Slow rebound of cancellous bone after mainly steroid-induced osteoporosis in ovariectomized sheep

OBJECTIVES: A sheep model of osteoporosis suitable for implant testing for osteoporotic fractures was evaluated with regard to normalization of hormonal status and possible rebound of bone mineral density subsequent to the termination of steroid application. DESIGN: Osteoporosis was induced in 10 aged, female white alpine sheep. The sheep underwent ovariectomy, were kept in open, single-box husbandry, received a vitamin D(3) restricted diet, and a total dose of 2000 mg methylprednisolone (4 single doses of 500 mg at 3-week intervals). After 12 weeks, osteoporosis induction was discontinued, and bone mineral density was monitored for another 28 weeks. Eight healthy sheep served as controls for final measurements. MAIN OUTCOME MEASUREMENTS: The bone mineral density of cancellous bone in both distal radii was monitored using peripheral quantitative computed tomography. Cortisone level was determined at 3-week intervals until week 21. Bone structural parameters were measured in biopsies of the lumbar vertebra 6 and the right iliac crest using micro CT. RESULTS: The linear rate of bone loss during osteoporosis induction was 1.75% per week. Rebound of cancellous bone mineral density started between 6 and 11 weeks after the end of steroid treatment with a linear coefficient of 0.22% per week. Whereas structural changes in the iliac crest revealed significant differences at the end of the study, the values of L6 showed only slight changes. The level of basal cortisone dropped below detection limit during induction but recovered to physiological values 6 weeks after the end of steroid administration. In 2 animals, massive loss of weight and in 4 animals alopecia disseminata occurred. CONCLUSIONS: Because the rebound of bone mineral density after the end of steroid administration is significantly slower than the initial decrease, this opens a sufficient time window for testing of implants for osteoporotic fractures. The significantly changed structural parameters at the end of the study also suggest osteoporosis like conditions during testing.