Effect of a bisphosphonate and selective estrogen receptor modulator on bone remodeling in streptozotocin-induced diabetes and ovariectomized rat model.

BACKGROUND CONTEXT: Diabetes and menopause can cause severe osteoporosis. In general, menopause and diabetes can lead to an imbalance in bone turnover, which results in secondary osteoporosis. However, the efficacy of antiresorptive drugs against this form of osteoporosis has not been extensively evaluated. OBJECTIVE: The aim of this study was to determine the changes in vertebral bone remodeling when postmenopausal osteoporosis is accompanied by diabetes and to compare the efficacy of bisphosphonates and selective estrogen-receptor modulators (SERMs) against these outcomes. STUDY DESIGN: Streptozotocin-induced diabetic, ovariectomized Sprague-Dawley rats were used as the disease model. Alendronate and raloxifene were used as the bisphosphonate and SERM, respectively. METHODS: We divided 62 female rats into five groups: (1) control (n=14), (2) DM (diabetes) (n=12), (3) DM+OVX (diabetes+ovariectomy) (n=12), (4) DM+OVX+A (diabetes+ovariectomy+alendronate) (n=12), and (5) DM+OVX+R (diabetes+ovariectomy+raloxifene) (n=12). Serum biochemical markers of bone turnover, including osteocalcin and the C-telopeptide of type I collagen (CTX-1), were analyzed. We measured histomorphometric parameters of the fourth lumbar vertebrae using microcomputed tomography. Mechanical strength was evaluated by a compression test. RESULTS: In the DM and DM+OVX group, only the levels of osteocalcin significantly decreased compared with those of the control group at 8 weeks after OVX. At 12 weeks, the serum CTX-1 levels in the DM+OVX+A and DM+OVX+R groups were significantly lower than those of the DM+OVX group, but there were no changes in the levels of osteocalcin. Bone mineral density and mechanical strength were higher in the DM+OVX+A and DM+OVX+R groups than in the DM and DM+OVX groups (p<.05). CONCLUSIONS: Even if postmenopausal osteoporosis is accompanied by diabetes in this animal model, both alendronate and raloxifene seem to show antiresorptive effects, decreased bone turnover rates, and improved bone mechanical strength. Therefore, alendronate and raloxifene are effective in the treatment of osteoporosis even for bone loss caused by DM and postmenopausal osteoporosis.

The effects of osteoporosis on distraction osteogenesis: an experimental study in an ovariectomised rabbit model.

The effects of oestrogen deficiency-associated osteoporosis on callus distraction were investigated in rabbits. Twenty-four female New Zealand rabbits 5 to 6 months old were used. Ovariectomy was performed on 12 rabbits, which composed the osteoporotic model group. Six weeks later, osteotomy was carried out and Ilizarov external fixators were applied to the right proximal tibial metaphyses in both the osteoporotic model group and the control group. Beginning one week postosteotomy, the metaphyses were distracted 0.35 mm twice daily for 3 weeks, and the average length increase obtained for both groups was 17.2 mm (minimum: 16.8, maximum: 19 mm). Following a postdistraction waiting period of 6 weeks for newbone formation, the subjects were sacrified and specimens were examined histopathologically. Radiography was carried out at one-week intervals during the distraction period and at 2-week intervals during the waiting period, and scintigraphy was performed at the end of each period. On histopathologic examination, a significant difference in callus remodeling was observed between the control and osteoporotic model groups. On radiologic evaluation it was observed that, while both groups had inadequate callus tissue at the end of the waiting period, callus formation and remodeling occurred later in the model group than in the control group, and the new bone was more osteoporotic. Osteoporosis associated with estrogen deficiency adversely affects the outcome of callus distraction. Nonetheless, radiographic findings in rabbits indicate that the effects may not be so great as to preclude clinical procedures. It was concluded that these results should be supported with clinical studies.