Elsevier

Bone

Volume 35, Issue 3, September 2004, Pages 750-759
Bone

Femoral bone structural geometry adapts to mechanical loading and is influenced by sex steroids: The Penn State Young Women's Health Study

https://doi.org/10.1016/j.bone.2004.05.008Get rights and content

Abstract

We used 10 years of longitudinal data from Penn State Young Women's Health Study to explore predictors of adult bone structural geometry and strength. One hundred twelve participants were enrolled in the study at age 12. We report findings on the 76 participants who remained in the study for 10 years. Measurements were recorded biannually for the first 4 years and annually thereafter. Proximal femur DXA scans (Hologic QDR 2000) were taken from 17–22 years and analyzed using a hip structure analysis program to assess areal bone mineral density (BMD, g/cm2), subperiosteal width, cortical thickness, bone cross-sectional area (CSA), and section modulus (Z) at the narrow neck and femoral shaft. Total body lean mass (g) was measured with DXA total body scans. Nutrition, anthropometry, and sex steroids [testosterone (T) and estradiol (E2)] were measured from ages 12–22 years. Multiple regression models were used to assess predictors of change in bone variables (17–22 years) and absolute bone values (average of age 21 and 22 years, n = 79). Neck Z (+3.1%) and width (+1.3%), but not BMD (−0.8%), increased significantly from age 17 to 22 years. At the shaft, all variables increased (+1.0–4.0%, P < 0.01). After controlling for baseline (age 17) height, weight and bone measurement, weight change (neck) or lean mass (shaft), and age of menarche were the primary predictors of change in bone strength. After controlling for height and weight, only lean mass predicted absolute young adult Z at both the neck (r2 = 0.48, P < 0.01) and the shaft (r2 = 0.67, P < 0.01). When lean mass was removed from the model, sports exercise score replaced lean mass as a predictor of Z at both neck (r2 = 0.40, P < 0.01) and shaft (r2 = 0.60, P < 0.01) sites. For neck and shaft cortical thickness and BMD, both estradiol and sports score/lean mass were positive predictors (r2 = 0.15–0.40, P < 0.01). For neck bone width, testosterone levels (negative) and lean mass (positive) were significant (r2 = 0.48). Results were similar for each geometric variable at the shaft site. These data suggest that bone adapts its bending strength primarily to mechanical loading (represented by lean mass and sports exercise score) and that sex steroids are associated with bone geometric structure.

Introduction

Optimizing bone strength during growth is accepted as an important means for prevention of bone fragility and related fractures in later life [1]. A majority of the previous studies of bone development have measured bone mineral density (BMD, g/cm2) as the primary surrogate for bone strength. These studies identified a number of factors including genetics, nutrition, hormones, and physical activity as determinants of young adult BMD [1], [2], [3].

Although we have learned a great deal from these studies and BMD is a useful clinical outcome, BMD is used based on its ability to predict fractures in elderly bones, but in actuality, it is not a mechanical strength characteristic per se. Using BMD or bone mass as the primary outcome in young bones is somewhat problematic because it implies that bones should be as heavy as possible to maintain their strength. From a functional standpoint, bone should adapt its mechanical strength primarily to the effective stresses from skeletal loading activity to make it as strong as necessary, rather than as heavy as possible [4], [5], [6], [7]. Theoretically, other factors, such as hormones or nutrition, may mediate bone adaptation by raising or lowering the (re)modeling thresholds [8]. These ideas, based on Frost's concept of the mechanostat [4], [9] and the Utah paradigm [10], imply that bone geometry and structural strength must be assessed to fully understand bone adaptation. Changes in bone geometry can occur that may increase bone mechanical strength but will not necessarily be apparent in BMD [11], [12]. Using engineering principals and existing DXA scans, we can explore these concepts from a functional/mechanical perspective.

Bone strength is influenced by both material and structural parameters. Of these, we can measure cortical bone geometry and estimate mechanical strength [such as section modulus (Z), an estimate of bone bending strength] from DXA images. Measuring bone geometry and structural strength parameters helps provide a biological explanation for changes seen in bone mineral content (BMC) and BMD. To assess these parameters during late adolescence, we used longitudinal data from the Penn State Young Women's Health Study and applied a DXA-based Hip Structure Analysis program to proximal femur scans [13] to (1) determine if changes in proximal femur BMD correspond to changes in mechanical strength from age 17 to 22 and (2) explore predictors of young adult femoral bone structure and strength. We expected that bone bending strength (measured by section modulus), but not BMD, would continue to increase during young adulthood (17–22 years). We hypothesized that bone bending strength would adapt primarily to mechanical load (as represented by lean mass or physical activity) and that other factors (sex steroids and nutrition) would influence that adaptation.

Section snippets

Participants

The Penn State Young Women's Health Study is a prospective epidemiological study, which was started in 1990 with the enrollment of 112 healthy, premenarchal girls, aged 11.9 ± 0.5 years at entry. The study population is representative of White adolescent girls attending public school in central Pennsylvania. Details of the recruitment, baseline measurements, and the effects of the calcium supplementation component on bone gain have been reported [14], [15], [16], [17]. The study was approved by

Results

Descriptive characteristics of the population and bone values at ages 17 and 22 years are reported (Table 1). Calcium (955 ± 244 mg/day) and calorie (1858 ± 271 kcal/days) intake, averaged over the 15 visits from ages 12 to 22, were within the normal range for young adults. Age of menarche averaged 13.4 ± 1.0 years and ranged from 11.6 to 17.5 years. All but two of the girls had achieved menarche by age 15 and 90% between the ages of 12 and 14. Average levels of urinary and serum estradiol and

Discussion

To our knowledge, these are the first longitudinal data of bone structural geometry with comprehensive sex steroid, nutrition, and physical activity measurements across this age span. Although there was no change in BMD (g/cm2) or bone cross-sectional area at the femoral neck, section modulus (bone bending strength) did continue to increase over ages 17–22 in these healthy Caucasian women. While lean mass and sex steroids were associated with BMD and structural geometry, only lean mass was

Acknowledgements

We thank Tammy Oreskovic, MS, and Kirsti Uusi-Raasi, PhD, for their assistance with HSA analyses and initial data analyses. We are deeply appreciative to the efforts of the research coordinator, Nan Johnson-Rollings, RN, whose devotion to the study was essential to its success; the staff of the General Clinical Research Center at the MS Hershey Medical Center for their excellent care of the participants; the Core Endocrine Laboratory of the Department of Pathology for their assay expertise; and

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    Presented in part at the 25th Annual Meeting of the American Society of Bone and Mineral Research, Minneapolis, MN, 2003.

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