Osteocalcin is inversely associated with adiposity and leptin in adolescent boys
-
Jaak Jürimäe
,
Evelin Lätt
Abstract
Background/Aims: Recently, osteocalcin (OC), an osteoblast-derived hormone, has been found to correlate with adiposity, adipocytokines and insulin resistance in adults, but few studies have investigated this in children. The aim of this study was to investigate these associations in adolescent boys, for whom it is a time of significant bone mineral accrual, taking into account possible confounders related to adipose and bone tissues.
Participants/Methods: Participants were 141 adolescent boys (mean age 13.9±0.7 years), who were divided into tertiles according to OC levels. Across these groups, differences in total body fat mass (FM), body fat distribution, adiponectin, leptin and insulin resistance values were examined with relation to age, pubertal stage, daily energy and calcium intakes, and physical activity.
Results: Mean body mass index (BMI), FM, body fat% and leptin differed significantly between subjects in the three OC tertiles after adjustment for age, pubertal stage, energy and calcium intakes, and physical activity. There were no differences in fat free mass (FFM), bone mineral content, energy and calcium intakes, physical activity, adiponectin and insulin resistance values between study groups. For the entire cohort, mean serum OC was 130.2±45.2 ng/mL and was related to body mass, BMI, FM, body fat distribution and leptin. Circulating OC was not associated with FFM, daily energy and calcium intakes, physical activity, adiponectin or insulin resistance (insulin, glucose, homeostasis model assessment-insulin resistance) values.
Conclusions: In male adolescents, OC is inversely related to body adiposity and leptin values, even after consideration of several factors that may affect bone and adipose tissues.
Acknowledgments
This study was supported by the Estonian Ministry of Education and Science grant GKKSP 9168.
References
1. Jürimäe J. Interpretation and application of bone turnover markers in children and adolescents. Curr Opin Pediatr 2010;22:494–500.10.1097/MOP.0b013e32833b0b9eSearch in Google Scholar PubMed
2. Rochefort GY, Rocher E, Aveline PC, Garnero P, Bab I, et al. Osteocalcin-insulin relationship in obese children: a role for the skeleton in energy metabolism. Clin Endocrinol 2011;75:265–70.10.1111/j.1365-2265.2011.04031.xSearch in Google Scholar PubMed
3. Polgreen LE, Jacobs Jr DR, Nathan BM, Steinberger J, Moran A, et al. Association of osteocalcin with obesity, insulin resistance, and cardiovascular risk factors in young adults. Obesity 2012;20:2194–201.10.1038/oby.2012.108Search in Google Scholar PubMed PubMed Central
4. Karsenty G. Convergence between bone and energy homeostasis: leptin regulation of bone mass. Cell Metab 2006;4:341–8.10.1016/j.cmet.2006.10.008Search in Google Scholar PubMed
5. Lee NK, Sowa H, Hinoi E, Ferron M, Ahn JD, et al. Endocrine regulation of energy metabolism by the skeleton. Cell 2007;130:456–69.10.1016/j.cell.2007.05.047Search in Google Scholar PubMed PubMed Central
6. Lee NK, Karsenty G. Reciprocal regulation of bone and energy metabolism. Trends Endocrinol Metab 2008;19:161–6.10.1016/j.tem.2008.02.006Search in Google Scholar PubMed
7. Ferron M, Hinoi E, Karsenty G, Ducy P. Osteocalcin differentially regulates beta cell and adipocyte gene expression and affects the development of metabolic diseases in wild-type mice. Proc Natl Acad Sci USA 2008;105:5266–70.10.1073/pnas.0711119105Search in Google Scholar PubMed PubMed Central
8. Buday B, Pach FP, Literati-Nagy B, Vitai M, Vecsei Z, et al. Serum osteocalcin is associated with improved metabolic state via adiponectin in females versus testosterone in males. Gender specific nature of the bone-energy homeostasis axis. Bone 2013;57:98–104.10.1016/j.bone.2013.07.018Search in Google Scholar PubMed
9. Chen L, Li Q, Yang Z, Ye Z, Huang Y, et al. Osteocalcin, glucose metabolism, lipid profile and chronic low-grade inflammation in middle-aged and elderly. Diabet Med 2013;30:309–17.10.1111/j.1464-5491.2012.03769.xSearch in Google Scholar PubMed
