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.
Author(s): Miller PD, Roux C, Boonen S, Barton IP, Dunlap LE, Burgio DE.
Affiliation(s): University of Colorado Health Science Center, Colorado Center for Bone Research,
Lakewood, USA. MillerCCBR@aol.com
Publication date & source: 2005, J Bone Miner Res. , 20(12):2105-15
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.INTRODUCTION: 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.
MATERIALS AND 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.
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