Romosozumab and antiresorptive treatment: the importance of treatment sequence

Cosman, Felicia; Kendler, David L.; Langdahl, Bente; Leder, Benjamin Z.; Lewiecki, E. Michael; Miyauchi, Akimitsu; Rojeski, Maria; McDermott, Michele; Oates, Mary; Milmont, Cassandra E; Libanati, Cesar; Ferrari, Serge

doi:10.1007/s00198-021-06174-0

Cited by 58 publications

(27 citation statements)

References 59 publications

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“…Lower BMD gains were also noted when romosozumab treatment was preceded by denosumab. 32 Taken together, romosozumab used before rather than after alendronate leads to more significant bone mineral density increases and BMD responder rates. Therefore, with BMD gain with treatment being an essential indicator for bone strength and reduction in fracture risk, using romosozumab before an antiresorptive agent might be the ideal sequence for treatment.…”

Section: Switching High-risk Patients Previously On Bisphosphonates T...mentioning

confidence: 99%

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Romosozumab for the treatment of osteoporosis in women: Efficacy, safety, and cardiovascular risk

Lim

2022

Womens Health (Lond Engl)

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Increased understanding of the Wnt signaling pathway has led to the development of romosozumab, one of the most potent osteoanabolic agents to date for osteoporosis treatment. Romosozumab is a monoclonal antibody that inhibits sclerostin, a natural inhibitor of the Wnt signaling pathway. Romosozumab, by inhibiting sclerostin activates the Wnt signaling pathway, leading to increased bone formation and decreased bone resorption. The pivotal ARCH and FRAME studies established romosozumab’s fracture reduction efficacy. Romosozumab was superior to alendronate in fracture reduction and bone mineral density gain in the ARCH study. Romosozumab treatment should be followed sequentially with a potent antiresorptive agent. The antifracture efficacy gained from romosozumab is maintained or improved after transitioning to an antiresorptive agent. As one of the most potent osteoanabolic agents, the introduction of romosozumab has significantly increased our ability to treat osteoporosis. Studies have provided important information on using romosozumab with other osteoporosis medications to optimize osteoporosis treatment. Romosozumab used before antiresorptive medications is associated with more significant bone mineral density increases than when an antiresorptive agent is used before romosozumab. Romosozumab is recommended for osteoporosis treatment in patients at very high risk for fracture with low cardiovascular risk. Romosozumab is generally well tolerated, with 4%–5% of patients having injection site reactions. The ARCH trial showed a higher risk of cardiovascular events in patients receiving romosozumab. Romosozumab carries a black box warning that romosozumab should not be initiated in patients with myocardial infarction or stroke in the preceding year. However, the information on romosozumab and increased cardiovascular risk is conflicting. The risk of cardiovascular disease with romosozumab is unclear. While romosozumab has demonstrated significant osteoanabolic effect and antifracture efficacy and will benefit high fracture risk patients, further studies are needed to investigate the cardiovascular safety of romosozumab.

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Section: Switching High-risk Patients Previously On Bisphosphonates T...mentioning

confidence: 99%

“…Therefore, with BMD gain with treatment being an essential indicator for bone strength and reduction in fracture risk, using romosozumab before an antiresorptive agent might be the ideal sequence for treatment. 32 …”

Section: Switching High-risk Patients Previously On Bisphosphonates T...mentioning

confidence: 99%

Romosozumab for the treatment of osteoporosis in women: Efficacy, safety, and cardiovascular risk

Lim

2022

Womens Health (Lond Engl)

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“…45,46 The ARCH trial demonstrated a small increase in the incidence of cardiovascular events in the romosozumab arm, which was not seen in other trials. 47 More supporting data are required, but romosozumab is currently not recommended for patients with a high risk of myocardial infarction or stroke. Other common adverse effects include injection-site reactions.…”

Section: Romosozumabmentioning

confidence: 99%

“…More research is required to determine if the gains in bone density also correlate with a reduced fracture risk in these patients. 47 Given this evidence, for some treatment-naïve patients who present with severe osteoporosis (T-score less than -3.0) following a fracture, the option of first-line treatment with an anabolic drug such as romosozumab should be discussed with the patient. However, this is not a PBS-listed indication.…”

