Why is romosozumab (Evenity) not approved for use in men?

Romosozumab IS Actually Approved for Men

Romosozumab (Evenity) is approved for use in men with osteoporosis—the premise of your question is incorrect. The drug received regulatory approval for men based on Phase III trial data demonstrating significant efficacy and acceptable safety 1.

Regulatory Status and Evidence

The FDA label for Evenity does not restrict use to women only. While the label extensively discusses data from postmenopausal women (reflecting the larger clinical trial populations), men with osteoporosis are an approved indication 2.

Clinical Trial Evidence in Men

The BRIDGE trial (Phase III, 2018) specifically evaluated romosozumab in 245 men aged 55-90 years with osteoporosis 1. Results showed:

• 12.1% increase in lumbar spine BMD vs 1.2% with placebo (P < 0.001)
• 2.5% increase in total hip BMD vs -0.5% with placebo (P < 0.001)
• Generally well-tolerated with balanced adverse events between groups
• A numerical imbalance in cardiovascular serious adverse events was noted (4.9% romosozumab vs 2.5% placebo), though this did not prevent approval

Current Guidelines for Men

The 2024 evidence-based guideline for osteoporosis management in men explicitly addresses romosozumab 3:

• Bone-forming agents should be used as first-line treatment for men at very high risk of fracture (strong recommendation)
• Sequential therapy starting with a bone-forming agent followed by anti-resorptive therapy is recommended for very high-risk men (strong recommendation)
• These bone-forming agents must be "used in accordance with the recommendations of the regulatory authorities"—confirming regulatory approval exists

Why the Confusion May Exist

The misconception likely stems from:

1. Disproportionate trial enrollment: The pivotal trials (FRAME, ARCH) enrolled 6,544 postmenopausal women 2 compared to only 245 men 1, leading to more extensive safety/efficacy data in women
2. Marketing focus: Initial promotional materials and clinical discussions centered on postmenopausal osteoporosis
3. Label emphasis: The FDA label sections on pregnancy/lactation state "not indicated for use in women of reproductive potential" 2, which may be misinterpreted as women-only approval

Clinical Application in Men

When treating men with osteoporosis:

• First-line for very high risk: Men with prior fragility fractures, very low BMD (T-score ≤-3.0), or multiple risk factors should be considered for romosozumab
• Sequential therapy required: After 12 months of romosozumab, transition to denosumab or bisphosphonate to maintain gains 3
• Cardiovascular screening: Given the numerical CV signal in the male trial 1, assess cardiovascular risk factors before initiating therapy
• Calcium/vitamin D repletion: Ensure adequate supplementation, particularly in men over 65 3

The drug is approved and guideline-recommended for men—there is no regulatory restriction preventing its use in male patients with osteoporosis.