Effects of bisphosphonates on the incorporation of calcium-45 and 3H-proline in orthotopic and in demineralized matrix-induced bone in rats.

The influence of the two bisphosphonates, 1-hydroxyethylidene-1, 1-bisphosphonate (HEBP) and dichloromethylene bisphosphonate (Cl2MBP), on bone formation was studied in demineralized matrix-induced bone in young rats. Cl2MBP was given in doses of 0.3 and 3 mg P/kg per day and HEBP 2,4, and 8 mg P/kg per day starting immediately after implantation of the bone matrix and continued until sacrifice at 3 weeks. Rates of collagen synthesis and mineralization of implants, femurs, and incisor teeth were quantified by assay of 3H-proline and 45Ca injected 24 h before death. New bone formation in implants was also evaluated by histologic examinations. Implants from Cl2MBP-treated animals had wider bone trabeculae than controls but were colonized by normal appearing hematopoietic tissue. Implants and femurs from both Cl2MBP groups had a higher ash content than controls, but uptake of the two isotopes was not affected. These results indicate that Cl2MBP, at these dose levels, inhibits bone resorption without affecting bone formation in rats. The uptake of 45Ca in implants decreased with increasing doses of HEBP; almost no ash or 45Ca activity was encountered with the highest dose. The bone in implants from this group appeared less mature, and only scanty areas of bone marrow were seen. The uptake of 3H-proline was not affected by HEBP. It appears that, in rats, HEBP primarily inhibits mineralization and resorption, whereas matrix formation remains largely unaffected.