help button home button Endocrine Society JCEM
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
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 Roemmich, J. N.
Right arrow Articles by Rogol, A. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Roemmich, J. N.
Right arrow Articles by Rogol, A. D.
The Journal of Clinical Endocrinology & Metabolism Vol. 88, No. 2 599-604
Copyright © 2003 by The Endocrine Society

Relationship of Leptin to Bone Mineralization in Children and Adolescents

James N. Roemmich, Pamela A. Clark, Christos S. Mantzoros, Cathy M. Gurgol, Art Weltman and Alan D. Rogol

University of Virginia Health System, Department of Pediatrics, Division of Endocrinology (J.N.R., P.A.C., A.D.R.); Department of Medicine and University of Virginia Department of Human Services (A.W.); and Department of Pharmacology (A.D.R.), Charlottesville, Virginia 22908; Department of Medicine (C.S.M.), Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215; and Department of Pediatrics (C.M.G.), School of Medicine and Biomedical Sciences, University at Buffalo, Buffalo, New York 14214

Address all correspondence and requests for reprints to: James N. Roemmich, M.D., Ph.D., Department of Pediatrics, School of Medicine and Biomedical Sciences, State University of New York at Buffalo, Farber Hall, Room G56, 3435 Main Street, Building 26, Buffalo, New York 14214-3000. E-mail: roemmich{at}buffalo.edu.


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Serum leptin concentrations and bone mass are concordant in several respects. Obesity is associated with increased serum leptin concentrations and bone mineral, whereas undernutrition reduces serum leptin concentrations and bone mineral. Furthermore, both bone mineral and serum leptin concentrations increase at the initiation of puberty. However, there is a lack of empirical evidence of an independent association of serum leptin concentrations and bone mineral in youth. Thus, we used hierarchical regression to determine whether serum leptin concentrations were related to bone mineral in boys (n = 28) and girls (n = 31). Bone mineral content, density, and apparent density of the total body and body regions were measured by dual-energy x-ray absorptiometry and statistically adjusted for chronological age, fat mass, bone-free fat-free mass, and serum IGF-I and estradiol concentrations. Sequential addition of serum log(10) leptin concentrations to the block of body size variables and the block of hormone variables did not increase R2 for any of the total or regional bone mineral content, bone mineral density, and bone mineral apparent density variables. We conclude that serum leptin concentrations do not add to the prediction of bone mineral in youth after accounting for age, fat mass, bone-free fat-free mass, and serum IGF-I and estradiol concentrations.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
ADIPOSITY, SERUM LEPTIN concentrations, and bone mass are concordant in several respects. Increased adiposity is associated with greater serum leptin concentrations (1, 2), bone mineral mass (3, 4, 5), and a lower risk of osteoporosis (6, 7). Undernutrition reduces serum leptin concentrations (8, 9) and bone mineralization in adults and youth (10, 11). Furthermore, both serum leptin concentrations and bone mineral increase at the initiation of puberty (12, 13, 14, 15). These relationships have led to the hypothesis that leptin may modulate bone mineral, but the mechanism remains unclear. Leptin replacement in ob/ob mice increases bone mineral content (BMC) and bone mineral density (BMD), despite reductions in body weight, by stimulating differentiation and maturation of osteoblastic leptin receptors (16). However, ob/ob and db/db mice have a 2- to 3-fold greater bone mass than wild-type mice, and the phenotype is expressed in young animals before they become obese, suggesting the loss of an inhibitory leptin signal on bone mineralization in ob/ob and db/db mice (17, 18).

Human studies have shown that serum leptin concentrations and bone mass are directly related (15, 19, 20). Evidence for a stimulatory role of leptin on bone mineralization in humans includes direct relationships between serum leptin concentrations and bone mineral mass and BMD in lean women (19) and lean girls (20). However, all have shown rather weak associations and suffer from incomplete control for potential confounding factors such as prevailing serum hormone concentrations.

