Eighty-eight rats underwent intramedullary pin fixation and fracture of both tibiae. Half of the animals were given clodronate 50 mg/kg s.c. weekly. Clodronate treatment did not affect the growth of fibrocartilage or the endochondral and membranous new bone formation. The regaining of tensile load capacity of fractured bone remained unaffected by the drug. Calluses were remodeled to lamellar bone in both groups. However, although the total area invaded by mineralized tissue in callus remained unaffected by the drug, the areas of hematopoietic bone marrow tissue within mineralized callus were observed to be markedly smaller in clodronate-treated animals than in controls. The calluses in the clodronate group were significantly heavier and contained more calcium at 2 months after fracture than those in the controls.
Clodronate (dichloromethylidene biphosphonate) inhibits bone resorption by the osteoclast cells [3]. It has been
proven that the biphosphonates reduce bone resorption in growing bone [8,12], in the iliac crest during immobilization in man [2], in orthotopic and heterotopic bone formation [1], and in long bones with malignant osteolysis [7]. In Finland, clodronate is used for the adjunct therapy for osseous metastases, Paget's disease and malignant hypercalcemia. So far, no experimental data exists on whether clodronate treatment can be begun at the time of a bone fracture. This experimental work was undertaken to find out if the local primary response to bone fracture or callus remodeling is inhibited by clodrohate treatment.
Methods
Eighty-eight male adult Albino-Original rats weighing 309 + 72 g (mean + SD) were used. The rats were fed standard animal food (EVOS Mice and Rat Food R3) containing lwt % calcium, 0.9 wt % phosphorus and 1500 IU/kg vitamin D3. Access to tap water was