HomeLarge Type Edition
HOME ARCHIVE SEARCH TABLE OF CONTENTS
This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Services
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
PubMed
Right arrow PubMed Citation
The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 59:1285-1289 (2004)
© 2004 The Gerontological Society of America

Age-Related Femoral Bone Loss in Men: Evidence for Hyperparathyroidism and Insulin-Like Growth Factor-1 Deficiency

Hubert Blain1, Anne Vuillemin2,3, Arielle Blain1, Francis Guillemin2, Nicole De Talance4, Brigitte Doucet5 and Claude Jeandel1,

1 Centre de Gérontologie Clinique Antonin Balmès, CHU Montpellier, France.
2 UPRES EA 3444, Ecole de Santé Publique, Université Henri Poincaré, Nancy, France.
3 Faculté du Sport, Université Henri Poincaré, Nancy, France.
4 Laboratoire de Biologie Cellulaire, Explorations Fonctionnelles Métaboliques, CHU-Brabois, Vandoeuvre-les-Nancy, France.
5 Laboratoire Central de Chimie, Hôpital Central, Nancy, France.

Address correspondence to Dr. Claude Jeandel, Service de Médecine Interne-Gériatrie, Centre de Prévention et de Traitement des Maladies du Vieillissement; 39 avenue Charles Flahault 34295 Montpellier Cedex 5, France. E-mail: c-jeandel{at}chu-montpellier.fr


   Abstract
Top
 Abstract
Methods
 Results
 Discussion
 REFERENCES
 
Background. We sought to determine the extent to which the age-related decline of femoral neck (FN) bone mineral density (BMD) might be explained by the age-related change of body composition and biological parameters and the mechanisms by which these factors might influence FN BMD in men.

Methods. The relationships between FN BMD and anthropometric, hormonal, and biochemical parameters and bone turnover markers were studied in 82 men aged 25–86 years.

Results. Age was associated with a decline of FN BMD and osteocalcin (OC), bone alkaline phosphatase (bALP), and urinary C-telopeptide (p <.05). The significant relationship between FN BMD and OC (p <.01) did not remain after adjustment for age. With use of multiple linear regression and adjusting for all significant variables associated with FN BMD in univariate analysis (p <.01) (age, weight, lean and fat mass, height, and levels of dehydroepiandrosterone sulfate, insulin-like growth factor [IGF-1], testosterone, and parathyroid hormone [PTH]), age accounted for 29.5% of FN BMD variance. When age was excluded from the model, PTH accounted for 19.5% and IGF-1 for 10% of the FN BMD variance. Bone turnover markers were significantly intercorrelated, and levels of IGF-1 were positively associated with those of bALP and OC (p <.05).

Conclusions. These results show that age is a strong predictor of FN BMD in men, resulting in a decline of bone remodeling, especially of bone formation. The results also show that, after taking into account anthropometric and other biological factors possibly involved in bone aging, the major part of the effect of age on bone is explained by the age-related increase of PTH and decrease of IGF-1 in men, suggesting that all measures taken to limit these age-related changes may be effective in the prevention of the age-related decline of FN BMD in men.

ALTHOUGH not as common as in women, osteoporosis and its clinical end point of fracture are still significant problems both clinically and economically in men (1,2). Twenty-five percent of all hip fractures occur in men, resulting in increased debility and increased mortality, exceeding that of women (3). Bone mass and density are good surrogate measures of bone strength because bone mineral density (BMD) predicts fracture risk in men (4). After reaching peak bone mass at about age 20–30 years, men maintain a stable bone density before experiencing substantial age-related decrease in femoral neck (FN) BMD (5). Because women have been the main focus of osteoporosis research, much less is known regarding mechanisms of age-related bone loss in men.

