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Exp Clin Endocrinol Diabetes 2013; 121(08): 498-504
DOI: 10.1055/s-0033-1347198
Article
© Georg Thieme Verlag KG Stuttgart · New York

Alterations in Markers of Bone Metabolism and Adipokines Following a 3-month Lifestyle Intervention Induced Weight Loss in Obese Prepubertal Children

J. Gajewska
1   Screening Department, Institute of Mother and Child, Warsaw
,
H. Weker
2   Department of Nutrition, Institute of Mother and Child, Warsaw
,
J. Ambroszkiewicz
1   Screening Department, Institute of Mother and Child, Warsaw
,
K. Szamotulska
3   Department of Epidemiology, Institute of Mother and Child, Warsaw
,
M. Chełchowska
1   Screening Department, Institute of Mother and Child, Warsaw
,
E. Franek
4   Department of Internal Medicine, Endocrinology and Diabetology, Central Clinical Hospital MSW, Warsaw
5   Department of Human Epigenetics, Medical Research Center, Polish ­Academy of Sciences, Warsaw, Poland
,
T. Laskowska-Klita
1   Screening Department, Institute of Mother and Child, Warsaw
› Author Affiliations
Further Information

Publication History

received 12 February 2013
first decision 18 April 2013

accepted 08 May 2013

Publication Date:
14 June 2013 (online)

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Abstract

Background:

Adipokines may influence bone metabolism in children, but this phenomenon is not well understood. Therefore, we studied the relationships between bone markers and adipokines during weight loss in obese children.

Materials and methods:

We determined serum leptin, soluble leptin receptor (sOB-R), adiponectin, BALP (bone alkaline phosphatase), CTX-I (C-terminal telopeptide of type I collagen), body composition and bone mineral density (by dual-energy X-ray absorptiometry) in 100 obese prepubertal children before and after 3 months of lifestyle intervention (low-energy diet, physical activity). The control group consisted of 70 non-obese children.

Results:

Obese children had higher BALP activity by about 20% (p<0.001) and similar value of CTX-I compared with non-obese children. After weight loss (−0.96 BMI-SDS mean change), the BALP value in obese patients decreased (p<0.001), whereas CTX-I concentration was unchanged. Changes in BALP were positively correlated with changes in BMI (Body Mass Index) (r=0.352, p<0.001), but not associated with adipokine levels. Trend analysis using SDS-BMI subgroups showed that greater reduction of body mass was associated with a greater decrease of BALP (p=0.035) and leptin values (p<0.001), as well as a greater increase of sOB-R (p<0.003).

Conclusions:

Obesity during the prepubertal period is associated with an alteration in the adipokines profile and greater whole-body bone mass as a result of increased bone formation rather than reduced bone resorption. Changes in bone metabolism during lifestyle intervention seem to be related to weight loss but not to changes in adipokines. Further studies should elucidate the influence of long-term therapy on bone mass in childhood.

