This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dennison, E. Articles by Cooper, C. Search for Related Content PubMed PubMed Citation Articles by Dennison, E. Articles by Cooper, C.

Profiles of Endogenous Circulating Cortisol and Bone Mineral Density in Healthy Elderly Men¹

Medical Research Council Environmental Epidemiology Unit, University of Southampton, Southampton General Hospital (E.D., C.F., S.K., D.B., D.P., C.C.), Southampton, United Kingdom SO16 6YD; and Cobbold Laboratories, Middlesex Hospital (P.H.), London, United Kingdom W1N 8AA

Address all correspondence and requests for reprints to: Prof. C. Cooper, Medical Research Council Environmental Epidemiology Unit, Southampton General Hospital, Southampton, United Kingdom SO16 6YD.

	Abstract

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Exogenous glucocorticoids are known to increase the risk of osteoporosis. However, the contribution made by endogenous circulating cortisol concentrations to adult skeletal status remains unknown. We examined this issue in a sample of 34 healthy men, aged 61–72 yr. Venous blood samples were obtained under standard conditions every 20 min over a 24-h period. Measurements were made of serum cortisol and cortisol-binding globulin. Bone mineral density was measured at the lumbar spine and proximal femur using dual energy x-ray absorptiometry. Measurements were made at baseline and 4 yr later. There was a weak negative association between integrated cortisol concentration and lumbar spine bone density (r = -0.37; P < 0.05); similar relationships (P < 0.05) existed at three of five proximal femoral sites. There were also statistically significant positive associations between the trough cortisol concentration and bone loss rate at the lumbar spine (r = 0.38; P < 0.05), femoral neck (r = 0.47; P < 0.001), and the trochanteric region (r = 0.41; P = 0.02) over the 4-yr follow-up period. The cross-sectional relationships between cortisol concentration and bone density were removed by adjustment for body mass index, but the influence on bone loss rate remained significant after adjusting for adiposity, cigarette smoking, alcohol consumption, dietary calcium intake, physical activity, and serum testosterone and estradiol levels. These observations suggest that the endogenous cortisol profile of healthy elderly men is a determinant of their bone mineral density and their rate of involutional bone loss.

	Introduction

Top Abstract Introduction Subjects and Methods Results Discussion References

 
APPROXIMATELY one quarter of the 1.3 million fractures in the United States and 1.2 million fractures in Europe each year attributed to osteoporosis occur in men (1, 2), and the estimated lifetime fracture risk at the hip, spine, or distal forearm in 50-yr-old U.S. white men is 13.1% (3). Although an underlying cause of osteoporosis cannot be detected in the majority of male cases, the 2 most frequently reported risk factors are hypogonadism and the use of exogenous glucocorticoids (4). Studies in both men and women have documented the diverse effects of exogenous glucocorticoids on bone cell function, bone remodeling, and rate of bone loss (5). However, far less is known of the contribution made by endogenous circulating cortisol levels to adult skeletal status. We provide the first study to examine this issue in a sample of 34 healthy elderly men selected from the general population.

	Subjects and Methods

Top Abstract Introduction Subjects and Methods Results Discussion References

 
We studied 34 healthy men, aged 61–72 yr, who were born and still lived in Hertfordshire. These men were selected from a larger group (n = 224) participating in a study examining the relationship between growth in infancy and subsequent risk of osteoporosis (6). The group was known to be representative of elderly British men with regard to body build and cigarette smoking (7). None of the men was using prescribed corticosteroids (oral or inhaled).

