help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Journal of Clinical Endocrinology & Metabolism , doi:10.1210/jc.2005-2601
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bajoria, R.
Right arrow Articles by Chatterjee, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bajoria, R.
Right arrow Articles by Chatterjee, R.
Right arrowPubmed/NCBI databases
*Substance via MeSH
Related Collections
Right arrow Pediatric Endocrinology
Right arrow Calcium and Bone Metabolism
Right arrow Metabolism
The Journal of Clinical Endocrinology & Metabolism Vol. 91, No. 11 4696-4701
Copyright © 2006 by The Endocrine Society

Type 1 Collagen Marker of Bone Turnover, Insulin-Like Growth Factor, and Leptin in Dichorionic Twins with Discordant Birth Weight

Rekha Bajoria, Suren R. Sooranna and Ratna Chatterjee

Academic Unit of Obstetrics and Gynaecology (R.B.), St. Mary’s Hospital for Women and Children, Manchester M13 0JH, United Kingdom; Department of Maternal and Fetal Medicine (S.R.S.), Chelsea and Westminster Hospital, London SW10 9NH, United Kingdom; and Reproductive Medicine Unit (R.C.), University College London, London WC1E 6HX, United Kingdom

Address all correspondence and requests for reprints to: Ratna Chatterjee, M.D., Ph.D., University College London, Department of Obstetrics and Gynaecology, 88-96 Chenies Mews, London WC1E 6HX, United Kingdom. E-mail: r.chatterjee{at}ucl.ac.uk.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Objective: We investigated the relationship between IGF-I-IGF binding protein (IGFBP)-1 and leptin levels with type 1 collagen markers of bone turnover in dichorionic twins with or without discordant birth weight of 20% or greater.

Methods: Maternal and cord bloods were collected from gestational age-matched dichorionic twins with (n = 16) or without (n = 16) discordant birth weight. The samples were assayed for cross-linked carboxyl terminal telopeptide (ICTP, a marker of bone resorption) and propeptide (PICP, a marker of bone formation) of type I collagen, leptin, IGF-I, and IGFBP-1 by RIA.

Results: The intrauterine growth-restricted (IUGR) twins of the discordant group had higher fetal ICTP (P < 0.001) and IGFBP-1 (P < 0.001) levels, whereas PICP (P < 0.001), IGF-I (P < 0.001), and leptin (P < 0.001) were lower than the cotwins with normal weight (AGA). In contrast, concentrations of IGF-I, IGFBP-1, ICTP, PICP, and leptin were comparable between concordant twin pairs. Leptin levels were positively correlated with PICP (r = 0.61; P < 0.001) and negatively with ICTP (r = –0.57; P < 0.001) in concordant and AGA twins but not in IUGR twins. In IUGR twins, IGF-I had positive association with PICP (r = 0.76; P < 0.001) and negative association with ICTP (r= –0.76; P < 0.001), whereas IGFBP-1 was negatively correlated with PICP levels (r = –0.65; P < 0.01). No such association was found in concordant and AGA twins.

Conclusion: These data suggest that IUGR twins had high bone turnover, which is independent of maternal factors and perhaps may be due to altered IGF axis.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
CURRENT EVIDENCE suggests that low-birth-weight infants have low bone mass and a higher risk of osteoporosis and fracture in later life (1, 2). Maternal smoking, fat stores, and physical activity have previously been documented as determinants of neonatal whole-body bone mineral content (3). More recent data indicate that maternal undernutrition influences fetal skeletal development via alteration in fetal hormonal milieu (1). In preterm growth-restricted infants, IGF-I regulates type-1 collagen turnover, as indicated by elevated carboxyl terminal propeptide (PICP) and carboxyl terminal telopeptide (ICTP) concentrations (4). Another factor that may play a role in bone mass and body composition is leptin. Leptin is secreted by adipose tissue and has emerged as a potential candidate for explaining the protective effect of fat mass on bone (5). Singleton studies have shown that the IGF axis or leptin predicts neonatal bone mass (6, 7). Furthermore, from singleton studies, the individual effects of gene, maternal lifestyle, seasonal variation, and intrauterine environment on the fetal bone mass cannot be ascertained.

