Bone resorption in orthotopic and heterotopic bone of dichloromethylene bisphosphonate-treated rats

The effect of the bisphosphonate dichloromethylene bisphosphonate (Cl2MBP) on orthotopic and heterotopic bone, induced by implants of demineralized bone matrix (DBM) in rats, was analyzed, with special reference to bone resorption. The heterotopic bone was formed by induction for 3 weeks; at this time, the rats were given daily subcutaneous injections of 3 mg/kg of body weight of Cl2MBP or saline, until sacrifice. Prior to the start of treatment, the animals were given 45Ca and [3H]proline to label the inorganic and organic components of bone, respectively. Groups of rats were sacrificed at intervals from 1 to 31 days after isotope injection, and the net formation of bone and the elimination rates of the two isotopes were studied in the heterotopic bone, in diaphyseal and metaphyseal bone, and in teeth. The treatment with Cl2MBP caused a doubling of the daily net increase in mineral of the induced heterotopic bone, and a less pronounced increase in the ash content of tibiae. The treatment decreased the elimination rates of both isotopes in the orthotopic and heterotopic bone, showing that decreased bone resorption is the cause of the increased net bone formation.