Puberty is a critical time for maximizing bone mineral and thereby delaying or preventing later osteoporosis. Peak bone mass is attained by the end of second decade, and bone accrual is maximal during midpuberty, which coincides with rising sex steroid secretion and peak GH-IGF-I secretion. Both estradiol and the GH-IGF-I axis stimulate bone mineral accrual (21, 22, 23, 24). Only two studies have investigated the relationship of fasting serum leptin concentrations with bone mineral in youth. These studies (15, 20) did not include boys and did not adjust for the potential confounding effects of estradiol or the GH-IGF-I axis on bone. The purpose of the present investigation was to determine whether serum leptin concentrations are independently related to BMC, BMD, and bone mineral apparent density (BMAD) after statistical correction for chronological age, fat mass (FM), bone-free fat-free mass (FFM), and serum estradiol and IGF-I concentrations in healthy, normal weight, prepubertal, and pubertal boys and girls.


   Subjects and Methods
Top
 Abstract
 Introduction
 Subjects and Methods
Results
 Discussion
 References
 
Subjects

Boys (n = 28) and girls (n = 31) enrolled in a longitudinal study of the endocrine control of growth, maturation, and body composition were evaluated. Entrance and continued participation in the study required normal growth, including a height, height velocity, and weight within two SDs of the mean for chronological age. Stage of secondary sex characteristics was assessed by the method of Tanner (25) by an experienced pediatric endocrinologist. The study was reviewed and approved by the University of Virginia Human Investigation Committee. Informed consent was obtained from a parent and assent from each child. The present study provides a cross-sectional analysis of the bone mineral, body composition, and serum leptin, IGF-I, and estradiol concentrations of these youth.

Bone mineral/regional body composition

BMC, BMD, and BMAD of the whole body, femoral neck, midradius, and lumbar spine 2–4 were measured by dual-energy x-ray absorptiometry (DEXA; QDR 2000, Hologic, Inc., Waltham, MA). Transverse scans were made with a pencil beam from head to toe at 1-cm intervals. All scans were analyzed with Hologic enhanced whole body software (version 5.64) by the same technician. BMADs of the whole body and specific regions were calculated as described by Katzman et al. (26). Total BMC data were also presented as BMC/height, because of uncertainty of the accuracy of the total body reference volume prediction equation of Katzman et al. (26).

Body composition

Body composition was estimated by a four-compartment model (27). Body density was measured by underwater weighing. Residual volume was measured, on land, by nitrogen washout, with the subject seated in the same position as that used during the underwater weighing. Total body water was measured by deuterium dilution (27). Measurement of BMC was made by DEXA using a QDR 2000 bone densitometer (Hologic, Inc.). The four-compartment model of Lohman (28) was used to estimate the percentage body fat, FM, and FFM. The validation of the use of this model in our laboratory has been reported (27). BMC was subtracted from the four-compartment FFM, for a measure of bone-free lean tissue mass, which was then used in the hierarchical regression analyses.

Anthropometry

All height measures were completed by a trained anthropometrist (J.N.R.) as recommended (29).

Assays

Blood for hormone analyses was withdrawn at 0600 h after, an overnight stay, at the University of Virginia General Clinical Research Center. Starting with breakfast the previous day, the subjects consumed meals and snack constant for energy, fat (30% of calories), protein (15% of calories), and carbohydrate (55% of calories) at standard times. Serum leptin concentration was measured by RIA as previously described (14). The sensitivity of the leptin assay is 31 pM, with an intraassay coefficient of variation (CV) of 8.3–3.4% and interassay CV of 6.2–3.0% within the range of 306-1600 pM. IGF-I concentrations were measured by RIA (Nichols Institute Diagnostics, San Juan Capistrano, CA). IGF-I concentrations were measured after acid-ethanol extraction and had intraassay CV of 2.4% and 3.0% at 0.07 nM and 0.12 nM and interassay CV of 5.2% and 8.4% at 0.07 nM and 0.11 nM, respectively. The sensitivity was 0.01 nM. Serum estradiol concentration was measured by RIA, using kits from Diagnostic Products (Los Angeles, CA). The sensitivity of the estradiol assay was 36.7 pM, with an intraassay CV of 4–7% within the range of 183.6–4038.1 pM. The interassay CV ranged from 4.2–8.1% within the range of 183.6–3762.8 pM. Estradiol concentrations were not considered in relation to ovarian cycles.