A number of anthropometric factors including body weight, lean mass, and fat mass (6) and a number of hormonal and growth factors including parathyroid hormone (PTH) (7), insulin-like growth factor-1 (IGF-1) (8), leptin (9), testosterone (6), estradiol (7), and dehydroepiandrosterone sulfate (DHEA) (10) have been hypothesized to be mediators of the effect of age on bone in men. However, because interactions exist between hormonal factors, growth factors, and body composition (10–15)<--?1-->and because no studies have measured all these factors simultaneously, their respective roles in the age-related decline of FN BMD as well as their mechanisms of action on bone remain to be elucidated in men.

The main objective of this study was to examine the respective roles of age, body composition, and hormonal and nonhormonal factors on FN BMD in healthy men and to examine the relationships between these factors and bone turnover markers.


   METHODS
Top
 Abstract
 Methods
Results
 Discussion
 REFERENCES
 
Participants
A total of 82 men aged between 25 and 86 years were recruited in various cultural associations. Included were Caucasian men aged 25 years or older in apparent good health. Excluded were patients with endocrinologic (e.g., hyperthyroidism, Cushing disease, diabetes mellitus) or rheumatologic (e.g., rheumatoid arthritis, ankylosing spondylitis) diseases or those under treatment that could influence BMD (e.g., fluoride, calcium, corticosteroid, vitamin D, calcitonin, anti-vitamin K, diuretic, testosterone, or growth hormone [GH]). Men regularly involved in sport activities that could influence BMD (e.g., weightlifters) or involved in competitive sports for >6 hours per week were not included in the current study. The men were included in the study after providing written informed consent. Eligible participants visited the study center for a clinical examination, an interview for medical history, and biological and BMD measurements. The study was approved by the Ethics Committee of Lorraine County.

Protocol
Blood and 24-hour urine samples were obtained from all volunteers. The participants reported to the laboratory at 9 AM after an overnight fast. Blood and urine samples were collected after a 30-minute rest in the supine position. The blood samples were allowed to clot and then centrifuged; aliquots were stored at –80°C until analyzed. Height and weight measurements to the nearest 0.5 cm and 0.1 kg, respectively, were used to calculate the body mass index (kg/m2). Information on dietary calcium intake was recorded, and measurements of BMD and anthropometry were taken in all volunteers after breakfast.

Biochemical Measurements
Serum intact parathyroid hormone (PTH) was determined by a radioimmunometric assay (CIS Bio International, Gif-sur-Yvette, France) with an intra-assay variation of 4.2% and an interassay variation of 3.4%. Radioimmunoassays using standard techniques were also used to measure serum DHEA (Immunotech S.A., Marseille, France) (intra-assay variation of 4.5%, interassay variation of 7.2%), IGF-1 (Immunotech S.A.) (intra-assay variation of 7.1%, interassay variation of 11.9%), GH (Immunotech S.A.) (intra-assay variation of 0.6%, interassay variation of 13.5%), estradiol (Immunotech S.A.) (intra-assay variation of 6.3%, interassay variation of 6.1%), testosterone (CIS Bio International) (intra-assay variation of 3.8%, interassay variation of 4.8%), and leptin (Linco Research, St. Charles, MO) (intra-assay variation of 3.9%, interassay variation of 4.7%).

Serum osteocalcin (OC) was determined by a radioimmunometric assay (CIS Bio International) with an intra-assay variation of 3.9% and an interassay variation of 6.2%, as was bone alkaline phosphatase (bALP) (tandem-R Ostase; Hybritech, Beckman Coulter, S.A., Paris, France), with an intra-assay variation of 6.7% and an interassay variation of 8.1%. Urine C-telopeptide of type I collagen (CTx) levels were determined by an immunoenzymatic method (Cross-laps EIA; CIS Bio International), with an intra-assay variation of 5.4% and an interassay variation of 8.6%.

Standard colorimetric dry chemical assays were used to measure serum creatinine and total calcium (Synchron Automate CX3; Beckman Coulter). Creatinine clearance was calculated according to the Cockcroft and Gault formula.<--?3-->Serum levels of 25(OH)D and 1,25(OH)2D were determined by an immunoradiometric assay (INCSTAR Corp., Dia-Sorin, Paris, France) with a coefficient of variation of <10%.