Section: Sequential Treatment With First-line Anabolicsmentioning

confidence: 99%

Treating osteoporosis: risks and management

Zhu¹,

March²

2022

Aust Prescr

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Osteoporosis, osteopenia and minimal trauma fractures are becoming increasingly common in the ageing population. Fractures cause increases in morbidity and mortality and have a significant financial impact on the healthcare system and society.Addressing risk factors for osteoporosis early may prevent or delay the onset of fractures and use of drugs. Calcium and vitamin D supplementation may benefit people with a high risk of deficiency (e.g. institutionalised older people) but may not be required in people without risk factors. Impact and resistance exercises and physical activity can increase bone density and prevent falls.Antiresorptive drugs such as bisphosphonates and denosumab remain first-line treatment options for osteoporosis. The ongoing need for bisphosphonates should be assessed after five years and treatment may then be interrupted in some patients. Progressive bone loss will recur slowly. Denosumab therapy should not be interrupted without switching to another therapy, as posttreatment bone loss can progress rapidly. All patients will need ongoing monitoring and most will require some long-term therapy once started.Raloxifene may be considered in women who do not tolerate first-line antiresorptive drugs. Romosozumab is a new anabolic treatment for osteoporosis and, together with teriparatide, is subsidised as second-line therapy for individuals with severe disease and multiple fractures. Specialist referral should be considered for patients who sustain fractures while undergoing osteoporosis therapy.predicted using the Garvan Fracture Risk or FRAX calculators. 6,7 Age, a family history of hip fractures and previous fractures are key risk factors. All men and women over the age of 50 years who have sustained a fracture have a higher risk of subsequent fractures and should be assessed and considered for treatment. Bone mineral density testing is also recommended and subsidised for all men and women over 70 years of age. Along with falls-risk screening, it is recommended as part of general health checks for all individuals, yet medical record audits indicate that this prevention strategy is currently underused. 8 Osteoporosis can be defined using bone mineral density testing, which generates a T-score and Z-score. The T-score reflects the number of deviations from the peak bone mass of age-, sex-and ethnicity-matched norms. A T-score less than -2.5 indicates a significant reduction in bone mass. The Z-score reflects the number of standard deviations from the average bone mass of age-, sex-and ethnicity-matched norms. A Z-score less than -2.0 should prompt a more complete search for secondary causes of osteoporosis. Management strategiesAddressing lifestyle risk factors, appropriately treating predisposing conditions and minimising the unnecessary prescription of drugs associated with osteoporosis may slow the decline in bone

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“…In contrast, transition to romosozumab resulted in a 10% gain at the spine and 3% gain at hip sites (96). Some studies suggest that anabolic agents produce smaller gains in BMD when administered after an anti-resorptive agent compared with their use in treatment-naïve patients (96,97). Such analyses need to factor in the earlier BMD gains from anti-resorptive use when assessing the total BMD benefit.…”

Section: Treatment Ordermentioning

confidence: 99%

EXTENSIVE EXPERTISE IN ENDOCRINOLOGY: Osteoporosis management

Reid

2022

European Journal of Endocrinology

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Fractures occur in about half of older white women, and almost a third of older white men. However, 80% of the older individuals who have fractures do not meet the bone density definition of osteoporosis, suggesting that this definition is not an appropriate threshold for offering treatment. Fracture risk can be estimated based on clinical risk factors with or without bone density. A combination of calculated risk, fracture history, and bone density is used in treatment decisions. Medications available for reducing fracture risk act either to inhibit bone resorption or to promote bone formation. Romosozumab is unique in that it has both activities. Bisphosphonates are the most widely used interventions because of their efficacy, safety and low cost. Continuous use of oral bisphosphonates for >5 years increases the risk of atypical femoral fractures, so is usually punctuated with drug holidays of 6-24 months. Denosumab is a further potent antiresorptive agent given as six-monthly subcutaneous injections. It is comparable to the bisphosphonates in efficacy and safety but has a rapid offset of effect after discontinuation so must be followed by an alternative drug, usually a bisphosphonate. Teriparatide stimulates both bone formation and resorption, substantially increases spine density and reduces vertebral and non-vertebral fracture rates, though data for hip fractures are scant. Treatment is usually limited to 18-24 months, followed by transition to an anti-resorptive. Romosozumab is given as monthly subcutaneous injections for one year, followed by an anti-resorptive. This sequence prevents more fractures than anti-resorptive therapy alone. Because of cost, anabolic drugs are usually reserved for those at very high fracture risk. 25-hydroxyvitamin D levels should be maintained above 30 nmol/L, using supplements if sunlight exposure is limited. Calcium intake has little effect on bone density and fracture risk but should be maintained above 500 mg/day using dietary sources.

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Romosozumab and antiresorptive treatment: the importance of treatment sequence

Cited by 58 publications

References 59 publications

Romosozumab for the treatment of osteoporosis in women: Efficacy, safety, and cardiovascular risk

Romosozumab for the treatment of osteoporosis in women: Efficacy, safety, and cardiovascular risk

Treating osteoporosis: risks and management

EXTENSIVE EXPERTISE IN ENDOCRINOLOGY: Osteoporosis management

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