What is the recommended Romosuzumab (sclerostin inhibitor) regimen for a postmenopausal woman with osteoporosis and high risk of fracture, considering her renal function and potential need for calcium and vitamin D supplements?

Romosozumab Regimen for Postmenopausal Osteoporosis

Romosozumab is administered as 210 mg subcutaneously once monthly for exactly 12 months (two 105 mg injections given consecutively at each monthly visit), and must be followed by an antiresorptive agent such as denosumab or alendronate to maintain bone gains. 1

Dosing and Administration

• Each monthly dose requires two separate 105 mg subcutaneous injections administered one after the other by a healthcare provider, totaling 210 mg per month 1
• Injection sites include the abdomen, thigh, or upper arm 1
• Treatment duration is strictly limited to 12 monthly doses because the anabolic effect wanes after this period 2, 1
• Sequential antiresorptive therapy is mandatory after completing romosozumab to prevent bone loss and maintain BMD gains 2, 3, 1

Calcium and Vitamin D Supplementation

All patients must receive adequate calcium and vitamin D supplementation throughout romosozumab treatment to prevent hypocalcemia, which is a contraindication to therapy 2, 1

• Calcium: 1,000-1,200 mg daily 2
• Vitamin D: 600-800 IU daily (target serum level ≥20 ng/mL) 2
• Patients with severe renal impairment or on dialysis require closer monitoring of serum calcium levels due to increased hypocalcemia risk 1

Patient Selection Criteria

Romosozumab should only be used in postmenopausal women at very high risk of fracture, not as first-line therapy 2, 1

Very high risk is defined by:

• History of osteoporotic fracture (particularly multiple fractures) 1
• Multiple risk factors for fracture 1
• Failure of or intolerance to bisphosphonates or other available osteoporosis therapy 1

Critical Cardiovascular Contraindications

Romosozumab carries an FDA boxed warning for increased risk of myocardial infarction, stroke, and cardiovascular death 1

Absolute contraindications:

• Myocardial infarction or stroke within the preceding year 1

Relative contraindications requiring careful risk-benefit assessment:

• Documented coronary heart disease 2
• Other significant cardiovascular risk factors 1

If a patient experiences MI or stroke during therapy, romosozumab must be discontinued immediately 1

Sequential Therapy Protocol

After completing 12 months of romosozumab, transition to antiresorptive therapy is essential 3, 1, 4

Preferred sequential agents:

• Denosumab 60 mg subcutaneously every 6 months 4, 5
• Alendronate (oral bisphosphonate) 2, 6

The romosozumab-to-denosumab sequence demonstrated:

• 66% relative risk reduction in new vertebral fractures through 36 months 4
• 27% reduction in clinical fractures 4
• Continued BMD gains during the denosumab phase while maintaining the substantial BMD increases achieved with romosozumab 4, 5

Renal Function Considerations

Patients with severe renal impairment (CrCl <30 mL/min) or on dialysis are at greater risk of hypocalcemia 1

• Monitor serum calcium levels more frequently in this population 1
• Ensure aggressive calcium and vitamin D supplementation 1
• Romosozumab is not contraindicated in renal impairment, but requires enhanced monitoring 1

Expected Outcomes

BMD increases are substantial and rapid with romosozumab:

• Lumbar spine: 14-17% increase at 12 months 4, 7, 8
• Total hip: 4-5% increase at 12 months 4, 7
• Femoral neck: 4-6% increase at 12 months 4, 8

Bone turnover marker changes occur within the first week:

• P1NP (bone formation marker) peaks at month 1, then declines 7, 8
• CTX (bone resorption marker) decreases rapidly and remains suppressed through 12 months 7, 8

Common Pitfalls to Avoid

• Do not use romosozumab as first-line therapy—bisphosphonates remain the appropriate initial treatment for most patients with osteoporosis 2
• Do not extend treatment beyond 12 months—the anabolic effect is lost after this period 2, 1
• Do not fail to plan sequential therapy—bone loss will occur without subsequent antiresorptive treatment 3, 1
• Do not overlook cardiovascular history—this is the most critical safety concern 9, 1
• Do not neglect calcium and vitamin D supplementation—hypocalcemia is a contraindication and can develop during treatment 1