10. Rui X, Xu B, Su J, Pan C, Zhan C, et al. Differential pattern for regulating insulin secretion, insulin resistance, and lipid metabolism by osteocalcin in male and female T2DM patients. Med Sci Monit 2014;20:711–19.10.12659/MSM.890130Search in Google Scholar PubMed PubMed Central
11. Pittas AG, Harris SS, Eliades M, Stark P, Dawson-Hughes B. Association between serum osteocalcin and markers of metabolic phenotype. J Clin Endocrinol Metab 2009;94:827–32.10.1210/jc.2008-1422Search in Google Scholar PubMed PubMed Central
12. Gravenstein KS, Napora JK, Short RG, Ramachandran R, Carlson OD, et al. Cross-sectional evidence of a signaling pathway from bone homeostasis to glucose metabolism. J Clin Endocrinol Metab 2011;96:E884–90.10.1210/jc.2010-2589Search in Google Scholar PubMed PubMed Central
13. Lu C, Ivaska KK, Alen M, Wang Q, Törmäkangas T, et al. Serum osteocalcin is not associated with glucose but is inversely associated with leptin across generations of nondiabetic women. J Clin Endocrinol Metab 2012;97:4106–14.10.1210/jc.2012-2045Search in Google Scholar PubMed
14. Kanazawa I, Yamaguchi T, Yamamoto M, Yamauchi M, Kurioka S, et al. Serum osteocalcin level is associated with glucose metabolism and atherosclerosis parameters in type 2 diabetes mellitus. J Clin Endocrinol Metab 2009;94: 45–9.10.1210/jc.2008-1455Search in Google Scholar PubMed
15. Foresta C, Strapazzon G, De Toni L, Gianesello L, Calcagno A, et al. Evidence for osteocalcin production by adipose tissue and its role in human metabolism. J Clin Endocrinol Metab 2010;95:3502–6.10.1210/jc.2009-2557Search in Google Scholar PubMed
16. Dubnov-Raz G, Ish-Shalom S, Chodick G, Rozen GS, Giladi A, et al. Osteocalcin is independently associated with body mass index in adolescent girls. Pediatr Obes 2012;7:313–18.10.1111/j.2047-6310.2012.00058.xSearch in Google Scholar PubMed
17. Kim GS, Jekal Y, Kim HS, Im JA, Park JY, et al. Reduced serum total osteocalcin is associated with central obesity in Korean children. Obes Res Clin Pract 2014;8:e201–98.10.1016/j.orcp.2012.12.003Search in Google Scholar PubMed
18. Wang JW, Tang QY, Ruan HJ, Cai W. Relation between serum osteocalcin levels and body composition in obese children. J Pediatr Gastroenterol Nutr 2014;58:729–32.10.1097/MPG.0000000000000243Search in Google Scholar PubMed
19. Abseyi N, Siklar Z, Berberoglu M, Hacihamdioglu B, Savas Erdeve S, et al. Relationships between osteocalcin, glucose metabolism, and adiponectin in obese children: is there crosstalk between bone tissue and glucose metabolism? J Clin Res Pediatr Endocrinol 2012;4:182–8.10.4274/Jcrpe.831Search in Google Scholar
20. Flemming GM, Petzold S, Meigen C, Körner A, Kiess W, et al. Is circulating osteocalcin related to adipokines and overweight/obesity in children and adolescents? Exp Clin Endocrinol Diab 2012;120:383–7.10.1055/s-0032-1306287Search in Google Scholar PubMed
21. Reinehr T, Roth CL. A new link between skeleton, obesity and insulin resistance: relationships between osteocalcin, leptin and insulin resistance in obese children before and after weight loss. Int J Obes 2010;34:852–8.10.1038/ijo.2009.282Search in Google Scholar PubMed
22. Vaitkeviciute D, Lätt E, Mäestu J, Jürimäe T, Saar M, et al. Physical activity and bone mineral accrual in boys with different body mass parameters during puberty: a longitudinal study. PloS One 2014;9:e107759.10.1371/journal.pone.0107759Search in Google Scholar PubMed PubMed Central
23. Tanner J. Growth at adolescence, 2nd ed. Oxford: Blackwell Scientific Publications, 1962.Search in Google Scholar
24. Leone M, Comtois AS. Validity and reliability of self-assessment of sexual maturity in elite adolescent athletes. J Sports Med Phys Fitness 2007;47:361–5.Search in Google Scholar
25. Pomerants T, Tillmann V, Karelson K, Jürimäe J, Jürimäe T. Ghrelin response to acute aerobic exercise in boys at different stages of puberty. Horm Metab Res 2006;38:752–7.10.1055/s-2006-955087Search in Google Scholar PubMed
26. Pomerants T, Tillmann V, Jürimäe J, Jürimäe T. The influence of serum ghrelin, IGF axis and testosterone on bone mineral density in boys at different stages of sexual maturity. J Bone Miner Metab 2007;25:193–7.10.1007/s00774-006-0744-6Search in Google Scholar PubMed
