Positive Correlation between Serum Osteocalcin and Testosterone in Male Hyperthyroidism Patients with High Bone Turnover

Abstract

Purpose: Animal studies suggested that there is an independent bone-osteocalcin-gonadal axis, except of the hypothalamic-pituitary-gonadal axis. Based on this hypothesis, the higher osteocalcin during the high bone turnover should be followed by higher testosterone formation. Yet such clinical evidence is limited. The patients with uncontrolled hyperthyroidism are proper model with high bone turnover. If this hypothesis is true, there should be high testosterone level in patients with uncontrolled hyperthyroidism. Therefore, Graves’ disease patients were recruited to study the correlation between osteocalcin and testosterone.

Materials and Methods: 50 male hyperthyroidism patients with Graves’ disease and 50 health persons matched by age and gender were enrolled in our cross-section study. Serum markers for thyroid hormone, sex hormone and bone metabolic markers including free triiodothyronine (FT3), free thyroxine (FT4), thyroid-stimulating hormone (TSH), testosterone, luteinizing hormone (LH), follicle-stimulating hormone (FSH) and osteocalcin (OC), C-terminal telopeptide fragments of type I collagen (CTX) were examined. The demographic parameters such as duration of disease were also collected. All data was analyzed by SPSS 20.0.

Results: High testosterone and osteocalcin level was observed in the hyperthyroidism patients (T 36.35±10.72 nmol/l and OC 46.79±26.83 ng/ml). In simple Pearson correlation, testosterone was positively associated with OC (r=0.486, P<0.001), and this positive relation still existed after adjusted for age, BMI, smoking, drinking, duration of disease, FT3, FT4, LH, FSH, CTX in multi-linear regression analysis (See Model 1–4).

Conclusion: In male hyperthyroidism patients, osteocalcin was positively correlated with serum testosterone, which indirectly supports the hypothesis that serum osteocalcin participates in the regulation of sex hormone.

Key words

osteocalcin - testosterone - hyperthyroidism

^* Dr. Ni Zhong and Dr. Bei Xu contribute equally to this paper

• References

• 1 Kumar TR. Functional analysis of LHβ knockout mice. Molecular and cellular endocrinology 2007; 269: 81-84
• 2 Themmen APNHI. Mutations of Gonadotropins and Gonadotropin Receptors: Elucidating the Physiology and Pathophysiology of Pituitary-Gonadal Function. Endocr Rev 2000; 21: 551-583
• 3 Ma X, Dong Y, Matzuk MM et al. Targeted disruption of luteinizing hormone-subunit leads to hypogonadism, defects in gonadal steroidogenesis, and infertility. Proceedings of the National Academy of Sciences 2004; 101: 17294-17299
• 4 Oury F, Ferron M, Huizhen W et al. Osteocalcin regulates murine and human fertility through a pancreas-bone-testis axis. The Journal of clinical investigation 2013; 123: 2421-2433
• 5 Bolland MJ, Grey A, Horne AM et al. Testosterone levels following decreases in serum osteocalcin. Calcified tissue international 2013; 93: 133-136
• 6 Li Y, Li K. Osteocalcin Induces Growth Hormone/Insulin-Like Growth Factor-1 System by Promoting Testosterone Synthesis in Male Mice. Hormone and metabolic research=Hormon- und Stoffwechselforschung=Hormones et metabolisme 2014;
• 7 Fukumoto S, Martin TJ. Bone as an endocrine organ. Trends in endocrinology and metabolism: TEM 2009; 20: 230-236
• 8 Karsenty G, Oury F. Biology without walls: The novel endocrinology of bone. Annu Rev Physiol 2012; 74: 87-105
• 9 Karsenty G, Ferron M. The contribution of bone to whole-organism physiology. Nature 2012; 481: 314-320
• 10 Hannemann A, Breer S, Wallaschofski H et al. Osteocalcin is associated with testosterone in the general population and selected patients with bone disorders. Andrology 2013; 1: 469-474
• 11 Cui R, Su B, Sheng C et al. Total osteocalcin in serum predicts testosterone level in male type 2 diabetes mellitus. International journal of clinical and experimental medicine 2014; 7: 1145-1149
• 12 Xu Y, Wang L, He J et al. Prevalence and control of diabetes in Chinese adults. Jama 2013; 310: 948-959
• 13 Nardozza Junior A, Szelbracikowski Sdos S, Nardi AC et al. Age-related testosterone decline in a Brazilian cohort of healthy military men. International braz j urol: official journal of the Brazilian Society of Urology 2011; 37: 591-597
• 14 Shamim MO, Khan FMA, Arshad R. Association between serum total testosterone and Body Mass Index in middle aged healthy men. Pak J Med Sci 2015; 31: 355-359
• 15 Maneesh M, Dutta S, Chakrabarti A et al. Alcohol abuse-duration dependent decrease in plasma testosterone and antioxidants in males. Indian journal of physiology and pharmacology 2006; 50: 291-296
• 16 Wang W, Yang X, Liang J et al. Cigarette smoking has a positive and independent effect on testosterone levels. Hormones 2013; 12: 567-577
• 17 Ford HC, Cooke RR, Keightley EA et al. Serum levels of free and bound testosterone in hyperthyroidism. Clinical endocrinology 1992; 36: 187-192
• 18 Kugelberg E. Reproductive endocrinology: osteocalcin and male fertility. Nature reviews Endocrinology 2013; 9: 441
• 19 Strapazzon G, Garolla A, Carraro U et al. Osteocalcin and its association with testosterone in patients with metabolic diseases. Osteoporosis international: a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA 2013; 24: 2539-2540
• 20 Schwetz V, Gumpold R, Graupp M et al. Osteocalcin is not a strong determinant of serum testosterone and sperm count in men from infertile couples. Andrology 2013; 1: 590-594
• 21 Limonard EJ, van Schoor NM, de Jongh RT et al. Osteocalcin and the pituitary-gonadal axis in older men: a population-based study. Clinical endocrinology 2015; 82: 753-759
• 22 Kostoglou-Athanassiou I, Ntalles K, Gogas J et al. Sex hormones in postmenopausal women with breast cancer on tamoxifen. Hormone research 1997; 47: 116-120
• 23 Zahringer S, Tomova A, von Werder K et al. The influence of hyperthyroidism on the hypothalamic-pituitary-gonadal axis. Experimental and clinical endocrinology & diabetes: official journal, German Society of Endocrinology [and] German Diabetes Association 2000; 108: 282-289
• 24 Skjoldebrand Sparre L, Kollind M, Carlstrom K. Ovarian ultrasound and ovarian and adrenal hormones before and after treatment for hyperthyroidism. Gynecologic and obstetric investigation 2002; 54: 50-55
• 25 Deb P, Gupta SK, Godbole MM. Effects of short-term testosterone replacement on areal bone mineral density and bone turnover in young hypogonadal males. Indian journal of endocrinology and metabolism 2012; 16: 947-951
• 26 Ferron M, Lacombe J. Regulation of energy metabolism by the skeleton: Osteocalcin and beyond. Archives of biochemistry and biophysics 2014;
• 27 Overvad S, Bay K, Bojesen A et al. Low INSL3 in Klinefelter syndrome is related to osteocalcin, testosterone treatment and body composition, as well as measures of the hypothalamic-pituitary-gonadal axis. Andrology 2014; 2: 421-427
• 28 Karsenty G, Oury F. Regulation of male fertility by the bone-derived hormone osteocalcin. Molecular and cellular endocrinology 2014; 382: 521-526