Effect of External Mechanical Stimuli on Human Bone: a narrative review.

Bone is a living composite material that has the capacity to adapt and respond to both internal and external stimuli. This capacity allows bone to adapt its structure to habitual loads and repair microdamage. Although human bone evolved to adapt to normal physiologic loading (for example from gravitational and muscle forces), these same biological pathways can potentially be activated through other types of external stimuli such as pulsed electromagnetic fields, mechanical vibration, and others. This review summarizes what is currently known about how human bone adapts to various types of external stimuli. We highlight how studies on sports-specific athletes and other exercise interventions have clarified the role of mechanical loading on bone structure. We also discuss clinical scenarios, such as spinal cord injury, where mechanical loading is drastically reduced, leading to rapid bone loss and permanent alterations to bone structure. Finally, we highlight areas of emerging research and unmet clinical need.

Dominant and nondominant distal radius microstructure: Predictors of asymmetry and effects of a unilateral mechanical loading intervention.

Most information about distal radius microstructure is based on the non-dominant forearm, with little known about the factors that contribute to bilateral asymmetries in the general population, or what factors may influence bilateral changes over time. Here, we analyzed bilateral high resolution peripheral quantitative computed tomography (HRpQCT) data collected over a 12-month period as part of a clinical trial that prescribed a well-controlled, compressive loading task to the nondominant forearm. Baseline data from 102 women age 21-40, and longitudinal data from 66 women who completed the 12-month trial, were examined to determine factors responsible for side-to-side asymmetries in bone structure and change in structure over time. Cross-sectionally, the dominant radius had 2.4%-2.7% larger cross-sectional area, trabecular area, and bone mineral content than the nondominant radius, but no other differences were noted. Those who more strongly favored their dominant arm had significantly more, thinner, closely spaced trabecular struts in their dominant versus nondominant radius. Individuals assigned to a loading intervention had significant bilateral gains in total bone mineral density (2.0% and 1.2% in the nondominant versus dominant sides), and unilateral gains in the nondominant (loaded) cortical area (3.1%), thickness (3.0%), bone mineral density (1.7%) and inner trabecular density (1.3%). Each of these gains were significantly predicted by loading dose, a metric that included bone strain, number of cycles, and strain rate. Within individuals, change was negatively associated with age, meaning that women closer to age 40 experienced less of a gain in bone versus those closer to age 21. We believe that dominant/nondominant asymmetries in bone structure reflect differences in habitual loads during growth and past ability to adapt, while response to loading reflects current individual physiologic capacity to adapt.

Relating Bone Strain to Local Changes in Radius Microstructure Following 12 Months of Axial Forearm Loading in Women.

Work in animal models suggests that bone structure adapts to local bone strain, but this relationship has not been comprehensively studied in humans. Here, we quantified the influence of strain magnitude and gradient on bone adaptation in the forearm of premenopausal women performing compressive forearm loading (n = 11) and nonloading controls (n = 10). High resolution peripheral quantitative computed tomography (HRpQCT) scans of the distal radius acquired at baseline and 12 months of a randomized controlled experiment were used to identify local sites of bone formation and resorption. Bone strain was estimated using validated finite element (FE) models. Trabecular strain magnitude and gradient were higher near (within 200 µm) formation versus resorption (p < 0.05). Trabecular formation and resorption occurred preferentially near very high (>95th percentile) versus low (<5th percentile) strain magnitude and gradient elements, and very low strain elements were more likely to be near resorption than formation (p < 0.05). In the cortical compartment, strain gradient was higher near formation versus resorption (p < 0.05), and both formation and resorption occurred preferentially near very high versus low strain gradient elements (p < 0.05). At most, 54% of very high and low strain elements were near formation or resorption only, and similar trends were observed in the control and load groups. These findings suggest that strain, likely in combination with other physiological factors, influences adaptation under normal loads and in response to a novel loading intervention, and represents an important step toward defining exercise interventions to maximize bone strength.

Bone Adaptation in Adult Women Is Related to Loading Dose: A 12-Month Randomized Controlled Trial.

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. Sixty-six 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 ± 2.7%, low strain rate: 2.7 ± 2.1%, high strain rate: 3.4 ± 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 µÎµ at 1878 µÎµ/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. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.

Distal radius microstructure and finite element bone strain are related to site-specific mechanical loading and areal bone mineral density in premenopausal women.

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.

Exercise Early and Often: Effects of Physical Activity and Exercise on Women's Bone Health.

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.