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Is there a potential dual effect of denosumab for treatment of osteoporosis and sarcopenia?

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Abstract

Background

The prevalence of sarcopenia with osteoporosis results in a higher risk of falling and fractures. It was noted that patients who had completed their planned 5-year denosumab therapy course as treatment for these conditions started to sustain falls.

Purpose

To assess (a) whether denosumab has a unique dual effect on both bone and muscle in comparison to other anti-resorptive agents and (b) its effectiveness in the follow-up period post-treatment completion compared to other anti-resorptive agents.

Method

One hundred thirty-five patients diagnosed to have postmenopausal/senile osteoporosis and who were prescribed denosumab were compared to a control group of 272 patients stratified into 2 subgroups – 136 prescribed alendronate and 136 prescribed zoledronate. All patients were assessed for: BMD (DXA), falls risk (FRAS), fracture risk (FRAX), and sarcopenia measures. All were re-assessed after 5 years of denosumab/alendronate therapy and 3 years of zoledronate and 1 year after stopping the osteoporosis therapy.

Results

No significant baseline demographic differences between the 3 groups. On completion of the 5-year denosumab therapy, there was significant decrease in falls risk (P = 0.001) and significant improvements in all sarcopenia measures (P = 0.01). One-year post-discontinuation of denosumab, a significant worsening of both falls risk and sarcopenia measures (P = 0.01) noticed.

Conclusion

Denosumab displayed positive impact and significant improvements in BMD and sarcopenia measures. It also enhanced multidirectional agility as depicted by Timed Up and Go (TUG). Collectively, this would explain the reduction of falls risk which got worse on stopping the medication.

Key points

• The coexistence of osteoporosis and sarcopenia has been recently considered in some groups as a syndrome termed 'osteosarcopenia'.

• Bone and muscle closely interact with each other not only anatomically, but also at the chemical and metabolic levels.

Denosumab displayed positive impact and significant improvements in all sarcopenia measures, and enhanced multidirectional agility with consequent reduction in falls risk.

Denosumab can be considered as a first osteoporosis therapeutic option in this group of patients presenting with osteosarcopenia manifestations.

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Data availability

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Acknowledgements

We acknowledge all nurses, technicians, and all stuff who participated in this study.

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Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were performed by Dr. Yasser El Miedany, Dr. Maha El Gaafary, Dr. Mathias Toth, Dr. Mohamed Osama Hegazi, Dr. Nadia El Aroussy, Dr. Waleed Hassan, Dr. Samah Almedany, Dr. Annie Nasr, Dr. Sami Bahlas, and Dr. Salwa Galal. The first draft of the manuscript was written by Dr. Salwa Galal and Prof. Yasser El Miedany. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Salwa Galal.

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Conflict of interest

Yasser El-Miedany, Maha El Gaafary, Mathias Toth, Mohamed Osama Hegazi, Nadia El Aroussy, Waleed Hassan, Samah Almedany, Annie Nasr, Sami Bahlas, and Salwa Galal declare that they have no conflict of interest and have full control of all primary data and that they agree to allow the journal to review their data if requested.

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Miedany, Y.E., Gaafary, M.E., Toth, M. et al. Is there a potential dual effect of denosumab for treatment of osteoporosis and sarcopenia?. Clin Rheumatol 40, 4225–4232 (2021). https://doi.org/10.1007/s10067-021-05757-w

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  • DOI: https://doi.org/10.1007/s10067-021-05757-w

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