiber intake and sex with long-term changes in BMD in response to weight-loss diet interventions.
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Impact of postpartum tenofovir-based antiretroviral therapy on bone mineral density in breastfeeding women with HIV enrolled in a randomized clinical trial.
Stranix-Chibanda, L, Tierney, C, Sebikari, D, Aizire, J, Dadabhai, S, Zanga, A, Mukwasi-Kahari, C, Vhembo, T, Violari, A, Theron, G, et al
PloS one. 2021;(2):e0246272
Abstract
OBJECTIVES We set out to evaluate the effect of postnatal exposure to tenofovir-containing antiretroviral therapy on bone mineral density among breastfeeding women living with HIV. DESIGN IMPAACT P1084s is a sub-study of the PROMISE randomized trial conducted in four African countries (ClinicalTrials.gov number NCT01066858). METHODS IMPAACT P1084s enrolled eligible mother-infant pairs previously randomised in the PROMISE trial at one week after delivery to receive either maternal antiretroviral therapy (Tenofovir disoproxil fumarate / Emtricitabine + Lopinavir/ritonavir-maternal TDF-ART) or administer infant nevirapine, with no maternal antiretroviral therapy, to prevent breastmilk HIV transmission. Maternal lumbar spine and hip bone mineral density were measured using dual-energy x-ray absorptiometry (DXA) at postpartum weeks 1 and 74. We studied the effect of the postpartum randomization on percent change in maternal bone mineral density in an intention-to-treat analysis with a t-test; mean and 95% confidence interval (95%CI) are presented. RESULTS Among 398/400 women included in this analysis, baseline age, body-mass index, CD4 count, mean bone mineral density and alcohol use were comparable between study arms. On average, maternal lumbar spine bone mineral density declined significantly through week 74 in the maternal TDF-ART compared to the infant nevirapine arm; mean difference (95%CI) -2.86 (-4.03, -1.70) percentage points (p-value <0.001). Similarly, maternal hip bone mineral density declined significantly more through week 74 in the maternal TDF-ART compared to the infant nevirapine arm; mean difference -2.29% (-3.20, -1.39) (p-value <0.001). Adjusting for covariates did not change the treatment effect. CONCLUSIONS Bone mineral density decline through week 74 postpartum was greater among breastfeeding HIV-infected women randomized to receive maternal TDF-ART during breastfeeding compared to those mothers whose infants received nevirapine prophylaxis.
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Reduction in Bone Loss from 5 to 20 Weeks Postpartum in Adolescents Supplemented with Calcium Plus Vitamin D during Pregnancy Is Not Sustained at 1 Year Postpartum: Follow-up Study of a Randomized Controlled Trial.
Diogenes, MEL, Bezerra, FF, Donangelo, CM
The Journal of nutrition. 2021;(3):548-555
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BACKGROUND Calcium plus vitamin D supplementation of pregnant Brazilian adolescents with habitually low calcium intake (∼600 mg/d) reduced bone loss during the first 20 wk postpartum. OBJECTIVE We investigated maternal bone mass changes during the first year postpartum as a follow-up of the clinical trial. METHODS Pregnant adolescents (14-19 y) received calcium (600 mg/d) plus cholecalciferol (200 IU/d) supplementation (n = 30) or placebo (n = 26) from 26 wk of gestation until parturition. Bone area and bone mineral content and bone mineral density (BMD) at total body, lumbar spine, and hip (total and femoral neck) were assessed by DXA at 3 time points postpartum (5 wk, 20 wk, and 56 wk). Intervention group, time postpartum, and group × time interaction effects were tested by repeated-measures mixed-effects models adjusting for calcium intake, return of menses, breastfeeding practices, and body weight. RESULTS Time (P < 0.05) but not group affected several absolute bone measurements. There was a group × time interaction for femoral neck BMD (P = 0.045). Mean ± SE values (g/cm2) at 5 wk, 20 wk, and 56 wk were, respectively, 1.025 ± 0.026, 0.980 ± 0.026, and 1.022 ± 0.027 for the placebo group and 1.057 ± 0.025, 1.030 ± 0.024, and 1.055 ± 0.025 for the supplemented group. An interaction also was observed for percentage change in femoral neck BMD relative to 5 wk (P = 0.049), with a more pronounced decrease in the placebo group (-4.58 ± 0.42%) than in the supplemented group (-3.15% ± 0.42%) at 20 wk (P = 0.019), and no difference between groups at 56 wk (-0.44% ± 0.71% in the placebo and -0.76% ± 0.62% in the supplemented group; P = 0.65). CONCLUSIONS Calcium plus vitamin D supplementation of the adolescent mothers reduces the magnitude of bone loss at the femoral neck from 5 to 20 wk postpartum without an effect on bone changes after 1 y postpartum, indicating that there is no sustained effect of the supplement tested.
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Exercise attenuates bone mineral density loss during diet-induced weight loss in adults with overweight and obesity: A systematic review and meta-analysis.
