Endocrine Abstracts

Bone is involved in both phosphate-calcium and energetic metabolism. Osteocalcin, secreted by the osteoblasts, stimulates insulin secretion and improves insulin sensitivity. FGF-23, secreted by the osteoclasts, increases phosphate urinary excretion and is a marker of insulin resistance. Relationship between insulin-resistance, body fat and bone metabolism remains unclear. Therefore, the aim of this study was to evaluate osteocalcin and FGF-23 levels in diseases differing by body fat and insulin resistance levels, using lipodystrophies, as a model of insulin-resistance without obesity, obese people with and without insulin-resistance, and control subjects.

The population, recruited from the PHRC-Clin.gov2009-AO-1169-48 trial, was divided in five groups: LMNA-mutated lipodystrophies (LDM, n=11), non-mutated lipodystrophies (LDNM, n=21), obese diabetic patients (OD, n=13), obese non-diabetic patients (OND, n=13), normal-weighed controls (T, n=19). Bone and metabolic biomarkers, as well as DEXA-assessed body composition were compared between these five groups.

Osteocalcin, crosslaps, leptin, BMI, body fat mass, lean-body-mass/height², fasting blood glucose and C peptide, HbA1c and HOMA-IR levels were significantly different between the five groups, with a trend for T-score, calcemia and 25-OHD. Blood phosphate, PTH, FGF-23 and urinary calcium levels were similar.

The two-by-two groups comparison showed a lower level of osteocalcin in the LDNM (median (IQR): 12 (11–14) ng/ml) and LDM (14 (12–19)) groups compared to controls (24 (23–29)), and in the LDNM compared to OND (17 (13–21)) groups. Osteocalcin was correlated positively to crosslaps (r=0.74, P<0.0001) and negatively to HOMA-IR (LDNM:4 (0.6–11); LDM:3 (2–5); OD:4 (3–6); OND:1.6 (1–3); T:1.1 (0.8–1.4); r=−0.50, P<0.0001), lean-body-mass/height² (r=−0.41, P=0.0003) and T-score (r=−0.35, P=0.0024), but not to body fat or leptin (LDNM:15 (8–22); LDM:6 (4–12); OD:27 (24–41); OND:49 (32–67); T:5 (4–12) ng/ml).

Conclusion: The comparison of subjects differing by the level of insulin-resistance and body fat, two characteristics often confounded, shows that osteocalcin is negatively correlated with insulin-resistance and T-score, without any influence of body fat or leptin. The role of lean mass in the regulation of osteocalcin has to be further investigated.