We used twins as a model to dissect the individual effect of gene, maternal environment, and placenta on in utero programing for adult disease. A recent study in mono- and dizygotic (DZ) twins has shown that the low-birth-weight twin has higher blood pressure in childhood and adult life than its heavier cotwin due to placental rather than maternal or genetic factors (8). It is plausible that a similar link may exist between low birth weight and bone acquisition in utero. We studied unlike sex pair dichorionic twin pregnancies, i.e. DZ, to evaluate the relationship between low birth weight and bone acquisition in utero. DZ twining is a powerful clinical model over monochorionic (MC) twins because it obviates the problems of intertwin vascular anastomosis unique to MC placentation (9). Although MC twins with identical genomes have a distinct advantage, the influence of intertwin transfusion on fetal growth cannot be totally ruled out. Furthermore, DZ twins can be considered to be the closest match to singleton fetuses at least on two regards. First, similar to singleton pregnancies, the DZ fetuses are unrelated in terms of genetic predisposition to low birth weight, type 2 diabetes, or cardiovascular disease. Second, each twin has a distinct placenta in a similar maternal environment.

The discovery of specific biochemical markers of bone turnover has made it possible to study comprehensive changes in bone metabolism in twins with discordant birth weight (10). The type 1 collagen is the only collagen found in mineralized bone, with PICP and ICTP being the markers of synthesis and degradation (10). The specificity of circulating levels of both peptides as markers of bone change has been confirmed by histomorphometry and calcium kinetic studies (11, 12).

We therefore aimed to evaluate hormonal and bone growth factors involved in the regulation of bone remodeling in twins with or without discordant birth weight and sought for a relation between the IGF-I-IGF binding protein (IGFBP)-1 axis and serum leptin and bone status. Such information is pertinent for a better understanding of the factor(s) influencing fetal bone acquisition in utero and also future planning of strategies for prevention of osteoporosis in later life.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
We studied 32 dichorionic twin pregnancies at the St. Mary’s Hospital (Manchester, UK). Chorionicity was established prenatally by ultrasound scan at 15–19 wk (9). Twins with intrafetal septal thickness of more than 2 mm with twin peak signs were classed as dichorionic. The chorionicity was confirmed by histological examination of the placenta and membranes at birth. We studied only unlike-sex twin pairs. Pregnancies complicated by death of one or both twins in utero or at birth, fetal aneuploidy, and structural abnormalities were excluded. Patients with diabetes, hypertension, or renal or cardiac disease were also excluded from the study. All twins were of unlike-sex pair.

The diagnosis of discordant growth was made when the difference in birth weight was 20% or greater with absence of polyhydramnios in the larger twin’s sac and the smaller twin had an abdominal circumference in the fifth centile or less with abnormal umbilical artery Doppler waveforms. This constituted the study group (9).

Twins with differences in birth weight of 10% or less and normal amniotic fluid volumes in both sacs constituted the concordant/control group. All pregnancies were monitored by serial ultrasound scans for fetal growth, amniotic fluid volume, and umbilical artery Doppler waveforms.

Collection of blood samples

Maternal blood samples were obtained from antecubital vein. Umbilical venous blood was collected immediately after the delivery of each twin from a segment of cord that was clamped at both ends. Blood samples were collected into tubes that contained ethylenediamine-tetra acetic acid. The samples were centrifuged immediately after collection in a laboratory that is located on the delivery suite, and the plasma was stored at –70 C until batch assay was performed. Additional umbilical arterial and venous samples from each set of twins were also obtained at birth for determination of hemoglobin and acid base status within minutes of collection of samples on a gas radiometer (ABL 330; Radiometer, Copenhagen, Denmark) and hemoglobin analyzer machine (Coulter Electronics, Luton, UK). Informed consent was obtained from all women who were recruited for collection of maternal samples as required by the hospital research ethics committee.

Measurement of bone markers, leptin, and IGF

The plasma PICP and ICTP were determined by RIA (Orion Diagnostica, Espoo, Finland). We measured PICP and ICTP in the plasma as described previously (13). There was no difference in values in serum and plasma. PICP assay had an intraassay coefficient of variation of 2.1–3.7% and an interassay coefficient of variation of 3.6–6.6%.

