: Considerable attention has recently focused on dietary protein's role in the mature skeleton, prompted partly by an interest in nonpharmacologic approaches to maintain skeletal health in adult ...life.
The aim was to conduct a systematic review and meta-analysis evaluating the effects of dietary protein intake alone and with calcium with or without vitamin D (Ca±D) on bone health measures in adults.
Searches across 5 databases were conducted through October 2016 including randomized controlled trials (RCTs) and prospective cohort studies examining
) the effects of "high versus low" protein intake or
) dietary protein's synergistic effect with Ca±D intake on bone health outcomes. Two investigators independently conducted abstract and full-text screenings, data extractions, and risk of bias (ROB) assessments. Strength of evidence was rated by group consensus. Random-effects meta-analyses for outcomes with ≥4 RCTs were performed.
Sixteen RCTs and 20 prospective cohort studies were included in the systematic review. Overall ROB was medium. Moderate evidence suggested that higher protein intake may have a protective effect on lumbar spine (LS) bone mineral density (BMD) compared with lower protein intake (net percentage change: 0.52%; 95% CI: 0.06%, 0.97%,
: 0%;
= 5) but no effect on total hip (TH), femoral neck (FN), or total body BMD or bone biomarkers. Limited evidence did not support an effect of protein with Ca±D on LS BMD, TH BMD, or forearm fractures; there was insufficient evidence for FN BMD and overall fractures.
Current evidence shows no adverse effects of higher protein intakes. Although there were positive trends on BMD at most bone sites, only the LS showed moderate evidence to support benefits of higher protein intake. Studies were heterogeneous, and confounding could not be excluded. High-quality, long-term studies are needed to clarify dietary protein's role in bone health. This trial was registered at www.crd.york.ac.uk as CRD42015017751.
Previous clinical trials and systematic reviews on the effects of supplemental vitamin D on musculoskeletal outcomes are conflicting. In this paper, we review the literature and summarize the effects ...of a high daily dose of 2 000 IU vitamin D on musculoskeletal outcomes in generally healthy adults, in men (≥50 years) and women (≥55 years) in the 5.3-year US VITamin D and OmegA-3 TriaL (VITAL) trial (n = 25 871) and women and men (≥70 years) in the 3-year European DO-HEALTH trial (n = 2 157). These studies found no benefit of 2 000 IU/d of supplemental vitamin D on nonvertebral fractures, falls, functional decline, or frailty. In VITAL, supplementation with 2 000 IU/d of vitamin D did not reduce the risk of total or hip fractures. In a subcohort of VITAL, supplemental vitamin D did not improve bone density or structure (n = 771) or physical performance measures (n = 1 054). In DO-HEALTH, which investigated additive benefits of vitamin D with omega-3 and a simple home exercise program, the 3 treatments combined showed a significant 39% decreased odds of becoming prefrail compared to the control. The mean baseline 25(OH)D levels were 30.7 ± 10 ng/mL in VITAL and 22.4 ± 8.0 ng/mL in DO-HEALTH and increased to 41.2 ng/mL and 37.6 ng/mL in the vitamin D treatment groups, respectively. In generally healthy and vitamin D-replete older adults not preselected for vitamin D deficiency or low bone mass or osteoporosis, 2 000 IU/d of vitamin D had no musculoskeletal health benefits. These findings may not apply to individuals with very low 25(OH)D levels, gastrointestinal disorders causing malabsorption, or those with osteoporosis.
Protein may have both beneficial and detrimental effects on bone health depending on a variety of factors, including protein source.
The aim was to conduct a systematic review and meta-analysis ...evaluating the effects of animal versus plant protein intake on bone mineral density (BMD), bone mineral content (BMC) and select bone biomarkers in healthy adults.
Searches across five databases were conducted through 10/31/16 for randomized controlled trials (RCTs) and prospective cohort studies in healthy adults that examined the effects of animal versus plant protein intake on 1) total body (TB), total hip (TH), lumbar spine (LS) or femoral neck (FN) BMD or TB BMC for at least one year, or 2) select bone formation and resorption biomarkers for at least six months. Strength of evidence (SOE) was assessed and random effect meta-analyses were performed.
Seven RCTs examining animal vs. isoflavone-rich soy (Soy+) protein intake in 633 healthy peri-menopausal (n = 1) and post-menopausal (n = 6) women were included. Overall risk of bias was medium. Limited SOE suggests no significant difference between Soy+ vs. animal protein on LS, TH, FN and TB BMD, TB BMC, and bone turnover markers BSAP and NTX. Meta-analysis results showed on average, the differences between Soy+ and animal protein groups were close to zero and not significant for BMD outcomes (LS: n = 4, pooled net % change: 0.24%, 95% CI: -0.80%, 1.28%; TB: n = 3, -0.24%, 95% CI: -0.81%, 0.33%; FN: n = 3, 0.13%, 95% CI: -0.94%, 1.21%). All meta-analyses had no statistical heterogeneity.
