Is Evenity (romosozumab) appropriate for an adult with a femoral‑neck T‑score of –3.4?

Is Evenity Recommended for a Femoral Neck T-Score of -3.4?

Yes, Evenity (romosozumab) is strongly recommended for a femoral neck T-score of -3.4, as this represents severe osteoporosis with very high fracture risk, and romosozumab has demonstrated superior fracture reduction compared to both placebo and bisphosphonates in this population. 1, 2

Why This T-Score Qualifies for Evenity

• A femoral neck T-score of -3.4 meets the diagnostic threshold for osteoporosis (T-score ≤ -2.5) and specifically falls into the "very high fracture risk" category defined by major guidelines as T-scores below -3.0. 1, 2

• This T-score indicates approximately 70-80% lower bone mineral density than young healthy adults, representing significantly compromised bone strength with substantially increased risk for both vertebral and hip fractures. 2

• The FDA-approved indication for Evenity specifically includes postmenopausal women with osteoporosis at high risk of fracture, which is defined by T-score criteria that your patient clearly meets. 3

Evidence Supporting Romosozumab at This Severity

• In the pivotal FRAME trial, romosozumab enrolled postmenopausal women with T-scores ≤ -2.5 at the total hip or femoral neck and demonstrated a 73% reduction in new vertebral fractures at 12 months compared to placebo (0.5% vs 1.8%, p<0.001). 3, 4

• When romosozumab was followed by denosumab for an additional 12 months, the vertebral fracture risk reduction was maintained at 75% through 24 months (0.6% vs 2.5%, p<0.001). 3, 4

• The 2023 American College of Physicians guideline states that romosozumab followed by alendronate probably reduces hip fractures (12 fewer events per 1000 patients), clinical vertebral fractures (13 fewer per 1000), and any clinical fracture (33 fewer per 1000) compared to bisphosphonate alone, with moderate-certainty evidence. 1

• The 2024 Mayo Clinic guideline specifically notes that sequential use of romosozumab followed by alendronate was more effective than alendronate alone in reducing hip fracture risk in females with high risk due to age and fracture history (RR 0.62; 95% CI 0.42-0.91). 1

Positioning in Treatment Algorithm

Romosozumab should be considered as first-line therapy for this patient, not as a second-line option after bisphosphonate failure. 1, 2

• The 2024 guideline on osteoporotic fractures identifies anabolic agents as appropriate initial therapy for patients with very high fracture risk, which includes T-scores < -3.0. 1

• While bisphosphonates remain a reasonable first-line option, romosozumab's dual mechanism (increasing bone formation while decreasing bone resorption) provides more rapid and robust BMD gains than antiresorptive therapy alone. 5, 4

• The treatment difference in BMD at 12 months with romosozumab versus placebo was 12.7% at the lumbar spine, 5.8% at the total hip, and 5.2% at the femoral neck—substantially greater than typical bisphosphonate responses. 3

Critical Treatment Protocol

Romosozumab must be administered for exactly 12 months, followed immediately by an antiresorptive agent (denosumab or bisphosphonate) to maintain gains. 1, 3, 6

• After romosozumab discontinuation, BMD returns to approximately baseline levels within 12 months in the absence of follow-on antiresorptive therapy, making sequential therapy mandatory. 3

• The dosing is 210 mg subcutaneously once monthly for 12 months. 3, 4

• All patients must receive calcium supplementation (500-1000 mg daily) and vitamin D (600-800 IU daily) throughout treatment. 3

Absolute Contraindications to Screen For

Do not prescribe romosozumab if the patient has:

• History of myocardial infarction or stroke, as romosozumab is contraindicated in these patients. 5, 6

• Hypocalcemia, which must be corrected before initiating therapy. 5

• In the ARCH trial comparing romosozumab to alendronate, romosozumab increased risk for cardiovascular events (hazard ratio 1.9; 95% CI 1.1-3.1), making cardiovascular history a critical exclusion. 1

Pre-Treatment Requirements

• Verify serum calcium is normal and correct any hypocalcemia before the first dose. 5

• Obtain cardiovascular history specifically asking about prior MI, stroke, or high cardiovascular risk. 1, 6

• Ensure adequate vitamin D status (25-hydroxyvitamin D ≥ 30 ng/mL) before starting therapy. 3

• Consider vertebral fracture assessment (VFA) with DXA, as the International Society for Clinical Densitometry recommends VFA for patients with T-scores less than -1.0 to identify existing vertebral fractures. 2

Monitoring During Treatment

• Perform follow-up DXA scan at 12 months (after completing romosozumab) and then according to standard osteoporosis monitoring protocols after transitioning to antiresorptive therapy. 2

• Monitor for injection site reactions, arthralgia, and headache, which are the most common adverse effects. 6

• Watch for signs of atypical femoral fracture or osteonecrosis of the jaw, though these are rare (one atypical femoral fracture and two cases of osteonecrosis of the jaw were observed in the romosozumab group in the FRAME trial). 3, 4

Alternative if Romosozumab is Contraindicated

If cardiovascular contraindications exist, use oral or intravenous bisphosphonates as first-line therapy, or denosumab 60 mg subcutaneously every 6 months. 1

• The 2024 guideline on osteoporosis in men (applicable principles for severe osteoporosis) supports bisphosphonates or denosumab as first-line therapy when anabolic agents are not appropriate. 1

• Denosumab reduces hip fracture risk by 39% (RR 0.61; 95% CI 0.37-0.98) and clinical vertebral fractures by 68% compared to placebo. 1

• Zoledronic acid 5 mg intravenously annually is an alternative that improves adherence compared to oral bisphosphonates. 1