Romosozumab

• Postmenopausal Osteoporosis
• High-Risk Osteoporotic Fractures
• Severe Osteoporosis

Romosozumab is a humanized monoclonal antibody that inhibits sclerostin, providing a unique dual mechanism of action that both increases bone formation and decreases bone resorption. It is used to treat osteoporosis in postmenopausal women at high risk for fracture.

Mechanism of Action

Romosozumab targets sclerostin, a key regulator of bone metabolism:

• Sclerostin inhibition: Binds and neutralizes sclerostin, a glycoprotein secreted by osteocytes
• Increases bone formation: Sclerostin normally inhibits the Wnt signaling pathway; blocking it promotes osteoblast activity
• Decreases bone resorption: Reduces osteoclast-mediated bone breakdown
• Dual anabolic/antiresorptive effect: Unique among osteoporosis treatments

This dual mechanism results in rapid gains in bone mineral density.

Available Formulations

Romosozumab is available as:

• Prefilled syringes: 105 mg/1.17 mL (two injections needed for 210 mg dose)

Medical Uses

FDA-Approved Indication:

• Treatment of osteoporosis in postmenopausal women at high risk for fracture, defined as:
  • History of osteoporotic fracture, or
  • Multiple risk factors for fracture, or
  • Patients who have failed or are intolerant to other osteoporosis therapy

Not approved for prevention of osteoporosis or use in men.

Dosing Guidelines

Postmenopausal Osteoporosis:

• 210 mg subcutaneously once monthly (administered as two 105 mg injections)
• Treatment duration: 12 months (12 doses)

Transition Therapy:

• After completing romosozumab, transition to an antiresorptive agent (e.g., bisphosphonate or denosumab) to maintain benefits

Administration:

• Give as two separate subcutaneous injections in thigh, abdomen, or upper arm
• Different injection sites for each injection

Important Safety Information

Black Box Warning:

• Cardiovascular risk: May increase risk of myocardial infarction, stroke, and cardiovascular death
• Do not initiate in patients who have had MI or stroke within the preceding year
• Consider whether benefits outweigh risks in patients with cardiovascular risk factors
• Discontinue if patient experiences MI or stroke during treatment

Contraindications:

• Hypocalcemia (correct before initiating)
• History of MI or stroke within the preceding year

Warnings and Precautions:

• Hypocalcemia: May cause; supplement with calcium and vitamin D
• Osteonecrosis of the jaw
• Atypical femur fractures
• Hypersensitivity reactions

Drug Interactions

No formal drug interaction studies have been conducted. As a monoclonal antibody, romosozumab is not expected to interact via cytochrome P450 pathways.

Considerations:

• Ensure adequate calcium and vitamin D intake
• Avoid concurrent use with other bone-active biologics (e.g., denosumab)

Special Populations

• Hepatic Impairment: Not formally studied; likely no impact
• Renal Impairment: No adjustment; monitor calcium more closely in severe impairment
• Pregnancy: No data; not indicated for use in women of reproductive potential
• Lactation: Not applicable (postmenopausal women)
• Elderly: Most clinical trial participants were elderly; no adjustment
• Men: Not approved