Endocrinol Metab > Volume 37(3); 2022 > Article
Yi: Sclerostin as a Putative Myokine in Sarcopenia
Sclerostin is an osteocyte-derived circulating protein that suppresses the Wnt/β-catenin signaling pathway and bone formation [1]. Sclerostin deficiency in humans and mice causes inherited high bone mass conditions characterized by exaggerated bone formation [1,2]. Many studies have demonstrated the role of sclerostin as a regulator of bone mass, and emerging studies have suggested that circulating sclerostin could serve as a biomarker for non-skeletal diseases [3,4]. However, relatively few studies have shown the effects of sclerostin on muscle physiology and pathology in humans.
Sarcopenia, an age-associated multifactorial disease, includes a notable decline in muscle mass and strength, neuromuscular function, and performance [5-8]. Despite its effects on mortality and morbidity, sarcopenia biomarkers remain unknown. Based on the coexistence of sarcopenia and osteoporosis in the population with aging and frailty, as well as considerable overlap in the pathophysiology of these two diseases, in an article titled, “Decreased serum level of sclerostin in older adults with sarcopenia,” Ahn et al. [9] investigated whether circulating sclerostin is associated with sarcopenic indices in older adults. The authors showed that higher circulating levels of sclerostin were significantly associated with a lower risk of sarcopenia, low muscle mass, and muscle weakness in Korean older adults [9]. These data were statistically significant, even after considering the confounding effects of age, sex, and body mass index. These findings are consistent with previous investigations showing a negative correlation between serum sclerostin levels and skeletal muscle mass index in Korean subjects without diabetes [10]. Therefore, it is plausible to predict that sclerostin could serve as a potential novel biomarker for sarcopenia.
However, this observational study could not determine the causal relationship between the variables. Thus, it would be interesting to determine how decreased serum sclerostin levels affect muscle mass and function, which may provide a new therapeutic target for sarcopenia. Moreover, further studies are needed to clarify the role of sclerostin in the muscle-bone relationship in a variety of racial and ethnic populations. Since it has been recognized that many hormones and growth factors regulate muscle mass and protein metabolism [7,11,12], it would be valuable to investigate the role of sclerostin in the myopathies of endocrine disorders.



No potential conflict of interest relevant to this article was reported.


1. Baron R, Kneissel M. WNT signaling in bone homeostasis and disease: from human mutations to treatments. Nat Med 2013;19:179-92.
2. Li X, Ominsky MS, Niu QT, Sun N, Daugherty B, D’Agostin D, et al. Targeted deletion of the sclerostin gene in mice results in increased bone formation and bone strength. J Bone Miner Res 2008;23:860-9.
3. Modder UI, Hoey KA, Amin S, McCready LK, Achenbach SJ, Riggs BL, et al. Relation of age, gender, and bone mass to circulating sclerostin levels in women and men. J Bone Miner Res 2011;26:373-9.
4. Saeki C, Tsubota A. Influencing factors and molecular pathogenesis of sarcopenia and osteosarcopenia in chronic liver disease. Life (Basel) 2021;11:899.
5. Nga HT, Jang IY, Kim DA, Park SJ, Lee JY, Lee S, et al. Serum GDF15 level is independent of sarcopenia in older Asian adults. Gerontology 2021;67:525-31.
6. Larsson L, Degens H, Li M, Salviati L, Lee YI, Thompson W, et al. Sarcopenia: aging-related loss of muscle mass and function. Physiol Rev 2019;99:427-511.
7. Dao T, Green AE, Kim YA, Bae SJ, Ha KT, Gariani K, et al. Sarcopenia and muscle aging: a brief overview. Endocrinol Metab (Seoul) 2020;35:716-32.
8. Tian J, Chung HK, Moon JS, Nga HT, Lee HY, Kim JT, et al. Skeletal muscle mitoribosomal defects are linked to low bone mass caused by bone marrow inflammation in male mice. J Cachexia Sarcopenia Muscle 2022;13:1785-99.
9. Ahn SH, Jung HW, Lee E, Baek JY, Jang IY, Park SJ, et al. Decreased serum level of sclerostin in older adults with sarcopenia. Endocrinol Metab (Seoul) 2022;37:487-96.
10. Kim JA, Roh E, Hong SH, Lee YB, Kim NH, Yoo HJ, et al. Association of serum sclerostin levels with low skeletal muscle mass: the Korean Sarcopenic Obesity Study (KSOS). Bone 2019;128:115053.
11. Rooyackers OE, Nair KS. Hormonal regulation of human muscle protein metabolism. Annu Rev Nutr 1997;17:457-85.
12. Setoyama D, Lee HY, Moon JS, Tian J, Kang YE, Lee JH, et al. Immunometabolic signatures predict recovery from thyrotoxic myopathy in patients with Graves’ disease. J Cachexia Sarcopenia Muscle 2022;13:355-67.
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Hyon-Seung Yi

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