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Horm Metab Res 2013; 45(05): 332-337
DOI: 10.1055/s-0032-1331216
Original Basic
© Georg Thieme Verlag KG Stuttgart · New York

Two Models of Early Weaning Decreases Bone Structure by Different Changes in Hormonal Regulation of Bone Metabolism in Neonate Rat

L. de Albuquerque Maia
1   Department of Physiological Sciences, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
,
P. C. Lisboa
1   Department of Physiological Sciences, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
,
E. de Oliveira
1   Department of Physiological Sciences, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
,
N. da Silva Lima
1   Department of Physiological Sciences, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
,
C. A. S. da Costa
1   Department of Physiological Sciences, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
,
E. G. de Moura
1   Department of Physiological Sciences, State University of Rio de Janeiro, Rio de Janeiro, RJ, Brazil
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Publikationsverlauf

received 01. August 2012

accepted 08. November 2012

Publikationsdatum:
21. Dezember 2012 (online)

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Abstract

During the last decade a great concern has developed for determining what factors influence bone mineral accretion in healthy children. Mother’s milk represents the primary source of calcium and other nutrients in the neonate. The development of bone and adipose tissue has common origins. Since early weaning decreases adipogenesis in neonate, our aim was to evaluate bone metabolism in 2 models of early weaning (EW) in neonate rats. Lactating rats were separated into 3 groups: control: pups had free access to milk; MEW: dams were involved with a bandage mechanically (M) interrupting lactation in the last 3 days; and PEW: dams were pharmacologically (P) treated to block prolactin (0.5 mg bromocryptine/twice a day) 3 days before standard weaning. Significant difference had p<0.05. At weaning, MEW and PEW pups presented lower body weight ( − 18% and  − 15%), total body fat ( − 26% and  − 27%), total bone mineral density ( − 7% and  − 6%), total bone mineral content ( − 30% and  − 32%), bone area ( − 28% and  − 30%), serum osteocalcin ( − 20% and  − 55%), and higher C-terminal cross-linked telopeptide of type I collagen (CTX-I) (1.3 and 1.1-fold increase). However, serum ionized calcium was lower only in MEW pups ( − 34%), 25-hydroxyvitamin D was higher (1.4-fold increase), and PTH was lower ( − 26%) only in PEW group. The present study shows that both early weaning models leads to an impairment of osteogenesis associated with lower adipogenesis by different mechanisms, involving mainly changes in vitamin D and PTH.

