In 2011 over 1.7 million people were hospitalized because of a fragility fracture, and direct costs associated with osteoporosis treatment exceeded 70 billion dollars in the United States. Failure to reach and maintain optimal peak bone mass during adulthood is a critical factor in determining fragility fracture risk later in life. Physical activity is a widely accessible, low cost, and highly modifiable contributor to bone health. Exercise is especially effective during adolescence, a time period when nearly 50% of peak adult bone mass is gained. Here, we review the evidence linking exercise and physical activity to bone health in women. Bone structure and quality will be discussed, especially in the context of clinical diagnosis of osteoporosis. We review the mechanisms governing bone metabolism in the context of physical activity and exercise. Questions such as, when during life is exercise most effective, and what specific types of exercises improve bone health, are addressed. Finally, we discuss some emerging areas of research on this topic, and summarize areas of need and opportunity.

Although strong evidence exists that certain activities can increase bone density and structure in people, it is unclear what specific mechanical factors govern the response. This is important because understanding the effect of mechanical signals on bone could contribute to more effective osteoporosis prevention methods and efficient clinical trial design. The degree to which strain rate and magnitude govern bone adaptation in humans has never been prospectively tested. Here, we studied the effects of a voluntary upper extremity compressive loading task in healthy adult women during a 12-month prospective period. A total of 102 women age 21 to 40 years participated in one of two experiments: (i) low (n = 21) and high (n = 24) strain magnitude; or (ii) low (n = 21) and high (n = 20) strain rate. Control (n = 16) no intervention. Strains were assigned using subject-specific finite element models. Load cycles were recorded digitally. The primary outcome was change in ultradistal radius integral bone mineral content (iBMC), assessed with QCT. Interim time points and secondary outcomes were assessed with high resolution pQCT (HRpQCT) at the distal radius. Sixtysix participants completed the intervention, and interim data were analyzed for 77 participants. Likely related to improved compliance and higher received loading dose, both the low-strain rate and high-strain rate groups had significant 12-month increases to ultradistal iBMC (change in control: −1.3 AE 2.7%, low strain rate: 2.7 AE 2.1%, high strain rate: 3.4 AE 2.2%), total iBMC, and other measures. "Loading dose" was positively related to 12-month change in ultradistal iBMC, and interim changes to total BMD, cortical thickness, and inner trabecular BMD. Participants who gained the most bone completed, on average, 128 loading bouts of (mean strain) 575 με at 1878 με/s. We conclude that signals related to strain magnitude, rate, and number of loading bouts contribute to bone adaptation in healthy adult women, but only explain a small amount of variance in bone changes.

While weight-bearing and resistive exercise modestly increases aBMD, the precise relationship between physical activity and bone microstructure, and strain in humans is not known. Previously, we established a voluntary upper-extremity loading model that assigns a person's target force based on their subject-specific, continuum FE-estimated radius bone strain. Here, our purpose was to quantify the inter-individual variability in radius microstructure and FE-estimated strain explained by site-specific mechanical loading history, and to determine whether variability in strain is captured by aBMD, a clinically relevant measure of bone density and fracture risk. Seventy-two women aged 21–40 were included in this cross-sectional analysis. High resolution peripheral quantitative computed tomography (HRpQCT) was used to measure macro- and micro-structure in the distal radius. Mean energy equivalent strain in the distal radius was calculated from continuum finite element models generated from clinical resolution CT images of the forearm. Areal BMD was used in a nonlinear regression model to predict FE strain. Hierarchical linear regression models were used to assess the predictive capability of intrinsic (age, height) and modifiable (body mass, grip strength, physical activity) predictors. Fifty-one percent of the variability in FE bone strain was explained by its relationship with aBMD, with higher density predicting lower strains. Age and height explained up to 31.6% of the variance in microstructural parameters. Body mass explained 9.1% and 10.0% of the variance in aBMD and bone strain, respectively, with higher body mass indicative of greater density. Overall, results suggest that meaningful differences in bone structure and strain can be predicted by subject characteristics.

Aging is associated with increasing incidence of osteoporosis; a skeletal disorder characterized by compromised bone strength that may predispose patients to an increased risk of fracture. It is imperative to identify novel ways in which to attenuate such declines in the functional properties of bone. The purpose of this study was to identify, through in silico, in vitro, and in vivo approaches, a protein secreted from skeletal muscle that is putatively involved in bone formation. We performed a functional annotation bioinformatic analysis of human skeletal muscle‐derived secretomes (n = 319) using DAVID software. Cross‐referencing was conducted using OMIM, Unigene, UniProt, GEO, and CGAP databases. Signal peptides and transmembrane residues were analyzed using SignalP and TMHMM software. To further investigate functionality of the identified protein, L6 and C2C12 myotubes were grown for in vitro analysis. C2C12 myotubes were subjected to 16 h of glucose deprivation (GD) prior to analysis. In vivo experiments included analysis of 6‐week calorie restricted (CR) rat muscle samples. Bioinformatic analysis yielded 15 genes of interest. GEO dataset analysis identified BMP5, COL1A2, CTGF, MGP, MMP2, and SPARC as potential targets for further processing. Following TMHMM and SignalP processing, CTGF was chosen as a candidate gene. CTGF expression level was increased during L6 myoblast differentiation (P <0.01). C2C12 myotubes showed no change in response to GD. Rat soleus muscle samples exhibited an increase in CTGF expression (n = 16) in response to CR (35%) (P <0.05). CTGF was identified as a skeletal muscle expressed protein through bioinformatic analysis of skeletal muscle‐derived secretomes and in vitro/in vivo analysis. Future study is needed to determine the role of muscle‐derived CTGF in bone formation and remodeling processes.

Background Many athletes are beginning intense training before puberty, a time of increased bone accrual when up to 25% of total bone mineral accrual occurs. Female athletes experiencing late or delayed pubertal onset may have open epiphyseal plates open that are vulnerable to injury. This investigation’s purpose was to determine whether a delay in puberty (primary amenorrhea) affects the growth plate immediately post-puberty and at maturity. Methods Forty-eight female Sprague–Dawley rats (23days-of-age) were randomly assigned to four groups (n=12); short-term control (C-ST), long-term control (C-LT), short-term GnRH antagonist (G-ST) and long-term GnRH antagonist (G-LT). At 25days-of-age, daily gonadotropin-releasing hormone antagonist (GnRH-a; Cetrotide™, Serono, Inc.) injections were administered delaying pubertal onset. Left tibias were analyzed. Stained frontal slices of proximal tibia (5 μm thick) were analyzed in hypertrophic, proliferative and reserve zones for total height, zone height, and cell/ column counts. All procedures were approved by (IACUC) at Brooklyn College. Results Growth plate height was 19.7% wider in delayed puberty (G-ST) group and at maturity was 27.9% greater in G-LT group compared to control (C-LT) (p<0.05). No significant differences were found in short or long-term growth plate zone heights or cell/column counts between groups (p>0.05). Growth plate zone height normalized to total height resulted in 28.7 % larger reserve zone in the short term GnRH-a group (G-ST) but the proliferative zone was 8.5 % larger in the long-term group compared to the control group (p<0.05). Normalized to growth plate height a significant decrease was found in column counts in proliferative zones of the short and long-term GnRH-a groups. Conclusions Current data illustrates delayed puberty using GnRH-a injections results in significant growth plate height and decreases proliferative column counts and zone height\potentially contributing to decreases in bone mass at maturity.