Bone-derived hormones may become useful biomarkers for the incidence and progression of diabetes, as well as targets for the prevention and treatment of the disease, according to a review article published in the International Journal of Molecular Sciences.

Researchers summarized the role of bone-derived hormones in glucose metabolism, diabetic kidney disease, and cardiovascular disorders, focusing on fibroblast growth factor 23 (FGF23), osteocalcin, sclerostin, and lipocalin 2.1

The effects of FGF23 on glucose metabolism in humans are not clear, as some studies have found that diabetes is associated with higher blood FGF23 levels, and others did not find these associations. Recent reports have shown that an increased blood FGF23 level may predict all-cause and cardiovascular mortality in patients with type 2 diabetes. One study found that the association in patients with an estimated glomerular filtration rate (eGFR) >60 mL/min/1.73 m2 remained after adjustment for eGFR, linking a higher FGF23 level with adverse outcomes, including in patients without impaired kidney function.2


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“Future studies should clarify whether FGF23 is merely a disease severity marker or a contributor to adverse outcomes in type 2 diabetes and establish whether antidiabetic medication can modify blood FGF23 levels,” stated the researchers.

Osteocalcin is directly associated with glucose metabolism and is used as a bone metabolism marker in clinical settings. A recent study found an association between baseline osteocalcin levels and risk of incident diabetic kidney disease.3 Other research has found that blood levels of undercarboxylated osteocalcin and osteocalcin were significantly lower in patients with coronary artery disease and type 2 diabetes compared with levels in patients with coronary artery disease without type 2 diabetes. Lower undercarboxylated osteocalcin levels also have been associated with adverse cardiovascular risk in patients with coronary artery disease.

Sclerostin, which is primarily expressed in osteocytes and suppresses bone formation, may become a reliable diagnostic and prognostic biomarker of cardiovascular risk in patients with type 2 diabetes, according to the researchers. Studies have shown that the blood sclerostin level may be a useful biomarker of early atherosclerosis in obese individuals without a previous history of cardiometabolic disorders. “It is suggested that sclerostin is not only involved in the regulation of bone formation but also in the pathophysiological process of atherosclerosis,” stated the investigators.

Recent evidence has indicated that higher blood lipocalin 2 levels are associated with obesity, insulin resistance, and dyslipidemia in patients with type 2 diabetes. Thus far, the relationship between bone-derived lipocalin 2 and diabetic complications has not been clarified. Clinical studies have shown that increased systemic levels of blood lipocalin 2 are associated with coronary artery disease severity and an increased risk of incidence cardiovascular diseases.

“We believe that the potential applications of bone-derived hormones in the treatment of diabetes are worthy of further study and hope that other new antidiabetic drugs emerge,” stated the researchers. “Furthermore, there are possibly new bone-derived hormones to be identified. If proven to also be true in humans, bone will be established as a new player in diabetes and diabetic complications.”

Disclosure: The study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

References

1. Takashi Y, Kawanami D. The role of bone-derived hormones in glucose metabolism, diabetic kidney disease, and cardiovascular disorders. Int J Mol Sci. 2022;23(4):2376. doi:10.3390/ijms23042376

2. Yeung SMH, Binnenmars SH, Gant CM, et al. Fibroblast growth factor 23 and mortality in patients with type 2 diabetes and normal or mildly impaired kidney function. Diabetes Care. 2019;42(11):2151-2153. doi:10.2337/dc19-0528

3. Ye X, Yu R, Jiang F, et al. Osteocalcin and risks of incident diabetes and diabetic kidney disease: a 4.6-year prospective cohort study. Diabetes Care. Published online January 28, 2022. doi:10.2337/dc21-2113