All of the men completed an interviewer-administered questionnaire, which included questions on medical and drug history, current alcohol intake, cigarette smoking, current physical activity (including time spent walking, gardening, doing housework, carrying loads, and other leisure activities), and dietary calcium intake. Measurements were made of height (using a portable stadiometer) and of weight (using seca scales). Bone mineral density was measured in each patient at baseline and 4 yr later by dual energy x-ray absorptiometry at the lumbar spine and proximal femur. Measurements in the baseline study were performed on a QDR 1000 instrument (Hologic, Inc., Waltham, MA); this was replaced by a new QDR 4500 instrument for the follow-up study. To ensure comparability between readings, 23 individuals were invited to have 2 bone density scans at follow-up, 1 on each instrument. This permitted calculation of a conversion algorithm that was linear across the bone mineral values studied and yielded the equations: spine bone density QDR 1000 = -0.063 + 1.082 x spine bone density QDR 4500 and femoral neck bone density QDR 1000 = -0.037 + 1.021 x femoral neck bone density QDR 4500. From these measurements, we were able to derive annual bone loss rates both as absolute values and as a percentage of original bone density. Bone area and bone mineral density (BMD) were obtained directly from the scans. As BMD represents an areal density, we calculated the bone mineral apparent density (BMAD) using the method of Carter et al. (8). All three variables (area, BMD, and BMAD) were used in our analyses. Short term measurement precision was assessed using 6 healthy volunteers. Each measurement was made on 6 occasions; coefficients of variation were 1.8% for femoral neck BMD and 1.1% for lumbar spine BMD. Similar values (<2%) were obtained at all sites for replicate measurements made in 20 individuals from the study sample, measured twice, 2 months apart. Long term instrument precision using a spine phantom over the 4-yr period yielded a coefficient of variation of 0.34%.

Lateral thoracolumbar spine radiographs were obtained using a standard protocol. Radiographs were taken with the patient in the left lateral position, and the breathing technique was used to blur overlying rib and lung detail by motion. The thoracic film was centered at T7, and the lumbar film was centered at L2. Osteoarthritic change in the thoracolumbar spine was assessed using the Kellgren-Lawrence system (9). This uses a standard radiographic atlas to characterize the extent of disc narrowing, uncovertebral and apophyseal joint osteophyte, sclerosis, and cyst formation on a five-point scale (none, minimal, mild, moderate, severe).

Over a 6-month period from baseline, the 34 men were admitted to a metabolic unit. Each admission commenced in the early evening when an indwelling iv cannula was inserted. The men then rested overnight until 0730 h, from which time blood samples were withdrawn at 20-min intervals for a 24-h period. Standard meals were taken at 0800, 1230, and 1800 h, and a normal daily routine was encouraged within the confines of the hospital admission. Serum cortisol and GH were measured in all 72 samples.

Serum cortisol was measured by solid phase RIA (Coat-a-Count, Diagnostic Products, Los Angeles, CA). The within-assay coefficients of variation were 5.7%, 3.1%, and 2.6% at 28, 96, and 552 nmol/L, respectively. The between-assay coefficients of variation were 6.3% and 4.5% at 138 and 276 nmol/L, respectively. The sensitivity of the assay was 25 nmol/L. Cortisol-binding globulin was assayed using a commercial assay (Medgenics Diagnostics, Fleurus, Belgium).

Serum osteocalcin was measured using a RIA with antiserum raised to human osteocalcin, using human osteocalcin for tracer and standard (Nichols Institute Diagnostics, San Juan Capistrano, CA). The within-assay coefficient of variation was 3%, the between-assay coefficient of variation was 5% at 4.8 mg/L, and the detection limit was 0.3 mg/L. Serum estradiol and testosterone were measured by RIA (Diagnostic Products), as previously described (10).

Hormone profiles were analyzed to derive the following variables. The trough value was designated as that below which 5% of all values lay during the 24-h period and the peak value as that below which 95% of values fell during the 24 h; the median value was used as an estimate of total secretion over the 24 h. Cortisol measurements for each individual showed a skewed distribution and required log transformation. Integrated cortisol secretion was measured by taking the mean of all logarithmically transformed values. The relationship between measures of hormone secretion and bone mass were assessed using linear regression. Partial correlation coefficients, after adjusting for body mass index, were tested for statistical significance. Potential confounding variables were examined using multiple regression.

