title: Safety and efficacy of risedronate in patients with age-related reduced renal function as estimated by the Cockcroft and Gault method: a pooled analysis of nine clinical trials.
abstract: The incidences of osteoporosis and renal insufficiency increase with age. We studied the influence of renal function on the safety and efficacy of risedronate 5 mg daily in osteoporotic women. Risedronate was safe and effective in osteoporotic women with mild, moderate, or severe age-related renal impairment.
  
  
  BACKGROUND
  The incidences of both osteoporosis and renal insufficiency increase with age; thus, the effect of renal impairment on the safety and efficacy of osteoporosis treatments is a clinical concern. Risedronate is a pyridinyl bisphosphonate well established as safe and effective in the treatment and prevention of osteoporosis. Currently, there is little available information about the effect of bisphosphonate treatment in patients with renal insufficiency. This retrospective analysis was conducted to study the influence of renal function on the safety and efficacy of risedronate in a population of osteoporotic women.
  
  
  METHODS
  Combined data from nine randomized, double-blind, placebo-controlled phase III risedronate trials were analyzed. The patients in these studies had no markedly abnormal laboratory parameters that were considered clinically significant and no evidence of significant disease. This analysis included patients who received placebo (n = 4,500) or risedronate 5 mg (n = 4,496) for up to 3 years (average duration of exposure, 2 years) and who had renal impairment (creatinine clearance [CrCl] < 80 ml/min). CrCl was estimated by the Cockcroft and Gault method, based on age, weight, and serum creatinine. Patients were categorized as having mild (CrCl >or=50 to <80 ml/min), moderate (CrCl >or=30 to <50 ml/min), or severe (CrCl < 30 ml/min) renal impairment.
  
  
  RESULTS
  Of the patients studied, renal impairment at baseline was mild in 48% (mean [range] serum creatinine, 0.9 [0.4-1.6] mg/dl), moderate in 45% (1.1 [0.6-1.9] mg/dl), and severe in 7% (1.3 [0.7-2.7] mg/dl). In both the placebo and risedronate treatment groups, the patients with the most severe renal impairment were older and had more severe osteoporosis. The incidences of overall adverse events and of renal function-related adverse events were similar in the placebo and risedronate 5 mg groups regardless of renal function. Furthermore, evaluation of changes from baseline in serum creatinine revealed no difference in renal function between the placebo and risedronate 5 mg groups in any of the renal impairment subgroups at any time-point. In all three subgroups, risedronate effectively preserved BMD and reduced the incidence of vertebral fractures.
  
  
  CONCLUSIONS
  These findings show that risedronate is safe and effective in osteoporotic women with age-related mild, moderate, or severe renal impairment.
authors.affiliation: University of Colorado Health Science Center, Colorado Center for Bone Research, Lakewood, USA. MillerCCBR@aol.com
authors.forename: Paul D
authors.initials: PD
authors.lastname: Miller
authors.forename: Christian
authors.initials: C
authors.lastname: Roux
authors.forename: Steven
authors.initials: S
authors.lastname: Boonen
authors.forename: Ian P
authors.initials: IP
authors.lastname: Barton
authors.forename: Lisa E
authors.initials: LE
authors.lastname: Dunlap
authors.forename: David E
authors.initials: DE
authors.lastname: Burgio
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000009:adverse effects / Q000627:therapeutic use; D016723:Bone Remodeling / Q000187:drug effects; D002118:Calcium / Q000097:blood; D017326:Clinical Trials, Phase III as Topic; D003401:Creatine / Q000097:blood; D004311:Double-Blind Method; D012968:Etidronic Acid / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D007677:Kidney Function Tests; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D010758:Phosphorus / Q000097:blood; D016032:Randomized Controlled Trials as Topic; D051436:Renal Insufficiency, Chronic / Q000097:blood / Q000150:complications* / Q000503:physiopathology; D012189:Retrospective Studies; D000068296:Risedronic Acid; D016896:Treatment Outcome; D014552:Urinary Tract Infections / Q000150:complications
chemical_list: D050071:Bone Density Conservation Agents; D010758:Phosphorus; D000068296:Risedronic Acid; D012968:Etidronic Acid; D003401:Creatine; D002118:Calcium