According to the results of a subgroup analysis, treatment with raloxifene safely increases bone mineral density (BMD) in postmenopausal women with chronic kidney disease and cuts the risk of vertebral fractures. While patients with chronic renal disease are known to be at increased risk for bone loss, women with elevated creatinine levels are usually excluded from trials of osteoporosis drugs, according to the report in the April 9th online issue of the Journal of the American Society of Nephrology. The authors note that the majority of clinical trials evaluating pharmacological therapies in preventing fractures in postmenopausal women have excluded those with renal impairment. It is therefore uncertain whether the beneficial effects of osteoporosis therapy extend to those with kidney disease, and whether such therapies are safe in this patient population. They therefore used data from the Multiple Outcomes of Raloxifene Evaluation (MORE) trial to examine the efficacy and safety of raloxifene in risk subgroups defined at baseline according to presence and severity of chronic kidney disease (CKD). MORE was a multicentre, international placebo controlled trial of the effects of raloxifene on BMD and fracture incidence in postmenopausal women over three years (n=7316). Baseline serum creatinine values were used to assign participants to a category of creatinine clearance (calculated using Cockcroft-Gault formula). Among the cohort, 1480 (20%) had a CrCl of <45 ml/min, 3493 (48%) had a CrCl of 45 to 59 ml/min, and 2343 (32%) had CrCl =60 ml/min. Among the women with a CrCl <45 ml/min, only 55 had a CrCl <30 ml/min, and the lowest was CrCl 20.0 ml/min. There were several differences in baseline characteristics across categories of CrCl; e.g. women with lower CrCl were more likely to be older and more years postmenopausal; to have a lower body mass index (BMI); to have a lower baseline BMD and to have prevalent fractures. BMD was measured at baseline and then annually with dual x-ray absorptiometry (DEXA). The main findings were as follows: • In the placebo group, a lower CrCl at baseline correlated with higher annual losses of BMD at the femoral neck, but this trend did not reach statistical significance (p=0.09). In the raloxifene group, lower CrCl at baseline correlated with greater increases in the femoral neck BMD (P=0.01 for trend). • Compared with placebo, the effect of raloxifene on increasing femoral neck BMD was 1.0% per year among women with a CrCl <45 ml/min, 0.7% per year among women with a CrCl of 45 to 59 ml/min, and 0.6% per year among women with a CrCl =60 ml/min (P <0.001 for all comparisons between pooled raloxifene treatment group and placebo group). • Raloxifene was associated with an overall decrease in the incidence of vertebral fractures (odds ratio [OR] 0.57; 95% CI 0.47 to 0.69), and there was no evidence that this effect differed according to CrCl at baseline. In addition, the effect of raloxifene on rate of change in spine BMD did not differ according to renal function. • Women with reduced kidney function overall were more likely to experience one or more serious adverse effects and to discontinue the study permanently as a result of an adverse event; however, the rates of adverse events were similar between the raloxifene and placebo groups within each category of kidney function. The authors conclude that their results support the use of raloxifene as a safe and effective means to increase BMD and prevent vertebral fractures in postmenopausal women with osteoporosis and compromised kidney function. [Editor’s note: as this was a subgroup analysis, the findings need to be confirmed in a prospective trial adequately powered to test this].
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