27. Lätt E, Jürimäe J, Haljaste K, Cicchella A, Purge P, et al. Longitudinal development of physical and performance parameters during biological maturation of young male swimmers. Percept Motor Skills 2009;108:297–307.10.2466/pms.108.1.297-307Search in Google Scholar
28. Jürimäe J, Jürimäe T, Ring-Dimitriou S, LeMura LM, Arciero PJ, et al. Plasma adiponectin and insulin sensitivity in overweight and normal-weight middle-aged premenopausal women. Metab Clin Exp 2009;58:638–43.10.1016/j.metabol.2008.12.009Search in Google Scholar PubMed
29. Hanks LJ, Casazza K, Ashraf A, Fernandez JR. Calcium homeostasis may influence resting energy expenditure with effects most apparent in early pubertal girls. Acta Paediatr 2012;101:e363–8.10.1111/j.1651-2227.2012.02717.xSearch in Google Scholar PubMed PubMed Central
30. Ivuskans A, Mäestu J, Jürimäe T, Lätt E, Purge P, et al. Sedentary time has a negative influence on bone mineral parameters in peripubertal boys: a 1-year prospective study. J Bone Miner Metab 2015;33:85–92.10.1007/s00774-013-0556-4Search in Google Scholar PubMed
31. Wallace TM, Levy JC, Matthews DR. Use and abuse of HOMA modeling. Diab Care 2004;27:1487–95.10.2337/diacare.27.6.1487Search in Google Scholar PubMed
32. Kindblom JM, Ohlsson C, Ljunggren O, Karlsson MK, Tivesten A, et al. Plasma osteocalcin is inversely related to fat mass and plasma glucose in elderly Swedish men. J Bone Miner Res 2009;24:785–91.10.1359/jbmr.081234Search in Google Scholar PubMed
33. Boucher-Berry C, Speiser PW, Carey DE, Shelov SP, Accacha S, et al. Vitamin D, osteocalcin, and risk for adiposity as co-morbidities in middle school children. J Bone Miner Res 2012;27:283–93.10.1002/jbmr.550Search in Google Scholar
34. Pollock NK, Bernard PJ, Gower BA, Gundberg CM, Wenger K, et al. Lower uncarboxylated osteocalcin concentrations in children with prediabetes is associated with beta-cell function. J Clin Endocrinol Metab 2011;96:E1092–9.10.1210/jc.2010-2731Search in Google Scholar
35. Luo XH, Guo JL, Yuan LQ, Xie H, Zhou HD, et al. Adiponectin stimulates human osteoblasts proliferation and differentation via the MAPK signaling pathway. Exp Cell Res 2005;309:99–109.10.1016/j.yexcr.2005.05.021Search in Google Scholar
36. Ducy P, Amling M, Takeda S, Priemel M, Schilling AF, et al. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell 2000;100:197–207.10.1016/S0092-8674(00)81558-5Search in Google Scholar
37. van Coeverden SC, Netelenbos JC, de Ridder CM, Roos JC, Popp-Snijders C, et al. Bone metabolism markers and bone mass in healthy pubertal boys and girls. Clin Endocrinol 2002;57:107–116.10.1046/j.1365-2265.2002.01573.xSearch in Google Scholar PubMed
38. Jürimäe J, Pomerants T, Tillmann V, Jürimäe T. Bone metabolism markers and ghrelin in boys at different stages of sexual maturation. Acta Paediatr 2009;98:892–6.10.1111/j.1651-2227.2008.01193.xSearch in Google Scholar PubMed
39. Lucey AJ, Paschos GK, Thorsdottir I, Martinez JA, Cashman KD, et al. Young overweight and obese women with lower circulating osteocalcin concentrations exhibit higher insulin resistance and concentrations of C-reactive protein. Nutr Res 2013;33:67–75.10.1016/j.nutres.2012.11.011Search in Google Scholar PubMed
©2015 by De Gruyter
Articles in the same Issue
- Frontmatter
- Highlight: Obesity
- Childhood obesity at the crossroads
- Obesogenic environments: environmental approaches to obesity prevention
- Childhood obesity and eating behaviour
- Hypothalamic obesity in children: pathophysiology to clinical management
- The reliability of body mass index in the diagnosis of obesity and metabolic risk in children
- Determining abdominal obesity cut-offs and relevant risk factors for anthropometric indices in Turkish children and adolescents
- The effect of body mass index on blood pressure varies by race among obese children
- Insulin secretion response during oral glucose tolerance test is related to low cardiorespiratory fitness in obese adolescents
- Is there a relationship between cardiovascular risk factors and dehydroepiandrosterone sulfate levels in childhood obesity?
