Alendronate Treatment in Women With Normal to Severely Impaired Renal Function: An Analysis of the Fracture Intervention Trial

Authors


  • Presented, in part, as an abstract at the 27th American Society for Bone and Mineral Research Annual Meeting, Nashville, TN, September 23–27, 2005.

    Dr Hochberg has served as a consultant to Merck & Co., Roche, Proctor & Gamble, Novartis, GlaxoSmithKline, and Amgen. Dr Cauley receives research funding from Eli Lilly & Co., Novartis, Merck & Co., and Pfizer & Co. She also serves as a consultant to Eli Lilly & Co. and Novartis in addition to serving on the Speakers Bureau for Merck & Co. All other authors state that they have no conflicts of interest.

Abstract

To determine if alendronate had differential effects on BMD and fracture by renal function, we performed a secondary data analysis of women participating in the FIT. Alendronate increased BMD and decreased fractures to a similar degree among women with and without reduced renal function. There was no increase in adverse events among women with impaired renal function treated with alendronate. Alendronate is safe and effective among this group of women with reduced renal function.

Introduction: Alendronate is cleared by the kidney and may have sustained effects on bone in subjects with impaired renal function. We hypothesized that, with decreasing renal function, alendronate treatment would result in greater increases in BMD and greater decreases in fractures and that the frequency of adverse events would be increased.

Materials and Methods: We studied women participating in the Fracture Intervention Trial (FIT), a randomized controlled trial of alendronate or placebo (n = 6458). We estimated baseline creatinine clearance (eGFR) using the Cockcroft Gault Formula.

Results: Five hundred eighty-one (9.9%) participants had a severely reduced eGFR (<45 ml/minute). Alendronate increased BMD regardless of eGFR, but women with reduced eGFR had a 5.6% (95% CI: 4.8–6.5) increase in total hip BMD compared with 4.8% (95% CI: 4.6–5.0) among women with normal to moderate renal dysfunction (interaction: p = 0.04). Compared with placebo, alendronate increased spine BMD by 6.6 ± 5.8%, but there was no significant interaction for the increase in spine BMD (interaction: p = 0.75). Treatment with alendronate reduced the risk of clinical fractures to a similar degree in those with (OR: 0.78; 95% CI: 0.51–1.21) and without reduced renal function (OR: 0.80; 95% CI; 0.70–0.93; p for interaction = 0.89). Treatment with alendronate reduced the risk of spine fractures to a similar degree in those with (OR: 0.72; 95% CI: 0.31–1.7) and without reduced renal function (OR: 0.50; 95% CI: 0.32–0.76; p for interaction = 0.44). There were no differences in adverse events by renal function.

Conclusions: Alendronate is safe and effective at increasing BMD and decreasing fractures among this group of women with reduced renal function.

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