Bone Densitometry and Body Composition Measurements
FN BMD (g/cm2) of each participant as well as body composition represented by lean mass and fat mass (kg) were determined by using dual-energy X-ray absorptiometry (Norland XR-26, software version 2.5.2; Norland Corp., Ft. Atkinson, WI). The coefficient of variation for our instrument during measurement on a standard phantom was <1%. FN BMD was measured twice in eight men of various ages, with repositioning between scans, providing a short-term in vivo coefficient of variation of FN BMD, lean mass, and fat mass of <3%.

Statistical Analysis
Standard statistical methods were used to calculate means and standard deviations. The Kolmogorov–Smirnov test was used to test for normal distribution of all data. Associations are given as Pearson correlation coefficients. Multivariate techniques were used to assess the individual contributions of the factors significantly associated with BMD at different sites (p <.1). Final models retained variables at p <.05. The validity of the models was expressed by the multiple R2 coefficient, which represents the part of the variance of the dependent variable explained by the covariates entered into the model. All statistical analyses were performed using the BMDP statistical package (BMDP/Dynamic release 7.0; BMDP Statistical Software; SPSS, Inc., Chicago, IL).


   RESULTS
Top
 Abstract
 Methods
 Results
Discussion
 REFERENCES
 
Participant characteristics, BMD values, and biological data for the 82 men involved in the study are shown in Table 1. Increase in age was associated with a significant decrease of FN BMD (r = –.54, p <.001), height, and lean mass. Age was associated with a significant decrease of serum DHEA, IGF-1, testosterone, calcium, OC, bALP, and urinary CTx and with a significant increase of serum PTH (Table 2).


View this table:
[in this window]
[in a new window]
  		Table 1. Characteristics of the 82 Men Studied.

 

View this table:
[in this window]
[in a new window]
  		Table 2. Correlations with Age and Femoral Neck Bone Mineral Density (BMD).

 
FN BMD was positively associated with height, weight, lean mass, DHEA, IGF-1, and OC and negatively associated with serum levels of PTH. After adjustment for age, FN BMD remained significantly associated with height (r =.24, p <.05) and lean mass (r =.23, p <.05).

After adjustment for age, serum IGF-1 was significantly associated with DHEA (r =.35, p <.001) and GH (r =.44, p <.001). Leptin was the only biological factor associated with body composition (leptin and fat mass: r =.66, p <.001). After adjustment for age, IGF-1 was positively associated with bALP (r =.22, p <.05) and OC (r =.38, p <.001). OC, bALP, and urinary CTx were significantly and positively intercorrelated (OC and bALP [r =.41, p <.001], OC and urinary CTx [r =.57, p <.001], bALP and urinary CTx [r =.39, p <.001]).

With use of multiple linear regression and adjusting for all significant variables associated with FN BMD in the univariate analysis (age, weight, lean mass, DHEA, IGF-1, PTH), age accounted for 29% and lean mass for 4% of FN BMD variance. After adjustment for height, the relationship between FN BMD and lean mass diminished greatly, and age was the only factor associated with hip BMD, accounting for 29.5% of FN BMD variance. When age was excluded from the model, PTH accounted for 19.5% and IGF-1 10% of the variance of FN BMD.


   DISCUSSION
Top
 Abstract
 Methods
 Results
 Discussion
REFERENCES
 
The current study shows that, having taken into account anthropometric and other biological factors possibly involved in bone aging, the effect of age on bone in men can mainly be explained by the age-related increase of PTH and decrease of IGF-1.

This study found an expected age-related decline of hip BMD (16,17) and a significant decline of markers of bone formation (bALP and OC) and bone resorption (urine CTx), markers that were observed to be strongly intercorrelated. These results are in agreement with previous studies that showed that biochemical markers decrease in men until at least 60 years of age (5,16,17). FN BMD was associated with OC, but this relationship did not remain after adjustment for age. Taken together, these results support the concept that the age-related decline of FN BMD in men may be accounted for by the age-related decline of bone formation that is coupled with bone resorption (18).

