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Relationships between serum leptin levels and bone mineral parameters in school-aged children: a 3-year follow-up study

Abstract

Leptin regulates bone cell differentiation and functions via direct and indirect actions in experimental settings. Epidemiologically, however, the impact of leptin on the regulation of bone metabolism remains unclear. While some studies have reported a positive relationship between leptin and bone mineral parameters, other studies found an inverse or no association. We analyzed data from a population-based follow-up survey of community-dwelling children in Hamamatsu, Japan, to investigate relationships between leptin levels and bone mineral parameters. Multiple regression analysis was performed. Multicollinearity was quantified using the variance infiltration factor (VIF). Among 408 children who participated in the baseline survey (at age 11.2 years), 254 (121 boys and 133 girls) completed the follow-up survey (at age 14.2 years). Leptin levels were strongly related to fat mass (r = 0.87 in boys, r = 0.80 in girls). Leptin levels at baseline were significantly (P < 0.05) positively related to total body less head (TBLH) areal bone mineral density (aBMD) at follow-up in girls (standardized partial regression coefficient: β = 0.302, VIF = 2.246), after adjusting for body fat percentage (%). On the other hand, leptin levels were inversely related to TBLH aBMD in boys (β = − 0.395, VIF = 4.116), after adjusting for body fat mass (kg). Positive relationships between leptin levels and bone mineral parameters were observed with VIF values < 4.0, whereas inverse relationships were observed with VIF values ≥ 4.0. These findings suggest that positive relationships between leptin levels and bone mineral parameters are weak, or not always observed, due to statistical problems (i.e., multicollinearity) and other factors derived from adipose tissue.

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References

  1. 1.

    Matkovic V, Jelic T, Wardlaw GM, Ilich JZ, Goel PK, Wright JK, Andon MB, Smith KT, Heaney RP (1994) Timing of peak bone mass in Caucasian females and its implication for the prevention of osteoporosis. Inference from a cross-sectional model. J Clin Investig 93:799–808

  2. 2.

    Bailey DA, McKay HA, Mirwald RL, Crocker PR, Faulkner RA (1999) A six-year longitudinal study of the relationship of physical activity to bone mineral accrual in growing children: the university of Saskatchewan bone mineral accrual study. J Bone Miner Res 14:1672–1679

  3. 3.

    Weaver CM, Gordon CM, Janz KF, Kalkwarf HJ, Lappe JM, Lewis R, O’Karma M, Wallace TC, Zemel BS (2016) The National Osteoporosis Foundation’s position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations. Osteoporos Int 27:1281–1386

  4. 4.

    Iwaniec UT, Turner RT (2016) Influence of body weight on bone mass, architecture and turnover. J Endocrinol 230:R115–R130

  5. 5.

    Upadhyay J, Farr OM, Mantzoros CS (2015) The role of leptin in regulating bone metabolism. Metabolism 64:105–113

  6. 6.

    Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372:425–432

  7. 7.

    Thomas T, Burguera B, Melton LJ 3rd, Atkinson EJ, O’Fallon WM, Riggs BL, Khosla S (2001) Role of serum leptin, insulin, and estrogen levels as potential mediators of the relationship between fat mass and bone mineral density in men versus women. Bone 29:114–120

  8. 8.

    Thomas T, Burguera B (2002) Is leptin the link between fat and bone mass? J Bone Miner Res 17:1563–1569

  9. 9.

    Dalskov S, Ritz C, Larnkjaer A, Damsgaard CT, Petersen RA, Sorensen LB, Ong KK, Astrup A, Michaelsen KF, Molgaard C (2016) Associations between adiposity, hormones, and gains in height, whole-body height-adjusted bone size, and size-adjusted bone mineral content in 8- to 11-year-old children. Osteoporos Int 27:1619–1629

  10. 10.

    Garnett SP, Hogler W, Blades B, Baur LA, Peat J, Lee J, Cowell CT (2004) Relation between hormones and body composition, including bone, in prepubertal children. Am J Clin Nutr 80:966–972

  11. 11.

    Rhie YJ, Lee KH, Chung SC, Kim HS, Kim DH (2010) Effects of body composition, leptin, and adiponectin on bone mineral density in prepubertal girls. J Korean Med Sci 25:1187–1190

  12. 12.

    Parm AL, Jurimae J, Saar M, Parna K, Tillmann V, Maasalu K, Neissaar I, Jurimae T (2011) Plasma adipocytokine and ghrelin levels in relation to bone mineral density in prepubertal rhythmic gymnasts. J Bone Miner Metab 29:717–724

  13. 13.

    Afghani A, Goran MI (2009) The interrelationships between abdominal adiposity, leptin and bone mineral content in overweight Latino children. Horm Res 72:82–87

  14. 14.

    do Prado WL, de Piano A, Lazaretti-Castro M, de Mello MT, Stella SG, Tufik S, do Nascimento CM, Oyama LM, Lofrano MC, Tock L, Caranti DA, Damaso AR (2009) Relationship between bone mineral density, leptin and insulin concentration in Brazilian obese adolescents. J Bone Miner Metab 27:613–619

  15. 15.

