Hostname: page-component-78c5997874-fbnjt Total loading time: 0 Render date: 2024-11-19T09:34:09.854Z Has data issue: false hasContentIssue false

Osteoprotegerin in pregnant adolescents differs by race and is related to infant birth weight z-score

Published online by Cambridge University Press:  01 October 2011

B. Essley
Affiliation:
Division of Nutritional Sciences, Cornell University, Ithaca, New York, USA
T. McNanley
Affiliation:
Department of Obstetrics and Gynecology, University of Rochester School of Medicine, Rochester, New York, USA
B. Cooper
Affiliation:
Department of Obstetrics and Gynecology, University of Rochester School of Medicine, Rochester, New York, USA
A. McIntyre
Affiliation:
Department of Obstetrics and Gynecology, University of Rochester School of Medicine, Rochester, New York, USA
F. Witter
Affiliation:
Department of Obstetrics and Gynecology, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
Z. Harris
Affiliation:
Department of Pediatrics, Johns Hopkins School of Medicine, Baltimore, Maryland, USA
K. O'Brien*
Affiliation:
Division of Nutritional Sciences, Cornell University, Ithaca, New York, USA
*
*Address for correspondence: Prof. K. O'Brien, Division of Nutritional Sciences, Cornell University, 230 Savage, Ithaca, NY 14853, USA. (Email [email protected])

Abstract

Osteoprotegerin (OPG) is involved in the regulation of bone turnover, but little is known about this protein during pregnancy or among neonates. We undertook a prospective longitudinal study to identify relationships between OPG, markers of bone turnover and birth outcomes in 155 pregnant adolescents (13–18 years) and their newborns. Maternal blood samples were collected at mid-gestation and at delivery. Cord blood was obtained at delivery. Serum OPG, estradiol and markers of bone formation (osteocalcin) and resorption (N-telopeptide) were assessed in all samples. Placental OPG expression was assessed in placental tissue obtained at delivery. Bone markers and OPG increased significantly from mid-gestation (26.0 ± 3.4 weeks) to delivery (39.3 ± 2.6 weeks). Neonatal OPG was significantly lower, but bone turnover markers were significantly higher than maternal values at mid-gestation and at parturition (P < 0.001). African-American adolescents had higher concentrations of OPG than Caucasian adolescents at mid-gestation (P = 0.01) and delivery (P = 0.04). Gestational age and estradiol were also predictors of maternal OPG at mid-gestation and delivery. OPG concentrations in cord blood were correlated with maternal OPG concentrations and were negatively associated with infant birth weight z-score (P = 0.02) and ponderal index (P = 0.02). In conclusion, maternal OPG concentrations increased across gestation and were significantly higher than neonatal OPG concentrations. Maternal and neonatal OPG concentrations were not associated with markers of bone turnover or placental OPG expression, but neonatal OPG was inversely associated with neonatal anthropometric measures. Additional research is needed to identify roles of OPG during pregnancy.

Type
Original Articles
Copyright
Copyright © Cambridge University Press and the International Society for Developmental Origins of Health and Disease 2011

