Can the positive association of osteocalcin with testosterone be unmasked when the preeminent hypothalamic-pituitary regulation of testosterone production is impaired? The model of spinal cord injury.

PURPOSE: Osteocalcin (OCN), released from the bone matrix during the resorption phase, in its undercarboxylated form, stimulates testosterone (T) biosynthesis in mouse and a loss-of-function mutation of its receptor was associated with hypergonadotropic hypogonadism in humans. Nevertheless, when population-based studies have explored the OCN-T association, conflicting results have been reported. Hypothesizing that the evidence of a positive association between OCN and T could have been hindered by the preeminent role of a well-functioning hypothalamus-pituitary axis in promoting T biosynthesis, we explored this association in men with chronic spinal cord injury (SCI), exhibiting high prevalence of non-hypergonadotropic androgen deficiency. METHODS: Fifty-five consecutive men with chronic SCI underwent clinical/biochemical evaluations, including measurements of total T (TT), OCN and 25(OH)D levels. Free T (FT) levels were calculated by the Vermeulen formula. Comorbidity was scored by Charlson comorbidity index (CCI). RESULTS: A biochemical androgen deficiency (TT < 300 ng/dL) was observed in 15 patients (27.3%). TT was positively correlated with OCN, 25(OH)D and leisure time physical activity and negatively correlated with age, BMI and CCI. OCN was also positively correlated with calculated FT and negatively correlated with BMI and HOMA-IR. At the multiple linear regression analyses, a positive association of OCN with TT and calculated FT persisted after adjustment for confounders. CONCLUSIONS: The positive association here found between OCN and T levels in men with chronic SCI reinforces the notion that a bone-testis axis is also functioning in humans and suggests that it can be unmasked when the preeminent hypothalamic-pituitary regulation of T production is impaired.

Osteocalcin increase after bariatric surgery predicts androgen recovery in hypogonadal obese males.

OBJECTIVE: Bone modulates testis function through osteocalcin (OCN) production. This paper assesses the association between serum OCN and androgen production recovery in morbidly obese males at 9 months after bariatric surgery. SUBJECTS: A cohort of n=103 obese males with mean±s.d. body mass index (BMI) 47.7±8.2 kg m(-2), age 42±11 years, consisting of n=76 patients undergoing gastric bypass and n=27 in the waiting list for surgery. RESULTS: At 9 months from surgery, a significant increase was observed in mean±s.d. total OCN (tOCN=10.4±10.3 ng ml(-1), P<0.001) and undercarboxylated OCN (ucOCN=5.4±3.7 ng ml(-1), P<0.001), total testosterone (TT, 5.6±6.5 nM, P<0.001) and calculated free testosterone (cFT, 0.035±0.133 nM, P<0.006), sex hormone binding globulin (SHBG, 21.2±16.7 nM, P<0.001) and decrease in estradiol (E2, -30.1±51.9 pM, P<0.001) levels only in operated patients, with a significant reduction in BMI (24%) and waist (20%). A positive correlation existed between tOCN and ucOCN (age-adjustment (age-adj.): ß=0.692, P<0.001) and their variations (age-adj.: ß=0.629, P<0.001) after surgery. Multivariate analysis in operated patients showed a significant positive association between variations in tOCN and TT (age-adj.: ß=0.289, P=0.012), SHBG (age-adj.: ß=0.326, P=0.005) but not with cFT variation. tOCN, but not luteinizing hormone (LH) variation was the only significant predictive factor of cFT recovery in the hypogonadal (TT<12 nM) operated subjects even after age- and BMI-adjustment (adj.: ß=0.582, P<0.05). cFT improvement was significantly higher when considering operated patients with tOCN increase (0.045±0.123 vs -0.02±0.118 nM, P=0.015), hypogonadism (0.059±0.111 vs -0.059±0.138 nM, P=0.002) and younger than 35 years (0.102±0.108 vs -0.019±0.123 nM, P=0.009). CONCLUSION: OCN recovery observed after bariatric surgery is significantly associated with cFT improvement independently of BMI variation and age in hypogonadal morbidly obese males.