Plasma IGF-I and IGFBP-1 were determined by RIA as described previously (14). The concentration of leptin was measured by RIA, using commercially available kits obtained from Linco Research (St. Louis, MO). The intraassay coefficient of variation for leptin was less than 5%. Leptin data of four twin sets has been published previously (15).

Data analysis

Clinical data such as birth weight and gestational age were expressed as medians and ranges, whereas peptide and hormone concentrations were expressed as mean ± SEM. The paired t test was used to compare values within twin pairs and the Student’s t test for comparison between groups. Fisher’s exact test was used for blocked comparisons. Pearson correlation was used to find any association between variables. P < 0.05 was considered significant. Percentage growth discordance was defined as the difference in birth weight and was expressed as a proportion of the birth weight of the larger twin. In the control group, the heavier twin was labeled as twin 1, and the lighter one was labeled as twin 2.


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
There were 16 dichorionic twins with discordant birth weights of 20% or greater, and 16 pairs had an interpair birth weight difference of 10% or less. The clinical parameters of concordant (n = 16) and discordant (n = 16) dichorionic twins are given in Table 1Go. The gestational ages at delivery were comparable in the two groups. In the discordant group, growth-restricted twins were more hypoxic and acidemic than the appropriate-for-gestational-age (AGA) cotwins. All growth-restricted twins had abnormal umbilical artery Doppler waveform, and nine had absent end diastolic flow.


View this table:
[in this window]
[in a new window]
  		TABLE 1. Clinical features of twins with and without discordant birth weight

 
In the discordant twins, PICP levels of the growth-restricted twins were lower than those of the AGA twins (1414 ± 120 vs. 2087 ± 141 µg/liter; P < 0.01) and concordant twins (P < 0.01) (Fig. 1AGo). In contrast, growth-restricted twins had higher ICTP concentrations than those of AGA cotwins (151 ± 6 vs. 126 ± 5 µg/liter; P < 0.001) and concordant twins (P < 0.01) (Fig. 1BGo). There were no significant differences in the ICTP (125 ± 7 vs. 129 ± 7 µg/liter; P = NS) and PICP (1955 ± 161 vs. 1933 ± 159 µg/liter; P= NS) concentrations between concordant twin pairs and AGA twins of the discordant group (P = NS). The maternal concentrations of ICTP (9 ± 1 µg/liter vs. 7 ± 1 µg/liter; P = NS) and PICP (120 ± 3 vs. 124 ± 5 µg/liter; P = NS) were comparable in the two groups and were lower than those of fetal levels.


Figure 1
View larger version (31K):
[in this window]
[in a new window]
  		FIG. 1. Fetal concentration of PICP (A) and ICTP (B) in dichorionic twins with discordant and concordant birth weight. NS, Not significant.

 
In growth-restricted twins, IGF-I concentration was lower (35 ± 4 vs. 73 ± 6 ng/ml; P < 0.001) (Fig. 2AGo), whereas that of IGFBP-1 was higher (966 ± 111 vs. 300 ± 44 ng/ml; P < 0.001) than the AGA cotwin (Fig. 2BGo). No such differences in IGF-I (73 ± 4 vs. 74 ± 5 ng/ml; P = NS) and IGFBP-1 (375 ± 63 vs. 352 ± 52 ng/ml; P = NS) were found between concordant twin pairs. The maternal concentrations of IGF-I (290 ± 37 vs. 230 ± 28 ng/ml; P = NS) and IGFBP-1 (316 ± 24 vs. 299 ± 32 ng/ml; P = NS) were comparable in concordant and discordant MC twins.


Figure 2
View larger version (32K):
[in this window]
[in a new window]
  		FIG. 2. Fetal concentrations of IGF-I (A), IGFBP-1 (B), and leptin (C) in dichorionic twins with discordant and concordant birth weight. NS, Not significant.