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1.Center for Disease Control and Prevention. Vital signs: teen pregnancy – United States, 1991–2009. Morb Mortal Wkly Rep. 2011; 60, 414420.Google Scholar
2.Felice, ME, Feinstein, RA, Fisher, MM, et al. . Adolescent pregnancy – current trends and issues: 1998 American Academy of Pediatrics Committee on Adolescence, 1998–1999. Pediatrics. 1999; 103, 516520.Google Scholar
3.Black, AJ, Topping, J, Durham, B, Farquharson, RG, Fraser, WD. A detailed assessment of alterations in bone turnover, calcium homeostasis, and bone density in normal pregnancy. J Bone Miner Res. 2000; 15, 557563.CrossRefGoogle ScholarPubMed
4.Naylor, KE, Iqbal, P, Fledelius, C, Fraser, RB, Eastell, R. The effect of pregnancy on bone density and bone turnover. J Bone Miner Res. 2000; 15, 129137.CrossRefGoogle Scholar
5.Cross, NA, Hillman, LS, Allen, SH, Krause, GF, Vieira, NE. Calcium homeostasis and bone metabolism during pregnancy, lactation, and postweaning: a longitudinal study. Am J Clin Nutr. 1995; 61, 514523.CrossRefGoogle ScholarPubMed
6.Kovacs, CS. Calcium and bone metabolism in pregnancy and lactation. J Clin Endocrinol Metab. 2001; 86, 23442348.Google ScholarPubMed
7.Kolthoff, N, Eiken, P, Kristensen, B, Nielsen, SP. Bone mineral changes during pregnancy and lactation: a longitudinal cohort study. Clin Sci (Lond). 1998; 94, 405412.CrossRefGoogle ScholarPubMed
8.Sowers, M, Wallace, RB, Lemke, JH. Correlates of forearm bone mass among women during maximal bone mineralization. Prev Med. 1985; 14, 585596.CrossRefGoogle ScholarPubMed
9.Sowers, MF, Scholl, T, Harris, L, Jannausch, M. Bone loss in adolescent and adult pregnant women. Obstet Gynecol. 2000; 96, 189193.Google ScholarPubMed
10.Simonet, WS, Lacey, DL, Dunstan, CR, et al. . Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell. 1997; 89, 309319.CrossRefGoogle ScholarPubMed
11.Hofbauer, LC, Heufelder, AE. Role of receptor activator of nuclear factor-kappaB ligand and osteoprotegerin in bone cell biology. J Mol Med. 2001; 79, 243253.CrossRefGoogle ScholarPubMed
12.Hong, JS, Santolaya-Forgas, J, Romero, R, et al. . Maternal plasma osteoprotegerin concentration in normal pregnancy. Am J Obstet Gynecol. 2005; 193, 10111015.CrossRefGoogle ScholarPubMed
13.Naylor, KE, Rogers, A, Fraser, RB, et al. . Serum osteoprotegerin as a determinant of bone metabolism in a longitudinal study of human pregnancy and lactation. J Clin Endocrinol Metab. 2003; 88, 53615365.CrossRefGoogle Scholar
14.Uemura, H, Yasui, T, Kiyokawa, M, et al. . Serum osteoprotegerin/osteoclastogenesis-inhibitory factor during pregnancy and lactation and the relationship with calcium-regulating hormones and bone turnover markers. J Endocrinol. 2002; 174, 353359.CrossRefGoogle ScholarPubMed
15.Barker, DJ. The origins of the developmental origins theory. J Intern Med. 2007; 261, 412417.CrossRefGoogle ScholarPubMed
16.Gluckman, PD, Hanson, MA, Cooper, C, Thornburg, KL. Effect of in utero and early-life conditions on adult health and disease. N Engl J Med. 2008; 359, 6173.CrossRefGoogle ScholarPubMed
17.Cooper, C, Westlake, S, Harvey, N, et al. . Review: developmental origins of osteoporotic fracture. Osteoporos Int. 2006; 17, 337347.CrossRefGoogle ScholarPubMed
18.Schlussel, MM, Dos, SV, Kac, G. Birth weight and adult bone mass: a systematic literature review. Osteoporos Int. 2010; 21, 19811991.CrossRefGoogle ScholarPubMed
19.Kramer, MS, Platt, RW, Wen, SW, et al. . A new and improved population-based Canadian reference for birth weight for gestational age. Pediatrics. 2001; 108, E35E42.CrossRefGoogle ScholarPubMed
20.Gundberg, CM, Cole, DE, Lian, JB, Reade, TM, Gallop, PM. Serum osteocalcin in the treatment of inherited rickets with 1,25-dihydroxyvitamin D3. J Clin Endocrinol Metab. 1983; 56, 10631067.CrossRefGoogle Scholar
21.Andreasyan, K, Ponsonby, AL, Dwyer, T, et al. . Higher maternal dietary protein intake in late pregnancy is associated with a lower infant ponderal index at birth. Eur J Clin Nutr. 2007; 61, 498508.CrossRefGoogle ScholarPubMed
22.Lonergan, M, Aponso, D, Marvin, KW, et al. . Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), TRAIL receptors, and the soluble receptor osteoprotegerin in human gestational membranes and amniotic fluid during pregnancy and labor at term and preterm. J Clin Endocrinol Metab. 2003; 88, 38353844.CrossRefGoogle ScholarPubMed
