Treatment with risedronate increases bone mineral density, decreases markers of bone turnover, and has favorable effects on microarchitecture and material properties of bone and, of primary importance, decreases the risk of a variety of osteoporosis-related fractures. It is likely that the fracture reduction is due to a combination of these effects, though the contribution of each component is not clearly understood. It is also unknown how long the different effects of treatment would persist once treatment is stopped, and specifically the influence of changes in surrogate markers, such as BMD and bone turnover markers, on fracture risk after discontinuation of treatment. Patients who received risedronate 5 mg daily (N=398) or placebo (N=361) during the VERT-NA study stopped therapy per protocol after 3 years, but continued to receive 500 IU vitamin D per day if levels were low and calcium 1000 mg daily and were reassessed one year later.
One year after stopping risedronate, urinary NTX increased significantly, from a median of 30.3 nM/uM creatinine at the end of treatment (p<0.05 vs placebo) to 50.9 nM/uM creatinine after 1 year off treatment (n.s. vs placebo). Bone-specific alkaline phosphatase returned to pretreatment levels after stopping treatment and was no different from placebo. Lumbar spine BMD decreased by 1% in the year off treatment but remained 4.4% higher than baseline (p£ 0.001) and higher than placebo (p<0.001). Similar results were seen at the femoral neck and trochanter. Despite the decrease in BMD and return of bone turnover markers to placebo levels, the incidence of new vertebral fractures continued to be reduced in the former risedronate group (11.6% placebo vs. 6.5% former risedronate group, RR 0.53 [0.32, 0.89], p=0.016). As changes in surrogate markers have been of limited value in predicting the magnitude of fracture risk reduction, our results show that these changes are also of limited value in assessing the anti-fracture effect once treatment is stopped. In the year following discontinuation of risedronate treatment, BMD decreased in the spine and hip (although still higher than controls), bone turnover markers increased (similar to controls); nevertheless, vertebral fracture risk remained lower than in controls.
Disclosure Information:
Faculty Member's Name: Nelson B. Watts, M.D.
Grants/Research Support: Amgen, Aventis, Eli Lilly, Merck, Novartis, Procter & Gamble Pharmaceuticals
Consultant: Aventis, Eli Lilly, Merck, Novartis, Procter & Gamble Pharmaceuticals, Wyeth
Stock Shareholder (directly purchased): none
Other Financial or Material Support: none
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