Generic Name

Evenity

Mechanism

• Sclerostin blockade: Romosozumab binds the extracellular domain of sclerostin, a glycoprotein expressed by osteocytes that antagonizes the Wnt/β‑catenin signaling pathway.
• Enhanced osteoblast activity: By disinhibiting Wnt signalling, it promotes osteoblast differentiation and matrix production, increasing bone formation.
• Suppressed osteoclastogenesis: Reduced sclerostin levels lead to lower RANKL expression and higher osteoprotegerin, dampening osteoclast differentiation and activity, thus reducing bone resorption.
• Clinical result: Net gain in bone mineral density (BMD) and improved bone microarchitecture, translating into a markedly reduced fracture risk.

Pharmacokinetics

• Route & absorption: Subcutaneous injection; absorption begins within 24 h, peak serum concentration ~7–10 days post‑dose.
• Distribution: Large volume of distribution (~200 L), consistent with monoclonal antibody properties.
• Half‑life: Approximately 32 days; steady state achieved after 6–7 months with monthly dosing.
• Metabolism & elimination: Proteolytic catabolism to peptides; no significant renal or hepatic clearance pathways.
• Special populations: No dose adjustment required in mild‑to‑moderate renal impairment or hepatic dysfunction. Pregnancy category B; use only if clearly needed.

Indications

• Postmenopausal women with osteoporosis or men 50 years or older with osteoporosis who are at high risk for fracture (T‑score ≤ –2.5 g/cm² or history of fragility fracture).
• Contra-indicated in patients with a history of atypical femoral fractures, hyperparathyroidism, or active malignancy of any type.

Contraindications

• Contraindications
• Known hypersensitivity to romosozumab or any excipient.
• Active malignancy (except non‑melanoma skin cancers).
• Hyperparathyroidism or hypocalcemia uncorrected.
• Pregnancy and lactation (data insufficient).
• Warnings
• Cardiovascular risk: Observed a possible increase in serious cardiovascular events in patients with a recent history of cardiovascular disease. Routine cardiovascular risk assessment is recommended before initiation.
• Hypocalcemia: May precipitate hypocalcemia; monitor serum calcium before and during therapy.
• Osteonecrosis of the jaw (ONJ): Rare but possible, particularly in patients previously treated with bisphosphonates or denosumab.
• Atypical femoral fractures: Rare; avoid in patients with a history of atypical fractures.

Dosing

• Standard dose: 140 mg administered once monthly via subcutaneous injection.
• Schedule: 12 consecutive monthly injections are the recommended maximum duration (± 1 month window).
• Administration guidelines:
• Inject into the thigh or abdomen using a prefilled syringe.
• Rotate injection sites to minimize local reactions.
• Discontinue immediately if severe local reaction or allergy signs develop.

Adverse Effects

Monitoring

• Baseline: Serum calcium, phosphate, magnesium, 25‑hydroxy‑vitamin D, renal function, cardiac risk assessment (history, ECG if indicated).
• During therapy:
• Serum calcium every 3–6 months.
• Bone turnover markers (e.g., serum P1NP, CTX) at baseline, 3–6 months, and at end of therapy to gauge response.
• BMD via DXA at baseline and after 12 months.
• Watch for signs of cardiovascular events; consider repeat ECG or cardiology referral if symptoms develop.
• After discontinuation: Monitor BMD and fracture risk; transition to a bisphosphonate or denosumab if needed to maintain gains.

Clinical Pearls

• Use‑case selection: Romosozumab is most valuable in “rapid‑buildup” scenarios—e.g., a postmenopausal woman with a recent hip fracture who needs immediate BMD increase while other agents are less effective in the short term.
• Cardiovascular safety: Exclude patients with known heart attack or stroke within the preceding 3 months; if included, counsel regarding symptom recognition and prompt medical evaluation.
• Switching strategy: Patients completing a 12‑month course should promptly transition to a bone‑maintenance therapy (bisphosphonate or denosumab) as there is a risk of rapid BMD loss once romosozumab is stopped.
• Pregnancy & lactation: The drug is contraindicated; patients should use reliable contraception during the entire treatment period and for at least 6 months afterward.
• Cost‑effectiveness: While expensive, the fracture‑reduction benefit can translate into long‑term savings by preventing costly hip and vertebral fracture sequelae.

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• Key terms: romosozumab, sclerostin inhibitor, bone formation, osteoporosis treatment, postmenopausal women, bone mineral density, fracture risk, cardiovascular safety