We found a significant negative relationship between FN BMD and serum PTH and significant positive relationships between FN BMD and lean mass (6), IGF-1 (8), DHEA (10), and testosterone (6). To further assess whether these relationships could be explained by the age-related increase of PTH (19) and the age-related decrease of lean mass and other growth and hormonal factors (20), all factors associated with hip BMD were entered into a multiple linear regression. Age and lean mass were the only two factors significantly associated with hip BMD and accounted for 29% and 4% of FN BMD variance, respectively. After adjustment for height, the relationship between FN BMD and lean mass diminished greatly, and only age remained associated with hip BMD. These results show that age is a strong predictor of hip BMD (21) and are consistent with the hypothesis that a part of the relationship between lean mass and hip BMD may be due to an allometric effect (22).

To better assess the respective roles of the age-related changes in body composition and biological factors on hip BMD, age was not entered into the second multivariate model. In this analysis, PTH accounted for 19% and IGF-1 accounted for 10% of FN BMD variance, suggesting that the age-related increase of PTH (7,23) and decrease of IGF-1 (8,16) may explain the major part of the effect of age on FN BMD in men.

The inverse <--?4-->relationship between the calculated creatinine clearance and both age and PTH in the current study reinforces the hypothesis that the age-related decline of renal function may be a major cause of the age-related rise of PTH levels (24). The age-related decline of serum calcium levels and the lack of influence of age on dietary calcium and 25(OH)D<--?5-->in this study support the concept that the age-related decline of calcium absorption may be another major cause of the age-related rise of PTH levels (25). As in previous studies conducted in Europe, we found a high prevalence of serum 25(OH)2D deficiency (<15 ng/mL in 52% of participants) and low calcium intake (<1 g/day in 40% of participants) in our sample of men, suggesting that a sufficient dietary intake of calcium and vitamin D (25[OH]2D) should be encouraged throughout life to prevent secondary hyperparathyroidism in men (26). The lack of a relationship between PTH and bone turnover markers in the current study and others (15) illustrates the complex influence of PTH on bone, which is dependent on the level of vitamin D insufficiency, vitamin D resistance, and renal impairment (27,28).

The age-related decrease of IGF-1 was another significant predictor of FN BMD in our model, and IGF-1 was found to be significantly associated with bALP and OC (16). These results are compatible with the hypothesis that the age-related decline of IGF-1 that parallels the decrease of IGF-1 levels in bone (29) may account for a part of the age-related decline of FN BMD by limiting bone formation (30) coupled with bone resorption (31).

Whereas the effect of age on FN was mostly explained by PTH and IGF-1 levels, the best predictive model in our study and others (23) accounted for only 30% of the observed variability of FN BMD. These findings show that a large part of FN BMD variance is unrelated to age and therefore suggest that others factors such as genetics, environment, and lifestyle certainly have an effect on FN (32–35).

The current study may have practical, clinical, and therapeutic implications as it suggests that all measures taken to limit the age-related increase of PTH, such as those that prevent renal dysfunction and high blood pressure (36) and ensure sufficient sun exposure and calcium and vitamin D intake (37), and all measures taken to limit the age-related decrease of IGF-1, such as those that maintain physical activity (38) and ensure sufficient dietary protein intake (39,40), may be effective in the prevention of the age-related decline of FN BMD in men. In this regard, the findings of the current study support the need for further investigations to assess the efficacy of vitamin D and calcium supplementation, protein supplementation, exercise training, and medications like GH (41) in preventing osteopenia and lowering the rate of hip fracture in selected aging men.

This study should be interpreted in the light of several considerations. First, by excluding men with activities, diseases, or drugs that may have effects on bone metabolism, these results cannot be extrapolated to the general population. Second, this study looked at the correlation between BMD and variables, but correlation does not necessarily imply causation. Third, the results were based on a single serum sample and a single urine measurement, which may underestimate the relationships between the parameters measured and BMD. Finally, these data are cross-sectional and need to be confirmed in a longitudinal study.

