Alendronate treatment in women with normal to severely impaired renal function: An analysis of the fracture intervention trial

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% Cl: 0.51-1.21) and without reduced renal function (OR: 0.80; 95 % Cl; 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% Cl: 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.