Key words

obesity - bone markers - leptin - weight-loss therapy - prepubertal period
 

  • References

  • 1 Timpson NJ, Sayers A, Davey-Smith G et al. How does body fat influence bone mass in childhood? A mendelian randomization approach. J Bone Miner Res 2009; 24: 522-533
    CrossrefPubMedGoogle Scholar
  • 2 Dimitri P, Wales JK, Bishop N. Fat and bone in children: differential effects of obesity on bone size and mass according to fracture history. J Bone Miner Res 2010; 25: 527-536
    CrossrefPubMedGoogle Scholar
  • 3 Dimitri P, Bishop N, Walsh JS et al. Obesity is a risk factor for fracture in children but is protective against fracture in adults: a paradox. Bone 2012; 50: 457-466
    CrossrefPubMedGoogle Scholar
  • 4 Redman LM, Rood J, Anton SD et al. Calorie restriction and bone health in young, overweight individuals. Arch Intern Med 2008; 168: 1859-1866
    CrossrefPubMedGoogle Scholar
  • 5 Conroy R, Girota M, Shane E et al. Leptin administration does not prevent the bone mineral metabolism changes induced by weight loss. Metabolism 2011; 60: 1222-1226
    CrossrefPubMedGoogle Scholar
  • 6 Magnusson P, Larsson L, Magnusson M et al. Isoforms of bone alkaline phosphatase: characterization and origin in human trabecular and cortical bone. J Bone Miner Res 1999; 14: 1926-1933
    CrossrefPubMedGoogle Scholar
  • 7 Golub EE, Boesze-Battaglia K. The role of alkaline phosphatase in mineralization. Curr Opin Orthop 2007; 18: 444-448
    CrossrefPubMedGoogle Scholar
  • 8 Fledelius C, Johnsen AH, Cloos PAC et al. Characterization of urinary degradation products from type I collagen: identification of a β-isomerized Asp-Gly sequence within the C-terminal telopeptide (1) region. J Biol Chem 1997; 272: 9755-9763
    CrossrefPubMedGoogle Scholar
  • 9 Dimitri P, Wales JK, Bishop N. Adipokines, bone-derived factors and bone turnover in obese children; evidence for altered fat-bone signaling resulting in reduced bone mass. Bone 2011; 48: 189-196
    CrossrefPubMedGoogle Scholar
  • 10 Bini V, Baroncelli GI, Papi F et al. Relationships of serum leptin levels with biochemical markers of bone turnover and with growth factors in normal weight and overweight children. Horm Res 2004; 61: 170-175
    CrossrefPubMedGoogle Scholar
  • 11 Rajakumar K, Fernstrom JD, Holick MF et al. Vitamin D status and response to vitamin D3 in obese vs. non-obese African American children. Obesity 2008; 16: 90-95
    CrossrefPubMedGoogle Scholar
  • 12 Reinehr T, Roth CL. A new link between skeleton, obesity and insulin resistance: relationship between osteocalcin, leptin and insulin resistance in obese children before and after weight loss. Int J Obes 2010; 34: 852-858
    CrossrefPubMedGoogle Scholar
  • 13 Tanner JM. Growth at Adolescence. 2nd Edition. Oxford: Blackwell Scientific Publications; 1962
    Google Scholar
  • 14 Palczewska I, Niedzwiedzka Z. Somatic development indices in children and youth of Warsaw. Med Wieku Rozwoj 2001; 5: 18-118
    PubMedGoogle Scholar
  • 15 Weker H. Simly obesity in children. A study on the role of nutritional factors. Med Wieku Rozwoj 2006; 10: 3-191
    PubMedGoogle Scholar
  • 16 Dzieniszewski J, Szponar L, Szczygieł B, Socha J. (ed.). Scientific foundations of nutrition in hospitals in Poland. Warsaw: National Food and Nutrition Institute; 2001
  • 17 Oblacińska A, Weker H. Prevention of obesity in children and adolescents. Kraków: HELP-MED; 2008
    Google Scholar
  • 18 Venner AA, Lyon ME, Doyle Baker P. Leptin: a potential biomarker for childhood obesity?. Clin Biochem 2006; 39: 1047-1056
    CrossrefPubMedGoogle Scholar
  • 19 Fleisch AF, Agarwal N, Roberts MD et al. Influence of serum leptin on weight and body fat growth in children at high risk for adult obesity. J Clin Endocrinol Metab 2007; 92: 948-954
    CrossrefPubMedGoogle Scholar
  • 20 Gajewska J, Weker H, Ambroszkiewicz J et al. Can leptin and soluble leptin receptor concentrations be used in assessing the efficacy of weight reduction programme in prepubertal obese children? Preliminary report. Med Wieku Rozwoj 2009; 13: 237-243
    PubMedGoogle Scholar
  • 21 Martos-Moreno GA, Barrios V, Martinez G et al. Effect of weight loss on high-molecular weight adiponectin in obese children. Obesity 2010; 18: 2288-2294
    CrossrefPubMedGoogle Scholar
  • 22 Reinehr T, Roth C, Menke T et al. Adiponectin before and after weight loss in obese children. J Clin Endocrinol Metab 2004; 89: 3790-3794
    CrossrefPubMedGoogle Scholar
  • 23 Cambuli VM, Musiu MC, Incani M et al. Assessment of adiponectin and leptin as biomarkers of positive metabolic outcome after lifestyle intervention in overweight and obese children. J Clin Endocrinol Metab 2008; 93: 3051-3057
    CrossrefPubMedGoogle Scholar