 
In the discordant group, fetal leptin concentrations were lower in the growth-restricted twins than those of AGA cotwins (2.0 ± 0.3 vs. 4.4 ± 0.3 ng/ml; P < 0.001) and concordant twin pairs (P < 0.001) (Fig. 2CGo). No such differences were found between concordant twin pairs (5.1 ± 0.3 vs. 5.2 ± 0.4 ng/ml; P = NS) (Fig. 2BGo). The maternal concentrations of leptin (25 ± 5 vs. 22 ± 5 ng/ml; P = NS) were comparable in concordant and discordant dichorionic twins.

Because there was weak association among fetal leptin, ICTP (r = 0.37; P < 0.05), and PICP (r = –0.31; P < 0.05) in all twins of both groups, correlation was done separately in growth-restricted and AGA twins. Fetal leptin concentrations in the concordant group and AGA twins of the discordant group were positively associated with PICP (r = 0.61; P < 0.001) (Fig. 3AGo) and negatively associated with ICTP (r = –0.57; P < 0.001) (Fig. 3BGo). No such association was present in the growth-restricted twins of the discordant birth weight group.


Figure 3
View larger version (14K):
[in this window]
[in a new window]
  		FIG. 3. Correlation between leptin and fetal PICP (A) (r = 0.61; P < 0.001) and ICTP (B) (r = –0.57; P < 0.001) in AGA twins and twins of concordant birth weight.

 
Similarly, because there was a weak correlation among ICTP (r = –0.31; P = 0.045), PICP (r = 0.38; P < 0.05), and IGF-I in all twins, association was done separately in growth-restricted and AGA twins. In growth-restricted twins, fetal IGF-I levels were positively associated with PICP (r = 0.76; P < 0.001) (Fig. 4AGo) and negatively with ICTP (r = –0.76; P < 0.001) (Fig. 4BGo). Similarly, IGFBP-1 concentration was negatively correlated with PICP (r = 0.65; P < 0.01) (Fig. 4CGo). There was a weak association with ICTP (r = –0.47; P = 0.045). No correlation among IGF-I, IGFBP-1, PICP, and ICTP was found in the concordant and AGA twins.


Figure 4
View larger version (24K):
[in this window]
[in a new window]
  		FIG. 4. Correlation between fetal IGF-I and PICP (r = 0.76; P < 0.001) (A), IGF-I and ICTP (r = –0.76; P < 0.001) (B), IGFBP-1 and PICP (r = –0.65; P < 0.01) (C), and in umbilical arterial pO2 and IGFBP-1 (r = –0.75; P < 0.001) (D) in growth-restricted twins of discordant birth weight.

 
There was a negative correlation between concentrations of IGFBP-1 and cord arterial blood oxygen tension (pO2) in the growth-restricted twins (r = –0.75; P < 0.001) (Fig. 4DGo). There was no correlation among IGF-I, leptin, PICP, ICTP, and acid base status in the growth-restricted and AGA twins.


   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
Our data suggest that in growth-restricted dichorionic twins, the resorption marker ICTP was high, whereas the bone formation marker PICP was low, and both were closely related in twins with appropriate growth. The overall consequence of these findings is less bone formation in growth-restricted twins. This is in accordance with the literature where reduced bone mineral content is a well-recognized feature of preterm and term infants with growth restriction (4, 16). However, our findings of imbalance in coupling of the type 1 collagen marker in growth-restricted twins is at variance with that reported for small-for-gestational-age infants in whom PICP and ICTP levels were comparable with those of AGA infants (17, 18). The differences in observations between our findings and others may be attributed to study population, severity of intrauterine growth restriction, and influence of maternal factors.

The disparity in bone acquisition between dichorionic twin pairs with discordant weights confirms our observation in monozygotic twins (19). This suggests that the dynamics of uncoupling of PICP and ICTP in growth-restricted twins may be a consequence of placental factors rather than the maternal variables and genome. We have recently shown that trophoblast invasion of maternal spiral arteries in growth-restricted twins is abnormal (20) with impairment of placental transfer of oxygen and nutrients (21). Thus, the uncoupling of bone marker may also be a direct or an indirect consequence of fetal acidosis and hypoxia observed in growth-restricted twins in this study. In addition, most of the intrauterine growth-restricted (IUGR) twins had absent end-diastolic flow velocitometry of the umbilical artery, which was further indicative of fetal hypoxia.

