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 Mora, S.
Right arrow Articles by Gilsanz, V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mora, S.
Right arrow Articles by Gilsanz, V.
The Journal of Clinical Endocrinology & Metabolism Vol. 84, No. 8 2780-2783
Copyright © 1999 by The Endocrine Society

Original Studies

Serum Levels of Insulin-Like Growth Factor I and the Density, Volume, and Cross-Sectional Area of Cortical Bone in Children

Stefano Mora1, Pisit Pitukcheewanont, Jerald C. Nelson and Vicente Gilsanz

Departments of Radiology and Pediatrics, Childrens Hospital Los Angeles (S.M., P.P., V.G.), Los Angeles, California 90027; and Quest Diagnostics, Inc., Nichols Institute (J.C.N.), San Juan Capistrano, California 92690

Address all correspondence and requests for reprints to: Vicente Gilsanz, M.D., Radiology Department, Childrens Hospital Los Angeles, 4650 Sunset Boulevard, M.S.# 81, Los Angeles, California 90027. E-mail: gilsanz{at}hsc.usc.edu


   Abstract
Top
 Abstract
Introduction
 Subjects and Methods
 Results
 Discussion
 References
 
Insulin-like growth factor I (IGF-I) is a major regulator of bone growth during childhood. However, beyond knowledge that IGF-I influences longitudinal growth, its associations to changes in the cross-sectional dimensions, the volume, or the material density of bone during growth are unknown. We assessed the relationships between serum IGF-I and measurements of cross-sectional area, cortical bone area, and cortical bone density at the midshaft of the femur in 197 normal healthy white children and adolescents (103 boys and 94 girls; aged 7.8–18.2 yr). Bone determinations were obtained using computed tomography, and levels of IGF-I were measured by RIA after an extraction procedure. IGF-I correlated significantly with both cross-sectional area (r = 0.49; P < 0.0001) and cortical bone area (r = 0.50; P < 0.0001), but did not correlate with the material density of cortical bone (r = -0.08). Multiple regression analyses showed that circulating levels of IGF-I were associated with cross-sectional area (P = 0.03) and cortical bone area (P = 0.04) values, even after correcting for the confounding effects of age, gender, weight, and femoral length. We conclude that IGF-I is a major determinant of the cross-sectional properties of bone, but does not influence the material density of bone, in the appendicular skeleton.


   Introduction
Top
 Abstract
 Introduction
Subjects and Methods
 Results
 Discussion
 References
 
INSULIN-LIKE growth factors (IGF) have been the focus of extensive investigation since they were discovered to stimulate cartilage sulfation approximately 2 decades ago (1). Considerable data are available regarding the role of insulin-like growth factor I (IGF-I) as a promoter of cell growth and differentiation (2). Studies have found IGF-I to be an important regulator of osteoblastic differentiation, proliferation, and collagenase activity, and consequently a major determinant of bone matrix apposition (3, 4, 5, 6, 7, 8). In addition, it has been found that IGF-I stimulates the activation and formation of osteoclasts (9, 10), and that osteoblasts mediate IGF-I-stimulated formation of osteoclasts (11). IGF-I may thus modulate osteoblast-osteoclast interactions and serve as a coupling agent in the bone-remodeling cycle (12).

Compared to the comprehensive investigations on the role of IGF-I in regulating bone growth, information regarding its affects on bone mass and/or bone density is limited and conflicting. In elderly subjects with osteoporosis, levels of IGF-I are consistently lower than those in controls (13, 14, 15), but a clear relationship between IGF-I measurements and bone mineral density values has not been established; some investigators report an association (13, 16, 17, 18, 19, 20), whereas others do not (21, 22). Increases in skeletal and serum IGF-I levels during childhood parallel increases in bone mass during growth, suggesting a relationship between elevated IGF-I levels and bone gains (23, 24, 25). More recent studies in experimental animals and humans have suggested that IGF-I asserts its affect on bone mass acquisition mainly by increasing bone size. Rosen et al. demonstrated that rats treated with IGF-I had greater bone size but lower bone density than untreated animals (26). Similarly, studies by Bachrach and colleagues indicate that childhood onset of GH resistance, which is associated with a marked deficiency of IGF-I, results in smaller bones, but normal bone density (27). However, the structural basis for the relationship between increases in bone mass and serum IGF-I levels in healthy children has not yet been definitively established.

