Bone turnover markers are decreased in GC-treated subjects with DM. Decreased OC levels in GC-treated patients were associated with an increased risk of DM. These results suggest the involvement of OC in glucose homeostasis regulation in DM.
Osteocalcin (OC) is involved in the regulation of glucose homeostasis. Glucocorticoid (GC) treatment is associated with impaired osteoblast function, decreased OC levels, and the development and/or worsening of pre-existing diabetes mellitus (DM). Whether decreased OC levels in GC-treated subjects contribute to DM is not well known. The aim of this study was to analyse whether OC levels in GC-treated patients are associated with the presence of DM.
One hundred twenty-seven patients (aged 61.5 ± 17.9 years) on GC treatment were included. GC dose, treatment duration, presence of DM and bone formation (OC, bone ALP, PINP) and resorption markers (urinary NTX, serum CTX) were analysed. The cut-offs of each bone turnover marker (BTM) for the presence of DM were evaluated and optimised with the Youden index and included in the logistic regression analysis.
Among the patients, 17.3% presented DM. No differences were observed in GC dose or duration or the presence of fractures. Diabetics showed lower levels of OC (7.57 ± 1.01 vs. 11.56 ± 1; p < 0.001), PINP (21.48 ± 1.01 vs. 28.39 ± 1; p = 0.0048), NTX (24.91 ± 1.01 vs. 31.7 ± 1; p = 0.036) and CTX (0.2 ± 1.01 vs. 0.3 ± 1; p = 0.0016). The discriminating BTM cut-offs for DM presence were < 9.25 ng/mL for OC, < 24 ng/mL for PINP, < 27.5 nMol/mM for NTX and < 0.25 ng/mL for CTX. In a multivariate logistic regression model adjusted for GC dose, BMI, age and the above four BTMs, only OC remained independently associated with DM presence. Thus, in a model adjusted for GC dose, BMI and age, OC was significantly associated with DM (OR: 6.1; 95%CI 1.87–19.89; p = 0.001).
Decreased OC levels in GC-treated patients are associated with increased odds of DM, and only OC was independently associated with DM in a model including four BTMs.
This is a preview of subscription content, access via your institution.
Buy single article
Instant access to the full article PDF.
Tax calculation will be finalised during checkout.
Buckley L, Humphrey MB (2018) Glucocorticoid-induced osteoporosis. N Engl J Med 379:2547–2556
Simmons LR, Molyneaux L, Yue DK, Chua EL (2012) Steroid-induced diabetes: is it just unmasking of type 2 diabetes? ISRN Endocrinol. 2012:910905
Patti A, Gennari L, Merlotti D, Dotta F, Nuti R (2013) Endocrine actions of osteocalcin. Int J Endocrinol 2013:846480
Cooper MS, Seibel MJ, Zhou H (2016) Glucocorticoids, bone and energy metabolism. Bone 82:64–68
Desentis-Desentis MF, Rivas-Carrillo JD, Sánchez-Enríquez S (2020) Protective role of osteocalcin in diabetes pathogenesis. J Bone Miner Metab 38:765–771
Moriishi T, Komori T (2020) Lack of reproducibility in osteocalcin-deficient mice. PLoS Genet 16(6):e1008939
Diegel CR, Hann S, Ayturk UM, Hu JCW, Lim KE, Droscha CJ et al (2020) An osteocalcin-deficient mouse strain without endocrine abnormalities. PLoS Genet 16(5):e1008361
Liu DM, Guo XZ, Tong HJ, Tao B, Sun LH, Zhao HY, Ning G, Liu JM (2015) Association between osteocalcin and glucose metabolism: a meta-analysis. Osteoporos Int 26:2823–2833
Kunutsor SK, Apekey TA, Laukkanen JA (2015) Association of serum total osteocalcin with type 2 diabetes and intermediate metabolic phenotypes: systematic review and meta-analysis of observational evidence. Eur J Epidemiol 30:599–614
