Background: Approximately 10 million women in the United States have osteoporosis, and an additional 34 million have low bone mass (osteopenia). Current guidelines recommend pharmacologic therapy for postmenopausal women with low bone mass and moderate or high risk of fracture. Although bisphosphonate therapy prevents bone loss, many postmenopausal women do not adhere to long-term therapy. McClung and colleagues studied the effectiveness and tolerability of a once-yearly treatment with zoledronic acid (Zometa) in postmenopausal women with osteopenia. They also evaluated the effect of a single dose on the prevention of bone loss.
The Study: The authors conducted a randomized, double-blind, placebo-controlled trial in 25 centers. Participants were postmenopausal women who had low bone mass defined by T scores of the lumbar spine and femoral neck. Reasons for exclusion from the trial included vertebral fractures; low vitamin D levels; renal insufficiency; hyper- or hypocalcemia; or use of bisphosphonate, estrogen, calcitonin, or other antiosteoporotic medication. After baseline screening, 581 participants were randomly assigned to one of three study groups. The randomization was stratified to ensure equitable distribution of women less than five years and five or more years from menopause.
In the annual treatment group, 198 women received a 5-mg infusion of zoledronic acid at randomization and at month 24. In the single-dose treatment group, 181 women received the same zoledronic acid infusion at randomization, but placebo at month 24. The 202 women in the placebo group received placebo at randomization and at month 24. All patients also received daily calcium and vitamin D supplements. Bone mineral density was measured at six, 12, and 24 months. Blood markers of bone resorption and bone turnover, plus patient reports of adverse effects, were assessed at months 1 and 3, then every three months thereafter until month 18, and finally at month 24.
The primary end point was the percentage change from baseline in lumbar spine bone mineral density at month 24. Secondary end points included biochemical markers of bone turnover and adverse events.
Results: Both groups of women who received zoledronic acid showed increased mean bone mineral density compared with placebo at the lumbar spine and proximal femur at months 12 and 24. Bone turnover markers were also significantly reduced in both groups of women receiving zoledronic acid therapy. Serious adverse events were reported by 10.6, 9.4, and 11.4 percent of patients in the annual, single-dose, and placebo treatment groups, respectively. The most common adverse events were pain, fever, nausea, and myalgia.
Conclusion: The authors conclude that both a single infusion of zoledronic acid and an annual infusion effectively prevent bone loss in the lumbar spine and proximal femur in postmenopausal women with low bone mineral density.