The recent adaptation of quantitative computed tomography (CT) to accurately measure the cross-sectional dimensions, volume, and density of bone in the appendicular skeleton has significantly improved our ability to noninvasively quantify the various structural components of bone mass. This study was designed to determine the possible association between variations in IGF-I levels and these skeletal parameters during childhood.


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

The study subjects were 197 healthy white children and adolescents (103 boys and 94 girls) between the ages of 7.8–18.2 yr, who were recruited from schools of Los Angeles County. The investigational protocol was approved by the institutional review board for clinical investigations at Childrens Hospital Los Angeles, and informed consent was obtained from all subjects and/or their parents.

Subjects were excluded if they had any chronic illness, if they had been ill for longer than 2 weeks during the previous 6 months, or if they had taken any medications, vitamin preparations, or calcium supplements within the previous 6 months. No subject had any physical impairment that would limit their physical activity.

Candidates underwent a physical examination by a pediatrician, and measurements of total height and trunk height were obtained to the nearest 0.25 cm using the Harpenden stadiometer and the Harpenden Sitting TableGo (Holtain Ltd., Crymmych, Wales), respectively, and measurements of weight were obtained to the nearest 0.1 kg using the Scale-Tronix (Scale-Tronix, Inc., Wheaton, IL). Children in whom either height or weight was not within the 5th and 95th percentiles for the mean age-adjusted normal values were excluded from further evaluation (28). Thereafter, body surface area and body mass index were calculated, as previously described (29). The length of the femur was calculated as the distance between the greater trochanter and the distal lateral condyle.


View this table:
[in this window]
[in a new window]
  		Table 1. Age, anthropometric measurements, femoral bone measurements, and IGF-I serum levels in 197 healthy children

 
IGF-I measurements

After an overnight fast, blood was drawn for determination of IGF-I. Levels of serum IGF-I were measured at Quest Diagnostics, Inc./Nichols Institute Diagnostics (San Juan Capistrano, CA) after acid-ethanol extraction to eliminate binding to serum proteins, using a RIA with rabbit anti-IGF-I and [125I]IGF-I. The assay was calibrated to the WHO First International Reference Preparation, 87/518. The bound-free separation was achieved using goat antirabbit {gamma}-globulin and polyethylene glycol. Samples were stored at -70 C until assayed in batches of approximately 25–50. The sensitivity of the assay was 1 ng/mL; interassay variability was lower than 9.2%, and intraassay variability was lower than 7.9%.

CT bone measurements

All CT bone measurements were performed with the same scanner (model CT-T 9800, General Electric Co., Milwaukee, WI) and mineral reference phantom for simultaneous calibration (CT-T bone densitometry package, General Electric). The scanning site was located by physical examination, and measurements of cortical bone density, cross-sectional area, and cortical bone area were obtained from a single 1.5-mm thick imaging scan at the midportion of the distance between the greater trochanter and the lateral condyle using 120 kVp, 70 mA, and 2 s. The outer and inner boundaries of the cortex, representing the periosteal and endosteal surfaces of the bone, respectively, were identified at the place of the maximum slope of the femoral profile through the bone. The area within the outer cortical shell represented the femoral cross-sectional area, and the area between the outer and inner cortical shells represented the cortical bone area (30). For the purposes of this study, measurements of cortical bone area reflect the volume of bone, and the density of cortical bone is defined as the amount of bone per pixel (milligrams per cm3) at the midshaft of the femur. Because of the thickness and the relative lack of porosity of cortical bone in the femur, CT values reflect the material or true density of the bone (the amount of collagen and mineral in a given volume of bone) (30). These measurements are analogous to in vitro determinations of the intrinsic mineral density of bone, which are commonly expressed as the ash weight per unit volume of bone (31).