Brennan-Speranza TC, Henneicke H, Gasparini SJ, Blankenstein KI, Heinevetter U, Cogger VC, Svistounov D, Zhang Y, Cooney GJ, Buttgereit F, Dunstan CR, Gundberg C, Zhou H, Seibel MJ (2012) Osteoblasts mediate the adverse effects of glucocorticoids on fuel metabolism. J Clin Invest 122:4172–4189
Ferris HA, Kahn CR (2012) New mechanisms of glucocorticoid-induced insulin resistance: make no bones about it. J Clin Invest 122:3854–3857
Florez H, Hernández-Rodríguez J, Carrasco JL, Prieto-González S, Muxi A, Filella X, Ruiz-Gaspà S, Gómez-Puerta JA, Cid M, Espinosa G, Monegal A, Guañabens N, Peris P (2020) Vertebral fracture risk in glucocorticoid-induced osteoporosis: the role of hypogonadism and corticosteroid boluses. RMD Open. 6:e001355
Lewiecki EM, Watts NB, McClung MR, Petak SM, Bachrach LK, Shepherd JA et al (2004) Official positions of the International Society for Clinical Densitometry. J Clin Endocrinol Metab 89:3651–3655
R Core Team. R: A language and environment for statistical computing. Vienna: R Foundation for Statistical Computing. https://www.R-project.org. 9 May 2021, date last acceded.
Skaltsa K, Jover L, Carrasco JL (2010) Estimation of the diagnostic threshold accounting for decision costs and sampling uncertainty. Biom J 52:676–697
Perez-Jaume S, Skaltsa K, Pallarès N, Carrasco J (2017) ThresholdROC: optimum threshold estimation tools for continuous diagnostic tests in R. J Stat Softw 82:1–21
Schwarz PE, Li J, Lindstrom J, Tuomilehto J (2009) Tools for predicting the risk of type 2 diabetes in daily practice. Horm Metab Res 41:86–97
Hygum K, Starup-Linde J, Harsløf T, Vestergaard P, Langdahl BL (2017) Mechanisms in endocrinology: diabetes mellitus, a state of low bone turnover—a systematic review and meta-analysis. Eur J Endocrinol 176:R137–R157
Krakauer JC, McKenna MJ, Buderer NF, Rao DS, Whitehouse FW, Parfitt AM (1995) Bone loss and bone turnover in diabetes. Diabetes 44:775–782
Silva BC, Leslie WD, Resch H, Lamy O, Lesnyak O, Binkley N et al (2014) Trabecular bone score: a noninvasive analytical method based upon the DXA image. J Bone Miner Res 29:518–530
Wang Q, Zhang B, Xu Y, Xu H, Zhang N (2013) The relationship between serum osteocalcin concentration and glucose metabolism in patients with type 2 diabetes mellitus. Int J Endocrinol 2013:842598
van Bommel EJM, de Jongh RT, Brands M, Heijboer AC, den Heijer M, Serlie MJ, van Raalte DH (2018) The osteoblast: Linking glucocorticoid-induced osteoporosis and hyperglycaemia? A post-hoc analysis of a randomised clinical trial. Bone 112:173–176
Mazziotti G, Maffezzoni F, Doga M, Hofbauer LC, Adler RA, Giustina A (2014) Outcome of glucose homeostasis in patients with glucocorticoid-induced osteoporosis undergoing treatment with bone active-drugs. Bone 67:175–180
This study was funded in part by the Societat Catalana de Reumatologia.
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Consent to participate
Informed consent was obtained from all individual participants included in the study.
Consent for publication
Conflicts of interest
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
About this article
Cite this article
Florez, H., Hernández-Rodríguez, J., Carrasco, J.L. et al. Low serum osteocalcin levels are associated with diabetes mellitus in glucocorticoid treated patients. Osteoporos Int (2021). https://doi.org/10.1007/s00198-021-06167-z
- Glucocorticoid-induced diabetes mellitus
- Glucocorticoid treatment
- Type 2 diabetes mellitus