Statistics

Two-way [sex (boys vs. girls) x maturation (prepubertal vs. pubertal)] ANOVA was used to test for group differences in total and regional BMC, BMD, and BMAD as well as body composition and serum hormone concentrations. Pearson correlations were used to examine the strength of the relationship between physical characteristics, serum hormone concentrations, and bone mineralization variables. Hierarchical regression was used to determine whether serum log(10) leptin concentrations were related to total and regional BMC, BMD, and BMAD after initial adjustment for a block of variables pertaining to body size (chronological age, FM, bone-free FFM) and then for a block of variables pertaining to serum IGF-I and estradiol concentrations. Thus, a series of three blocks was used in the hierarchical regression: block 1 (chronological age, FM, bone-free FFM), block 2 (serum IGF-I and estradiol concentrations), and block 3 (serum log(10) leptin concentrations). The predictors in block 2 were added to those of block 1 and that of block 3 added to blocks 1 and 2. The increase in R2 between consecutive blocks corresponds to the proportion of variance of the dependent variable that is shared by the newly added variable(s). The order of the blocks determines the variables that are being controlled. The effects of variables entered in earlier steps are partialed from relationships in later steps (30). The leptin concentrations were log transformed because the absolute values were not normally distributed.


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
The physical characteristics are shown in Table 1Go. The data are shown by pubertal stage within each sex. For analysis of the physical characteristics and serum hormone concentrations, the subjects were divided into prepubertal (genital or breast stage I) and pubertal groups (genital or breast stages II–V). Sex differences were observed with boys having a greater height (P = 0.01) and FFM (P < 0.001) and lower percent body fat (P = 0.002) than the girls. Pubertal boys and girls were older (P < 0.001), taller (P < 0.001), heavier (P < 0.001), and had a greater FM (P = 0.002) and FFM (P < 0.001) than prepubertal boys and girls. Serum leptin concentrations were greater (P = 0.006) in girls than boys, and serum IGF-I concentrations were greater (P < 0.001) in pubertal than prepubertal youth. Serum estradiol concentrations were greater in girls than boys (P = 0.05) and greater (P = 0.007) in pubertal than prepubertal youth.


View this table:
[in this window]
[in a new window]
  		Table 1. Physical characteristics and serum hormone concentrations of the subject groups

 
Means of the total and regional BMC, BMD, and BMAD are shown in Table 2Go. Girls had a greater lumbar spine BMD (P = 0.03) and lumbar spine BMAD (P = 0.001) and a smaller femoral neck BMC (P = 0.02). Pubertal youth had greater (P = 0.003 to <0.001) BMC, BMD, and BMAD for the total body and all regional sites except for the midradius BMAD [which was greater (P < 0.001) in prepubertal youth] and the femoral neck BMAD (for which there was no maturational difference).


View this table:
[in this window]
[in a new window]
  		Table 2. Total and regional BMC, BMD, and BMAD of the subject groups

 
Simple correlation coefficients between total and regional bone mineral data and the independent variables are shown in Table 3Go. For the total body and each region, the BMC and BMD were directly and significantly related to chronological age, FM, bone-free FFM, and serum IGF-I and estradiol concentrations. The BMAD of the total body and midradius was inversely related, and the BMAD of the lumbar spine positively related, to chronological age, FM, bone-free FFM and serum IGF-I and estradiol concentrations. Serum leptin concentrations were directly related to the lumbar spine BMD and BMAD.


View this table:
[in this window]
[in a new window]
  		Table 3. Correlation coefficients between total and regional bone mineral data and the independent variables

 
Hierarchical regression results are shown in Table 4Go. Block 1 consisted of physical characteristic variables including chronological age, FM, and bone-free FFM. The R2 for block 1 is shown in the second column of Table 4Go. These variables were added first so that the predictive value of the remaining independent variables could be determined while holding constant initial differences in age and body size. IGF-I and estradiol data were then added to the block of physical characteristics, and the R2 of the new model with two blocks of variables is shown in column 3 of Table 4Go. As shown in column 4, there was a significant incremental increase in R2 between blocks for total body BMC (P <= 0.001), BMD (P <= 0.001), and BMC/height (P <= 0.001); midradius BMC (P = 0.003), BMD (P = 0.003), and BMAD (P = 0.04); and lumbar spine BMC (P <= 0.001), BMD (P <= 0.001), and BMAD (P = 0.006). After accounting for physical characteristics and serum IGF-I and sex steroid concentrations, serum log(10) leptin concentrations did not significantly increase R2 (see columns 5 and 6 of Table 4Go) for any bone mineral variable.