Conclusion
The current study showed that, having taken into account anthropometric and other biological factors possibly involved in bone aging, the age-related increase of PTH and the age-related decrease of IGF-1 accounted for most of the effect of age in men on hip BMD, assessed at about 30% of hip BMD total variance. These results suggest that all measures taken to limit the age-related increase of PTH and the age-related decrease of IGF-1 may be effective in the prevention of the age-related decline of FN BMD in men.


   Acknowledgments
 
The authors acknowledge S. L. Salhi, PhD, for editorial assistance.

Received April 1, 2003

Accepted July 10, 2003


   REFERENCES
Top
 Abstract
 Methods
 Results
 Discussion
 REFERENCES
 

  1. Ray NF, Chan CK, Thamer M, Melton LJ, III. Medical expenditures for the treatment of osteoporosis fractures in the United States in 1995: report from the National Osteoporosis Foundation. J Bone Miner Res. 1995;12:24-33.
  2. Looker AC, Orwoll ES, Johnston CC, et al. Prevalence of low bone density in older U.S. Results from NHAES III. J Bone Miner Res. 1997;12:1761-1768.[Medline]
  3. Center JR, Nguyen TV, Schneider D, Sambrook PN, Eisman JA. Mortality after all major types of osteoporotic fracture: an observational study. Lancet. 1999;353:878-882.[Medline]
  4. Melton LJ, Atkinson EJ, O'Connor MK, O'Fallon M, Riggs BL. Bone density and fracture risk in men. J Bone Miner Res. 1998;13:1915-1923.[Medline]
  5. Wishart JM, Need AG, Horowitz M, Morris HA, Nordin BEC. Effect of age on bone density and bone turnover in men. Clin Endocrinol. 1995;42:141-146.[Medline]
  6. Edelstein SL, Barrett-Connor E. Relation between body size and bone mineral density in elderly men and women. Am J Epidemiol. 1993;138:160-169.[Abstract/Free Full Text]
  7. Center JR, Nguyen TV, Sambrook PN, Eisman JA. Hormonal and biochemical parameters in the determination of osteoporosis in elderly men. J Clin Endocrinol Metab. 1999;84:3626-3635.[Abstract/Free Full Text]
  8. Gillberg P, Olofsson H, Mallmin H, Blum WF, Ljunghall S, Nilsson AG. Bone mineral density in femoral neck is positively correlated with circulating insulin-like growth factor (IGF)-I and IGF-binding proteinn (IGFBP)-3 in Swedish men. Calcif Tissue Int. 2002;70:22-29.[Medline]
  9. Sato M, Takeda N, Sarui H, et al. Association between serum leptin concentrations and bone mineral density, and biochemical markers of bone turnover in adult men. J Clin Endocrinol Metab. 2001;86:5273-5276.[Abstract/Free Full Text]
  10. Villareal DT, Holloszy JO, Kohrt WM. Effects of DHEA replacement on bone mineral density and body composition in elderly women and men. Clin Endocrinol. 2000;53:561-568.[Medline]
  11. Dagogo-Jack S, Franklin SC, Vijayan A, Liu J, Askari H, Miller SB. Recombinant human insulin-like growth factor-I (IGF-I) therapy decreases plasma leptin concentration in patients with chronic renal insufficiency. Int J Obes Relat Metab Disord. 1998;22:1110-1115.[Medline]
  12. Ho KY, Evans WS, Blizzard RM, et al. Effects of sex and age on the 24-hour profile of growth hormone secretion in man: importance of endogenous estradiol concentrations. J Clin Endocrinol Metab. 1987;64:51-58.[Abstract/Free Full Text]
  13. Kawane T, Horiuchi N. Insulin-like growth factor I suppresses parathyroid hormone (PTH)/PTH-related protein receptor expression via a mitogen-activated protein kinase pathway in UMR-106 osteoblast-like cells. Endocrinology. 1999;140:871-879.[Abstract/Free Full Text]