The coefficients of variation for repeated CT measurements of cross-sectional area, cortical bone area, and cortical bone density were calculated to be between 0.6–2.5%. The time required for the procedure was approximately 10 min, and the radiation exposure was approximately 100 mrem (1.0 mJ/kg) localized to 1.5 mm at the midportions of the femurs; the effective radiation dose was approximately 1 mrem (32).

Statistical analysis

The results are expressed as the mean (SD), unless otherwise stated. Normal distribution of the data was ascertained using the Shapiro-Wilk W test. Body mass index and IGF-I were not normally distributed; therefore, in all the analyses their log-transformed values were used. The relationships among age, anthropometric variables, IGF-I serum levels, and CT bone measurements were assessed using simple correlation coefficient, as for a null hypothesis {rho} = 0. To test whether IGF-I exerted an independent effect on bone size measurements, multivariate analyses were performed. Gender, age, weight, and femur length were considered to be confounding variables, whereas IGF-I was the dependent variable, and femoral cortical bone area and cross-sectional area were the dependent variables. All tests were conducted at the {alpha} = 0.05 level and were two tailed. The statistical software JMP IN (SAS Institute, Inc., Cary, NC) was used for the analyses.


   Results
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
Discussion
 References
 
Table 1Go summarizes the ages, anthropometric measurements, quantitative CT bone measurement values, and IGF-I serum levels in 197 children and adolescents.

The correlation coefficients for age, anthropometric measurements, and femoral CT measurements are shown in Table 2Go. The cross-sectional and the cortical bone areas at the midshaft of the femur correlated strongly with age, weight, height, femur length, trunk height, and body surface area. In contrast, the material density of cortical bone at this location showed no correlation with age or any anthropometric variable. IGF-I serum levels showed close correlations with age (r = 0.39), weight (r = 0.48), and other anthropometric measurements, including CT values for femoral cortical bone area (r = 0.50; P < 0.0001) and femoral cross-sectional area (r = 0.49; P < 0.0001). IGF-I serum levels did not correlate with the material density of bone (r = -0.08; Table 2Go).


View this table:
[in this window]
[in a new window]
  		Table 2. Correlation coefficients for age, anthropometric measurements, femoral bone measurements, and IGF-I serum levels in 197 healthy children

 
The cross-sectional dimensions of the femur were used as dependent variables in multivariate analyses to ascertain whether the relationship observed between the cross-sectional properties and circulating IGF-I levels was independent of changes in age and anthropometry. The model was built to correct for differences in gender and age; we also accounted for the confounding effect of body size and included weight and femoral length in the model (Table 3Go). The model chosen explained 80% of the variability in femoral cortical bone area (r = 0.89; P < 0.0001) and 78% of the variability in femoral cross-sectional area (R = 0.88; P < 0.0001). IGF-I, therefore, exerts an effect on the cross-sectional properties of the femur that is independent of gender, age, and femoral length.


View this table:
[in this window]
[in a new window]
  		Table 3. Multiple regression models of IGF-I levels on measurements of femoral size

 

   Discussion
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
References
 
The objective of this study was to examine the possible relationships between changes in serum IGF-I values and increases in the cross-sectional dimensions and the density of bone in the appendicular skeleton during growth. We found that in healthy white children there is a direct relationship between levels of IGF-I and the cross-sectional area and the cortical bone area of the femur, but no association with measurements of the material density of cortical bone. Multivariate analyses showed that the relationships between IGF-I and femoral cross-sectional and cortical bone areas were still present even after accounting for the confounding effects of femoral length and body weight.

Several investigators have previously found a relationship between IGF-I serum levels and bone mass measurements (13, 16, 17, 18, 19, 20); higher circulating IGF-I concentrations corresponded to higher bone mass in both the axial and appendicular skeletons. These studies, however, employed dual energy x-ray absorptiometry (DXA) to obtain bone density and bone mass measurements. DXA bone density values are a measure of bone mineral mass normalized by the projected area of the bone (an index obtained from the scanner during the examination) and do not represent the true mineral density of bone (33). The current findings suggest that the structural basis for the relationship between IGF-I and DXA values observed in previous studies is independent of the true material density of the bone, but IGF-I may exert its affect on bone mineral density by increasing cross-sectional bone area (31). These findings corroborate previous studies in experimental animals treated with IGF-I and in humans deficient of IGF-I, suggesting that IGF-I is a major determinant of bone geometry, but not of bone density (26, 27).

