Serum Leptin, Parathyroid Hormone, 1,25-Dihydroxyvitamin D, Fibroblast Growth Factor 23, Bone Alkaline Phosphatase, and Sclerostin Relationships in Obesity

Background: Obesity is associated with hyperparathyroidism and increased bone mass and turnover, but their pathogeneses are unclear. Aims: Our aim was to determine in obesity interrelationships among serum levels of leptin, the mineral-regulating hormones, bone turnover markers, and sclerostin. Methods: This case-control study was performed in 20 women having bariatric surgery and 20 control women matched for race and age. Anthropometrics and fasting serum biochemistries were measured in controls and in bariatric patients the morning of surgery. Results: Body mass index (48.9 vs. 25.4 kg/m(2)), weight (128.6 vs. 71.9 kg), serum leptin (74.6 vs. 25.2 ng/ml), PTH (44.5 vs. 28.8 pg/ml), fibroblast growth factor 23 (FGF23) (42.4 vs. 25.9 pg/ml), and bone alkaline phosphatase (BAP) (25.8 vs. 17.5 U/liter) were higher, but height (162.3 vs. 167.7 cm) and 1,25-dihydroxyvitamin D (1,25D) (39.2 vs. 48.7 pg/ml) were lower in bariatric surgery patients than controls. There was no difference in serum sclerostin, amino-terminal collagen cross-links, 25-hydroxyvitamin D (25D), calcium, phosphate, and creatinine between groups. In the combined sample, leptin was positively related to PTH, FGF23, and BAP but not to 1,25D or sclerostin. Multiple regression analysis demonstrated that PTH was predicted by leptin and Ca(R-2 = 0.39); 1,25D by 25D, FGF23, and phosphate (R-2 = 0.43); FGF23 by leptin and 1,25D (R-2 = 0.27); BAP by leptin, PTH, and Ca (R-2 = 0.39); and sclerostin by leptin and PTH (R-2 = 0.20). Conclusions: Women having bariatric surgery had higher leptin, PTH, FGF23, and BAP and lower 1,25D than controls. Leptin predicted the serum levels of PTH, 1,25D, and FGF23, the mineral-regulating hormones, and BAP, a bone formation marker, in women with body mass index ranging from 13.9-65.8 kg/m(2). The results suggest that leptin has an endocrine or paracrine effect on PTH and FGF23 production and that PTH may be one of the signals in obesity that leads to increased bone mass. (J Clin Endocrinol Metab 97: 1655-1662, 2012)