  14. Barrett-Connor E, Goodman-Gruen D. Gender differences in insulin-like growth factor and bone mineral density association in old age: the Rancho Bernardo Study. J Bone Miner Res. 1998;13:1343-1349.[Medline]
  15. Fatayerji D, Mawer EB, Eastell R. The role of insulin-like growth factor I in age-related changes in calcium homeostasis in men. J Clin Endocrinol Metab. 2000;85:4657-4662.[Abstract/Free Full Text]
  16. Fatayerji D, Eastell R. Age-related changes in bone turnover in men. J Bone Miner Res. 1999;14:1203-1210.[Medline]
  17. Szulc P, Garnero P, Munoz F, Marchand F, Delmas PD. Cross-sectional evaluation of bone metabolism in men. J Bone Miner Res. 2001;16:1642-1650.[Medline]
  18. Clarke BL, Ebeling PR, Jones JD, et al. Changes in quantitative histomorphometry in aging healthy men. J Clin Endocrinol Metab. 1996;81:2264-2270.[Abstract]
  19. Orwoll ES, Meier DE. Alterations in calcium, vitamin D, and parathyroid hormone physiology in normal men with aging: relationship to the development of senile osteopenia. J Clin Endocrinol Metab. 1986;63:1262-1269.[Abstract/Free Full Text]
  20. O'Connor KG, Tobin JD, Harman SM, et al. Serum levels of insulin-like growth factor-I are related to age and not to body composition in healthy women and men. J Gerontol Med Sci. 1998;53A:M176-M182.
  21. Orwoll ES, Bevan L, Phipps KR. Determinants of bone mineral density in older men. Osteoporos Int. 2000;11:815-821.[Medline]
  22. Taaffe DR, Cauley JA, Danielson M, et al. Race and sex effects on the association between muscle strength, soft tissue, and bone mineral density in healthy elders: the health, aging and body composition study. J Bone Miner Res. 2001;16:1343-1352.[Medline]
  23. Martinez Diaz-Guerra G, Hawkins F, Rapado A, Ruiz Diaz MA, Diaz-Curiel M. Hormonal and anthropometric predictors of bone mass in healthy elderly men: major effect of sex hormone binding globulin, parathyroid hormone and body weight. Osteoporos Int. 2001;12:178-184.[Medline]
  24. Marcus R, Madvig P, Young G. Age-related changes in parathyroid hormone and parathyroid hormone action in normal humans. J Clin Endocrinol Metab. 1984;58:223-230.[Abstract/Free Full Text]
  25. Agnusdei D, Civitelli R, Camporeale A, et al. Age-related decline of bone mass and intestinal calcium absorption in normal males. Calcif Tissue Int. 1998;63:197-201.[Medline]
  26. Lips P, Wiersinga A, van Ginkel FC, et al. The effect of vitamin D supplementation on vitamin D status and parathyroid function in elderly subjects. J Clin Endocrinol Metab. 1988;67:644-650.[Abstract/Free Full Text]
  27. Rasmussen H, Wong M, Bikle D, Goodman D. Hormonal control of renal conversion of 25-hydroxycholecalciferol to 1,25-dihydroxycholecalciferol. J Clin Invest. 1972;51:2502-2505.
  28. Gallagher JC, Kinyamu HK, Fowler SE, Dawson-Hughes B, Dalsky GP, Sherman SS. Calciotropic hormones and bone markers in the elderly. J Bone Miner Res. 1998;13:475-482.[Medline]
  29. Nicolas V, Prewett A, Bettica P, et al. Age-related decreases in insulin-like growth factor-I and transforming growth factor-ß in femoral cortical bone from both men and women: implications for bone loss with aging. J Clin Endocrinol Metab. 1994;78:1011-1016.[Abstract]
  30. Hock J, Centrella M, Canalis E. Insulin-like growth factor-I has independent effects on bone matrix formation and cell replication. Endocrinology. 1988;122:254-260.[Abstract/Free Full Text]