	Results

Top Abstract Introduction Subjects and Methods Results Discussion References

 
Table 1 shows the anthropometric characteristics and bone density values of the 34 men. Their mean age was 66 yr (SD, 3 yr). Their mean body mass index was 27 kg/m² (SD, 2.8 kg/m²). Twenty-three (68%) men were exsmokers, 5 (15%) were current smokers, and 6 (18%) men had never smoked. The mean alcohol consumption was 8 (SD, 11) U/week (1 U alcohol = one small glass of wine, one measure of spirits, or half a pint of lager/beer) (11). Their mean lumbar spine BMD was 1.06 g/cm² (SD, 0.19 g/cm²), and mean femoral neck BMD was 0.82 g/cm² (SD, 0.14 g/cm²). Mean BMD values at baseline for the other hip regions are shown in Table 1. Over the 4-yr follow-up period, there was a mean bone loss rate of 0.05%/yr at the femoral neck (SD, 1.74%); loss rates at the other hip regions ranged from 0.14% (SD, 1.43%)/yr at the intertrochanteric region to a gain of 1.63% (SD, 3.81%)/yr at Wards triangle; at the lumbar spine there was a gain of 0.44%/yr (SD, 1.48%). Figure 1a shows the 24-h cortisol profile for one of the men, with peak, median, and trough values indicated. Figure 1b presents the mean values of plasma cortisol at each time point measured when data for all of the subjects were amalgamated. Although a circadian variation in the plasma cortisol concentration was apparent in the group as a whole, individual profiles did not reveal such a consistent pattern.

View larger version (18K): [in this window] [in a new window]   Figure 1. a, Cortisol profile of one of the men studied. Samples were obtained every 20 min over a 24-h period. The peak value is that above which 5% of the observations fall, the median is that above which 50% of the observations fall, and the trough is that above which 95% of the observations fall. b, Average plasma cortisol concentration over a 24-h period among 34 men, aged 61–72 yr.

View larger version (23K): [in this window] [in a new window]   Figure 2. Relation between characteristics of cortisol concentration and femoral neck bone density among 34 men, aged 61–72 yr (a), and femoral neck bone loss rate in 22 men undergoing replicate bone density measurements over a 4-yr period (b).

There was a high prevalence (62%) of moderate to severe radiographic osteoarthritis of the lumbar spine using the Kellgren-Lawrence scale. As this group of men gained bone at the lumbar spine over the 4-yr period, it was difficult to interpret correlations of cortisol profile with changes in bone mass, although the associations between integrated cortisol and baseline spine BMD and that between trough cortisol and the rate of change of spine BMD, remained significant after adjusting for osteoarthritis grade.

Cortisol-binding globulin was not associated with body mass index or with bone density at the proximal femur or spine, nor was it associated with bone loss rate at these sites. Adjustment for serum testosterone and estradiol concentrations in a multiple regression model did not appreciably alter the associations between integrated cortisol secretion and bone density or those between trough cortisol secretion and femoral neck/trochanteric bone loss.

	Discussion

Top Abstract Introduction Subjects and Methods Results Discussion References

 
We have explored the relationship between BMD in the proximal femur and lumbar spine, the rate of bone loss, and the profile of plasma cortisol concentration in a sample of elderly men. Our data show that trough and integrated cortisol concentrations are negatively associated with bone density and positively associated with bone loss rate at trabecular sites. Although relationships between cortisol concentration and baseline bone density were removed by adjustment for body mass index, those between basal cortisol concentration and rate of bone loss at the proximal femur remained after adjusting for anthropometric measures. These observations suggest that the endogenous secretory profile of cortisol in men is a determinant of their bone density in later life, and that perturbations in basal cortisol secretion might influence the risk of osteoporosis.