View this table:
[in this window]
[in a new window]
  		Table 4. Hierarchical regression results

 

   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
We have shown that, in normal weight children and adolescents, serum leptin concentrations are not related to total body nor regional BMC and BMD independent of chronological age, FM, bone-free FFM, and serum estradiol and IGF-I concentrations. To our knowledge, this is the first study to account for such a large number of variables that modulate bone mineral, which may explain why we did not demonstrate an independent relationship of serum leptin concentrations with bone mineral.

In the first block of the hierarchical regression model, bone mineralization data were adjusted for chronological age, FM, and bone-free FFM, because increases in bone mineral during childhood and adolescence are a reflection of increases in body size and body weight (26, 31). Body weight and its fat and fat-free subcomponents are directly related to the amount of bone mineral in youth (26) and adults (3). Body weight increases bone mineralization by increasing the mechanical loading on the bone (7). Bone-free FFM includes the skeletal muscles, which also exert mechanical (pulling) forces on bone when producing body movements or stabilizing forces. Adjusting for FM, which was measured very accurately in the present study, creates a very stringent test for the independent relationship of leptin with bone mineralization; because we have shown that, in these same subjects, leptin is secreted in direct proportion to the amount of FM (1). The high correlation between serum leptin concentrations and FM suggests that they convey similar information. Others have reported a direct relationship of FM with bone mineral and have hypothesized that additional FM acts as a mechanical stimulus for bone mineralization (3, 4, 5). Thus, a relationship between serum leptin concentrations and bone mineral could actually reflect the relationship of FM and bone mineral because of the collinearity of leptin and FM with bone mineral measures. The inclusion of FM in the first block of the model accounts for the variance contributed by leptin regarding body adiposity, so that any relationship between leptin and bone mineral is independent of the collinearity of leptin and FM. In the second block of the hierarchical regression, bone mineralization data were further adjusted for serum IGF-I and estradiol concentrations. IGF-I serves as a marker of the integrated GH-IGF-I axis, and both GH (21) and IGF-I (22) increase bone mineral, as does estradiol (23, 24). These hormonal variables increased R2 for BMC, BMD, and BMAD variables beyond that of the physical characteristics (Table 4Go). After statistically adjusting for all five of these factors, the serum leptin concentration was not related to total body or regional bone mineral (Table 4Go).

Previous investigations of children (32) and adults (22, 33, 34) have also reported no independent effect of leptin on bone mineral or markers of bone metabolism (33, 34). However, others have reported that the relationship between bone mineralization and serum leptin concentrations is significant and positive but low in magnitude (19, 35, 36), including studies of children (15, 20), but these studies did not statistically adjust for confounding correlated variables that also influence bone mineral, such as FM or serum estradiol and IGF-I concentrations. The importance of including FM in the model, because of the collinearity of leptin and FM with bone mineral measures, is discussed above.

The role of leptin on bone mineral of humans remains unclear. Though the results of the present study imply that leptin does not increase bone mineral of youth beyond the biomechanical influence of body weight and physiological influences of FM, sex steroids, and the GH-IGF-I axis, previous research suggests that leptin does play some function in bone physiology. For instance, leptin exerts a dosedependent increase in osteoblast differentiation and decrease in adipocyte differentiation in a bipotential human marrow stromal cell line (37). Leptin seems to have a more robust effect on bone mineral in ob/ob mice (16, 17, 18). However, data from ob/ob mice may not be applicable to human bone physiology, because the greater bone mass observed in ob/ob mice has not been observed in a man who does not produce leptin and is osteopenic, or in leptin-deficient women who have normal bone mass (38).