  31. Kawakami A, Nakashima T, Tsuboi M, et al. Insulin-like growth factor I stimulates proliferation and Fas-mediated apoptosis of human osteoblasts. Biochem Biophys Res Commun. 1998;247:46-51.[Medline]
  32. Livshits G, Yakovenko C, Kobyliansky E. Quantitative genetic analysis of circulating levels of biochemical markers of bone formation. Am J Med Genet. 2000;94:324-331.[Medline]
  33. Whiting SJ, Boyle JL, Thompson A, Mirwald RL, Faulkner RA. Dietary protein, phosphorus and potassium are beneficial to bone mineral density in adult men consuming adequate dietary calcium. J Am Coll Nutr. 2002;21:402-409.[Abstract/Free Full Text]
  34. Kenny AM, Prestwood KM, Marcello KM, Raisz LG. Determinants of bone density in healthy older men with low testosterone levels. J Gerontol Med Sci. 2000;55A:M492-M497.
  35. Izumotani K, Hagiwara S, Izumotani T, Miki T, Morii H, Nishizawa Y. Risk factors for osteoporosis in men. J Bone Miner Metab. 2003;21:86-90.[Medline]
  36. Van den Beld AW, de Jong FH, Grobbee DE, Pols HA, Lamberts SW. Measures of bioavailable serum testosterone and estradiol and their relationships with muscle strength, bone density, and body composition in elderly men. J Clin Endocrinol Metab. 2000;85:3276-3282.[Abstract/Free Full Text]
  37. Landin-Wilhelmsen K, Wilhelmsen L, Lappas G, et al. Serum intact parathyroid hormone in a random population sample of men and women: relationship to anthropometry, life-style factors, blood pressure, and vitamin D. Calcif Tissue Int. 1995;56:104-108.[Medline]
  38. Peacock M, Liu G, Carey M, et al. Effect of calcium or 25OH vitamin D3 dietary supplementation on bone loss at the hip in men and women over the age of 60. J Clin Endocrinol Metab. 2000;85:3009-3010.[Free Full Text]
  39. Poehlman ET, Copeland KC. Influence of physical activity on insulin-like growth factor-I in healthy younger and older men. J Clin Endocrinol Metab. 1990;71:1468-1473.[Abstract/Free Full Text]
  40. Schurch MA, Rizzoli R, Slosman D, Vadas L, Vergnaud P, Bonjour JP. Protein supplements increase serum insulin-like growth factor-I levels and attenuate proximal femur bone loss in patients with recent hip fracture. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1998;128:801-809.[Abstract/Free Full Text]
  41. Ahmad AM, Thomas J, Clewes A, et al. Effects of growth hormone replacement on parathyroid hormone sensitivity and bone mineral metabolism. Clin Endocrinol Metab. 2003;88:2860-2868.



This article has been cited by other articles:


Home page
 Eur J Heart FailHome page
E. A. Jankowska, J. Jakubaszko, A. Cwynar, J. Majda, B. Ponikowska, D. Kustrzycka-Kratochwil, K. Reczuch, L. Borodulin-Nadzieja, W. Banasiak, P. A. Poole-Wilson, et al.
Bone mineral status and bone loss over time in men with chronic systolic heart failure and their clinical and hormonal determinants
Eur J Heart Fail, January 1, 2009; 11(1): 28 - 38.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
S. Boonen, P. Lips, R. Bouillon, H. A. Bischoff-Ferrari, D. Vanderschueren, and P. Haentjens
Need for Additional Calcium to Reduce the Risk of Hip Fracture with Vitamin D Supplementation: Evidence from a Comparative Metaanalysis of Randomized Controlled Trials
J. Clin. Endocrinol. Metab., April 1, 2007; 92(4): 1415 - 1423.
[Abstract] [Full Text] [PDF]

This Article
Right arrow Abstract Freely available
Right arrow Full Text (PDF)
Services
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
PubMed
Right arrow PubMed Citation

HOME ARCHIVE SEARCH TABLE OF CONTENTS