Although our sample is relatively small, the men participating were known to be representative of the larger group from which they were selected with regard to height, weight, and body mass index (10). Their BMD values fell within the normal range provided by the instrument manufacturer, but our assessment of the rate of loss depended upon a conversion algorithm between two instruments. Measurements were made during a carefully regulated in-patient admission designed to minimize the possibility of artificially elevated cortisol levels due to stress. The means of characterizing the patterns of cortisol secretion are not widely agreed upon, and our derivation of peak, median, and trough values follow a simple mathematical procedure (12). Interpretation of results at the lumbar spine was made more difficult by a high prevalence of osteoarthritis at this site, which may have artificially elevated bone density values (13). Notwithstanding, our observations at the lumbar spine mirrored these at the proximal femur.

Exogenous glucocorticoids are well recognized as a cause of osteoporosis (14). Reduced bone mineral density has also been well documented in patients with Cushing’s disease, among whom a recovery is sometimes seen after surgical treatment (15). Similarly, lumbar spine bone density was inversely correlated with glucocorticoid replacement in a study of Dutch men with Addison’s disease (16). Our data suggest that bone density and the rate of involutional bone loss in healthy individuals might also be regulated by the hypothalamic-pituitary-adrenal (HPA) axis. Basal, rather than peak, levels of cortisol appear to influence bone turnover, and thereby modulate bone loss. Glucocorticoids exert their effects on bone at a number of levels. They promote negative calcium balance by reducing intestinal calcium absorption and renal tubular calcium reabsorption. This may provoke hyperparathyroidism and accelerated bone loss (14). In vitro studies have shown a number of cortisol-induced changes, including decreased type I collagen production (17); decreased osteoblast synthesis of insulin-like growth factor I (IGF-I) (18); reduced IGF-II receptor synthesis (19); increased interstitial collagenase transcript levels (20); decreased synthesis of IGF-binding protein-3, -4, and -5 (21); and increased formation of IGF-binding protein-6 (22). Individual subclasses of IGF-binding proteins act to either stabilize or inactivate IGF, and altered cytokine levels may influence osteoblast function. Further evidence that circulating cortisol may regulate bone formation comes from a recent study that demonstrated that elimination of the morning cortisol peak abolished the circadian rhythm of osteocalcin (23). These results are in accord with the histological observation that trabecular thinning (and therefore a relative deficit of bone formation) is the predominant microarchitectural change in steroid-treated patients (24).

Our study also confirms the previously reported negative relationship between circulating integrated cortisol concentration and body mass index (25). Obese subjects typically have a normal circadian rhythm of adrenal steroid secretion, but an accelerated degradation of cortisol, which is matched by an increased rate of production (26). The localization of fat is critical in this relationship. High concentrations of glucocorticoid receptors are found in abdominal fat, and the increased peripheral clearance of cortisol is probably mediated by such receptors (27). Thus, subjects with different body fat distributions might reasonably be expected to have different profiles of cortisol secretion; this hypothesis requires testing in future studies. Our findings also present a novel mechanism for the well established relationship between body mass index and bone mineral density: the endogenous cortisol profile might independently influence both the quantity and distribution of fat as well as the size and turnover rate of the skeleton.

In Cushing’s syndrome, the most consistently observed characteristic is elevation of mean cortisol secretion, with attenuation of variation around this mean (28). The normal circadian rhythm is rarely preserved, possibly due to an altered threshold for activation of the normal homeostatic mechanisms in the hypothalamus and pituitary. However, the reasons behind the pronounced diversity in cortisol profile that we observed among healthy men remain unknown, although individual stability of baseline cortisol levels over a period of 2.5 yr has been demonstrated (29). One explanation for the observation is that the pattern might be under genetic control. An alternative explanation is that the HPA axis might be programmed by environmental factors during early life; it has been shown that environmental exposures in prenatal and early postnatal life may imprint the rodent HPA axis, resulting in permanent modification of the neuroendocrine response to stress throughout life (30). In addition, recent epidemiological studies have suggested that plasma cortisol concentrations in male adults are negatively associated with birth weight (31).