The present study has three limitations. First, the population studied was comprised solely of white children. We chose to study children of only one ethnic background to avoid the confounding effect of race on bone growth in the appendicular skeleton (34). Second, although circulating levels of IGF-I parallel skeletal levels, they do not necessarily represent the IGF-I that promotes bone growth, as skeletal IGF-I is also available in the bone matrix itself and from activated osteoblasts (35). Third, in the current study we did not measure any of the binding proteins (IGFBP) that regulate local and systemic effects of IGF-I (2). IGF-I exists in the circulation bound to six IGFBPs. Serum IGF-I and IGFBP-3 show positive correlationships with bone mass at all sites. However, as recent studies indicate that the association between IGF-I and bone mass is independent of IGFBP-3 circulating levels, it is unclear what these measurements would have added to the results (18).

In conclusion, the action of IGF-I at the cellular level and its association with bone mass have justified the interest in IGF-I as a bone formation-stimulating drug in the treatment of osteoporosis. The findings in the present study corroborate previous evidence of a positive effect of IGF-I on bone mass. Our results in children further indicate that, at least in the appendicular skeleton, IGF-I exerts its effect on bone mass by increasing the cross-sectional and cortical areas of the long bones.


   Footnotes
 
1 Present address: Department of Pediatrics, Scientific Institute H, San Raffaele, 20132 Milan, Italy. Back

Received February 9, 1999.

Revised March 26, 1999.

Revised April 12, 1999.

Accepted April 14, 1999.


   References
Top
 Abstract
 Introduction
 Subjects and Methods
 Results
 Discussion
 References
 