- The effect of lifestyle change and metformin therapy on serum arylesterase and paraoxonase activity in obese children
- Childhood obesity, thyroid function, and insulin resistance – is there a link? A longitudinal study
- Associations between IGF-I, IGF-binding proteins and bone turnover markers in prepubertal obese children
- Osteocalcin is inversely associated with adiposity and leptin in adolescent boys
- Association between cardiovascular risk factors and carotid intima-media thickness in prepubertal Brazilian children
- Insulin resistance and cardiometabolic risk factors in obese children and adolescents: a hierarchical approach
- The role of apolipoprotein E polymorphism in improving dyslipidemia in obese adolescents following physical exercise and National Cholesterol Education Program Step II intervention
- Review article
- Is ultrasound useful in the diagnosis of adolescents with polycystic ovary syndrome?
- Original articles
- IGF-II expression and methylation in small for gestational age infants
- Early screening of FTO and MC4R variants in newborns of Greek origin
- Pitfalls in hormonal diagnosis of 17-beta hydroxysteroid dehydrogenase III deficiency
- The prevalence of vitamin D deficiency among schoolchildren: a cohort study from Xinxiang, China
- Management of testosterone therapy in adolescents and young men with hypogonadism: are we following adult clinical practice guidelines?
- Vitamin D status and its associations with components of metabolic syndrome in healthy children
- Metformin treatment improves weight and dyslipidemia in children with metabolic syndrome
- Patient reports
- Hypothyroidism caused by the combination of two heterozygous mutations: one in the TSH receptor gene the other in the DUOX2 gene
- Ovarian carcinoma in a 14-year-old with classical salt-wasting congenital adrenal hyperplasia and bilateral adrenalectomy
- An asymptomatic mother diagnosed with 3-methylcrotonyl-CoA carboxylase deficiency after newborn screening
- A new missense mutation in the BCKDHB gene causes the classic form of maple syrup urine disease (MSUD)
- Ovotesticular disorder of sex development with unusual karyotype: patient report
- First case report of medium-chain acyl-coenzyme A dehydrogenase deficiency in China
- Virilizing adrenal oncocytoma in a 9-year-old girl: rare neoplasm with an intriguing postoperative course
- Unexpected clinical features in a female patient with proopiomelanocortin (POMC) deficiency
- Sirolimus therapy in a patient with severe hyperinsulinaemic hypoglycaemia due to a compound heterozygous ABCC8 gene mutation
- Cross-reactivity of adrenal steroids with aldosterone may prevent the accurate diagnosis of congenital adrenal hyperplasia
- Hyperthyroidism hidden by congenital central hypoventilation syndrome
- The use of pamidronate for acute vitamin D intoxication, clinical experience with three cases
- Chondrocalcinosis related to familial hypomagnesemia with hypercalciuria and nephrocalcinosis
- Cushing syndrome related to leukemic infiltration of the central nervous system
- Hashimoto’s encephalopathy: a rare pediatric brain disease
- Short communication
- A novel ABCD1 gene mutation in a Chinese patient with X-linked adrenoleukodystrophy
Articles in the same Issue
- Frontmatter
- Highlight: Obesity
- Childhood obesity at the crossroads
- Obesogenic environments: environmental approaches to obesity prevention
- Childhood obesity and eating behaviour
- Hypothalamic obesity in children: pathophysiology to clinical management
- The reliability of body mass index in the diagnosis of obesity and metabolic risk in children
- Determining abdominal obesity cut-offs and relevant risk factors for anthropometric indices in Turkish children and adolescents
- The effect of body mass index on blood pressure varies by race among obese children
- Insulin secretion response during oral glucose tolerance test is related to low cardiorespiratory fitness in obese adolescents
- Is there a relationship between cardiovascular risk factors and dehydroepiandrosterone sulfate levels in childhood obesity?