In conclusion, this study suggests an association between basal plasma cortisol concentration and both bone mineral density and the subsequent loss rate of bone mineral among healthy elderly men. These relationships are consistent with the hypothesis that the HPA axis might influence the later risk of osteoporosis and, although preliminary, require further evaluation. The associations observed were relatively weak, and although of potential etiological relevance, quantification of circulating cortisol in a eugonadal individual as a diagnostic test in the evaluation of osteoporosis could not be supported. However, further studies of the relationship between the circulating cortisol profile and osteoporosis risk are now required.

	Acknowledgments

 
We thank the men who participated in the study, and the nurses and radiology staff who administered the bone density measurements. Computing support was provided by Vanessa Cox and Paul Winter, and the manuscript was prepared by Gill Strange. We are grateful to Jane Pringle, University College London, for measuring GH and cortisol, and to Prof. Richard Eastell, University of Sheffield, for measurements of osteocalcin. Elaine Dennison was in receipt of a Wellcome Training Fellowship in Epidemiology.

	Footnotes

 
¹ This work was supported by project grants from the Wessex Medical School Trust, Eli Lilly & Co. Laboratories, and the Medical Research Council of Great Britain.

² Recipient of a Wellcome Training Fellowship in Epidemiology.

Received November 3, 1998.

Revised February 24, 1999.

Revised May 19, 1999.

Accepted May 26, 1999.

	References

Top Abstract Introduction Subjects and Methods Results Discussion References

 