A recent study (22) suggested that chronic hypoxia suppresses markers of bone matrix synthesis in infants of smoker women. The double-negative action of acidosis on bone cells is shown in vitro studies (23, 24). In uncorrected acidosis, the ostoblast activity is reduced (25), and osteoclast resorptive activity (23) is increased to maximize the availability of hydroxyl ions to buffer protons. Our findings of lack of any correlation between acid base status and bone markers suggest that perhaps fetal acid base status has little or at least no direct effect on osteoblast/osteoclast activity in utero. We reported a similar observation in monozygotic twins (19), indicating that in fetal life, hypoxia is unlikely to influence bone metabolism directly.

It is possible that in intrauterine life hypoxia may indirectly influence bone turnover in the growth-restricted twin by increasing the production of IGFBP-1. This proposition is further substantiated by our finding of positive association between IGFBP-1 and pO2 in growth-restricted twins. Alternatively, elevated IGFBP-1 may be a consequence of impaired placental transport of essential amino acids and reduced insulin levels in the growth-restricted twins. We have recently shown that IGFBP-1 is negatively correlated with insulin and essential amino acids, and there is a positive association between amino acids and insulin in discordant dichorionic twins (26). Taken together, these data indicate that elevated IGFBP-1 is more likely to be due to impaired placental transfer function rather than reduced insulin level.

There is increasing evidence that the IGF axis plays a vital role in maintaining bone health by modulating osteoblast-osteoclast dynamics (27) and that perturbations of this axis may predispose to abnormal bone metabolism (28). More recently, studies in mice also suggest that IGF-I is a determinant of bone size and mass in postnatal life (29). Our data in dichorionic (dizygotic) twins also suggest that the IGF axis is associated with reduced bone formation and increased resorption in growth-restricted twins and thereby further amplify the importance of the IGF-IGFBP-1 axis in maintaining bone integrity (30). This observation is somewhat similar to our recent work on MC (monozygotic) twins, in which we also found a strong association between IGFBP-1 and bone markers (19). But unlike this study, we failed to find any association between IGF-I and bone markers in MC (monozygotic) twins, perhaps a reflection of a common genome (19). We appreciate that the association between IGFs and bone markers is based on a small sample size of 16 growth-restricted twins; a larger data set may be required to substantiate this finding. However, we expect a similar representation of the current finding in a larger cohort of twin pairs because our well-characterized cohort shows a highly significant correlation between IGF and bone markers. But the lack of association between the IGF axis and markers of bone turnover in 48 AGA twins suggests that IGF plays little or no role in maintaining bone mass, in which other factors such as leptin may be important.

Our data suggest that in twins with appropriate growth, leptin is positively correlated with PICP and negatively with ICTP. But no such association was found in the in the leptin-deficient growth-restricted twin. Our findings in twins with normal birth weight were consistent with previous studies in women and elderly men, which showed a strong positive association between circulating leptin levels and bone mineral density scores (31, 32, 33, 34). In contrast, some investigators have shown that leptin inhibits bone formation without affecting bone resorption (35, 36, 37). The discordance in the observations between different investigators suggests a dual mechanism: a direct stimulatory effect on bone growth and an indirect suppressive effect through the hypothalamus (38, 39). However, the role of leptin on fetal bone metabolism is unclear. Our data suggest that at least in twins with normal birth weight, leptin may promote bone acquisition through direct action. But this effect is less clear in growth-restricted twins in whom other variables may override the beneficial effect of leptin. In growth-restricted twins, leptin deficiency could be due to either reduced fat mass or intrauterine starvation as a consequence of abnormal placentation. Both these factors are shown to influence circulating leptin levels in fetal life (40, 41). Although in this study we did not measure fat mass, it is well established that the fat mass in growth-restricted infants is only 3% of body weight, compared with 15% in infants with normal birth weight (42, 43). This may adversely influence bone metabolism because increase in fat mass has a protective effect on the bone turnover (44). However, our data of lack of association between leptin and bone markers suggest that leptin deficiency is not the key regulator of bone acquisition in growth-restricted twins. Instead, the IGF system may be more important for bone turnover because a strong association exists between IGF system and bone markers in growth-restricted twins. We appreciate that bone remodeling is a complex process that is regulated by systemic hormones and local factors that affect osteoclast or osteoblast cells. Further studies are required to substantiate the hypothesis.

