Written by Kevin Liu
Spoon Feed
Even with infrequent administration, zoledronic acid effectively prevented morphometric vertebral fracture in early postmenopausal women.
One bisphosphonate to rule them all and in the matrix bind them…
The efficacy of bisphosphonates in reducing the risk of new morphometric fractures varies among different medications within its class. Among them, zoledronic acid reduced the risk of morphometric vertebral fractures by 70% compared to placebo (RR 0.30, 95%CI 0.24 to 0.38), with best-in-class performance supported by a network meta-analysis.
In this 10-year, double-blinded, placebo-controlled randomized trial conducted in New Zealand (LOTR shout-out), 1,054 early postmenopausal women between 50-60 years old with low bone mineral density (T-score between −2.5 and 0), but without osteoporosis or prior fractures, received either one dose of IV zoledronic acid every 5 years, one dose of zoledronic acid, or placebo only. Vertebral fractures occurred in 6.3% of women receiving two zoledronate doses and 6.6% of those receiving one dose, compared to 11.1% in the placebo group. Relative risk reduction for zoledronic acid was 0.56 (95%CI 0.34–0.92; P=0.04) for two doses and 0.59 (95%CI 0.36–0.97; P=0.08) for one dose for vertebral fractures. Secondary outcomes examining fragility fractures and major fractures also favored zoledronate. No osteonecrosis of the jaw or femur fractures occurred during these 10 years. This study supports the use of infrequent zoledronic acid to prevent fractures in early postmenopausal women without osteonecrosis.
How does this change my practice?
Of all the osteoporosis medications, zoledronic acid demonstrates the greatest efficacy – equal to denosumab – at reducing vertebral fractures and was the most cost-effective when priced in 2020 at $2259. This study confirms these robust benefits persist before osteoporosis and can prevent vertebral fractures in non-osteoporotic postmenopausal women. With a cost of $89 on goodRx, it is even more cost effective today than in 2020. With no occurrences of femur fracture or osteonecrosis occurring in major RCTs involving postmenopausal women, I have to find a good reason not to give zoledronic acid, especially if I’m using bisphosphonates.
Source
Fracture Prevention with Infrequent Zoledronate in Women 50 to 60 Years of Age. N Engl J Med. 2025 Jan 16;392(3):239-248. doi: 10.1056/NEJMoa2407031. PMID: 39813642
