title: Alendronate treatment in women with normal to severely impaired renal function: an analysis of the fracture intervention trial.
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.
  
  
  BACKGROUND
  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.
  
  
  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.
authors.affiliation: Division of Endocrinology, St Michael's Hospital and the University of Toronto, Toronto, ONT, Canada. sophie.jamal@utoronto.ca
authors.forename: Sophie A
authors.initials: SA
authors.lastname: Jamal
authors.forename: Douglas C
authors.initials: DC
authors.lastname: Bauer
authors.forename: Kristine E
authors.initials: KE
authors.lastname: Ensrud
authors.forename: Jane A
authors.initials: JA
authors.lastname: Cauley
authors.forename: Marc
authors.initials: M
authors.lastname: Hochberg
authors.forename: Areef
authors.initials: A
authors.lastname: Ishani
authors.forename: Steven R
authors.initials: SR
authors.lastname: Cummings
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D019386:Alendronate / Q000009:adverse effects / Q000627:therapeutic use*; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003404:Creatinine / Q000378:metabolism; D005260:Female; D050723:Fractures, Bone / Q000517:prevention & control*; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006801:Humans; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000150:complications* / Q000188:drug therapy* / Q000503:physiopathology; D051437:Renal Insufficiency / Q000150:complications* / Q000503:physiopathology
chemical_list: D050071:Bone Density Conservation Agents; D003404:Creatinine; D019386:Alendronate