Increasing sex difference in bone strength in old age: The Age, Gene/Environment Susceptibility-Reykjavik study (AGES-REYKJAVIK)

doi:10.1016/j.bone.2006.03.020

Bone

Volume 39, Issue 3, September 2006, Pages 644-651

https://doi.org/10.1016/j.bone.2006.03.020 Get rights and content

Abstract

Introduction

It is important to identify possible pathological mechanisms that underlie the known sexual dimorphism in bone fragility in old age. In this cross-sectional population-based study, we use data from three different skeletal sites to examine sex differences in volumetric bone density, geometry and strength indices and determine whether sex differences in these bone strength measures continue to increase into very old age.

Materials and methods

A total of 1715 elderly individuals (807 men and 908 women) age 67–93 years, participants in a population-based study, the Age, Gene/Environment Susceptibility-Reykjavik Study (AGES-REYKJAVIK) and not taking medications affecting bone metabolism, were studied. Quantitative computed tomography (QCT) was performed in the lumbar spine, hip and mid-femoral shaft to estimate volumetric trabecular, cortical and integral BMD, bone geometry and bone strength indices. Regression models were used to assess the effects of age and gender-adjustment for standing midlife height and current weight.

Results

At age 67–69 years, men had 24.9–31.7% larger cross-sectional bone size at measured sites than women. At all bone sites, women had two- to fivefold diminution in net bone mass with age compared to men but had comparable increments in bone size (1.8–6.0% per 10 years). This was reflected in significantly worse (more than twofold) bone strength measures with age in women, including compressive strength indices at the spine, femoral neck and trochanter and bending strength indices at the femoral neck.

Conclusion

With the limitations of a cross-sectional study, our data support the hypothesis that sex differences in bone strength continue into old age. These sex differences appear to be due to greater net bone loss in women rather than due to greater bone gain in men.

Introduction

Osteoporosis and its associated bone fractures have become an increasingly important public health problem due to rapidly aging populations. It is important to identify the possible pathological mechanisms underlying bone fragility in old age. To this end, it is of interest to consider the gender differences in bone fracture rates in terms of sexual dimorphism in age-related skeletal changes. The age-related changes underlying the increase in skeletal fragility comprise of bone mineral loss by trabecular resorption, endocortical thinning and increasing cortical porosity as well as a smaller amount of bone gained by apposition on the exterior cortex [1]. The net effect on bone strength is a function of the counterbalance (interaction) between deterioration of the mechanical properties of the bone tissue and the compensatory effects of the increase in bone size due to cortical apposition [1], [2].

Population studies of gender differences in age-related skeletal changes have utilized areal bone mineral density (aBMD) and bone mineral content (BMC) measurements by dual X-ray absorptiometry (DXA) [3], [4].

Although BMD and BMC measures by DXA are widely utilized in the diagnostic setting and are predictors of incident hip fractures, their utility in etiologic studies is limited due to the confounding effect of skeletal size on the areal BMD measurement and the inability of the projectional measurement to separately depict the metabolically distinct trabecular and cortical bone compartments. Furthermore, the DXA-derived indices of femoral neck strength combining areal BMD and femoral neck width are based on unvalidated assumptions about the shape of the femoral neck cortex.

While it has its own biases due to limited spatial resolution on images of thin structures, quantitative computed tomography (QCT) is a useful tool for population studies of age and gender effects on the skeleton [5]. QCT allows for apparent volumetric BMD measurements, which are unconfounded by bone size, measured directly, either as a cross-sectional area or volume. QCT measurements can distinguish between trabecular and cortical bone compartments, which may have different inherent rates of bone turnover and distinct patterns of age-related loss. Although the experience with this tool in population studies is limited, a small but important cross-sectional study comparing changes in bone density and shape with gender has recently been published [6].

We have undertaken a descriptive population study of elderly men and women who are enrolled in the Age/Gene/Environment Susceptibility-Reykjavik Study (AGES-REYKJAVIK). In order to improve our understanding of the sex difference in the age-related onset of bone fragility, we attempted to answer three key questions: (i) do cortical and trabecular BMD show different patterns of cross-sectional relationships by age?; (ii) does the cross-sectional trend by age in periosteal expansion at the spine and hip differ by sex?; and (iii) are age-related indices of bone strength different between sexes? Within the limitation of a cross-sectional study, we have investigated this question and tried to partly correct for possible secular changes in standing height by using current and available midlife height data on the same study group.

Section snippets

Study subjects

The study sample consisted of the first 2300 enrolled men and women aged 67–93 years (976 men and 1324 women). They were participants in the Age Gene/Environment Susceptibility-Reykjavik Study (AGES-REYKJAVIK), an ongoing population-based study of Icelandic men and women continuing the Reykjavik Study, which has been described in detail [7], [8]. As part of the AGES-REYKJAVIK examination, participants were asked to bring to the Clinic all medications and supplements used in the previous

Results

The age distribution is shown in Table 1 as well as current and midlife height and weight, showing a cohort effect associated with mean midlife height increased by 5.4 cm (3.1%) among men and 5.1 cm (3.2%) among women during the 27 years span in cohort birth year. Height loss from midlife ranged from 2.0 to 2.8 cm in men and from 2.1 to 4.5 cm in women in the younger and oldest age groups. The mean current age of the study group was no different from the total group without exclusions,

Discussion

While peak volumetric bone density appears to be similar in men and women, women are thought to incur an increased incidence of fracture in old age due to smaller bones and an enhanced rate of bone loss during the first years after the menopause [11]. In this cross-sectional population-based study, we determined, at three different skeletal sites, the sex differences in bone density, geometry and strength indices measures at age 67 and how these differences continued into old age. We have

Acknowledgments

This study was supported by a grant from the National Institute on Aging (NO1-AG-1-2100), Bethesda, USA and the Icelandic Government.

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Increasing sex difference in bone strength in old age: The Age, Gene/Environment Susceptibility-Reykjavik study (AGES-REYKJAVIK)

Abstract

Introduction

Materials and methods

Results

Conclusion

Introduction

Section snippets

Study subjects

Results

Discussion

Acknowledgments

Semin. Nucl. Med.

Bone

J. Arthroplasty

Bone

Lancet

Bone

Clinical review 137: sexual dimorphism in skeletal size, density, and strength

J. Clin. Endocrinol. Metab.

Bone loss and bone size after menopause

N. Engl. J. Med.

Progressive loss of bone in the femoral neck in elderly people: longitudinal findings from the Dubbo osteoporosis epidemiology study

BMJ

Hip and calcaneal bone loss increase with advancing age: longitudinal results from the study of osteoporotic fractures

J. Bone Miner. Res.