Effects of suppressed bone turnover by bisphosphonates on microdamage accumulation and biomechanical properties in clinically relevant skeletal sitesin beagles

We recently demonstrated that suppression of bone remodeling allows microda mage to accumulate, leading to reduced bone toughness in the rib cortex of dogs. This study evaluates the effects of reduced bone turnover produced by bisphosphonates on microdamage accumulation and biomechanical properties a t clinically relevant skeletal sites in the same dogs. Thirty-six female be agles, 1-2 years old, were divided into three groups. The control group was treated daily for 12 months with saline vehicle (CNT), The remaining two g roups were treated daily with risedronate at a dose of 0.5 mg/kg per day (R IS), or alendronate at 1.0 mg/kg per day (ALN) orally, The doses of these b isphosphonates were six times the clinical doses approved for treatment of osteoporosis in humans. After killing, the L-1 vertebra was scanned by dual -energy X-ray absorptiometry (DXA), and the L-2 vertebra and right ilium we re assigned to histomorphometry, The L-3 vertebra, left ilium, Th-2 spinous process, and right femoral neck were used for microdamage analysis. The L- 4 vertebra and Th-1 spinous process were mechanically tested to failure in compression and shear, respectively. One year treatment with risedronate or alendronate significantly suppressed trabecular remodeling in vertebrae (R IS 90%, ALN 95%) and ilium (RIS 76%, ALN 90%) without impairment of mineral ization, and significantly increased microdamage accumulation in all skelet al sites measured. Trabecular bone volume and vertebral strength increased significantly following 12 month treatment. However, normalized toughness o f the L-4 vertebra was reduced by 21% in both RIS (p = 0.06) and ALN (p = 0 .05) groups. When the two bisphosphonate groups were pooled in a post hoc f ashion for analysis, this reduction in toughness reached statistical signif icance (p = 0.02), This study demonstrates that suppression of trabecular b one turnover by high doses of bisphosphonates is associated with increased vertebral strength, even though there is significant microdamage accumulati on and a reduction in the intrinsic energy absorption capacity of trabecula r bone. (C) 2001 by Elsevier Science Inc. All rights reserved.