In conclusion, we have shown that, in boys and girls, serum leptin concentrations are not related to bone mineral independent of chronological age, FM, bone-free FFM, and serum IGF-I and estradiol concentrations and support neither the stimulatory (16) nor the inhibitory (17, 18) hypotheses of leptin on bone mineral. Our correlational study cannot prove or disprove a causal relationship between leptin and bone mineral. Future research should determine whether leptin indeed has a stimulatory influence on bone formation or whether the inhibitory hypothesis is valid. Furthermore, because of the potential importance of sex steroids and the GH-IGF-I axis on modifying the effect of leptin on bone mineral, research should determine whether the physiologic role of leptin on bone is similar in children, adolescents, and adults.


   Acknowledgments
 
We are indebted to Sandra Jackson and the nursing staff at the University of Virginia General Clinical Research Center, who provided patient care. We are grateful for the technical assistance provided for the DEXA scans by Christopher Puckett of the Department of Radiology at the University of Virginia. We also acknowledge the subjects for their enthusiasm for the research program for the past 2 yr.


   Footnotes
 
This work was supported in part by grants from the National Institutes of Health (HD-32631, to A.D.R.), General Clinical Research Center (MO1-RR-00847, to the University of Virginia; and RR-010302, to Beth Israel Hospital), Genentech, Inc. (to P.A.C.), and the University of Virginia Children’s Medical Center (to J.N.R.) .

Present address for P.A.C.: Department of Pediatrics, University of Louisville, 571 South Floyd Street, Suite 314, Louisville, Kentucky 40202.

Abbreviations: BMAD, Bone mineral apparent density; BMC, bone mineral content; BMD, bone mineral density; CV, coefficient(s) of variation; DEXA, dual-energy x-ray absorptiometry; FFM, fat-free mass; FM, fat mass.

Received December 18, 2001.

