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Anti-Sclerostin Monoclonal Antibody (Dual Anabolic/Anti-Resorptive) Pregnancy: Not applicable — postmenopausal women only. Not for use in pre-menopausal women.

Romosozumab (Anti-Sclerostin — Severe Osteoporosis)

Brand names: Evenity

Adult dose

Dose: 210 mg SC (two 105 mg injections given consecutively) once monthly for 12 months only; then transition to anti-resorptive therapy (alendronate or denosumab)
Route: Subcutaneous (two injections per monthly dose)
Frequency: Once monthly (maximum 12 doses only — then MUST switch to anti-resorptive)
Max: 210 mg/month; 12 months total treatment course
Unique dual mechanism: inhibits sclerostin → BOTH increases bone formation AND reduces bone resorption. Only anabolic agent that also reduces resorption. 12-month course only — efficacy diminishes after 12 months if not followed by anti-resorptive. MHRA approved for postmenopausal women at high fracture risk who have failed/are intolerant of other treatments.

Paediatric dose

Route:
Not licensed in paediatrics.

Dose adjustments

Renal

eGFR 30–60: use with caution; monitor calcium. eGFR <30: not recommended. Adjust calcium/vitamin D supplementation by eGFR.

Hepatic

No dose adjustment required.

Clinical pearls

  • ARCH trial (Saag et al. NEJM 2017): romosozumab → alendronate vs alendronate alone over 2 years — 48% reduction in new vertebral fractures, 27% reduction in non-vertebral fractures in romosozumab sequence. Significantly superior to alendronate alone; CV signal drove black box warning
  • CV risk black box (MHRA/FDA): in ARCH trial, MI/stroke rate higher in romosozumab arm vs alendronate at 12 months (2.5% vs 1.9%); not seen vs placebo in FRAME trial but design difference. MHRA mandates contraindication for patients with MI/stroke within prior year; careful risk-benefit in known CV disease
  • Sequential therapy is essential: romosozumab's 12-month anabolic window must be FOLLOWED by anti-resorptive (alendronate or denosumab); stopping without follow-on therapy loses bone density rapidly — the anabolic gains are retained when sequenced correctly (alendronate locks in gains)

Contraindications

  • Hypocalcaemia (must correct before starting — romosozumab causes hypocalcaemia)
  • History of MI or stroke within 1 year (MHRA black box warning — increased CV risk in ARCH trial vs alendronate)
  • Hypoparathyroidism (high hypocalcaemia risk)

Side effects

  • Hypocalcaemia (supplement calcium and vitamin D throughout treatment)
  • Arthralgia and musculoskeletal pain (injection site reactions)
  • Serious CV events — MHRA warning: higher MI/stroke rate vs alendronate in ARCH trial (2.5% vs 1.9% at 12 months; not placebo-controlled); avoid in patients with recent (within 1 year) MI or stroke
  • Osteonecrosis of the jaw (rare — same class risk as other bone-active agents)
  • Atypical femoral fracture (rare — after anti-resorptive sequence)

Interactions

  • Calcium supplementation (required — to counteract hypocalcaemia risk)
  • Other bone-active agents (do not combine with bisphosphonates during romosozumab course — sequential not concurrent use)

Monitoring

  • Serum calcium (before each injection — hypocalcaemia)
  • Vitamin D levels (supplement to >50 nmol/L)
  • CV risk assessment before prescribing (MI/stroke history)
  • DXA (bone density at baseline and after 12-month course — to document anabolic gain)
  • Dental assessment (osteonecrosis of jaw prophylaxis)

Reference: BNFc; BNF 90; Saag et al. NEJM 2017 (ARCH trial); MHRA Approval Evenity 2020; MHRA Drug Safety Update 2019 (CV risk); NICE TA791 (Romosozumab for Osteoporosis); NOF Guidelines 2023. Verify against your local formulary and the latest BNF before prescribing.

Related

Curated clinical cross-links plus same-class fallbacks.

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