In conclusion, our data suggest that growth-restricted twins have high bone turnover, perhaps due to altered IGF axis rather than leptin deficiency. This effect is independent of known maternal determinants.


   Footnotes
 
First Published Online August 29, 2006

Abbreviations: AGA, Appropriate for gestational age; DZ, dizygotic; ICTP, carboxyl terminal telopeptide; IGFBP, IGF binding protein; IUGR, intrauterine growth-restricted; MC, monochorionic; PICP, carboxyl terminal propeptide.; pO2, oxygen tension.

Received November 30, 2005.

Accepted August 23, 2006.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. Javaid MK, Cooper C 2002 Prenatal and childhood influences on osteoporosis. Best Pract Res Clin Endocrinol Metab 16:349–367[CrossRef][Medline]
  2. Yarbrough DE, Barrett-Connor E, Morton DJ 2000 Birth weight as a predictor of adult bone mass in postmenopausal women: the Rancho Bernardo Study. Osteoporos Int 11:626–630[CrossRef][Medline]
  3. Godfrey K, Walker-Bone K, Robinson S, Taylor P, Shore S, Wheeler T, Cooper C 2001 Neonatal bone mass: influence of parental birthweight, maternal smoking, body composition, and activity during pregnancy. J Bone Miner Res 16:1694–1703[CrossRef][Medline]
  4. Kajantie E, Hytinantti T, Koistinen R, Risteli J, Rutanen EM, Seppala M, Andersson S 2001 Markers of type I and type III collagen turnover, insulin-like growth factors, and their binding proteins in cord plasma of small premature infants: relationships with fetal growth, gestational age, preeclampsia, and antenatal glucocorticoid treatment. Pediatr Res 49:481–489[Medline]
  5. Thomas T, Burguera B 2002 Is leptin the link between fat and bone mass? J Bone Miner Res 17:1563–1569[CrossRef][Medline]
  6. Javaid MK, Godfrey KM, Taylor P, Robinson SM, Crozier SR, Dennison EM, Robinson JS, Breier BR, Arden NK, Cooper C 2005 Umbilical cord leptin predicts neonatal bone mass. Calcif Tissue Int 76:341–347[CrossRef][Medline]
  7. Javaid MK, Godfrey KM, Taylor P, Shore SR, Breier B, Arden NK, Cooper C 2004 Umbilical venous IGF-I concentration, neonatal bone mass, and body composition. J Bone Miner Res 19:56–63[CrossRef][Medline]
  8. Poulter NR, Chang CL, MacGregor AJ, Snieder H, Spector TD 1999 Association between birth weight and adult blood pressure in twins: historical cohort study. BMJ 319:1330–1333[Abstract/Free Full Text]
  9. Bajoria R 1998 Vascular anatomy of monochorionic placenta in relation to discordant growth and amniotic fluid volume. Hum Reprod 13:2933–2940[Abstract/Free Full Text]
  10. Risteli L, Risteli J 1993 Biochemical markers of bone metabolism. Ann Med 25:385–393[Medline]
  11. Eriksen EF, Charles P, Melsen F, Mosekilde L, Risteli L, Risteli J 1993 Serum markers of type I collagen formation and degradation in metabolic bone disease: correlation with bone histomorphometry. J Bone Miner Res 8:127–132[Medline]
  12. Charles P, Mosekilde L, Risteli L, Risteli J, Eriksen EF 1994 Assessment of bone remodeling using biochemical indicators of type I collagen synthesis and degradation: relation to calcium kinetics. Bone Miner 24:81–94[Medline]
  13. Ogueh O, Sooranna S, Nicolaides KH, Johnson MR 2000 The relationship between leptin concentration and bone metabolism in the human fetus. J Clin Endocrinol Metab 85:1997–1999[Abstract/Free Full Text]
  14. Bajoria R, Gibson MJ, Ward S, Sooranna SR, Neilson JP, Westwood M 2001 Placental regulation of insulin-like growth factor axis in monochorionic twins with chronic twin-twin transfusion syndrome. J Clin Endocrinol Metab 86:3150–3156[Abstract/Free Full Text]