Key words

lactation - bone - early weaning - calcium - vitamin D - PTH
 

  • References

  • 1 WHO . Infant and young child nutrition. 2001. Geneva, Switzerland: WHO Fifty-Fourth World Health Assembly;
    Google Scholar
  • 2 Su LL, Chong YS, Chan YH, Chan YS, Fok D, Tun KT, Ng FS, Rauff M. Antenatal education and postnatal support strategies for improving rates of exclusive breast feeding: randomised controlled trial. BMJ 2007; 335: 596-603
    CrossrefPubMedGoogle Scholar
  • 3 Kramer MS, Matush L, Bogdanovich N, Aboud F, Mazer B, Fombonne E, Collet JP, Hodnett E, Mironova E, Igumnov S, Chalmers B, Dahhou M, Platt RW. Health and development outcomes in 65-y-old children breastfed exclusively for 3 or 6 mo. Am J Clin Nutr 2009; 90: 1070-1074
    CrossrefPubMedGoogle Scholar
  • 4 Devlin MJ, Bouxsein ML. Influence of pre- and peri-natal nutrition on skeletal acquisition and maintenance. Bone 2012; 50: 444-451
    CrossrefPubMedGoogle Scholar
  • 5 Golding J, Rogers IS, Emmett PM. Association between breast feeding, child development and behavior. Early Hum Dev 1997; 29: S175-S184
    PubMedGoogle Scholar
  • 6 Oliveira L, dos S, da Silva LP, da Silva AI, Magalhães CP, de Souza SL, de Castro RM. Effects of early weaning on the circadian rhythm and behavioral satiety sequence in rats. Behav Processes 2011; 86: 119-124
    CrossrefPubMedGoogle Scholar
  • 7 Moura EG, Lisboa PC, Passos MC. Neonatal programming of neuroimmunomodulation – role of adipocytokines and neuropeptides. Neuroimmunomodulation 2008; 15: 176-188
    CrossrefPubMedGoogle Scholar
  • 8 Cooper C, Westlake S, Harvey N, Javaid K, Dennison E, Hanson M. Review: developmental origins of osteoporotic fracture. Osteoporos Int 2006; 17: 337-347
    CrossrefPubMedGoogle Scholar
  • 9 Mahajan A, Alexander LS, Seabolt BS, Catrambone DE, McClung JP, Odle J, Pfeiler TW, Loboa EG, Stahl CH. Dietary calcium restriction affects mesenchymal stem cell activity and bone development in neonatal pigs. J Nutr 2011; 141: 373-379
    CrossrefPubMedGoogle Scholar
  • 10 Ralston SH. Do genetic markers aid in risk assessment?. Osteoporos Int 1998; 8: S37-S42
    PubMedGoogle Scholar
  • 11 Kovacs CS. Vitamin D in pregnancy and lactation: maternal, fetal, and neonatal outcomes from human and animal studies. Am J Clin Nutr 2008; 88: 520 S-528S
    PubMedGoogle Scholar
  • 12 Bonomo IT, Lisboa PC, Passos MC, Pazos-Moura CC, Reis AM, Moura EG. Prolactin inhibition in lactating rats changes leptin transfer through the milk. Horm Metab Res 2005; 37: 220-225
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 13 Lisboa PC, Passos MC, Dutra SC, Bonomo IT, Denolato AT, Reis AM, Moura EG. Leptin and prolactin, but not corticosterone, modulate body weight and thyroid function in protein-malnourished lactating rats. Horm Metab Res 2006; 38: 295-299
    Artikel in Thieme ConnectPubMedGoogle Scholar
  • 14 Oliveira E, Pinheiro CR, Santos-Silva AP, Trevenzoli IH, Abreu-Villaça Y, Nogueira Neto JF, Reis AM, Passos MC, Moura EG, Lisboa PC. Nicotine exposure affects mother’s and pup’s nutritional, biochemical, and hormonal profiles during lactation in rats. J Endocrinol 2010; 205: 159-170
    CrossrefPubMedGoogle Scholar
  • 15 Ducy P, Amling M, Takeda S, Priemel M, Schilling AF, Beil FT, Shen J, Vinson C, Rueger JM, Karsenty G. Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell 2000; 100: 197-207
    CrossrefPubMedGoogle Scholar
  • 16 Bonomo IT, Lisboa PC, Pereira AR, Passos MC, de Moura EG. Prolactin inhibition in dams during lactation programs for overweight and leptin resistance in adult offspring. J Endocrinol 2007; 192: 339-344
    CrossrefPubMedGoogle Scholar
  • 17 de Moura EG, Bonomo IT, Nogueira-Neto JF, de Oliveira E, Trevenzoli IH, Reis AM, Passos MC, Lisboa PC. Maternal prolactin inhibition during lactation programs for metabolic syndrome in adult progeny. J Physiol 2009; 15: 4919-4929
    PubMedGoogle Scholar
  • 18 Bonomo IT, Lisboa PC, Passos MC, Alves SB, Reis AM, de Moura EG. Prolact inhibition at the end of lactation programs for a central hypothyroidism in adult rat. J Endocrinol 2008; 198: 331-337
    CrossrefPubMedGoogle Scholar
  • 19 Ben-Jonathan N, Hnasko R. Dopamine as a prolactin (PRL) inhibitor. Endocr Rev 2001; 22: 724-763