Accepted October 23, 2002.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. Roemmich JN, Clark PA, Berr SS, Mai V, Mantzoros CS, Flier JS, Weltman A, Rogol AD 1998 Gender differences in leptin levels during puberty are related to the subcutaneous fat depot and sex steroids. Am J Physiol 275:E543–E551
  2. Horlick MB, Rosenbaum M, Nicolson M, Levine LS, Fedun B, Wang J, Pierson Jr RN, Leibel RL 2000 Effect of puberty on the relationship between circulating leptin and body composition. J Clin Endocrinol Metab 85:2509–2518[Abstract/Free Full Text]
  3. Reid IR, Ames R, Evans MC, Sharpe S, Gamble G, France JT, Lim TM, Cundy TF 1992 Determinants of total body and regional bone mineral density in normal postmenopausal women—a key role for fat mass. J Clin Endocrinol Metab 75:45–51[Abstract]
  4. Khosla S, Atkinson EJ, Riggs BL, Melton 3rd LJ 1996 Relationship between body composition and bone mass in women. J Bone Miner Res 11:857–863[Medline]
  5. Young D, Hopper JL, Macinnis RJ, Nowson CA, Hoang NH, Wark JD 2001 Changes in body composition as determinants of longitudinal changes in bone mineral measures in 8- to 26-year-old female twins. Osteoporos Int 12:506–515[CrossRef][Medline]
  6. Tremollieres FA, Pouilles JM, Ribot C 1993 Vertebral postmenopausal bone loss is reduced in overweight women: a longitudinal study in 155 early postmenopausal women. J Clin Endocrinol Metab 77:683–686[Abstract]
  7. Kirchengast S, Peterson B, Hauser G, Knogler W 2001 Body composition characteristics are associated with the bone density of the proximal femur end in middle- and old-aged women and men. Maturitas 39:133–145[CrossRef][Medline]
  8. Dubuc GR, Phinney SD, Stern JS, Havel PJ 1998 Changes of serum leptin and endocrine and metabolic parameters after 7 days of energy restriction in men and women. Metabolism 47:429–434[CrossRef][Medline]
  9. Argente J, Barrios V, Chowen JA, Sinha MK, Considine RV 1997 Leptin plasma levels in healthy Spanish children and adolescents, children with obesity, and adolescents with anorexia nervosa and bulimia nervosa. J Pediatr 131:833–838[CrossRef][Medline]
  10. Soyka LA, Grinspoon S, Levitsky LL, Herzog DB, Klibanski A 1999 The effects of anorexia nervosa on bone metabolism in female adolescents. J Clin Endocrinol Metab 84:4489–4496[Abstract/Free Full Text]
  11. Karlsson MK, Weigall SJ, Duan Y, Seeman E 2000 Bone size and volumetric density in women with anorexia nervosa receiving estrogen replacement therapy and in women recovered from anorexia nervosa. J Clin Endocrinol Metab 85:3177–3182[Abstract/Free Full Text]
  12. Clayton PE, Gill MS, Hall CM, Tillmann V, Whatmore AJ, Price DA 1997 Serum leptin through childhood and adolescence. Clin Endocrinol (Oxf) 46:727–733[CrossRef][Medline]
  13. Lu PW, Cowell CT, Loyd-Jones SAL, Briody JN, Howman-Giles R 1996 Volumetric bone mineral density in normal subjects, aged 5–27 years. J Clin Endocrinol Metab 81:1586–1590[Abstract]
  14. Mantzoros CS, Flier JS, Rogol AD 1997 A longitudinal assessment of hormonal and physical alterations during normal puberty in boys. V. Rising leptin levels may signal the onset of puberty. J Clin Endocrinol Metab 82:1066–1070[Abstract/Free Full Text]
  15. Ibanez L, Potau N, Ong K, Dunger DB, De Zegher F 2000 Increased bone mineral density and serum leptin in non-obese girls with precocious pubarche: relation to low birth weight and hyperinsulinism. Horm Res 54:192–197[CrossRef][Medline]
  16. Steppan CM, Crawford DT, Chidsey-Frink KL, Ke H, Swick AG 2000 Leptin is a potent stimulator of bone growth in ob/ob mice. Regul Pept 92:73–78[CrossRef][Medline]
  17. 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]
  18. Amling M, Takeda S, Karsenty G 2000 A neuro (endo)crine regulation of bone remodeling. BioEssays 22:970–975[CrossRef][Medline]
  19. Pasco JA, Henry MJ, Kotowicz MA, Collier GR, Ball MJ, Ugoni AM, Nicholson GC 2001 Serum leptin levels are associated with bone mass in nonobese women. J Clin Endocrinol Metab 86:1884–1887[Abstract/Free Full Text]
  20. 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]
  21. Attie KM 2000 The importance of growth hormone replacement therapy for bone mass in young adults with growth hormone deficiency. J Pediatr Endocrinol Metab 13(Suppl 2):1011–1021
  22. Martini G, Valenti R, Giovani S, Franci B, Campagna S, Nuti R 2001 Influence of insulin-like growth factor-1 and leptin on bone mass in healthy postmenopausal women. Bone 28:113–117[Medline]
  23. Grumbach MM 2000 Estrogen, bone, growth and sex: a sea change in conventional wisdom. J Pediatr Endocrinol Metab 13:1439–1455
  24. Mauras N, Hayes V, O’Brien KO 2000 Estrogen treatment and estrogen suppression: metabolic effects in adolescence. J Pediatr Endocrinol Metab 13:1431–1437
  25. Tanner J 1962 Growth at adolescence. Oxford: Blackwell Scientific Publications
  26. 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[Abstract/Free Full Text]
  27. Roemmich JN, Clark PA, Weltman A, Rogol AD 1997 Alterations in growth and body composition during puberty. I. Comparing multicompartment body composition models. J Appl Physiol 83:927–935[Abstract/Free Full Text]
  28. Lohman TG 1992 Advances in body composition assessment. Champaign, IL: Human Kinetics Press
  29. Gordon CC, Chumlea WC, Roche AF1988 Stature, recumbent length and weight. In: Lohman T, Roche AF, Martorell R, eds. Anthropometric standardization reference manual. Champaign, IL: Human Kinetics Press; 3–8
  30. Licht M 1995 Multiple regression and correlation. In: Grimm LG, Yarnold PR, eds. Reading and understanding multivariate statistics. Washington, DC: American Psychological Association; 19–64
  31. Gilsanz V, Kovanlikaya A, Costin G, Roe TF, Sayre J, Kaufman F 1997 Differential effect of gender on the sizes of the bones in the axial and appendicular skeletons. J Clin Endocrinol Metab 82:1603–1607[Abstract/Free Full Text]
  32. Klein KO, Larmore KA, de Lancey E, Brown JM, Considine RV, Hassink SG 1998 Effect of obesity on estradiol level, and its relationship to leptin, bone maturation, and bone mineral density in children. J Clin Endocrinol Metab 83:3469–3475[Abstract/Free Full Text]
  33. Goulding A, Taylor RW1998 Plasma leptin values in relation to bone mass and density and to dynamic biochemical markers of bone resorption and formation in postmenopausal women. Calcif Tissue Int 63:456–458
  34. Rauch F, Blum WF, Klein K, Allolio B, Schonau E 1998 Does leptin have an effect on bone in adult women? Calcif Tissue Int 63:453–455[CrossRef][Medline]
  35. 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]
  36. Blain H, Vuillemin A, Guillemin F, Durant R, Hanesse B, de Talance N, Doucet B, Jeandel C 2002 Serum leptin level is a predictor of bone mineral density in postmenopausal women. J Clin Endocrinol Metab 87:1030–1035[Abstract/Free Full Text]
  37. Thomas T, Gori F, Khosla S, Jensen MD, Burguera B, Riggs BL 1999 Leptin acts on human marrow stromal cells to enhance differentiation to osteoblasts and to inhibit differentiation to adipocytes. Endocrinology 140:1630–1638[Abstract/Free Full Text]
  38. Ozata M 2002 Different presentation of bone mass in mice and humans with congenital leptin deficiency. J Clin Endocrinol Metab 87:951[Free Full Text]



