BONE MORPHOMETRIC CHANGES IN ADJUVANT-INDUCED POLYARTHRITIC OSTEOPENIA IN RATS - EVIDENCE FOR AN EARLY BONE-FORMATION DEFECT

Adjuvant polyarthritis (AP) in rats is known to result in extensive bo ne loss. This study investigates the mechanisms responsible for the ea rly trabecular osteopenia evaluated at a single point in time - 2 week s after adjuvant injection-in the hindpaw of female Lewis rats using b iochemical and histomorphometric methods. At this early point in time, the inflammation was generalized (inflammatory score, 20; albumin/glo bulin, -80% versus control). Histomorphometric analysis of the noninje cted femur showed that the trabecular bone volume was significantly de creased (-28% versus control) in both proximal and distal parts, and t he femur growth rate was unaffected. The trabecular osteopenia was ass ociated with a 90% decrease in osteoid surface and a concomitant thinn ing (-19%) of the trabeculae. Both the double-fluorescence-labeled sur face and the osteoblast surface were also markedly decreased (-75%). I n addition, the mineral apposition rate was reduced (-50%) and the bon e formation rate was decreased by as much as 90%. The trabecular bone volume was decreased in relation with the extent of double-fluorescenc e labeling (r = 0.38, p = 0.03) and bone formation rate (r = 0.42, p = 0.01), suggesting that the generalized osteopenia resulted from the r educed bone formation. This was associated with a 26% reduction in pla sma osteocalcin. Neither the osteoclast surface nor the number of oste oclasts was consistently affected. However, urinary hydroxyproline was increased by 100-200%, which likely reflected the cartilage and bone destruction at the site of injection. The present data show that the e arly extensive osteopenia observed 2 weeks after AP induction in rats results from defective bone formation with unchanged bone resorption. The role of cytokines in such an inhibitory effect on bone formation r emains to be determined.