    CrossrefPubMedGoogle Scholar
  • 20 Lima Nda S, de Moura EG, Passos MC, Nogueira Neto FJ, Reis AM, de Oliveira E, Lisboa PC. Early weaning causes undernutrition for a short period and programmes some metabolic syndrome components and leptin resistance in adult rat offspring. Br J Nutr 2011; 105: 1405-1413
    CrossrefPubMedGoogle Scholar
  • 21 Marques RG, Morales MM, Petroianu A. Brazilian law for scientific use of animals. Acta Cir Bras 2009; 24: 69-74
    CrossrefPubMedGoogle Scholar
  • 22 Lukaski HC, Hall CB, Marchello MJ, Siders WA. Validation of dual x-ray absorptiometry for body-composition assessment of rats exposed to dietary stressors. Nutrition 2001; 17: 607-613
    CrossrefPubMedGoogle Scholar
  • 23 Harvey N, Cooper C. The developmental origins of osteoporotic fracture. J Br Menopause Soc 2004; 10 ( 14–15) 29
    PubMedGoogle Scholar
  • 24 Wysolmerski JJ. The evolutionary origins of maternal calcium and bone metabolism during lactation. J Mammary Gland Biol Neoplasia 2002; 7: 267-276
    CrossrefPubMedGoogle Scholar
  • 25 Lee WT, Leung SS, Lui SS, Lau J. Relationship between long-term calcium intake and bone mineral content of children from birth to 5 years. Br J Nutr 1993; 70: 235-248
    CrossrefPubMedGoogle Scholar
  • 26 Rajakumar K, Fernstrom JD, Holick MF, Janosky JE, Greenspan SL. Vitamin D status and response to Vitamin D3 in obese vs non-obese African American children. Obesity 2008; 16: 90-95
    CrossrefPubMedGoogle Scholar
  • 27 Halloran BP, Barthell EN, DeLuca HF. Vitamin D metabolism in pregnancy and lactation in the rat. Proc Natl Acad Sci 1979; 76: 5549-5553
    CrossrefPubMedGoogle Scholar
  • 28 Ajibade DV, Dhawan P, Fechner AJ, Meyer MB, Pike JW, Christakos S. Evidence for a role of prolactin in calcium homeostasis: regulation of intestinal transient receptor potential vanilloid type 6, intestinal calcium absorption, and the 25-hydroxyvitamin D(3) 1alpha hydroxylase gene by prolactin. Endocrinology 2010; 151: 2974-2984
    CrossrefPubMedGoogle Scholar
  • 29 Christakos S, Dhawan P, Porta A, Mady LJ, Seth T. Vitamin D and intestinal calcium absorption. Mol Cell Endocrinol 2011; 347: 25-29
    CrossrefPubMedGoogle Scholar
  • 30 Alexe DM, Syridou G, Petridou ET. Determinants of early life leptin levels and later life degenerative outcomes. Clin Med Res 2006; 4: 326-335
    PubMedGoogle Scholar
  • 31 Bassilana F, Susa M, Keller HJ, Halleux C. Human mesenchymal stem cells undergoing osteogenic differentiation express leptin and functional leptin receptor. J Bone Miner Res 2000; 15: S378
    PubMedGoogle Scholar
  • 32 Thomas T, Gori F, Khosla S, Jensen MD, Burguera B, Riggs BL. Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes. Endocrinology 1999; 140: 1630-1638
    CrossrefPubMedGoogle Scholar
  • 33 Kume K, Satomura K, Nishisho S, Kitaoka E, Yamanouchi K, Tobiume S, Nagayama M. Potential role of leptin in endochondral ossification. J Histochem Cytochem 2002; 50: 159-169
    CrossrefPubMedGoogle Scholar
  • 34 Ogueh O, Sooranna S, Nicolaides KH, Johnson MR. The relationship between leptin concentration and bone metabolism in the human fetus. J Clin Endocrinol Metab 2000; 85: 1997-1999
    CrossrefPubMedGoogle Scholar
  • 35 Fu L, Patel MS, Bradley A, Wagner EF, Karsenty G. The molecular clock mediates leptin-regulated bone formation. Cell 2005; 122: 803-815
    CrossrefPubMedGoogle Scholar
  • 36 Matkovic V, Ilich JZ, Skugor M, Badenhop NE, Goel P, Clairmont A, Klisovic D, Nahhas RW, Landoll JD. Leptin is inversely related to age at menarche in human females. J Clin Endocrinol Metab 1997; 82: 3239-3245
    CrossrefPubMedGoogle Scholar
  • 37 Weiler HA, Kovacs H, Murdock C, Adolphe J, Fitzpatrick-Wong S. Leptin predicts bone and fat mass after accounting for the effects of diet and glucocorticoid treatment in piglets. Exp Biol Med 2002; 227: 639-644
    PubMedGoogle Scholar
  • 38 Steppan CM, Crawford DT, Chidsey-Frink KL, Ke H, Swick AG. Leptin is a potent stimulator of bone growth in ob/ob mice. Regul Pept 2000; 92: 73-78
    CrossrefPubMedGoogle Scholar
  • 39 Hamrick MW, Della-Fera MA, Choi YH, Pennington C, Hartzell D, Baile CA. Leptin treatment induces loss of bone marrow adipocytes and increases bone formation in leptin-deficient ob/ob mice. J Bone Miner Res 2005; 20: 994-1001
