Intravenous Zoledronic Acid in Postmenopausal Women with Low Bone Mineral Density
Commonly used in the treatment of osteoporosis, oral bisphosphonates are effective but must be taken daily on an empty stomach. Gastrointestinal intolerance can limit the maximum dosage. These issues may reduce compliance. An alternative route of delivery, the intravenous administration of bisphosphonates, has not been thoroughly studied. Reid et al (NEJM 346:653, 2002) examined the effects of intravenous zoledronic acid, the most potent clinically-studied bisphosphonate, on the inhibition of bone resorption in post-menopausal women.
Methods: The trial was randomized, double-blinded and placebo-controlled. Three hundred fifty-one postmenopausal women with low bone mineral density were randomized to receive placebo or zoledronic acid in doses of 0.25 mg, 0.5 mg, or 1 mg at three-month intervals. A fifth group received a total annual dose of 4 mg as a single annual dose and a sixth group received two doses of 2 mg each, six months apart.
Results: Bone mineral density of the lumbar spine was increased 4.3-5.1% in all of the zoledronic acid groups as compared to placebo (P<0.001). In the femoral neck, bone markers in the zoledronic acid groups were increased 3.1-3.5% as compared to the placebo group (P<0.001). Biochemical markers of bone resorption were comparably suppressed in all of the zoledronic acid groups compared to placebo. Muscle soreness and fever were more common in the zoledronic acid groups, but treatment-related dropout rates were not significantly different than those of the placebo group.
Conclusion: The results show that an annual infusion of zoledronic acid can produce an increase in bone mineral density similar to that of the daily administration of oral bisphosphonates. An annual infusion of zoledronic acid may be an effective treatment for post-menopausal osteoporosis.
Editorial Comment: This is encouraging news since many patients cannot tolerate the GI side effects of oral bisphosphonates such as alendronate (Fosamax®) or risedronate (Actonel®). In addition, the once yearly IV dosing will be more appealing to some patients than once weekly, or once daily, oral dosing.
The major weakness of this study is its reliance on bone mineral density as the outcome rather than fracture rate. However, as the authors note, a long-term placebo controlled trial with fractures, as the outcome is no longer medically ethical. Therefore, this study targeted women early in the menopause where bone loss is accelerated and bone density measurements and biomarkers are the only feasible outcome.