  1. Salmon Jr WD, Daughaday WH. 1957 A hormonally controlled serum factor which stimulates sulfate incorporation by cartilage in vitro. J Lab Clin Med. 49:825–836.[Medline]
  2. Jones JI, Clemmons DR. 1995 Insulin-like growth factors and their binding proteins: biological actions. Endocr Rev. 16:3–34.[Abstract/Free Full Text]
  3. Canalis E, Rydzel S, Delany AM, Varghese S, Jeffrey JJ. 1995 Insulin-like growth factors inhibit interstitial collagenase synthesis in bone cell cultures. Endocrinology. 136:1348–1354.[Abstract]
  4. Langdahl BL, Kassen M, Moller MK, Eriksen EF. 1998 The effects of IGF-I and IGF-II on proliferation and differentiation of human osteoblasts and interaction with growth hormone. Eur J Clin Invest. 28:176–183.[CrossRef][Medline]
  5. Kream BE, Petersen DN, Raisz LG. 1990 Cortisol enhances the anabolic effects of insulin-like growth factor I on collagen synthesis and procollagen messenger ribonucleic acid levels in cultured 21-day fetal rat calvariae. Endocrinology. 126:1576–1583.[Abstract/Free Full Text]
  6. McCarthy TL, Centrella M, Canalis E. 1989 Regulatory effects of insulin-like growth factors I and II on bone collagen synthesis in rat calvarial cultures. Endocrinology. 124:301–309.[Abstract/Free Full Text]
  7. Scheven BA, Hamilton NJ, Fakkeldjj TM, Duursma SA. 1991 Effects of recombinant human insulin-like growth factor I and II (IGF-I/-II) and growth hormone (GH) on the growth of normal adult human osteoblast-like cell and human osteogenic sarcoma cell. Growth Regul. 1:160.[Medline]
  8. Mohan S, Strong D, Lempert UG, Tremollieres F, Wergedal JE, Baylink DJ. 1992 Studies on regulation of insulin-like growth factor binding protein (IGFBP)-3 and IGFBP-4 production in human bone cells. Acta Endocrinol (Copenh). 127:555–564.[Abstract/Free Full Text]
  9. Mochizuki H, Hakeda Y, Wakatsuki N, et al. 1992 Insulin-like growth factor-I supports formation and activation of osteoclasts. Endocrinology. 131:1075–1080.[Abstract/Free Full Text]
  10. Slootweg MC, Most WW, van Bekk E, Schot LP, Papapoulos SE, Lowik CW. 1992 Osteoclast formation together with interleukin-6 production in mouse long bones is increased by insulin-like growth factor-I. J Endocrinol. 132:433–438.[Abstract/Free Full Text]
  11. Hill PA, Reynolds JJ, Meikle MC. 1995 Osteoblasts mediate insulin-like growth factor-I and -II stimulation of osteoclasts formation and function. Endocrinology. 136:124–131.[Abstract]
  12. Ohlsson C, Bengtsson B-Å, Isaksson OGP, Andreassen TT, Slootweg MC. 1998 Growth hormone and bone. Endocr Rev. 19:55–79.[Abstract/Free Full Text]
  13. Ljunghall S, Johansson A, Burman P, Kampe O, Lindh E, Karlsson FA. 1992 Low plasma levels of insulin-like growth factor I in male patients with idiopathic osteoporosis. J Intern Med. 232:59–64.[Medline]
  14. Read BY, Zerwekh JE, Sakhaee K, Breslau NA, Gottshalk F, Pak CYC. 1995 Serum IGF-I is low and correlated with osteoblastic surface in idiopathic osteoporosis. J Bone Miner Res. 10:1218–1224.[Medline]
  15. Kurland ES, Chan FKW, Rosen CJ, Bilezikian JP. 1998 Normal growth hormone secretory reserve in men with idiopathic osteoporosis and reduced circulating levels of insulin-like growth factor-I. J Clin Endocrinol Metab. 83:2576–2579.[Abstract/Free Full Text]
  16. Boonen S, Lesaffre E, Dequicker J, Aersens J, Pelemans W, Bouillon R. 1996 Relationship between basal IGF-I and femoral bone density in women over 70 years. J Am Geriatr Soc. 44:1301–1306.[Medline]
  17. Romagnoli E, Minisola S, Carnevale V, et al. 1993 Effect of estrogen deficiency on IGF-I plasma levels: relationship with bone mineral density in perimenopausal women. Calcif Tissue Int. 53:1–6.[CrossRef][Medline]
  18. Sugimoto T, Nishiyama K, Kuribayashi F, Chihara K. 1997 Serum levels of insulin-like growth factor (IGF) I, IGF-binding protein (IGFBP)-2, and IGFBP-3 in osteoporotic patients with and without spinal fractures. J Bone Miner Res. 12:1272–1279.[CrossRef][Medline]
  19. Barrett-Connor E, Goodman-Gruen D. 1998 Gender differences in insulin-like growth factor and bone mineral density association in old age: the Rancho Bernardo study. J Bone Miner Res. 13:1343–1349.[CrossRef][Medline]
  20. Rosen CJ, Kurland ES, Verault D, et al. 1998 Association between serum insulin-like growth factor-I (IGF-I) and a simple sequence repeat in IGF-I gene: implications for genetic studies of bone mineral density. J Clin Endocrinol Metab. 83:2286–2290.[Abstract/Free Full Text]
  21. Bennett A, Wahner H, Riggs B, Hintz R. 1984 Insulin-like growth factors I and II: aging and bone density in women. J Clin Endocrinol Metab. 59:701–704.[Abstract/Free Full Text]
  22. Rudman D, Drinka PJ, Wilson CR, et al. 1994 Relations of endogenous anabolic hormones and physical activity to bone mineral density and lean body mass in elderly men. Clin Endocrinol (Oxf). 40:653–661.[Medline]
  23. Juul A, Bang P, Hertel NT, et al. 1994 Serum insulin-like growth factor-I in 1030 healthy children, adolescents and adults: relation to age, sex, stage of puberty, testicular size, and body mass index. J Clin Endocrinol Metab. 78:744–752.[Abstract]
  24. Juul A, Holm K, Kastrup KW, et al. 1997 Free insulin-like growth factor-I serum levels in 1430 healthy children and adults, and its diagnostic value in patients suspected of growth hormone deficiency. J Clin Endocrinol Metab. 82:2497–2502.[Abstract/Free Full Text]
  25. Wilson DM, Killen JD, Hammer LD, et al. 1991 Insulin-like growth factor-I as a reflection of body composition, nutrition, and puberty in sixth and seventh grade girls. J Clin Endocrinol Metab. 73:907–912.
  26. Rosen HN, Chen V, Cittadini A, et al. 1995 Treatment with growth hormone and IGF-I in growing rats increases bone mineral content but not bone mineral density. J Bone Miner Res. 10:1352–1358.[Medline]
  27. Bachrach LK, Marcus R, Ott SM, et al. 1998 Bone mineral, histomorphometry, and body composition in adults with growth hormone receptor deficiency. J Bone Miner Res. 13:415–421.[CrossRef][Medline]
  28. Hamill PVV, Drizd TA, Johnson CL, Reed RB, Roche AF, Moore WM. 1979 Physical growth: National Center for Health Statistics percentiles. Am J Clin Nutr. 32:607–629.[Abstract/Free Full Text]
  29. Vaughan III, VC, Litt IF. 1987 Developmental pediatrics: assessment of growth and development. In: Behrman RE, Vaughan I, VC, eds. Nelson textbook of pediatrics, 13th Ed. Philadelphia: Saunders; 24–33.
  30. Hangartner TN, Gilsanz V. 1996 Evaluation of cortical bone by computed tomography. J Bone Miner Res. 11:1518–1525.[Medline]
  31. Gong JK, Arnold JS, Cohn SH. 1964 Composition of trabecular and cortical bone. Anat Rec. 149:325–331.
  32. Kalender WA. 1992 Effective dose values in bone mineral measurements by photon absorptiometry and computed tomography. Osteop Int. 2:82–87.[CrossRef][Medline]
  33. Mora S, Gilsanz V. 1998 Bone densitometry in children. In: Genant HK, Guglielmi G, Jergas M, eds. Bone densitometry and osteoporosis. Heidelberg: Springer-Verlag; 489–501.
  34. Gilsanz V, Skaggs DL, Kovanlikaya A, et al. 1998 Differential effect of race on the axial and appendicular skeletons of children. J Clin Endocrinol Metab. 83:1420–1427.[Abstract/Free Full Text]
  35. Bautista CM, Mohan S, Baylink DJ. 1990 Insulin-like growth factors I and II are present in skeletal tissues of ten vertebrates. Metabolism. 39:96–100.[Medline]



