Intracortical remodelling and porosity in the distal radius and post-mortem femurs of women: a cross-sectional study

Summary

Background

Osteoporosis research has focused on vertebral fractures and trabecular bone loss. However, non-vertebral fractures at predominantly cortical sites account for 80% of all fractures and most fracture-related morbidity and mortality in old age. We aimed to re-examine cortical bone as a source of bone loss in the appendicular skeleton.

Methods

In this cross-sectional study, we used high-resolution peripheral CT to quantify and compare cortical and trabecular bone loss from the distal radius of adult women, and measured porosity using scanning electron microscopy. Exclusion criteria were diseases or prescribed drugs affecting bone metabolism. We also measured bone mineral density of post-mortem hip specimens from female cadavers using densitometry. Age-related differences in total, cortical, and trabecular bone mass, trabecular bone of cortical origin, and cortical and trabecular densities were calculated.

Findings

We investigated 122 white women with a mean age of 62·8 (range 27–98) years. Between ages 50 and 80 years (n=89), 72·1 mg (95% CI 67·7–76·4) hydroxyapatite (68%) of 106·5 mg hydroxyapatite of bone lost at the distal radius was cortical and 34·3 mg (30·5–37·8) hydroxyapatite (32%) was trabecular; 17·1 mg (11·7–22·5) hydroxyapatite (16%) of total bone loss occurred between ages 50 and 64 years (n=34) and 89·4 mg (83·7–101·1) hydroxyapatite (84%) after age 65 years (n=55). Remodelling within cortex adjacent to the marrow accounted for 49·9 mg (45·4–53·7) hydroxyapatite (47%) of bone loss. Between ages 50–64 years (n=34) and 80 years and older (n=33), cortical density decreased by 127·8 mg (93·1–162·1) hydroxyapatite per cm³ (15%, p<0·0001) before porosity trabecularising the cortex was included, but 374·3 mg (318·2–429·5) hydroxyapatite per cm³ (43%, p<0·0001) after; trabecular density decreased by 18·2 mg (−1·4 to 38·2) hydroxyapatite per cm³ (14%, p=0·06) before cortical remnants were excluded, but 68·7 mg (37·7–90·4) hydroxyapatite per cm³ (52%, p<0·0001) after.

Interpretation

Accurate assessment of bone structure, especially porosity producing cortical remnants, could improve identification of individuals at high and low risk of fracture and therefore assist targeting of treatment.

Funding

Australia National Health and Medical Research Council.

Introduction

Bone modelling and remodelling are the final common pathways expressing all genetic and environmental factors affecting the attainment, maintenance, and decay of bone's material and structural strength.¹ During growth, this cellular machinery assembles the size, shape, and architecture of bone by depositing and removing material from the outer (periosteal) surface and the three (endocortical, intracortical, and trabecular) components of the inner (endosteal) surface (figure 1). At completion of growth, periosteal apposition slows and remodelling of the three inner surfaces maintains bone strength by removing and replacing old or damaged bone with an identical volume of new bone. Around midlife, remodelling becomes unbalanced so that every time bone matrix is remodelled, whether initiated for damage repair or adaptation to loading, more bone is removed than is replaced by cells of the basic multicellular unit, producing bone loss and structural decay.² Although this negative balance of a few percent can worsen as age advances, the driving force producing bone loss and structural decay is the remodelling intensity—the birth rate of the many new basic multicellular units arising on these surfaces after menopause in women and in both sexes late in life.³

The amount of bone loss and structural decay also relies on accessibility of the bone matrix to remodelling. This accessibility depends in part on how a volume of bone is designed in space. Remodelling is initiated on a bone surface. A volume of bone with a large exposed surface will be remodelled rapidly by the large number of basic multicellular units that can access and erode bone matrix beneath the surface.³ A volume of trabecular or spongy bone has a larger surface than does an equal volume of cortical or compact bone and is thus exposed to more remodelling and is lost more rapidly than is cortical bone.³ For this reason, trabecular bone loss and fractures of the vertebral body, which is a structure containing large amounts of trabecular bone, have dominated thinking and research into the structural basis of bone fragility for almost 70 years.4, 5

This focus neglects the role of decay of cortical bone in pathogenesis of bone fragility, which is an omission that is difficult to reconcile with the epidemiology of fractures. About 80% of all fractures in old age are non-vertebral, arise at sites that are mainly cortical, and occur after age 60 years when the rate of trabecular bone loss decelerates.6, 7 Moreover, only 20% of bone is trabecular—80% is cortical. Even if completely eroded, trabecular bone loss cannot account for the halving of bone mass with age in women. Although the low surface-to-volume ratio of cortical bone in early adulthood makes this volume less accessible to being remodelled than is trabecular bone, cortical bone is not compact—the structure is traversed by many Haversian and Volkmann canals, the lining of which provide a surface area for remodelling that can be larger in absolute terms than the surface area enveloping the four-fold smaller trabecular bone volume (figure 1). We therefore aimed to re-examine cortical bone as a source of bone loss in the appendicular skeleton.