Zoledronic Acid for Men with Osteoporosis

Osteoporosis is associated with morbidity and mortality in men; worldwide, among individuals >50 years of age, approximately 40% of all osteoporotic fractures occur in men, and mortality following osteoporotic fracture is higher in men than in women.

There have been studies focusing on the surrogate outcomes of bone mineral density and bone-turnover markers; however, data on the antifracture efficacy of therapies for men are limited. There remains a low awareness of osteoporosis in men, limiting the development of guidelines and recommendations for detecting and treating the disease.

Noting that men at risk for fractures are often not identified or treated, researchers recently conducted a multicenter, randomized, prospective trial to assess the effect of zoledronic acid on the risk of vertebral fracture among men with osteoporosis. They reported trial results in the New England Journal of Medicine [2012;367(18):1714-1723].

Zoledronic acid is a bisphosphonate administered intravenously; at a dose of 5 mg once a year, it has been shown to have antifracture efficacy in postmenopausal women with osteoporosis as well as positive effects on bone mineral density in men.

For this study, eligible men were 50 to 85 years of age, had primary osteoporosis or osteoporosis associated with low testosterone levels, had a bone mineral density T score of ≤–1.5 (based on the device-specific reference values for men) at the total hip or femoral neck, and 1 to 3 prevalent vertebral fractures of mild or moderate grade. Men who did not have fractures were eligible if they had a bone mineral density of ≤–2.5 at the total hip, femoral neck, or lumbar spine.

Eligible study participants were randomized to receive either zoledronic acid (n=533) or placebo (n=574). Baseline characteristics were similar between the 2 groups.

In the zoledronic group, a significantly lower proportion of men (1.6%) had ≥1 new morphometric vertebral fractures over 24 months, compared with those in the placebo group (4.9%). Thus, there was a 67% risk reduction with zoledronic acid (relative risk, 0.33; 95% confidence interval, 0.16-0.70; P=.002).

Significantly fewer men in the zoledronic acid group had ≥1 new moderate-to-severe morphometric vertebral fracture at month 12 (relative risk reduction, 81%; P=.01) and at month 24 (relative risk reduction [RRR], 63%; P=.03), compared with men in the placebo group. Similar results were seen for new or worsening morphometric vertebral fractures at month 12 (RRR, 55%; P=.07) and at month 24 (RRR, 59%; P=.007). Men in the zoledronic acid group had less height loss compared with those in the placebo group (P=.002).

Compared with placebo, zoledronic acid was associated with significant and sustained increases in bone mineral density at the lumbar spine, total hip, and femoral neck over a 24-month period (P<.05). Likewise, bone-turnover markers were lower in the men who received zoledronic acid compared with those in the placebo group (P<.05). Results were similar in men with low serum levels of total testosterone.

There were no significant differences between the groups in the incidence of death (2.6% in the zoledronic acid group vs 2.9% in the placebo group) or serious adverse events (25.3% vs 25.2%).

The researchers commented that the reduction in risk of new morphometric vertebral fractures in men with osteoporosis with 2 annual infusions of zoledronic acid over a 24-month period was “similar to that reported in postmenopausal women with osteoporosis who received zoledronic acid.” The similar results suggested that the “antifracture effect of zoledronic acid is independent of sex…[and] provides support for the value of antiresorptive therapy in men with osteoporosis,” they added.