1. Orwoll ES, Klein RF. 1996 Osteoporosis in men: epidemiology pathophysiology and clinical characterisation. In: Marcus R, Feldman D, Kelsey J, eds. Osteoporosis. San Diego: Academic Press; 745–784.
2. Cooper C. The epidemiology of osteoporosis in women and men. Osteop Int. In press.
3. Melton LJ, Chrischilles EA, Cooper C, Lane AW, Riggs BL. 1992 How many women have osteoporosis? J Bone Miner Res. 7:1005–1010.[Medline]
4. Baillie SP, Davison CE, Johnson FJ, Francis RM. 1992 Pathogenesis of vertebral crush fractures in men. Age Ageing. 21:139–141.[Abstract/Free Full Text]
5. Papapoulos SE. 1996 Glucocorticoid-induced osteoporosis. In: Papapoulos SE, Lips P, Pols HAP, Johnston CC, Delmes PD, eds. Osteoporosis 1996. Amsterdam: Elsevier; 359–367.
6. Cooper C, Fall C, Egger P, Hobbs R, Eastell R, Barker D. 1997 Growth in infancy and bone mass in later life. Ann Rheum Dis. 56:17–21.[Abstract/Free Full Text]
7. Egger P, Duggleby S, Hobbs R, Fall C, Cooper C. 1996 Cigarette smoking and bone mineral density in the elderly. J Epidemiol Comm Hlth. 50:47–50.[Abstract/Free Full Text]
8. Carter DR, Bouxsein ML, Marcus P. 1992 New approaches for interpreting projected bone densitometry data. J Bone Miner Res. 7:137–145.[Medline]
9. Kellgren JH, Lawrence JS. 1958 Osteoarthritis and disc degeneration in an urban population. Ann Rheum Dis17 :388–396.
10. Fall C, Hindmarsh P, Dennison E, Kellingray S, Barker D, Cooper C. 1998 Programming of growth hormone secretion and bone mineral density in elderly men: an hypothesis. J Clin Endocrinol Metab. 83:135–139.[Abstract/Free Full Text]
11. James WPT. 1993 Alcohol: its metabolism, and effects. In: Garrow JS, James WPT, eds. Human nutrition and dietetics, 9th Ed. London: Churchill Livingstone; 103–118.
12. Matthews DR, Hindmarsh PC, Pringle PJ, Brook CD. 1991 A distribution method for analysing the baseline of pulsatile endocrine signals as exemplified by 24-hour growth hormone profiles. Clin Endocrinol (Oxf). 35:245–252.[Medline]
13. Dawson-Hughes B, Dallal GE. 1990 Effect of radiographic abnormalities on rate of bone loss from the spine. Calcif Tissue Int. 46:280–281.[Medline]
14. Reid IR, Grey AB. 1993 Corticosteroid osteoporosis. In: Reid DM, ed. Bailliere’s clinical rheumatology. London: Bailliere Tindall; 573–587.
15. Hermus AR, Smals AG, Swinkels LM, et al. 1995 Bone mineral density and bone turnover before and after surgical cure of Cushing’s syndrome. J Clin Endocrinol Metab. 80:2859–2865.[Abstract/Free Full Text]
16. Zelissen PMJ, Croughs RJM, van Rijk PP, Raymakers JA. 1994 Effect of glucocorticoid replacement therapy on bone mineral density in patients with Addison’s disease. Ann Intern Med. 120:207–210.[Abstract/Free Full Text]
17. Delany AM, Gabbitas BY, Canalis E. 1995 Cortisol down-regulates osteoblast procollagen MRNA by transcriptional and post-transcriptional mechanisms. J Cell Biol. 57:488–494.
18. Delany AM, Canalis E. 1995 Transcriptional repression of insulin-like growth factor I by glucocorticoids in rat bone cells. Endocrinology. 136:4776–4781.[Abstract]
19. Rydziel S, Canalis E. 1995 Cortisol represses insulin-like growth factor II receptor transcription in skeletal cell cultures. Endocrinology. 136:4254–4260.[Abstract]
20. Delany AM, Jeffrey JJ, Rydziel S, Canalis E. 1995 Cortisol increases interstitial collagenase expression in osteoblasts by post-transcriptional mechanisms. J Biol Chem. 270:26607–26612.[Abstract/Free Full Text]
21. Gabbitas B, Pash JM, Delany AM, Canalis E. 1996 Cortisol inhibits the synthesis of insulin-like growth factor-binding-protein 5 in bone cell cultures by transcriptional mechanisms. J Biol Chem. 271:9033–9038.[Abstract/Free Full Text]
22. Gabbitas B, Canalis E. 1996 Cortisol enhances the transcription of insulin-like growth factor-binding protein 6 in cultured osteoblasts. Endocrinology. 137:1687–1692.[Abstract]
23. Heshmati HM, Riggs BL, Burritt MF, McAlister CA, Wollan PC, Khosla S. 1998 Effects of the circadian variation in serum cortisol on markers of bone turnover and calcium homeostasis in normal postmenopausal women. J Clin Endocrinol Metab. 83:751–756.[Abstract/Free Full Text]
24. Dempster DW. 1989 Bone histomorphometry in glucocorticoid-induced osteoporosis. J Bone Miner Res. 4:137–141.[Medline]
25. Kopelman PG. 1994 Hormones and obesity. Bailliere Clin Endocrinol Metab. 8:549–579.[CrossRef][Medline]
26. Galvao-Tales A, Graves L, Burke CW, et al. 1976 Free cortisol in obesity: effect of fasting. Acta Endocrinol (Copenh). 81:321–329.[Abstract/Free Full Text]
27. Bronnegard M, Arner P, Hellstrom L, et al. 1990 Glucocorticoid receptor messenger ribonucleic acid in different regions of human adipose tissue. Endocrinology. 127:1689–1696.[Abstract]
28. Tourniaire J, Chalendar D, Rebattu B, et al. 1986 The 24 hour cortisol secretory pattern in Cushing’s syndrome. Acta Endocrinol (Copenh). 112:230–237.[Abstract/Free Full Text]
29. Huizenga NATM, Koper JW, de Lange P, et al. 1998 Interperson variability but intraperson stability of baseline plasma cortisol concentrations, and its relation to feedback sensitivity of the hypothalamo-pituitary-adrenal axis to a low dose of dexamethasone in elderly individuals. J Clin Endocrinol Metab. 83:47–54.[Abstract/Free Full Text]
30. Levitt NS, Lindsay RS, Holmes MC, Seckl JR. 1996 Dexamethasone in the last week of pregnancy attenuates hippocampal glucocorticoid receptor gene expression and elevates blood pressure in the adult offspring in the rat. Neuroendocrinology. 64:412–418.[Medline]
31. Phillips DIW, Barker DJP, Fall CHD, et al. 1998 Elevated plasma cortisol concentrations: a link between low birthweight and the insulin resistance syndrome? J Clin Endocrinol Metab. 83:757–760.[Abstract/Free Full Text]

