Does Evenity Elevate Alkaline Phosphatase?
No, Evenity (romosozumab) does not elevate alkaline phosphatase—in fact, it typically causes a transient increase in bone formation markers like P1NP initially, but alkaline phosphatase is not reported as a significant adverse effect or biochemical change associated with this medication. 1, 2, 3
Mechanism and Biochemical Effects
Romosozumab is a humanized monoclonal antibody that inhibits sclerostin, thereby increasing bone formation while simultaneously decreasing bone resorption—a dual mechanism that distinguishes it from other osteoporosis therapies. 2, 3, 4
Expected Bone Turnover Marker Changes
- P1NP (bone formation marker) initially increases after romosozumab initiation, then gradually decreases to below baseline by month 12 and remains suppressed through month 24 of treatment. 5
- β-CTX (bone resorption marker) rapidly decreases after treatment initiation and remains below baseline throughout the 24-month treatment period. 5
- TRACP-5b (another bone resorption marker) shows significant changes during romosozumab treatment, with percent change from baseline after 1 month correlating with BMD gains at 4–6 months. 6
Alkaline phosphatase elevation is not listed among the biochemical changes or adverse effects in pivotal trials or clinical studies of romosozumab. 1, 2, 3, 5
Clinical Trial Safety Data
In the FRAME and ARCH pivotal phase III trials, romosozumab demonstrated a generally manageable tolerability profile without alkaline phosphatase elevation being reported as a concern. 2
Key Safety Considerations (Not ALP-Related)
- Cardiovascular events: Romosozumab increased risk for cardiovascular events compared with alendronate (hazard ratio 1.9), and is contraindicated in patients with a history of myocardial infarction or stroke. 1, 4
- Hypocalcemia: Must be corrected prior to initiating romosozumab, as the drug can cause or worsen hypocalcemia. 1, 3, 4
- Osteonecrosis of the jaw and atypical femoral fractures: Similar to other bone-targeting agents, these rare complications can occur. 1
A 6-month Japanese study of 185 patients found no fatal adverse events including cardiovascular disease, and no new fractures during treatment—again, with no mention of alkaline phosphatase elevation. 6
Common Pitfalls to Avoid
- Do not confuse bone formation marker increases (P1NP) with alkaline phosphatase elevation. While both can reflect bone turnover, romosozumab's effect on P1NP is transient and expected, whereas ALP elevation is not a recognized feature of romosozumab therapy. 6, 5
- Do not attribute an elevated alkaline phosphatase in a patient on romosozumab to the drug itself. Instead, pursue standard diagnostic evaluation for ALP elevation (confirm hepatic vs. bone origin with GGT, evaluate for cholestatic liver disease, bone metastases, Paget's disease, etc.). 7
- Recognize that romosozumab is used in postmenopausal women with very high fracture risk—typically after a recent major fracture within 2 years—and these patients may have other comorbidities (malignancy, liver disease, metabolic bone disorders) that could independently elevate alkaline phosphatase. 1, 4
Monitoring Recommendations
- Bone turnover markers (P1NP, TRACP-5b, β-CTX) can be measured at baseline and 1 month after initiation to predict treatment response, as early changes correlate with subsequent BMD gains at 4–6 months. 6
- Routine alkaline phosphatase monitoring is not indicated specifically for romosozumab therapy, as it is not a recognized adverse effect or treatment-related biochemical change. 2, 3, 6, 5
- If alkaline phosphatase is elevated in a patient receiving romosozumab, evaluate for alternative causes using standard diagnostic algorithms (measure GGT to confirm hepatic origin, obtain abdominal ultrasound or MRCP for cholestatic disease, consider bone imaging if bone origin is suspected). 7