  15. Sooranna SR, Ward S, Bajoria R 2001 Fetal leptin influences birth weight in twins with discordant growth. Pediatr Res 49:667–672[Medline]
  16. Petersen S, Gotfredsen A, Knudsen FU 1989 Total body bone mineral in light-for-gestational-age infants and appropriate-for-gestational-age infants. Acta Paediatr Scand 78:347–350[Medline]
  17. Namgung R, Tsang RC, Specker BL, Sierra RI, Ho ML 1993 Reduced serum osteocalcin and 1,25-dihydroxyvitamin D concentrations and low bone mineral content in small for gestational age infants: evidence of decreased bone formation rates. J Pediatr 122:269–275[Medline]
  18. Namgung R, Tsang RC, Sierra RI, Ho ML 1996 Normal serum indices of bone collagen biosynthesis and degradation in small for gestational age infants. J Pediatr Gastroenterol Nutr 23:224–228[CrossRef][Medline]
  19. Bajoria R, Sooranna SR, Ward S, Chatterjee R 2006 Elevated IGFBP-1 cause high bone turnover in growth-restricted monochorionic twins with discordant birth weight. Bone 38:929–934[Medline]
  20. Matijevic R, Ward S, Bajoria R 2002 Non-invasive method of evaluation of trophoblast invasion of spiral arteries in monochorionic twins with discordant birthweight. Placenta 23:93–99[CrossRef][Medline]
  21. Bajoria R, Sooranna SR, Ward S, D’Souza S, Hancock M 2001 Placental transport rather than maternal concentration of amino acids regulates fetal growth in monochorionic twins: implications for fetal origin hypothesis. Am J Obstet Gynecol 185:1239–1246[CrossRef][Medline]
  22. Colak O, Alatas O, Aydogdu S, Uslu S 2002 The effect of smoking on bone metabolism: maternal and cord blood bone marker levels. Clin Biochem 35:247–250[CrossRef][Medline]
  23. Krieger NS, Frick KK, Bushinsky DA 2004 Mechanism of acid-induced bone resorption. Curr Opin Nephrol Hypertens 13:423–436[CrossRef][Medline]
  24. Garrett IR, Boyce BF, Oreffo RO, Bonewald L, Poser J, Mundy GR 1990 Oxygen-derived free radicals stimulate osteoclastic bone resorption in rodent bone in vitro and in vivo. J Clin Invest 85:632–639[Medline]
  25. Brandao-Burch A, Utting JC, Orriss IR, Arnett TR 2005 Acidosis inhibits bone formation by osteoblasts in vitro by preventing mineralization. Calcif Tissue Int 77:167–174[CrossRef][Medline]
  26. Bajoria R, Sooranna SR, Ward S, Hancock M 2002 Placenta as a link between amino acids, insulin-IGF axis, and low birth weight: evidence from twin studies. J Clin Endocrinol Metab 87:308–315[Abstract/Free Full Text]
  27. Rosen CJ 2004 Insulin-like growth factor I and bone mineral density: experience from animal models and human observational studies. Best Pract Res Clin Endocrinol Metab 18:423–435[CrossRef][Medline]
  28. Smink JJ, Koster JG, Gresnigt MG, Rooman R, Koedam JA, Van Buul-Offers SC 2002 IGF and IGF-binding protein expression in the growth plate of normal, dexamethasone-treated and human IGF-II transgenic mice. J Endocrinol 175:143–153[Abstract]
  29. He J, Rosen CJ, Adams DJ, Kream BE 2006 Postnatal growth and bone mass in mice with IGF-I haploinsufficiency. Bone 38:826–835[Medline]
  30. Govoni KE, Baylink DJ, Mohan S 2005 The multi-functional role of insulin-like growth factor binding proteins in bone. Pediatr Nephrol 20:261–268[CrossRef][Medline]
  31. Dennison EM, Syddall HE, Fall CH, Javaid MK, Arden NK, Phillips DI, Cooper C 2004 Plasma leptin concentration change in bone density among elderly men and women: the Hertfordshire Cohort Study. Calcif Tissue Int 74:401–406[CrossRef][Medline]