This article has been cited by other articles:

				A. V. Diez Roux, N. Ranjit, L. Powell, S. Jackson, T. T. Lewis, S. Shea, and C. Wu Psychosocial factors and coronary calcium in adults without clinical cardiovascular disease. Ann Intern Med, June 6, 2006; 144(11): 822 - 831. [Abstract] [Full Text] [PDF]

				C. A. Rideout, W. Linden, and S. I. Barr High cognitive dietary restraint is associated with increased cortisol excretion in postmenopausal women. J. Gerontol. A Biol. Sci. Med. Sci., June 1, 2006; 61(6): 628 - 633. [Abstract] [Full Text] [PDF]

				R. S. Weinstein 11{beta}-HSD: Guardian or Gate Crasher? IBMS BoneKEy, September 1, 2005; 2(9): 6 - 13. [Full Text] [PDF]

				J H Davies, B A J Evans, and J W Gregory Bone mass acquisition in healthy children Arch. Dis. Child., April 1, 2005; 90(4): 373 - 378. [Abstract] [Full Text] [PDF]

				J. Z. Kasa-Vubu, M. Sowers, W. Ye, N. E. Carlson, and T. Meckmongkol Differences in Endocrine Function With Varying Fitness Capacity in Postpubertal Females Across the Weight Spectrum Arch Pediatr Adolesc Med, April 1, 2004; 158(4): 333 - 340. [Abstract] [Full Text] [PDF]

				S. W. Donahue, M. R. Vaughan, L. M. Demers, and H. J. Donahue Bone formation is not impaired by hibernation (disuse) in black bears Ursus americanus J. Exp. Biol., December 1, 2003; 206(23): 4233 - 4239. [Abstract] [Full Text] [PDF]

				M. Cifuentes, A. B. Morano, H. A. Chowdhury, and S. A. Shapses Energy Restriction Reduces Fractional Calcium Absorption in Mature Obese and Lean Rats J. Nutr., September 1, 2002; 132(9): 2660 - 2666. [Abstract] [Full Text] [PDF]

				R. Eastell, D.M. Reid, J. Compston, C. Cooper, I. Fogelman, R.M. Francis, S.M. Hay, D.J. Hosking, D.W. Purdie, S.H. Ralston, et al. Secondary prevention of osteoporosis: when should a non-vertebral fracture be a trigger for action? QJM, November 1, 2001; 94(11): 575 - 597. [Abstract] [Full Text] [PDF]

				C. R. Gale, C. N. Martyn, S. Kellingray, R. Eastell, and C. Cooper Intrauterine Programming of Adult Body Composition J. Clin. Endocrinol. Metab., January 1, 2001; 86(1): 267 - 272. [Abstract] [Full Text]

				C. Cooper, K. Walker-Bone, N. Arden, and E. Dennison Novel insights into the pathogenesis of osteoporosis: the role of intrauterine programming Rheumatology, December 1, 2000; 39(12): 1312 - 1315. [Full Text] [PDF]

				G. A. Laughlin and E. Barrett-Connor Sexual Dimorphism in the Influence of Advanced Aging on Adrenal Hormone Levels: The Rancho Bernardo Study J. Clin. Endocrinol. Metab., October 1, 2000; 85(10): 3561 - 3568. [Abstract] [Full Text]

This Article Abstract Full Text (PDF) Submit a related Letter to the Editor Purchase Article View Shopping Cart Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Dennison, E. Articles by Cooper, C. Search for Related Content PubMed PubMed Citation Articles by Dennison, E. Articles by Cooper, C.