Bisphosphonate Inhibits Bone Turnover in OPG−/− Mice Via a Depressive Effect on Both Osteoclasts and Osteoblasts

Abstract

Osteoclast differentiation and functioning are strictly controlled by RANKL expressed on osteoblast membrane surfaces, but whether osteoclasts exert control over osteoblasts remains unclear. In the present study, we examined the effect of an osteoclast inhibitor, a bisphosphonate (BP), on the response of maxillary bone to mechanical stress in a high-turnover osteoporosis model (OPG(-/-) mice, a model of juvenile Paget disease). Mechanical stress was induced by use of orthodontic elastics to move the maxillary first molar. BP was administered once per day beginning 5 days before elastic insertion. Relative to wild type (WT), in the OPG(-/-) mice tooth movement distance was greater, resorption of the interradicular septum occurred to a greater extent, the osteoclast count was higher, and serum alkaline phosphatase (ALP) was higher. However, administration of BP to OPG(-/-) mice reduced tooth movement distance, increased bone volume at the interradicular septum, decreased the osteoclast count, and reduced serum ALP. BP administration also caused a temporal shift in peak Runx2 staining in OPG(-/-) mice, such that the overall staining time course was similar to that observed for WT mice. We conclude that BP administration not only inhibited osteoclast activity in OPG(-/-) mice but also systemically and locally inhibited osteoblast activity. It is possible that osteoclasts are able to exert some negative control over osteoblasts.