Risedronate reduces intracortical porosity in women with osteoporosis

Abstract

Nonvertebral fractures account for 80% of all fractures and their accompanying morbidity and mortality. Despite this, the effect of drug therapy on cortical morphology has received limited attention, partly because cortical bone is believed to remodel less and decrease less with age than trabecular bone. However, the haversian canals traversing the cortex provide a surface for remodeling that produces bone loss, porosity, and cortical fragility. We developed a new method of 3D micro-computed tomography (microCT) to quantify intracortical porosity and the effects of treatment. Women with osteoporosis randomized to risedronate (5 mg/day, n = 28) or placebo (n = 21) had paired transiliac biopsies at baseline and 5 years imaged using 3D microCT. Pores determined from 8 to 12 slices were stratified by their minor axis length into those 25 to 100 microm (closing cone of haversian canals), 100 to 300 microm (cutting cone of haversian canals), and >300 microm (coalescent cavities). Porosity was analyzed as pore area (percent bone area) and pore density (pore number/mm(2)). Medians are reported. Risedronate reduced pore area in the 25 to 100, 100 to 300, and 300 to 500 microm ranges over 5 years (p = .0008, .04, NS, respectively) corresponding to an 18% to 25% reduction. In the placebo group, pore area was unchanged. At 5 years, pore area and pore number/mm(2) in the 25 to 100 microm range were each 17% lower in the risedronate group than in the placebo group (p = .02 and .04, respectively). Risedronate is likely to maintain bone strength and reduce nonvertebral fracture risk in part by reducing remodeling and therefore the number and size of intracortical cavities.