Anti-sclerostin antibody treatment suppresses skeletal muscle atrophy after ovariectomy in female mice

Aging-associated decline in muscle mass and strength, so-called sarcopenia, is well known as a major scientific and public health problem. Furthermore, it is well known that skeletal muscle atrophy in postmenopausal women is induced by estrogen deficiency. Prevention of skeletal muscle atrophy is an important issue for a healthy life expectancy. Recent publications report a negative correlation between blood levels of sclerostin (Sost), which inhibits bone formation, and muscle mass suggests the involvement of Sost in skeletal muscle atrophy. Therefore, in the present study, we investigated the effects of an anti-sclerostin antibody (romosozumab) on ovariectomy (OVX)-associated skeletal muscle atrophy in female mice. Female C57BL/6J mice were divided into the age-matched sham-operated control group (Cont group, n=8), the OVX group (n=8), and the age-matched romosozumab-treated group (ROMO group, n=8). Mice of OVX group were used 15 weeks after the OVX operation. Romosozumab (3 mg/kg) was administrated twice with 4-week interval. Four weeks after the second administration of romosozumab, soleus, gastrocnemius, plantaris, tibialis anterior and extensor digitorum longus muscles of all groups were dissected. All animal experimental procedures in this study were reviewed and approved by the Animal Use Committee of Toyohashi SOZO University. Body weight was significantly highest in the OVX group, lowest in the Cont group, and intermediate in the ROMO groups. Conversely, the wet weight of all muscles was lowest in the OVX group, highest in the Cont group, and intermediate in the ROMO groups. There was no significant difference in muscle weight between the Cont group and the ROMO group. Results indicated that OVX induced skeletal muscle atrophy, and that OVX-associated skeletal muscle atrophy was partially attenuated by administration of an anti-sclerostin antibody. Administration of romosozumab, anti-sclerostin antibody, administration may be a potential therapy for age-associated skeletal muscle atrophy in postmenopausal women. This work was supported by KAKENHI from the JSPS, and a research grant from DAIKO FOUNDATION, Graduate School of Health Sciences, Toyohashi SOZO university. This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.