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. 1997 Oct 1;100(7):1755–1759. doi: 10.1172/JCI119701

Sex steroids and bone mass in older men. Positive associations with serum estrogens and negative associations with androgens.

C W Slemenda 1, C Longcope 1, L Zhou 1, S L Hui 1, M Peacock 1, C C Johnston 1
PMCID: PMC508359  PMID: 9312174

Abstract

The purpose of this study was to determine whether bone density in older men was associated with serum sex steroids or sex hormone binding globulin (SHBG). Bone density and sex steroids were measured in men over age 65 at 6-mo intervals for an average of 2.1 yr. Bone density was significantly positively associated with greater serum E2 concentrations (+0.21 < r < +0.35; 0.01 < P < 0.05) at all skeletal sites. There were weak negative correlations between serum testosterone and bone density (-0.20 < r < -0.28; 0.03 < P < 0.10) at the spine and hip. SHBG was negatively associated only with bone density in the greater trochanter (r = -0.26, P < 0.05). Greater body weight was associated with lower serum testosterone and SHBG, and greater E2. Because of these associations, regression models which adjusted for age, body weight, and serum sex steroids were constructed; these accounted for 10-30% of the variability in bone density, and showed consistent, significant positive associations between bone density and serum E2 concentrations in men, even after adjustments for weight and SHBG. These data suggest that estrogens may play an important role in the development or maintenance of the male skeleton, much as is the case for the female skeleton. These data also indicate that, within the normal range, lower serum testosterone concentrations are not associated with low bone density in men.