These results do not support soy protein consumption as more advantageous than animal protein, or vice versa. Future studies are needed examining the effects of different protein sources in different populations on BMD, BMC, and fracture.
A study ancillary to a large trial showed that supplemental vitamin D
3
did not lower the risk of fractures among generally healthy midlife and older adults not selected for vitamin D deficiency, low ...bone mass, or osteoporosis.
Heavier individuals have higher hip BMD and more robust femur geometry, but it is unclear whether values vary in proportion with body weight in obesity. We studied the variation of hip BMD and ...geometry across categories of body mass index (BMI) in a subset of postmenopausal non‐Hispanic whites (NHWs) from the Women's Health Initiative Observational Cohort (WHI‐OS). The implications on fracture incidence were studied among NHWs in the entire WHI‐OS. Baseline DXA scans of hip and total body from 4642 NHW women were divided into BMI (kg/m2) categories: underweight (<18.5), healthy weight (18.5–24.9), overweight (25–29.9), and mild (30–34.9), moderate (35–39.9), and extreme obesity (>40). Femur BMD and indices of bone axial (cross‐sectional area CSA) and bending strength (section modulus SM) were extracted from DXA scans using the hip structure analysis (HSA) method and compared among BMI categories after adjustment for height, age, hormone use, diabetes, activity level, femur neck‐shaft angle, and neck length. The association between BMI and incident fracture was studied in 78,013 NHWs from the entire WHI‐OS over 8.5 ± 2.6 (SD) yr of follow‐up. Fracture incidence (cases/1000 person‐years) was compared among BMI categories for hip alone, central body (hip, pelvis, spine, ribs, and shoulder girdle), upper extremity (humerus and distal), and lower extremity (femur shaft and distal but not hip). Femur BMD, CSA, and SM were larger in women with higher BMI, but values scaled in proportion to lean and not to fat or total body mass. Women with highest BMI reported more falls in the 12 mo before enrollment, more prevalent fractures, and had lower measures of physical activity and function. Incidence of hip fractures and all central body fractures declined with BMI. Lower extremity fractures distal to the hip trended upward, and upper extremity incidence was independent of BMI. BMD, CSA, and SM vary in proportion to total body lean mass, supporting the view that bones adapt to prevalent muscle loads. Because lean mass is a progressively smaller fraction of total mass in obesity, femur BMD, CSA, and SM decline relative to body weight in higher BMI categories. Traumatic forces increase with body weight, but fracture rates at the hip and central body were less frequent with increasing BMI, possibly because of greater soft tissue padding. There was no evident protective effect in fracture rates at less padded distal extremity sites. Upper extremity fractures showed no variation with BMI, and lower extremity fracture rates were higher only in the overweight (BMI = 25–29.9 kg/m2).
Vitamin D metabolites are important effectors of bone and mineral homeostasis. Extrarenal conversion of 25-hydroxyvitamin D (25OHD) to the biologically active form of vitamin D, ...1α,25-dihydroxyvitamin D 1,25(OH)2D is catalyzed in several cell types by the 1α-hydroxylase (CYP27B1), but little is known about the expression or regulation of CYP27B1 in human bones. We examined whether human bone marrow stromal cells (hMSCs, also known as mesenchymal stem cells) participate in vitamin D metabolism and whether vitamin D hydroxylases in hMSCs are influenced by the vitamin D status of the individual from whom the hMSCs were obtained. We also investigated the effects of vitamin D metabolites on osteoblast differentiation and the role of IGF-I in the regulation of CYP27B1. In a series of 27 subjects, vitamin D hydroxylases in hMSCs were expressed at different levels and were correlated with serum 25OHD, 1,25(OH)2D, and PTH. In vitro treatment with 25OHD up-regulated CYP27B1 and IGF-I in hMSCs; IGF-I also up-regulated CY27B1 expression and stimulated osteoblast differentiation. When hydroxylation of 25OHD was blocked by ketoconazole, a cytochrome P450 inhibitor, 25OHD was no longer able to induce CYP27B1 expression. In summary, these findings show that human bone marrow stromal cells have the molecular machinery both to metabolize and respond to vitamin D. We propose that circulating 25OHD, by virtue of its local conversion to 1,25(OH)2D catalyzed by basal CYP27B1 in hMSCs, amplifies vitamin D signaling through IGF-I up-regulation, which in turn induces CYP27B1 in a feed-forward mechanism to potentiate osteoblast differentiation initiated by IGF-I.
Human bone marrow stromal cells include osteoblast progenitors and have the molecular machinery to metabolize, regulate, and respond to vitamin D, with amplification through IGF-I induction.
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