Romosozumab in the treatment of osteoporosis

Romosozumab is a monoclonal antibody that binds to sclerostin and inhibits its action

• sclerostin
  • is produced by osteocytes
  • increases bone resorption and decreases bone formation
• romosozumab is given by monthly subcutaneous injection

NICE recommend that:

• romosozumab is recommended as an option for treating severe osteoporosis in people after menopause who are at high risk of fracture, only if:
  • they have had a major osteoporotic fracture (spine, hip, forearm or humerus fracture) within 24 months (so are at imminent risk of another fracture) and
  • the company provides romosozumab according to the commercial arrangement
• the NICE committee state (2)
  • "..Current treatments for people with severe osteoporosis after menopause include bisphosphonates, such as alendronic acid, and other types of medicines, such as denosumab or teriparatide. The company proposes that romosozumab would only be used when there is an imminent fracture risk. It defines this as when a person has severe osteoporosis and has had a major osteoporotic fracture within 24 months. This is narrower than the marketing authorisation...Clinical trial evidence suggests that romosozumab followed by alendronic acid is more effective at reducing the risk of fractures than alendronic acid alone. Comparing romosozumab indirectly with other bisphosphonates and other medicines for this condition suggests that romosozumab is likely to be at least as effective at reducing the risk of fractures in people with osteoporosis after menopause. But the extent of the benefit is uncertain because of differences between the trial populations in the indirect comparisons.."

Notes:

• adverse events (1)
  • common adverse events in the trials included arthralgia, muscle spasms and headache
  • injection-site reactions were more frequent with romosozumab than with placebo
  • hypersensitivity reactions can occur
  • approximately 18% of patients develop antibodies to romosozumab including 4.7% who develop neutralising antibodies
  • because osteonecrosis of the jaw has been reported, patients should have a dental examination before starting romosozumab
    
    
• discovery of sclerostin as a key inhibitor of bone formation was made by groups evaluating patients with 2 rare autosomal recessive syndromes associated with high bone mass (3)
  • Sclerostiosis is a disorder characterized by very high bone mass due to inactivating mutations of the SOST gene on chromosome 17q21, the gene that codes for sclerostin
    • excess bone growth during childhood results in frontal bossing, cranial and basilar stenosis, cranial nerve entrapment, and mandibular hypertrophy
  • Van Buchem disease
    • less severe disorder than sclerostiosis
    • have a separate noncoding deletion of a gene required for normal transcription of the SOST gene
  • heterozygous cases of both disorders have moderately high bone mass without other phenotypic or clinical features

Reference:

• Romosozumab for osteoporosis. Aust Prescr. 2021;44(3):109-110. doi:10.18773/austprescr.2021.021
• NICE (May 2022). Romosozumab for treating severe osteoporosis
• McClung MR. Romosozumab for the treatment of osteoporosis. Osteoporos Sarcopenia. 2018;4(1):11-15. doi:10.1016/j.afos.2018.03.002