  • 24 Gajewska J, Weker H, Ambroszkiewicz J et al. Changes in concentration of serum adiponectin multimeric forms following weight reduction programme in prepubertal obese children. Med. Wieku Rozwoj 2011; 15: 298-305
    PubMedGoogle Scholar
  • 25 Elefteriou F, Takeda S, Ebihara K et al. Serum leptin levels is regulator of bone mass. PNAS USA 2004; 101: 3258-3263
    CrossrefPubMedGoogle Scholar
  • 26 Janicka A, Wren TA, Sanchez MM et al. Fat mass is not beneficial to bone in adolescent and young adults. J Clin Endocrinol Metab 2007; 92: 143-147
    CrossrefPubMedGoogle Scholar
  • 27 Wang MC, Bachrach LK, Van Loan M et al. The relative contributions of lean tissue mass and fat mass to bone density in young women. Bone 2005; 37: 474-481
    CrossrefPubMedGoogle Scholar
  • 28 Sayers A, Timpson NJ, Sattar N et al. Adiponectin and its association with bone mass accrual in childhood. J Bone Miner Res 2010; 25: 2210-2220
    PubMedGoogle Scholar
  • 29 Mughal MZ, Khadilkar AV. The accrual of bone mass during childhood and puberty. Curr Opin Endocrinol Diabetes Obes 2011; 18: 28-32
    CrossrefPubMedGoogle Scholar
  • 30 Ali AT, Penny CB, Paiker JE et al. The effect of alkaline phosphatase inhibitors on intracellular lipid accumulation in preadipocytes isolated from human mammary tissue. Ann Clin Biochem 2006; 43: 207-213
    CrossrefPubMedGoogle Scholar
  • 31 Ali AT, Penny CB, Paiker JE et al. The relationship between alkaline phosphatase activity and intracellular lipid accumulation in murine 3T3-L1 cells and human preadipocytes. Anal Biochem 2006; 354: 247-254
    CrossrefPubMedGoogle Scholar
  • 32 Grinspoon SK, Baum HBA, Peterson S et al. Effect of rhIGF-I administration on bone turnover during short-term fasting. J Clin Invest 1995; 96: 900-906
    CrossrefPubMedGoogle Scholar
  • 33 Soyka LA, Grinspoon S, Levitsky LL et al. The effect of anorexia nervosa on bone metabolism in female adolescents. J Clin Endocrinol Metab 1999; 84: 4489-4496
    CrossrefPubMedGoogle Scholar
  • 34 Gordon CM, Goodman E, Emans SJ et al. Physiologic regulators of bone turnover in young women with anorexia nervosa. J Pediatr 2002; 141: 64-70
    PubMedGoogle Scholar
  • 35 Devlin MJ, Cloutier AM, Thomas NA et al. Caloric restriction leads to high marrow adiposity and low bone mass in growing mice. J Bone Miner Res 2010; 25: 2078-2088
    CrossrefPubMedGoogle Scholar
  • 36 Bredella MA, Fazeli PK, Miller KK et al. Increased bone marrow fat in anorexia nervosa. J Clin Endocrinol Metab 2009; 94: 2129-2136
    CrossrefPubMedGoogle Scholar
  • 37 Di Iorgi N, Rosol M, Mittelman SD et al. Reciprocal relation between marrow adiposity and the amount of bone in the axial and appendicular skeleton of young adults. J Clin Endocrinol Metab 2008; 93: 2281-2286
    CrossrefPubMedGoogle Scholar
  • 38 Ecklund K, Vajapeyam S, Feldman HA et al. Bone marrow changes in adolescent girls with anorexia nervosa. J Bone Miner Res 2010; 25: 298-304
    CrossrefPubMedGoogle Scholar
  • 39 Chao D, Espeland MA, Farmer D et al. Effect of voluntary weight loss on bone mineral density in older overweight women. J Am Geriatr Soc 2000; 48: 753-759
    PubMedGoogle Scholar
  • 40 Villareal DT, Fontana L, Weiss EP et al. Bone mineral density response to caloric restriction-induced weight loss or exercise-induced weight loss: a randomized controlled trial. Arch Intern Med 2006; 166: 2502-2510
    CrossrefPubMedGoogle Scholar
  • 41 Lucey AJ, Paschos GK, Cashman KD et al. Influence of moderate energy restriction and seafood consumption on bone turnover in overweight young adults. Am J Clin Nutr 2008; 87: 1045-1052
    PubMedGoogle Scholar
  • 42 Scariano JK, Garry PJ, Montoya GD et al. Serum leptin levels, bone mineral density and osteoblast alkaline phosphatase activity in elderly men and women. Mech Ageing Dev 2003; 124: 281-286
    CrossrefPubMedGoogle Scholar
  • 43 Grethen EG, Hill KM, Jones RM et al. Serum leptin, parathyroid hormone, 1,25-dihydroxyviyamin D, fibroblast growth factor 23, bone alkaline phosphatase, and sclerostin relationships in obesity. J Clin Endocrinol Metab 2012; 97: 1655-1662
    CrossrefPubMedGoogle Scholar
  • 44 Gordon CM. Leptin and the skeleton – where is the fat?. Metabolism 2011; 60: 1203-1206
    CrossrefPubMedGoogle Scholar
  • 45 Savage JS, Mitchell DC, Smiciklas-Wright H et al. Plausible reports of energy intake may predict body mass index in pre-adolescent girls. J Am Diet Assoc 2008; 108: 131-135
    CrossrefPubMedGoogle Scholar
  • 46 Crawford PB, Obarzanek E, Morrison J et al. Comparative advantage of 3-day food records over 24-hour recall and 5-day food frequency validated by observation of 9- and 10-year-old girls. J Am Diet Assoc 1994; 94: 626-630
    CrossrefPubMedGoogle Scholar