23.Briana, DD, Boutsikou, M, Baka, S, et al. . Circulating osteoprotegerin and sRANKL concentrations in the perinatal period at term. The impact of intrauterine growth restriction. Neonatology. 2009; 96, 132136.CrossRefGoogle ScholarPubMed
24.Dimitri, P, Wales, JK, Bishop, N. Adipokines, bone-derived factors and bone turnover in obese children; evidence for altered fat-bone signalling resulting in reduced bone mass. Bone. 2011; 48, 189196.CrossRefGoogle ScholarPubMed
25.Specker, B. Nutrition influences bone development from infancy through toddler years. J Nutr. 2004; 134, 691S695S.CrossRefGoogle ScholarPubMed
26.Namgung, R, Tsang, RC. Factors affecting newborn bone mineral content: in utero effects on newborn bone mineralization. Proc Nutr Soc. 2000; 59, 5563.CrossRefGoogle ScholarPubMed
27.Raman, L, Rajalakshmi, K, Krishnamachari, KA, Sastry, JG. Effect of calcium supplementation to undernourished mothers during pregnancy on the bone density of the bone density of the neonates. Am J Clin Nutr. 1978; 31, 466469.CrossRefGoogle ScholarPubMed
28.Viljakainen, HT, Korhonen, T, Hytinantti, T, et al. . Maternal vitamin D status affects bone growth in early childhood – a prospective cohort study. Osteoporos Int. 2011; 22, 883891.CrossRefGoogle ScholarPubMed
29.Javaid, MK, Crozier, SR, Harvey, NC, et al. . Maternal vitamin D status during pregnancy and childhood bone mass at age 9 years: a longitudinal study. Lancet. 2006; 367, 3643.CrossRefGoogle ScholarPubMed
30.Dennison, EM, Arden, NK, Keen, RW, et al. . Birthweight, vitamin D receptor genotype and the programming of osteoporosis. Paediatr Perinat Epidemiol. 2001; 15, 211219.CrossRefGoogle ScholarPubMed
31.Antoniades, L, MacGregor, AJ, Andrew, T, Spector, TD. Association of birth weight with osteoporosis and osteoarthritis in adult twins. Rheumatology (Oxford). 2003; 42, 791796.CrossRefGoogle ScholarPubMed
32.Dai, Y, Shen, L. Relationships between serum osteoprotegerin, matrix metalloproteinase-2 levels and bone metabolism in postmenopausal women. Chin Med J (Engl). 2007; 120, 20172021.CrossRefGoogle ScholarPubMed
33.Jiang, LS, Zhang, ZM, Jiang, SD, Chen, WH, Dai, LY. Differential bone metabolism between postmenopausal women with osteoarthritis and osteoporosis. J Bone Miner Res. 2008; 23, 475483.CrossRefGoogle ScholarPubMed
34.Ohwada, R, Hotta, M, Sato, K, Shibasaki, T, Takano, K. The relationship between serum levels of estradiol and osteoprotegerin in patients with anorexia nervosa. Endocr J. 2007; 54, 953959.CrossRefGoogle ScholarPubMed
35.Hofbauer, LC, Khosla, S, Dunstan, CR, et al. . Estrogen stimulates gene expression and protein production of osteoprotegerin in human osteoblastic cells. Endocrinology. 1999; 140, 43674370.CrossRefGoogle ScholarPubMed
36.Li, Q, Yu, K, Tian, X, et al. . 17beta-estradiol overcomes human myeloma RPMI8226 cell suppression of growth, ALP activity, and mineralization in rat osteoblasts and improves RANKL/OPG balance in vitro. Leuk Res. 2009; 33, 12661271.CrossRefGoogle ScholarPubMed
37.Looker, AC, IIIMelton, LJ, Harris, T, et al. . Age, gender, and race/ethnic differences in total body and subregional bone density. Osteoporos Int. 2009; 20, 11411149.CrossRefGoogle ScholarPubMed
38.Emery, JG, McDonnell, P, Burke, MB, et al. . Osteoprotegerin is a receptor for the cytotoxic ligand TRAIL. J Biol Chem. 1998; 273, 1436314367.CrossRefGoogle ScholarPubMed
39.Vitovski, S, Phillips, JS, Sayers, J, Croucher, PI. Investigating the interaction between osteoprotegerin and receptor activator of NF-kappaB or tumor necrosis factor-related apoptosis-inducing ligand: evidence for a pivotal role for osteoprotegerin in regulating two distinct pathways. J Biol Chem. 2007; 282, 3160131609.CrossRefGoogle ScholarPubMed
40.Collin-Osdoby, P, Rothe, L, Anderson, F, et al. . Receptor activator of NF-kappa B and osteoprotegerin expression by human microvascular endothelial cells, regulation by inflammatory cytokines, and role in human osteoclastogenesis. J Biol Chem. 2001; 276, 2065920672.CrossRefGoogle ScholarPubMed
41.Corallini, F, Celeghini, C, Rimondi, E, et al. . TRAIL down-regulates the release of osteoprotegerin (OPG) by primary stromal cells. J Cell Physiol. 2011; 226, 22792286.CrossRefGoogle ScholarPubMed
42.Anum, EA, Springel, EH, Shriver, MD, IIIStrauss, JF. Genetic contributions to disparities in preterm birth. Pediatr Res. 2009; 65, 19.CrossRefGoogle ScholarPubMed
43.Velez, DR, Fortunato, SJ, Morgan, N, et al. . Patterns of cytokine profiles differ with pregnancy outcome and ethnicity. Hum Reprod. 2008; 23, 19021909.CrossRefGoogle ScholarPubMed