Abstract
Osteoporotic patients treated with antiresorptive or anabolic agents experience an increase in bone mass and a reduction in incident fractures. However, the effects of these medications on bone quality and strength after a prolonged discontinuation of treatment are not known. We evaluated these effects in an osteoporotic rat model. Six-month-old ovariectomized (OVX) rats were treated with placebo, alendronate (ALN, 2 µg/kg), parathyroid hormone [PTH(1–34); 20 µg/kg], or raloxifene (RAL, 2 mg/kg) three times a week for 4 months and withdrawn from the treatments for 8 months. Treatment with ALN, PTH, and RAL increased the vertebral trabecular bone volume (BV/TV) by 47%, 53%, and 31%, with corresponding increases in vertebral compression load by 27%, 51%, and 31%, respectively (p < .001). The resulting bone strength was similar to that of the sham-OVX control group with ALN and RAL and higher (p < .001) with PTH treatment. After 4 months of withdrawal, bone turnover (BFR/BS) remained suppressed in the ALN group versus the OVX controls (p < .001). The vertebral strength was higher than in the OVX group only in ALN-treated group (p < .05), whereas only the PTH-treated animals showed a higher maximum load in tibial bending versus the OVX controls (p < .05). The vertebral BV/TV returned to the OVX group level in both the PTH and RAL groups 4 months after withdrawal but remained 25% higher than the OVX controls up to 8 months after withdrawal of ALN (p < .05). Interestingly, cortical bone mineral density increased only with PTH treatment (p < .05) but was not different among the experimental groups after withdrawal. At 8 months after treatment withdrawal, none of the treatment groups was different from the OVX control group for cortical or cancellous bone strength. In summary, both ALN and PTH maintained bone strength (maximum load) 4 months after discontinuation of treatment despite changes in bone mass and bone turnover; however, PTH maintained cortical bone strength, whereas ALN maintained cancellous bone strength. Additional studies on the long-term effects on bone strength after discontinuation and with combination of osteoporosis medications are needed to improve our treatment of osteoporosis. © 2011 American Society for Bone and Mineral Research.
Highlights
A number of drugs offer some protection against postmenopausal bone loss
As for preclinical studies, very limited data are available on the recovery of bone turnover after withdrawal of bisphosphonate therapy[9] and changes in areal bone mineral density (BMD) following discontinuation of Parathyroid hormone (PTH) treatment in rats.[10]. Using an osteoporotic rat model, we report a series of bone structural and material properties related to changes in bone turnover and bone mass during withdrawal of antiresorptive and anabolic agents commonly used for treatment of osteoporosis
The data obtained using micro– computed tomographic (mCT) from in vivo imaging of the proximal tibia 2 months after discontinuation of treatment indicated no difference between the PTH or RAL groups and OVX controls in Bone volume/total volume (BV/TV) (Fig. 2), Tb.N, and trabecular connectivity; the ALN group had higher values than the OVX control group for all these parameters ( p < .001), which remained higher until 8 months following treatment withdrawal
Summary
A number of drugs offer some protection against postmenopausal bone loss. Alendronate (ALN) and raloxifene (RAL) are antiresorptive agents that attenuate the decline in bone mineral density (BMD) and the risk of vertebral fractures in postmenopausal women.[1,2] Parathyroid hormone (PTH), given intermittently, is an anabolic agent that increases BMD and decreases the risk of vertebral and nonvertebral fractures in postmenopausal osteoporosis.[3] While bisphosphonates such as ALN may accumulate in the skeleton and have continual effects on suppression of bone resorption,(4) the effects of RAL and PTH on bone mass are not maintained long after discontinuation of the drugs, and bone loss resumes within a few months in osteoporotic patients.[5] Several clinical studies have examined the optimal treatment period and changes in areal BMD following discontinuation of these medications, but the effects on bone strength and quality have not been thoroughly investigated. It is not clear whether the anabolic treatment can offer more long-term protection against bone fracture than
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