Age-related bone loss is a serious health concern for Western societies. The acquisition and maintenance of the adult skeleton are influenced by several factors, including genetic, nutritional, mechanical, hormonal, and environmental factors. Exercise has been promoted as a means to increase peak bone mass and inhibit age-related bone loss. Cross-sectional studies generally confirm the positive effects of exercise on bone mass, however results from exercise intervention trials have been contradictory. While quantitative relationships between physical activity and bone mass have yet to be established, several theories have been proposed that describe mathematically the influence of mechanical loading on bone deposition and resorption. These bone remodeling theories, in conjunction with an evaluation of the mechanical loading provided to skeletal tissue by exercise, may provide im portant insights concerning the relationship between exercise and bone.

In this dissertation both experimental and analytic methods w ere used to explore the relationship between physical activity and adult bone density. New analytic methods were developed to assess bone density non-invasively and to estimate skeletal mechanical loading. A major component of this research was a randomized exercise intervention trial in young women. This study provided baseline cross-sectional data concerning the relation between bone density and physical activity, as well as longitudinal measures of bone response to exercise intervention. To examine further relations between exercise and bone, results from the intervention trial were analyzed using a computational time-dependent bone remodeling theory.

Non-invasive bone densitometry is a standard method for assessing bone mineral in the lum bar spine, proximal femur, and other skeletal regions. The most common densitometry techniques, dual-photon and dual-energy x-ray absorptiometry, report regional areal bone mineral densities (BMD, g/cm²). We demonstrate that, in many cases, these areal density measures can be misleading due to variations in bone thickness. We developed an analytic technique that uses traditional densitometry data to compute a new parameter. This new parameter, bone mineral apparent density (BMAD, g/cm²), accounts for bone size and is designed to be proportional to bone apparent density. These new methods were applied to lumbar spine measurements in young women and appear to offer advantages to conventional densitometry techniques.

A method for estimating the daily mechanical stimulus of the lumbar spine was developed. Self-reported activity diaries, anthropometry, and bone densitometry data are used to compute individual mechanical stimuli. Subjects' daily activities are categorized into 6 basic events:​ lying, sitting, standing, walking, running, or weight lifting. Load parameters for these events were taken from the literature or computed using a simple biomechanical model of the lumbar spine. This method allows for a quantitative analysis of the mechanical loading provided to the skeleton by exercise.

Healthy, premenopausal women were recruited to participate in an exercise intervention study. As a first step we conducted a cross-sectional analysis of the baseline data. We compared current physical activity, assessed by energy expenditure and lumbar spine daily stress stimulus, to baseline bone density in 51 women. Lumbar spine and femoral neck bone mineral density were m odestly correlated to body weight, body mass index (w t/h t^), and daily energy expenditure, but were independent of energy expenditure per body weight. Thus, increased body size may by the primary influence on bone mineral density. Lumbar spine daily stress stimulus was not related to any baseline bone mineral measures. We concluded that estimates of current physical activity have limited use in identifying bone density variations in normal young women. This finding suggests that a life history of genetic, metabolic, and mechanical events contribute to adult bone density.

The second component of this study was a formal, randomized exercise intervention. Thirty women who were randomly assigned to a running, weight training, or control group completed the study. After 8-months of progressive training, the bone mineral density of the lumbar spine increased (p<0.05) in the weight training (1.2±1.8%) and running (1.3±1.6%) groups, whereas no change was observed in the control group. None of the groups exhibited bone mineral changes at the proximal femur. The weight training group increased muscle strength (10-54%, p<0.01) in all muscle groups tested, whereas no changes were seen in the running or control groups. Aerobic performance improved only in the running group (16%, p<0.01). The results dem onstrate that 8 months of supervised progressive training in either running or resistance exercise modestly increases lumbar spine bone mineral density in young women.

We used a time-dependent bone remodeling algorithm to analyze the exercise intervention results. Changes in mechanical stimulus throughout the study were computed from subjects' daily activity diaries and detailed workout logs. For each subject we determined the remodeling rate law that best predicted the measured change in spine density. Changes in spine density due to exercise intervention were successfully emulated using a linear rate law. We found a broad range of rate law slopes. This range of rate law slopes suggests that each person may have her own 'rate law' or that other, non-stress related factors are confounding variables. The bone remodeling algorithm may be used to emulate the mean response of a group to exercise intervention. However, due to subject variability seen in this study, the model is not capable of predicting the response of individuals.

This dissertation adds a new perspective to the literature concerning exercise and bone density. For the first time, skeletal mechanical loading due to exercise is estimated and used to interpret results from exercise intervention trials. Further application of computational bone remodeling algorithms may provide insights into the design of exercise intervention protocols.