This article has been cited by other articles:


Home page
 J. Clin. Endocrinol. Metab.Home page
K. M. Hill, M. Braun, M. Kern, B. R. Martin, J. W. Navalta, D. A. Sedlock, L. McCabe, G. P. McCabe, M. Peacock, and C. M. Weaver
Predictors of Calcium Retention in Adolescent Boys
J. Clin. Endocrinol. Metab., December 1, 2008; 93(12): 4743 - 4748.
[Abstract] [Full Text] [PDF]

Home page
 Eur J EndocrinolHome page
J. Leger, I. Mercat, C. Alberti, D. Chevenne, P. Armoogum, J. Tichet, and P. Czernichow
The relationship between the GH/IGF-I axis and serum markers of bone turnover metabolism in healthy children
Eur. J. Endocrinol., November 1, 2007; 157(5): 685 - 692.
[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
D. Ma and G. Jones
The Association between Bone Mineral Density, Metacarpal Morphometry, and Upper Limb Fractures in Children: A Population-Based Case-Control Study
J. Clin. Endocrinol. Metab., April 1, 2003; 88(4): 1486 - 1491.
[Abstract] [Full Text] [PDF]

Home page
 Br. J. Sports. Med.Home page
K J MacKelvie, K M Khan, H A McKay, and C Sanborn
Is there a critical period for bone response to weight-bearing exercise in children and adolescents? a systematic review * Commentary
Br. J. Sports Med., August 1, 2002; 36(4): 250 - 257.
[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 Mora, S.
Right arrow Articles by Gilsanz, V.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mora, S.
Right arrow Articles by Gilsanz, V.

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