Mesinovic, J, Jansons, P, Zengin, A, de Courten, B, Rodriguez, AJ, Daly, RM, Ebeling, PR, Scott, D
Journal of sport and health science. 2021;(5):550-559
Abstract
BACKGROUND Weight-loss-induced fat loss improves cardiometabolic health in individuals with overweight and obesity; however, weight loss can also result in bone loss and increased fracture risk. Weight-loss-induced bone loss may be attenuated with exercise. Our aim was to compare changes in bone mineral density (BMD) in adults with overweight and obesity who undertook diet-induced weight loss alone or in combination with exercise. METHODS We included randomized controlled trials (RCTs) in adults with overweight or obesity (aged ≥18 years; body mass index ≥25 kg/m2) that prescribed diet-induced weight loss alone or in combination with supervised exercise, and measured any bone structural parameters. Risk of bias was assessed using the Cochrane Risk of Bias tool. Random-effects meta-analyses determined mean changes and net mean differences (95% confidence intervals (95%CIs)) in the percentage of areal BMD (aBMD) change between groups. RESULTS We included 9 RCTs. Diet-induced weight loss led to significant losses in femoral neck aBMD (mean change: -1.73% (95%CI: -2.39% to -1.07%), p < 0.001) and total hip aBMD (-2.19% (95%CI: -3.84% to -0.54%), p = 0.009). Femoral neck aBMD losses were significantly greater in the diet-induced weight loss group compared to the exercise plus diet-induced weight loss group (net difference: -0.88% (95%CI: -1.73% to -0.03%)); however, there were no differences in aBMD changes at any other skeletal site: total hip (-1.96% (95%CI: -4.59% to 0.68%)) and lumbar spine (-0.48% (95%CI: -1.81% to 0.86%)). aBMD changes did not differ significantly according to exercise modality (resistance exercise, aerobic exercise, or a combination of the two) during diet-induced weight loss. CONCLUSION Diet-induced weight loss led to greater femoral neck bone loss compared to diet-induced weight loss plus exercise. Bone loss at the total hip and lumbar spine was not attenuated by exercise during diet-induced weight loss. The lack of consistent skeletal benefits may be due to the insufficient duration and/or training intensities of most exercise interventions. Additional RCTs with appropriate, targeted exercise interventions should be conducted.
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Effects of Myo-inositol Hexaphosphate (SNF472) on Bone Mineral Density in Patients Receiving Hemodialysis: An Analysis of the Randomized, Placebo-Controlled CaLIPSO Study.
Bushinsky, DA, Raggi, P, Bover, J, Ketteler, M, Bellasi, A, Rodriguez, M, Sinha, S, Garg, R, Perelló, J, Gold, A, et al
Clinical journal of the American Society of Nephrology : CJASN. 2021;(5):736-745
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BACKGROUND AND OBJECTIVES In the CaLIPSO study, intravenous administration of SNF472 (300 or 600 mg) during hemodialysis significantly attenuated progression of coronary artery and aortic valve calcification. SNF472 selectively inhibits formation of hydroxyapatite, the final step in cardiovascular calcification. Because bone mineral is predominantly hydroxyapatite, we assessed changes in bone mineral density in CaLIPSO. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS Patients with coronary artery calcification at screening (Agatston score of 100-3500 U) were randomized 1:1:1 to receive placebo, 300 mg SNF472, or 600 mg SNF472 as an intravenous infusion during hemodialysis three times weekly for 52 weeks. Dual-energy x-ray absorptiometry (DXA) scans were obtained at baseline (screening) and end of treatment, and between-group changes from baseline were compared using analysis of covariance. RESULTS Among 274 randomized patients, 202 had evaluable DXA scans at baseline and postrandomization (the DXA-modified intention-to-treat population). Mean (95% confidence interval) changes in total-hip bone mineral density from baseline to week 52 were -1.5% (-2.7% to -0.3%), -1.5% (-2.7% to -0.4%), and -2.5% (-3.8% to -1.2%) in the placebo, 300 mg SNF472, and 600 mg SNF472 groups, respectively. Mean (95% confidence interval) changes in femoral-neck bone mineral density from baseline to week 52 were -0.3% (-1.6% to 1.0%), -1.0% (-2.3% to 0.2%), and -2.6% (-4.0% to -1.3%), respectively. Regression analyses showed no correlation between change in coronary artery calcium volume and change in bone mineral density at either location. Changes in serum alkaline phosphatase, calcium, magnesium, phosphate, and intact parathyroid hormone levels were similar across treatment groups. Clinical fracture events were reported for four of 90, three of 92, and six of 91 patients in the placebo, 300 mg SNF472, and 600 mg SNF472 groups, respectively. CONCLUSIONS Bone mineral density decreased modestly in all groups over 1 year. In the 600 mg SNF472 group, the reduction appeared more pronounced. Reported fractures were infrequent in all groups. CLINICAL TRIAL REGISTRY NAME AND REGISTRATION NUMBER Effect of SNF472 on Progression of Cardiovascular Calcification in End-Stage-Renal-Disease (ESRD) Patients on Hemodialysis (HD), NCT02966028.