Raloxifene (Evista) No Hazard to Women with Chronic Kidney Disease

MINNEAPOLIS, April 9, 2008-- Postmenopausal women with chronic kidney disease can take raloxifene (Evista) to prevent osteoporosis without the risk of exacerbating their renal conditions, according to investigators here.
Raloxifene, a selective estrogen receptor modulator, significantly improved bone mineral density and reduced the risk of vertebral fracture versus placebo, irrespective of a patient's baseline kidney function, Areef Ishani, M.D., of the University of Minnesota, and colleagues reported online in advance of the July issue of the Journal of the American Society of Nephrology.
The rate of adverse events and associated discontinuation did not differ between treatment groups across the range of kidney function included in the study.
"We found that the effect of raloxifene on rates of spinal bone loss, risk for fractures, and rates of adverse events was consistent across all risk subgroups defined by baseline [creatinine clearance or estimated glomerular filtration rate]," the authors concluded.
The prevalence of low bone mineral density and osteoporosis increases with greater severity of chronic kidney disease. Even so, most randomized clinical trials evaluating pharmacologic agents to prevent fractures in postmenopausal women have excluded patients with serum creatinine levels >2.0 mg/dL, the authors noted.
In an effort to clarify the impact of osteoporosis therapies in postmenopausal women with chronic kidney disease, Dr. Ishani and colleagues performed a post hoc analysis of data from the Multiple Outcomes of Raloxifene Evaluation (MORE). The trial involved 7,705 postmenopausal women, who were randomized to placebo or to one of two doses of raloxifene. The primary objective was to evaluate raloxifene's effect on the risk of vertebral fracture in women with established osteoporosis.
Dr. Ishani and colleagues limited their analysis to 7,316 MORE participants who had baseline serum creatinine measurements. The data were stratified by creatinine clearance values as estimated using the Cockcroft-Gault formula: <45 mL/min/1.732, 45 to 59 mL/min/1.732, and ≥60 mL/min/1.732.
For each category of kidney function, patients assigned to raloxifene had a net gain in bone mineral density during follow-up, compared with a loss in the placebo group. Statistically significant differences were observed for the femoral neck (P=0.012) and lumbar spine (P<0.001). Use of raloxifene also was associated with a 43% reduction in the incidence of vertebral fractures (OR 0.57, 95% CI 0.47 to 0.69) but had no effect on the risk of nonvertebral fracture (OR 0.94, 95%CI: 0.80 to 1.11).