    Roemmich JN, Clark PA, Mantzoros CS, Gurgol CM, Weltman A, Rogol AD (2003) Relationship of leptin to bone mineralization in children and adolescents. J Clin Endocrinol Metab 88:599–604

  16. 16.

    Slinker BK, Glantz SA (1985) Multiple regression for physiological data analysis: the problem of multicollinearity. Am J Physiol 249:R1–12

  17. 17.

    Gomez JM, Maravall FJ, Gomez N, Navarro MA, Casamitjana R, Soler J (2003) Interactions between serum leptin, the insulin-like growth factor-I system, and sex, age, anthropometric and body composition variables in a healthy population randomly selected. Clin Endocrinol (Oxf) 58:213–219

  18. 18.

    Ho-Pham LT, Lai TQ, Nguyen UD, Bui QV, Nguyen TV (2017) Delineating the relationship between leptin, fat mass, and bone mineral density: a mediation analysis. Calcif Tissue Int 100:13–19

  19. 19.

    VanItallie TB, Yang MU, Heymsfield SB, Funk RC, Boileau RA (1990) Height-normalized indices of the body’s fat-free mass and fat mass: potentially useful indicators of nutritional status. Am J Clin Nutr 52:953–959

  20. 20.

    Weber DR, Moore RH, Leonard MB, Zemel BS (2013) Reply to RF burton. Am J Clin Nutr 98:1368–1369

  21. 21.

    Crabtree NJ, Arabi A, Bachrach LK, Fewtrell M, El-Hajj Fuleihan G, Kecskemethy HH, Jaworski M, Gordon CM, International Society for Clinical Densitometry (2014) Dual-energy X-ray absorptiometry interpretation and reporting in children and adolescents: the revised 2013 ISCD Pediatric Official Positions. J Clin Densitom 17:225–242

  22. 22.

    Laskey MA (1996) Dual-energy X-ray absorptiometry and body composition. Nutrition 12:45–51

  23. 23.

    Katzman DK, Bachrach LK, Carter DR, Marcus R (1991) Clinical and anthropometric correlates of bone mineral acquisition in healthy adolescent girls. J Clin Endocrinol Metab 73:1332–1339

  24. 24.

    Cole TJ, Bellizzi MC, Flegal KM, Dietz WH (2000) Establishing a standard definition for child overweight and obesity worldwide: international survey. BMJ 320:1240–1243

  25. 25.

    Cole TJ, Flegal KM, Nicholls D, Jackson AA (2007) Body mass index cut offs to define thinness in children and adolescents: international survey. BMJ 335:194

  26. 26.

    Prentice A, Parsons TJ, Cole TJ (1994) Uncritical use of bone mineral density in absorptiometry may lead to size-related artifacts in the identification of bone mineral determinants. Am J Clin Nutr 60:837–842

  27. 27.

    Pan Y, Jackson RT (2008) Ethnic difference in the relationship between acute inflammation and serum ferritin in US adult males. Epidemiol Infect 136:421–431

  28. 28.

    Cao JJ (2011) Effects of obesity on bone metabolism. J Orthop Surg Res 6:30

  29. 29.

    Kawai M, de Paula FJ, Rosen CJ (2012) New insights into osteoporosis: the bone–fat connection. J Intern Med 272:317–329

  30. 30.

    Zaidi M, Buettner C, Sun L, Iqbal J (2012) Minireview: the link between fat and bone: does mass beget mass? Endocrinology 153:2070–2075

  31. 31.

    Suwa S, Tachibana K (1993) Standard growth charts for height and weight of Japanese children from birth to 17 years based on cross-sectional survey of national data. Clin Pediatr Endocrinol 2:87–97

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Acknowledgements

The authors thank the teaching staff of Aritama Elementary School, Sekishi Elementary School, Sekishi Junior High School, and Dr. Toshiko Okamoto for their support. This work was supported by Grants-in-Aid for Scientific Research (KAKENHI Grant Numbers 21657068, 22370092, 24370101, and 26291100) from the Japan Society for the Promotion of Science. The funding bodies had no role in designing the study, collecting, analyzing, and interpreting the data, writing the manuscript, or deciding where to submit the manuscript for publication.

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Correspondence to Katsuyasu Kouda.

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All authors have no conflict of interest for the present study.

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Kouda, K., Ohara, K., Fujita, Y. et al. Relationships between serum leptin levels and bone mineral parameters in school-aged children: a 3-year follow-up study. J Bone Miner Metab 37, 152–160 (2019). https://doi.org/10.1007/s00774-018-0909-0

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Keywords

  • Adipokines
  • Child
  • Densitometry
  • General population