    CrossrefPubMedGoogle Scholar
  • 40 Guillemant J, Cabrol S, Allemandou A, Peres G, Guillemant S. Vitamin D–dependent seasonal variation of PTH in growing male adolescents. Bone 1995; 17: 513-516
    CrossrefPubMedGoogle Scholar
  • 41 Sigurdsson G, Franzson L, Steingrimsdottir L, Sigvaldason H. The association between parathyroid hormone, vitamin D and bone mineral density in 70-year-old Icelandic women. Osteoporos Int 2000; 11: 1031-1035
    PubMedGoogle Scholar
  • 42 Souberbielle JC, Cormier C, Kindermans C, Gao P, Cantor T, Forette F, Baulieu EE. Vitamin D status and redefining serum parathyroid hormone reference range in the elderly. J Clin Endocrinol Metab 2001; 86: 3086-3090
    CrossrefPubMedGoogle Scholar
  • 43 Kawahara M, Iwasaki Y, Sakaguchi K, Taguchi T, Nishiyama M, Nigawara T, Tsugita M, Kambayashi M, Suda T, Hashimoto K. Predominant role of 25OHD in the negative regulation of PTH expression: clinical relevance for hypovitaminosis D. Life Sci 2008; 82: 677-683
    CrossrefPubMedGoogle Scholar
  • 44 Matsunuma A, Kawane T, Maeda T, Hamada S, Horiuchi N. Leptin corrects increased gene expression of renal 25-hydroxyvitamin D3-1 alpha-hydroxylase and -24-hydroxylase in leptin deficient, ob/ob mice. Endocrinology 2004; 145: 1367-1375
    PubMedGoogle Scholar
  • 45 Grethen E, Hill KM, Jones R, Cacucci BM, Gupta CE, Acton A, Considine RV, Peacock M. Serum leptin, parathyroid hormone, 1,25-dihydroxyvitamin D, fibroblast growth factor 23, bone alkaline phosphatase, and sclerostin relationships in obesity. J Clin Endocrinol Metab 2012; 97: 1655-1662
    CrossrefPubMedGoogle Scholar
  • 46 Tsuji K, Maeda T, Kawane T, Matsunuma A, Horiuchi N. Leptin stimulates fibroblast growth factor 23 expression in bone and suppresses renal 1alpha,25-dihydroxyvitamin D3 synthesis in leptin-deficient mice. J Bone Miner Res 2010; 25: 1711-1723
    CrossrefPubMedGoogle Scholar
  • 47 Zemel MB, Sun X. Calcitriol and energy metabolism. Nutr Rev 2008; 66: S139-S146
    CrossrefPubMedGoogle Scholar
  • 48 Nobre JL, Lisboa PC, Santos-Silva AP, Lima NS, Manhães AC, Nogueira-Neto JF, Cabanelas A, Pazos-Moura CC, Moura EG, de Oliveira E. Calcium supplementation reverts central adiposity, leptin, and insulin resistance in adult offspring programed by neonatal nicotine exposure. J Endocrinol 2011; 210: 349-359
    Google Scholar
  • 49 Lopes Nobre J, Lisboa PC, da Silva Lima N, Franco JG, Firmino Nogueira Neto J, de Moura EG, de Oliveira E. Calcium supplementation prevents obesity, hyperleptinaemia and hyperglycaemia in adult rats programmed by early weaning. Br J Nutr 2012; 9: 1-10
    PubMedGoogle Scholar
  • 50 Szulc P, Seeman E, Delmas PD. Biochemical measurements of bone turnover in children and adolescents. Osteoporos Int 2000; 11: 281-294
    CrossrefPubMedGoogle Scholar
  • 51 Kalra SP, Dube MG, Iwaniec UT. Leptin increases osteoblast-specific osteocalcin release through a hypothalamic relay. Peptides 2009; 30: 967-973
    CrossrefPubMedGoogle Scholar
  • 52 Gerdhem P, Ivaska KK, Alatalo SL, Halleen JM, Hellman J, Isaksson A, Pettersson K, Väänänen HK, Akesson K, Obrant KJ. Biochemical markers of bone metabolism and prediction of fracture in elderly women. J Bone Miner Res 2004; 19: 386-393
    PubMedGoogle Scholar
  • 53 Blain H, Vuillemin A, Guillemin F, Durant R, Hanesse B, de Talance N, Doucet B, Jeandel C. Serum leptin level is a predictor of bone mineral density in postmenopausal women. J Clin Endocrinol Metab 2002; 87: 1030-1035
    CrossrefPubMedGoogle Scholar
  • 54 Ravn P, Rix M, Andreassen H, Clemmesen B, Bidstrup M, Gunnes M. High bone turnover is associated with low bone mass and spinal fracture in postmenopausal women. Calcif Tissue Int 1997; 60: 255-260
    CrossrefPubMedGoogle Scholar
  • 55 Jones G, Riley M, Dwyer T. Breastfeeding in early life and bone mass in prepubertal children: a longitudinal study. Osteoporos Int 2000; 11: 146-152
    CrossrefPubMedGoogle Scholar
  • 56 Turner RT, Kalra SP, Wong CP, Philbrick KA, Lindenmaier LB, Boghossian S, Iwaniec UT. Peripheral leptin regulates bone formation. J Bone Miner Res. 2012 DOI: 10.1002/jbmr.1734
    PubMedGoogle Scholar