- The effect of lifestyle change and metformin therapy on serum arylesterase and paraoxonase activity in obese children
- Childhood obesity, thyroid function, and insulin resistance – is there a link? A longitudinal study
- Associations between IGF-I, IGF-binding proteins and bone turnover markers in prepubertal obese children
- Osteocalcin is inversely associated with adiposity and leptin in adolescent boys
- Association between cardiovascular risk factors and carotid intima-media thickness in prepubertal Brazilian children
- Insulin resistance and cardiometabolic risk factors in obese children and adolescents: a hierarchical approach
- The role of apolipoprotein E polymorphism in improving dyslipidemia in obese adolescents following physical exercise and National Cholesterol Education Program Step II intervention
- Review article
- Is ultrasound useful in the diagnosis of adolescents with polycystic ovary syndrome?
- Original articles
- IGF-II expression and methylation in small for gestational age infants
- Early screening of FTO and MC4R variants in newborns of Greek origin
- Pitfalls in hormonal diagnosis of 17-beta hydroxysteroid dehydrogenase III deficiency
- The prevalence of vitamin D deficiency among schoolchildren: a cohort study from Xinxiang, China
- Management of testosterone therapy in adolescents and young men with hypogonadism: are we following adult clinical practice guidelines?
- Vitamin D status and its associations with components of metabolic syndrome in healthy children
- Metformin treatment improves weight and dyslipidemia in children with metabolic syndrome
- Patient reports
- Hypothyroidism caused by the combination of two heterozygous mutations: one in the TSH receptor gene the other in the DUOX2 gene
- Ovarian carcinoma in a 14-year-old with classical salt-wasting congenital adrenal hyperplasia and bilateral adrenalectomy
- An asymptomatic mother diagnosed with 3-methylcrotonyl-CoA carboxylase deficiency after newborn screening
- A new missense mutation in the BCKDHB gene causes the classic form of maple syrup urine disease (MSUD)
- Ovotesticular disorder of sex development with unusual karyotype: patient report
- First case report of medium-chain acyl-coenzyme A dehydrogenase deficiency in China
- Virilizing adrenal oncocytoma in a 9-year-old girl: rare neoplasm with an intriguing postoperative course
- Unexpected clinical features in a female patient with proopiomelanocortin (POMC) deficiency
- Sirolimus therapy in a patient with severe hyperinsulinaemic hypoglycaemia due to a compound heterozygous ABCC8 gene mutation
- Cross-reactivity of adrenal steroids with aldosterone may prevent the accurate diagnosis of congenital adrenal hyperplasia
- Hyperthyroidism hidden by congenital central hypoventilation syndrome
- The use of pamidronate for acute vitamin D intoxication, clinical experience with three cases
- Chondrocalcinosis related to familial hypomagnesemia with hypercalciuria and nephrocalcinosis
- Cushing syndrome related to leukemic infiltration of the central nervous system
- Hashimoto’s encephalopathy: a rare pediatric brain disease
- Short communication
- A novel ABCD1 gene mutation in a Chinese patient with X-linked adrenoleukodystrophy
