An osteonecrosis model induced by oral bisphosphonate in ovariectomised rats

Objective To develop a model of osteonecrosis using oral bisphosphonate in ovariectomy‐induced osteoporotic rats. Materials and Methods Thirty‐six rats were subjected to ovariectomy or sham surgery. After 8 weeks, rats received oral alendronate (1.0 mg kg−1) or saline once weekly for 4 weeks; then, serum C‐telopeptide cross‐linked collagen type I levels were measured to evaluate bone metabolism. Twelve rats from each group were injected with either lipopolysaccharide or saline into the bone marrow of the mandibles and femurs, and the areas of osteonecrosis were evaluated by histomorphometry. Results Serum C‐telopeptide cross‐linked collagen type I levels were significantly increased in the ovariectomy group (105.1 ± 2.1 ng ml−1) compared with the sham group (78.9 ± 12.5 ng ml−1); they were significantly reduced following oral alendronate administration in the ovariectomy group (91.0 ± 4.4 ng ml−1). Following alendronate and lipopolysaccharide administration, extensive osteonecrosis was observed in the mandibles and femurs of ovariectomy (0.45 ± 0.08 mm2, 1.69 ± 0.72 mm2, respectively) and sham (1.12 ± 0.45 mm2, 1.84 ± 0.66 mm2, respectively) groups. Significantly wider osteonecrosis occurred in the mandibles of sham‐operated rats than ovariectomy rats following alendronate or lipopolysaccharide treatment. Conclusions We successfully developed a model of osteonecrosis in ovariectomised rats following oral bisphosphonate administration.