  32. Matkovic V, Ilich JZ, Skugor M, Badenhop NE, Goel P, Clairmont A, Klisovic D, Nahhas RW, Landoll JD 1997 Leptin is inversely related to age at menarche in human females. J Clin Endocrinol Metab 82:3239–3245[Abstract/Free Full Text]
  33. Odabasi E, Ozata M, Turan M, Bingol N, Yonem A, Cakir B, Kutlu M, Ozdemir IC 2000 Plasma leptin concentrations in postmenopausal women with osteoporosis. Eur J Endocrinol 142:170–173[Abstract]
  34. Iwamoto I, Douchi T, Kosha S, Murakami M, Fujino T, Nagata Y 2000 Relationships between serum leptin level and regional bone mineral density, bone metabolic markers in healthy women. Acta Obstet Gynecol Scand 79:1060–1064[CrossRef][Medline]
  35. Ducy P, Amling M, Takeda S, Priemel M, Schilling AF, Beil FT, Shen J, Vinson C, Rueger JM, Karsenty G 2000 Leptin inhibits bone formation through a hypothalamic relay: a central control of bone mass. Cell 100:197–207[CrossRef][Medline]
  36. Morberg CM, Tetens I, Black E, Toubro S, Soerensen TI, Pedersen O, Astrup A 2003 Leptin and bone mineral density: a cross-sectional study in obese and nonobese men. J Clin Endocrinol Metab 88:5795–5800[Abstract/Free Full Text]
  37. Sato M, Takeda N, Sarui H, Takami R, Takami K, Hayashi M, Sasaki A, Kawachi S, Yoshino K, Yasuda K 2001 Association between serum leptin concentrations and bone mineral density and biochemical markers of bone turnover in adult men. J Clin Endocrinol Metab 86:5273–5276[Abstract/Free Full Text]
  38. Bjorbaek C, Kahn BB 2004 Leptin signaling in the central nervous system and the periphery. Recent Prog Horm Res 59:305–331[Abstract/Free Full Text]
  39. Steppan CM, Crawford DT, Chidsey-Frink KL, Ke HZ, Swick AG 2000 Leptin is a potent stimulator of bone growth in ob/ob mice. Regul Pept 92:73–78[CrossRef][Medline]
  40. Eckert JE, Gatford KL, Luxford BG, Campbell RG, Owens PC 2000 Leptin expression in offspring is programmed by nutrition in pregnancy. J Endocrinol 165:R1–R6
  41. Bajoria R, Sooranna SR, Ward BS, Chatterjee R 2002 Prospective function of placental leptin at maternal-fetal interface. Placenta 23:103–115[CrossRef][Medline]
  42. Petersen S, Gotfredsen A, Knudsen FU 1988 Lean body mass in small for gestational age and appropriate for gestational age infants. J Pediatr 113:886–889[CrossRef][Medline]
  43. Catalano PM, Drago NM, Amini SB 1995 Factors affecting fetal growth and body composition. Am J Obstet Gynecol 172:1459–1463[CrossRef][Medline]
  44. Reid, IR 2002 Relationships among body mass, its components, and bone. Bone 5:547–555



This article has been cited by other articles:


Home page
 EndocrinologyHome page
A. Martin, V. David, L. Malaval, M.-H. Lafage-Proust, L. Vico, and T. Thomas
Opposite Effects of Leptin on Bone Metabolism: A Dose-Dependent Balance Related to Energy Intake and Insulin-Like Growth Factor-I Pathway
Endocrinology, July 1, 2007; 148(7): 3419 - 3425.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Right arrow Submit a related Letter to the Editor
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrow Request Copyright Permission
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Bajoria, R.
Right arrow Articles by Chatterjee, R.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Bajoria, R.
Right arrow Articles by Chatterjee, R.
Right arrowPubmed/NCBI databases
*Substance via MeSH
Related Collections
Right arrow Pediatric Endocrinology
Right arrow Calcium and Bone Metabolism
Right arrow Metabolism

HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Endocrinology Endocrine Reviews J. Clin. End. & Metab.
Molecular Endocrinology Recent Prog. Horm. Res. All Endocrine Journals