Muscle density predicts changes in bone density and strength: a prospective study in girls.

OBJECTIVE: We sought to determine whether muscle density, an index of skeletal muscle fat content, was predictive of 2-year changes in weight-bearing bone parameters in young girls. METHODS: Two-year prospective data from 248 girls, aged 8-13 years at baseline. Peripheral quantitative computed tomography was used to measure changes in bone strength indices (bone strength index [BSI, mg(2)/mm(4)] and strength-strain index [SSIp, mm(3)]) and volumetric bone mineral density [vBMD, mg/cm(3)] at distal metaphyseal and diaphyseal regions of the femur and tibia, as well as calf and thigh muscle density (mg/cm(3)), and muscle cross-sectional area (MCSA, mm(2)), indices of skeletal muscle fat content and muscle force production, respectively. RESULTS: After controlling for potential confounders, greater gains in femur BSI (44%, P<0.002), total femur vBMD (114%, P<0.04) and femur trabecular vBMD (306%, P<0.002) occurred in girls in the lowest versus the highest groups of baseline thigh muscle density. Greater gains in tibial BSI (25%, P<0.03) and trabecular vBMD (190%, P<0.002) were also observed in the lowest versus the highest baseline calf muscle density groups. CONCLUSION: Baseline muscle density is a significant predictor of changes in bone density and bone strength in young girls during a period of rapid skeletal development.

Isolation and characterization of human osteoblasts from needle biopsies without in vitro culture.

SUMMARY: We isolate and characterize osteoblasts from humans without in vitro culture. These techniques should be broadly applicable to studying the pathogenesis of osteoporosis and other bone disorders. INTRODUCTION: There is currently no data regarding the expression of specific genes or pathways in human osteoblasts that have not been subjected to extensive in vitro culture. Thus, we developed methods to rapidly isolate progressively enriched osteoblast populations from humans and characterized these cells. METHODS: Needle bone biopsies of the posterior iliac crest were subjected to sequential collagenase digests. The cells from the second digest were stained with an alkaline phosphatase (AP) antibody, and the AP+ cells were isolated using magnetic cell sorting. RESULTS: Relative to AP- cells, the AP+ cells contained virtually all of the mineralizing cells and were enriched for key osteoblast marker genes. The AP+ cells were further purified by depletion of cells expressing CD45, CD34, or CD31 (AP+/CD45/34/31- cells), which represented a highly enriched human osteoblast population devoid of hematopoietic/endothelial cells. These cells expressed osteoblast marker genes but very low to undetectable levels of SOST. We next used high-throughput RNA sequencing to compare the transcriptome of the AP+/CD45/34/31- cells to human fibroblasts and identified genes and pathways expressed only in human osteoblasts in vivo, but not in fibroblasts, including 448 genes unique to human osteoblasts. CONCLUSIONS: We provide a detailed characterization of highly enriched human osteoblast populations without in vitro culture. These techniques should be broadly applicable to studying the pathogenesis of osteoporosis and other bone disorders.

Associations of physical activity duration, frequency, and load with volumetric BMD, geometry, and bone strength in young girls.

SUMMARY: More efficacious physical activity (PA) prescriptions for optimal bone development are needed. This study showed that PA duration, frequency, and load were all independently associated with bone parameters in young girls. Increased PA duration, frequency, and load are all important osteogenic stimuli that should be incorporated into future PA interventions. INTRODUCTION: This study evaluated the associations of physical activity (PA) duration, frequency, load, and their interaction (total PA score = duration × frequency × load) with volumetric bone mineral density, geometry, and indices of bone strength in young girls. METHODS: Four hundred sixty-five girls (aged 8-13 years) completed a past year physical activity questionnaire (PYPAQ) which inquires about the frequency (days per week) and duration (average minutes per session) of leisure-time PA and sports. Load (peak strain score) values were assigned to each activity based on ground reaction forces. Peripheral quantitative computed tomography was used to assess bone parameters at metaphyseal and diaphyseal sites of the femur and tibia of the non-dominant leg. RESULTS: Correlations across all skeletal sites between PA duration, frequency, load and periosteal circumference (PC), bone strength index (BSI), and strength-strain index (SSI) were significant (p ≤ 0.05), although low (0.10-0.17). A 2.7-3.7% greater PC across all skeletal sites was associated with a high compared to a low PYPAQ score. Also, a high PYPAQ score was associated with greater BSI (6.5-8.7%) at metaphyseal sites and SSI (7.5-8.1%) at diaphyseal sites of the femur and tibia. The effect of a low PYPAQ score on bone geometric parameters and strength was greater than a high PYPAQ score. CONCLUSIONS: PA duration, frequency, and load were all associated with bone geometry and strength, although their independent influences were modest and site specific. Low levels of PA may compromise bone development whereas high levels have only a small benefit over more average levels.