Bmpr1a expression correlates with the osteogenic sensitivity of muscle progenitors

Abstract

At the knee metaphyses of long bones, in the rodent ovariectomy (OVX) model, there is a gradient of decreasing crossectional trabecular bone area with increasing distance from the growth plate. Here we re-analysed micro-CT image data from several OVX rodent studies to examine this “metaphyseal profile”. Four OVX studies were reviewed involving combined ovariectomy and drug treatment of young growing rats or mice aged (initially) 2–3 months. The 3D images of the whole metaphyses were analysed to assess the metaphyseal profile. These studies involved treatment with sex steroids, the bisphosphonate alendronate, PTH and the novel antiresorptive compound ABD295. Measured metaphyseal profiles of crossectional trabecular bone area (BA/TA) were generally close to linear. Where metaphyseal trabecular bone volume in OVX rodents was restored by a specific drug treatment to levels similar to sham control levels, this gave a uniform elevation of the metaphyseal profile, but without change to its slope. Conversely, however, treatments which elevated trabecular volume to levels substantially greater than in sham controls (“high-responding” groups)were found to engender anupturn in themetaphyseal profile in the region closest to the growth plate. Drugs causing such high responses (at high doses) included sex steroids and alendronate. These studies disclosed two distinct metaphyseal profiles that appear to represent a bimodal dose-dependent response to treatment. Partial or complete restoration of trabecular volume inOVXgroupswas shown to occur via a uniform alteration of the remodeling balance throughout the metaphysis. By contrast, in high-responding groups the upturned metaphyseal profile implicated an additional positive effect on the rate of trabecular bone formation near the growth plate.