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Carmel, IN, United States

Grethen E.,Indiana University | Hill K.M.,Indiana University | Jones R.,Indiana University | Cacucci B.M.,St. Vincent Bariatric Services | And 4 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2012

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/m2), 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 (R2 = 0.39); 1,25Dby25D, FGF23, and phosphate (R2 = 0.43); FGF23 by leptin and 1,25D (R2 = 0.27); BAP by leptin, PTH, and Ca (R2 = 0.39); and sclerostin by leptin and PTH (R2 = 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 mineralregulating 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. Copyright © 2012 by The Endocrine Society.


Bruno C.,Indiana University | Fulford A.D.,Indiana University | Potts J.R.,Indiana University | McClintock R.,Indiana University | And 5 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2010

Objective: The aim of the study was to examine serum markers of bone turnover at 6 and 18 months after Roux-en-Y gastric bypass surgery. Participants: Ten women and 10 men [body mass index (BMI), 50.2 ± 8.4 kg/m2] were studied at 6 months; 10 women and nine men (BMI, 47.2 ± 6.6 kg/m2) were studied at 18 months after surgery. Main Outcome Measures: Serum osteocalcin, bone specific alkaline phosphatase (BAP), N-telopeptide of type 1 collagen (NTX), PTH, 25-hydroxy vitamin D, and leptin were measured. Results: BMI was reduced 32.7 ± 6.2% at 6 months after surgery. Serum osteocalcin (6.9 ± 2.4 to 10.9 ± 2.6 ng/ml; P < 0.0001), BAP (14.2 ± 3.7 to 16.4 ± 4.5 ng/ml; P = 0.04), and NTX (10.9 ± 1.7 to 19.6 ± 5.3 nM bone collagen equivalents; P < 0.0001) were increased. Calcium, phosphate, and PTH were unchanged, but 25-hydroxy vitamin D increased (16.0 ± 8.9 vs. 26.9 ± 10.6 ng/ml; P <0.0001). The increase in NTX correlated with reduction in serum leptin (r = 0.58; P = 0.007). BMI was reduced 40.9 ± 7.5% at 18 months after surgery. Serum BAP (17.6 ± 5.3 to 22.2 ± 7.8 ng/ml; P = 0.0017) and NTX (10.8 ± 2.7 to 16.9 ± 5.5 nM bone collagen equivalents; P < 0.0001) were increased. Calcium, phosphate, and PTH were unchanged, but 25-hydroxy vitamin D increased (17.7 ± 7.6 to 25.6 ± 6.8 ng/ml; P < 0.0001). The increase in NTX correlated with reduction in BMI (r = 0.58; P = 0.009) and leptin (r = 0.45; P = 0.04) and the increase in serum 25-hydroxy vitamin D(r = 0.43; P = 0.05). In multiple regression (adjusted model R 2 0.263; P = 0.013), reduction in leptin was a significant predictor of increase in NTX (P = 0.016), but changes in BMI and 25-hydroxy vitamin D were not. Conclusions: Weight loss after bariatric surgery is associated with long-term increase in serum markers of bone turnover. The increase in NTX is related to the decrease in leptin, which may signal caloric restriction to the skeleton. Copyright © 2010 by The Endocrine Society.


Grethen E.,Indiana University | McClintock R.,Indiana University | Gupta C.E.,St. Vincent Bariatric Services | Jones R.,St. Vincent Bariatric Services | And 6 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2011

Background: Low vitamin D status and hyperparathyroidism occur in obesity and may be involved in pathogenesis of obesity-associated comorbid conditions. Aims: Our aims were to determine in obesity whether there was vitamin D insufficiency, assessed by serum 25-hydroxyvitamin D (s25D) and serum PTH (sPTH) and whether it related to comorbid conditions. Methods:Weconducted a case-control study of 48 women having bariatric surgery and 50 healthy women frequency matched for race, age, year, and season of study. Height, weight, s25D, sPTH, serum 1,25-dihydroxyvitamin D (s1,25D), serum bone alkaline phosphatase, serum cross-linked N-telopeptides of type 1 collagen, and serum calcium, phosphate, creatinine, glucose, and insulin were measured, and comorbid conditions were documented from patient files. Results: Weight (140 vs. 76 kg, P < 0.001), sPTH (44.4 vs. 25.6 pg/ml, P < 0.001), s1,25D (39 vs. 24 pg/ml, P<0.001), serum bone alkaline phosphatase (19 vs. 12 ng/ml, P<0.001), serum cross-linked N-telopeptides of type 1 collagen (9.6 vs. 7.9 nM bone collagen equivalents, P = 0.007), serum phosphate (3.45 vs. 3.24 mg/dl, P=0.043), and serum creatinine (1.05 vs. 0.87 mg/dl, P<0.001) were higher, and s25D (16 vs. 23 ng/ml, P <.001) was lower in bariatric-surgery women than control women. s25D was lower in bariatric-surgery women than controls in summer (17 vs. 26 ng/ml, P < 0.0001) but not winter (15 vs. 18 ng/ml, P > 0.2). Multiple regression analysis demonstrated that weight predicted s25D (P < 0.001) and sPTH (P = 0.001), but s25D did not predict sPTH or the presence of comorbid conditions except for osteoarthritis. Conclusion:Womenhaving bariatric surgery had lower s25D and higher sPTH. The major determinant of s25D and sPTH was weight. Hyperparathyroidism in obesity did not indicate vitamin D insufficiency. Low s25D was not associated with comorbid conditions, apart from osteoarthritis. Copyright © 2011 by The Endocrine Society.

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