Romosozumab use before antiresorptive agents tied to greater BMD responder rate in osteoporosis

Romosozumab is a bone-forming agent with the dual effect of increasing bone formation and decreasing bone resorption.

Felicia Cosman et al found in the study that - larger mean bone mineral density (BMD) increases and greater BMD responder rates were achieved when romosozumab was used before, versus after, an antiresorptive agent. Since BMD on treatment is a strong surrogate for bone strength and fracture risk, this analysis supports the thesis that initial treatment with romosozumab followed by an antiresorptive will result in greater efficacy versus the reverse sequence.

To evaluate whether treatment sequence affects romosozumab response, the authors reviewed randomized clinical trials where romosozumab was administered before (ARCH, FRAME) or following (STRUCTURE, Phase 2 extension) an antiresorptive (alendronate or denosumab, respectively).

The authors evaluated changes in total hip (TH) and lumbar spine (LS) BMD, the proportions of patients who achieved BMD gains≥3% and≥6% at the total hip and lumbar spine, and the profile of changes in levels of the bone formation marker procollagen type I N-terminal propeptide (PINP) and the bone resorption marker β-isomer of the C-terminal telopeptide of type I collagen (β-CTX) after 12 and 24 months of treatment with the different treatment sequences.

The observations of the study were :

• With 1-year romosozumab initial therapy in ARCH and FRAME, TH BMD increased 6.2% and 6.0%, and LS BMD increased 13.7% and 13.1%, respectively.

• When romosozumab was administered for 1 year after alendronate (STRUCTURE) or denosumab (Phase 2 extension), TH BMD increased 2.9% and 0.9%, respectively, and LS BMD increased 9.8% and 5.3%, respectively.

• Over 2 years, TH and LS BMD increased 7.1% and 15.2% with romosozumab/alendronate, 8.5% and 16.6% with romosozumab/denosumab, and 3.8% and 11.5% with denosumab/romosozumab, respectively.

• A greater proportion of patients achieved BMD gains≥6% when romosozumab was used first, particularly for TH, versus the reverse sequence (69% after romosozumab/denosumab; 15% after denosumab/romosozumab).

The authors commented that - ' Since osteoporosis is a chronic condition requiring long term therapy, for those patients at very high risk for fracture who will likely need both bone-forming and antiresorptive agents, improved clinical efficacy will be seen if the bone-forming agent is used as initial therapy.'

Further reading:

Romosozumab and antiresorptive treatment: the importance of treatment sequence

Felicia Cosman et al

Osteoporosis International (2022) 33:1243–1256

https://doi.org/10.1007/s00198-021-06174-0