Once-yearly 5 mg infusions do not reduce renal function in post-menopausal osteoporotic women


VIENNA —New data confirm the renal safety of a once-yearly infusion of zoledronic acid (Reclast) in postmenopausal women with osteoporosis, researchers reported here at the European League Against Rheumatism annual conference.

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Paul Miller, MD, director of the ColoradoCenter for Bone Research in Lakewood, and his associates randomized 7,736 postmenopausal osteoporotic women 65 to 89 years of age to once-yearly zoledronic 5 mg infused over 15 minutes, or to placebo.


“In postmenopausal women with osteoporosis, oral bisphosphonate therapy significantly increases bone mineral density and reduces fracture risk,” Dr. Miller pointed out. “But when administered orally, bisphosphonates require frequent admin-istration and are associated with highly variable absorption, gastrointestinal intolerance, and poor patient compliance.” 


IV administration eliminates the limitations of oral treatment while providing significant improvements in bone mineral density and fracture risk. Significant deterioration in renal function, however, has been linked to IV bisphosphonate use.


“Because both osteoporosis and renal dysfunction become more common with increasing age, the renal impact of anti-osteoporotic drugs is an important component of their safety profile,” Dr. Miller said.


The present analysis showed that while post-infusion increases in serum creatinine greater than 0.5 mg/dL occurred in more of the bisphosphonate-treated patients than in placebo recipients (1.34% vs. 0.43%), the changes were mild and transient. The long-term renal safety data, which reflects the aggregate effect of multiple annual doses of zoledronic acid 5 mg on renal function, showed no differences between treatment groups on multiple measures that included renal adverse events, serum creatinine levels, absolute creatinine clearance, and proteinuria. 


In fact, the mean absolute change from baseline in serum creatinine was 2.5 mg/dL at one year in the zoledronic acid group, 4.3 mg/dL at two years, and 6.7 mg/dL at three years. The corresponding values in the placebo group were 2.5 mg/dL, 4.1 mg/dL, and 6.7 mg/dL. The mean absolute change from baseline in creatinine clearance was -3.1 mL/min after the first year of zoledronic acid treatment, -5.7 mL/min after the second year, and -8.8 mL/min after the third year of treatment. The corresponding values were -3.4 mL/min, -5.7 mL/min, and -8.7 mL/min in the placebo group.


“Overall, the results of this study suggest that any long-term changes in renal function are not due to zolendronic treatment but rather to age and co-morbid conditions in osteoporotic women,” Dr. Miller reported.