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Selected References

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  1. Anderson F. H., Francis R. M., Faulkner K. Androgen supplementation in eugonadal men with osteoporosis-effects of 6 months of treatment on bone mineral density and cardiovascular risk factors. Bone. 1996 Feb;18(2):171–177. doi: 10.1016/8756-3282(95)00441-6. [DOI] [PubMed] [Google Scholar]
  2. Cauley J. A., Seeley D. G., Ensrud K., Ettinger B., Black D., Cummings S. R. Estrogen replacement therapy and fractures in older women. Study of Osteoporotic Fractures Research Group. Ann Intern Med. 1995 Jan 1;122(1):9–16. doi: 10.7326/0003-4819-122-1-199501010-00002. [DOI] [PubMed] [Google Scholar]
  3. Christian J. C., Yu P. L., Slemenda C. W., Johnston C. C., Jr Heritability of bone mass: a longitudinal study in aging male twins. Am J Hum Genet. 1989 Mar;44(3):429–433. [PMC free article] [PubMed] [Google Scholar]
  4. Cooper C., Atkinson E. J., O'Fallon W. M., Melton L. J., 3rd Incidence of clinically diagnosed vertebral fractures: a population-based study in Rochester, Minnesota, 1985-1989. J Bone Miner Res. 1992 Feb;7(2):221–227. doi: 10.1002/jbmr.5650070214. [DOI] [PubMed] [Google Scholar]
  5. Drinka P. J., Olson J., Bauwens S., Voeks S. K., Carlson I., Wilson M. Lack of association between free testosterone and bone density separate from age in elderly males. Calcif Tissue Int. 1993 Jan;52(1):67–69. doi: 10.1007/BF00675629. [DOI] [PubMed] [Google Scholar]
  6. Eyre D. New biomarkers of bone resorption. J Clin Endocrinol Metab. 1992 Mar;74(3):470A–470C. doi: 10.1210/jcem.74.3.1740477. [DOI] [PubMed] [Google Scholar]
  7. Kannus P., Parkkari J., Niemi S. Age-adjusted incidence of hip fractures. Lancet. 1995 Jul 1;346(8966):50–51. doi: 10.1016/s0140-6736(95)92679-8. [DOI] [PubMed] [Google Scholar]
  8. Kasperk C. H., Wergedal J. E., Farley J. R., Linkhart T. A., Turner R. T., Baylink D. J. Androgens directly stimulate proliferation of bone cells in vitro. Endocrinology. 1989 Mar;124(3):1576–1578. doi: 10.1210/endo-124-3-1576. [DOI] [PubMed] [Google Scholar]
  9. Katznelson L., Finkelstein J. S., Schoenfeld D. A., Rosenthal D. I., Anderson E. J., Klibanski A. Increase in bone density and lean body mass during testosterone administration in men with acquired hypogonadism. J Clin Endocrinol Metab. 1996 Dec;81(12):4358–4365. doi: 10.1210/jcem.81.12.8954042. [DOI] [PubMed] [Google Scholar]
  10. Lindsay R., Hart D. M., Aitken J. M., MacDonald E. B., Anderson J. B., Clarke A. C. Long-term prevention of postmenopausal osteoporosis by oestrogen. Evidence for an increased bone mass after delayed onset of oestrogen treatment. Lancet. 1976 May 15;1(7968):1038–1041. doi: 10.1016/s0140-6736(76)92217-0. [DOI] [PubMed] [Google Scholar]
  11. Longcope C., Hui S. L., Johnston C. C., Jr Free estradiol, free testosterone, and sex hormone-binding globulin in perimenopausal women. J Clin Endocrinol Metab. 1987 Mar;64(3):513–518. doi: 10.1210/jcem-64-3-513. [DOI] [PubMed] [Google Scholar]
  12. Mann T., Oviatt S. K., Wilson D., Nelson D., Orwoll E. S. Vertebral deformity in men. J Bone Miner Res. 1992 Nov;7(11):1259–1265. doi: 10.1002/jbmr.5650071120. [DOI] [PubMed] [Google Scholar]
  13. Meier D. E., Orwoll E. S., Keenan E. J., Fagerstrom R. M. Marked decline in trabecular bone mineral content in healthy men with age: lack of association with sex steroid levels. J Am Geriatr Soc. 1987 Mar;35(3):189–197. doi: 10.1111/j.1532-5415.1987.tb02308.x. [DOI] [PubMed] [Google Scholar]
  14. Melton L. J., 3rd, O'Fallon W. M., Riggs B. L. Secular trends in the incidence of hip fractures. Calcif Tissue Int. 1987 Aug;41(2):57–64. doi: 10.1007/BF02555245. [DOI] [PubMed] [Google Scholar]
  15. Morishima A., Grumbach M. M., Simpson E. R., Fisher C., Qin K. Aromatase deficiency in male and female siblings caused by a novel mutation and the physiological role of estrogens. J Clin Endocrinol Metab. 1995 Dec;80(12):3689–3698. doi: 10.1210/jcem.80.12.8530621. [DOI] [PubMed] [Google Scholar]
  16. Murphy S., Khaw K. T., Cassidy A., Compston J. E. Sex hormones and bone mineral density in elderly men. Bone Miner. 1993 Feb;20(2):133–140. doi: 10.1016/s0169-6009(08)80022-0. [DOI] [PubMed] [Google Scholar]
  17. Nguyen T., Sambrook P., Kelly P., Jones G., Lord S., Freund J., Eisman J. Prediction of osteoporotic fractures by postural instability and bone density. BMJ. 1993 Oct 30;307(6912):1111–1115. doi: 10.1136/bmj.307.6912.1111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Orwoll E. S., Klein R. F. Osteoporosis in men. Endocr Rev. 1995 Feb;16(1):87–116. doi: 10.1210/edrv-16-1-87. [DOI] [PubMed] [Google Scholar]
  19. Resch H., Pietschmann P., Woloszczuk W., Krexner E., Bernecker P., Willvonseder R. Bone mass and biochemical parameters of bone metabolism in men with spinal osteoporosis. Eur J Clin Invest. 1992 Aug;22(8):542–545. doi: 10.1111/j.1365-2362.1992.tb01503.x. [DOI] [PubMed] [Google Scholar]
  20. Slemenda C. W., Christian J. C., Reed T., Reister T. K., Williams C. J., Johnston C. C., Jr Long-term bone loss in men: effects of genetic and environmental factors. Ann Intern Med. 1992 Aug 15;117(4):286–291. doi: 10.7326/0003-4819-117-4-286. [DOI] [PubMed] [Google Scholar]
  21. Slemenda C. W., Peacock M., Hui S., Zhou L., Johnston C. C. Reduced rates of skeletal remodeling are associated with increased bone mineral density during the development of peak skeletal mass. J Bone Miner Res. 1997 Apr;12(4):676–682. doi: 10.1359/jbmr.1997.12.4.676. [DOI] [PubMed] [Google Scholar]
  22. Slemenda C., Longcope C., Peacock M., Hui S., Johnston C. C. Sex steroids, bone mass, and bone loss. A prospective study of pre-, peri-, and postmenopausal women. J Clin Invest. 1996 Jan 1;97(1):14–21. doi: 10.1172/JCI118382. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Smith D. M., Nance W. E., Kang K. W., Christian J. C., Johnston C. C., Jr Genetic factors in determining bone mass. J Clin Invest. 1973 Nov;52(11):2800–2808. doi: 10.1172/JCI107476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Smith E. P., Boyd J., Frank G. R., Takahashi H., Cohen R. M., Specker B., Williams T. C., Lubahn D. B., Korach K. S. Estrogen resistance caused by a mutation in the estrogen-receptor gene in a man. N Engl J Med. 1994 Oct 20;331(16):1056–1061. doi: 10.1056/NEJM199410203311604. [DOI] [PubMed] [Google Scholar]
  25. Snow-Harter C., Whalen R., Myburgh K., Arnaud S., Marcus R. Bone mineral density, muscle strength, and recreational exercise in men. J Bone Miner Res. 1992 Nov;7(11):1291–1296. doi: 10.1002/jbmr.5650071108. [DOI] [PubMed] [Google Scholar]

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