This article has been cited by other articles:


Home page
 Ann Clin BiochemHome page
A. A Venner, P. K Doyle-Baker, M. E Lyon, and T. S Fung
A meta-analysis of leptin reference ranges in the healthy paediatric prepubertal population
Ann Clin Biochem, January 1, 2009; 46(1): 65 - 72.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. Misra, R. Prabhakaran, K. K. Miller, M. A. Goldstein, D. Mickley, L. Clauss, P. Lockhart, J. Cord, D. B. Herzog, D. K. Katzman, et al.
Prognostic Indicators of Changes in Bone Density Measures in Adolescent Girls with Anorexia Nervosa-II
J. Clin. Endocrinol. Metab., April 1, 2008; 93(4): 1292 - 1297.
[Abstract] [Full Text] [PDF]

Home page
 Eur J EndocrinolHome page
P. Crabbe, S. Goemaere, H. Zmierczak, I. Van Pottelbergh, D. De Bacquer, and J.-M. Kaufman
Are serum leptin and the Gln223Arg polymorphism of the leptin receptor determinants of bone homeostasis in elderly men?
Eur. J. Endocrinol., May 1, 2006; 154(5): 707 - 714.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Clin. Nutr.Home page
S. P Garnett, W. Hogler, B. Blades, L. A Baur, J. Peat, J. Lee, and C. T Cowell
Relation between hormones and body composition, including bone, in prepubertal children
Am. J. Clinical Nutrition, October 1, 2004; 80(4): 966 - 972.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
M. E. Wilson, J. Fisher, K. Chikazawa, R. Yoda, A. Legendre, D. Mook, and K. G. Gould
Leptin Administration Increases Nocturnal Concentrations of Luteinizing Hormone and Growth Hormone in Juvenile Female Rhesus Monkeys
J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 4874 - 4883.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
A. M. Parfitt
What Is Bone Mineralization?
J. Clin. Endocrinol. Metab., October 1, 2003; 88(10): 5043 - 5043.
[Full Text]

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 Roemmich, J. N.
Right arrow Articles by Rogol, A. D.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Roemmich, J. N.
Right arrow Articles by Rogol, A. D.

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