Skip to main content
NCBI home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1992 Dec;90(6):2464–2471. doi: 10.1172/JCI116138

Estrogen status and heredity are major determinants of premenopausal bone mass.

R Armamento-Villareal 1, D T Villareal 1, L V Avioli 1, R Civitelli 1
PMCID: PMC443403  PMID: 1469098

Abstract

To analyze their relative effects on premenopausal bone mass, we have studied the impact of lifelong estrogen exposure, assessed by an estrogen score (ES; computed on age at menarche, average length of menstrual cycles since menarche, and use of birth control pills), heredity, and some environmental factors on vertebral bone density (VBD), of 63 premenopausal women (age, 19-40 yr). Compared with women with normal bone density (Z score > -1), subjects with low VBD (Z score < -1) had significantly lower ES (15.1 +/- 3.9 vs. 18.7 +/- 2.4, P = 0.001), higher age at menarche (13.8 +/- 1.7 vs. 12.6 +/- 1.4 yr, P = 0.005), and lower serum estradiol (46.9 +/- 37 vs. 86.6 +/- 57 pg/ml, P = 0.023) and estrone levels (107.4 +/- 60 vs. 178.8 +/- 9.0 pg/ml, P = 0.05). Likewise, women in the lowest quartile for VBD had significantly lower ES (15.3 +/- 4.5 vs. 18.1 +/- 2.7, P = 0.006) and higher age at menarche (13.9 +/- 1.9 vs. 12.8 +/- .4, P = 0.02) than those in the upper three quartiles. A higher proportion of subjects with irregular menses (52 vs. 23%, P = 0.03) and a positive family history of osteoporosis (86 vs. 61%, P = 0.04) was found in the low VBD group compared with subjects with normal VBD. VBD correlated positively with ES (r = 0.44, P = < 0.001) and negatively with age at menarche (r = -0.30, P = 0.03) by simple linear regression, whereas no correlation was found between VBD and age, body mass index, parity, lactation, physical activity, sunlight exposure, and dietary calcium and vitamin D intakes. The correlation between VBD and ES improved after correcting for the effect of all the other variables by partial correlation analysis (Pearson partial r = 0.57, P = < 0.01), which also disclosed a significant contribution of dietary calcium to VBD. However, ES was the only significant independent determinant of VBD, by stepwise multiple regression analysis (R2 = 0.24). Therefore, premenopausal estrogen exposure, and possibly genetic predisposition, rather than environmental factors, are the major determinants for the development of peak bone mass before menopause.

Full text

PDF
2464

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bachrach L. K., Katzman D. K., Litt I. F., Guido D., Marcus R. Recovery from osteopenia in adolescent girls with anorexia nervosa. J Clin Endocrinol Metab. 1991 Mar;72(3):602–606. doi: 10.1210/jcem-72-3-602. [DOI] [PubMed] [Google Scholar]
  2. Baran D., Sorensen A., Grimes J., Lew R., Karellas A., Johnson B., Roche J. Dietary modification with dairy products for preventing vertebral bone loss in premenopausal women: a three-year prospective study. J Clin Endocrinol Metab. 1990 Jan;70(1):264–270. doi: 10.1210/jcem-70-1-264. [DOI] [PubMed] [Google Scholar]
  3. Block J. E., Smith R., Glueer C. C., Steiger P., Ettinger B., Genant H. K. Models of spinal trabecular bone loss as determined by quantitative computed tomography. J Bone Miner Res. 1989 Apr;4(2):249–257. doi: 10.1002/jbmr.5650040218. [DOI] [PubMed] [Google Scholar]
  4. Buchanan J. R., Myers C., Lloyd T., Leuenberger P., Demers L. M. Determinants of peak trabecular bone density in women: the role of androgens, estrogen, and exercise. J Bone Miner Res. 1988 Dec;3(6):673–680. doi: 10.1002/jbmr.5650030613. [DOI] [PubMed] [Google Scholar]
  5. Cann C. E., Martin M. C., Genant H. K., Jaffe R. B. Decreased spinal mineral content in amenorrheic women. JAMA. 1984 Feb 3;251(5):626–629. [PubMed] [Google Scholar]
  6. Chesnut C. H., 3rd Theoretical overview: bone development, peak bone mass, bone loss, and fracture risk. Am J Med. 1991 Nov 25;91(5B):2S–4S. doi: 10.1016/0002-9343(91)90238-s. [DOI] [PubMed] [Google Scholar]
  7. Dalsky G. P., Stocke K. S., Ehsani A. A., Slatopolsky E., Lee W. C., Birge S. J., Jr Weight-bearing exercise training and lumbar bone mineral content in postmenopausal women. Ann Intern Med. 1988 Jun;108(6):824–828. doi: 10.7326/0003-4819-108-6-824. [DOI] [PubMed] [Google Scholar]
  8. Davee A. M., Rosen C. J., Adler R. A. Exercise patterns and trabecular bone density in college women. J Bone Miner Res. 1990 Mar;5(3):245–250. doi: 10.1002/jbmr.5650050307. [DOI] [PubMed] [Google Scholar]
  9. Dhuper S., Warren M. P., Brooks-Gunn J., Fox R. Effects of hormonal status on bone density in adolescent girls. J Clin Endocrinol Metab. 1990 Nov;71(5):1083–1088. doi: 10.1210/jcem-71-5-1083. [DOI] [PubMed] [Google Scholar]
  10. Drinkwater B. L., Bruemner B., Chesnut C. H., 3rd Menstrual history as a determinant of current bone density in young athletes. JAMA. 1990 Jan 26;263(4):545–548. [PubMed] [Google Scholar]
  11. Drinkwater B. L., Nilson K., Ott S., Chesnut C. H., 3rd Bone mineral density after resumption of menses in amenorrheic athletes. JAMA. 1986 Jul 18;256(3):380–382. [PubMed] [Google Scholar]
  12. Gruber H. E., Ivey J. L., Baylink D. J., Matthews M., Nelp W. B., Sisom K., Chesnut C. H., 3rd Long-term calcitonin therapy in postmenopausal osteoporosis. Metabolism. 1984 Apr;33(4):295–303. doi: 10.1016/0026-0495(84)90187-2. [DOI] [PubMed] [Google Scholar]
  13. Haddad J. G., Chyu K. J. Competitive protein-binding radioassay for 25-hydroxycholecalciferol. J Clin Endocrinol Metab. 1971 Dec;33(6):992–995. doi: 10.1210/jcem-33-6-992. [DOI] [PubMed] [Google Scholar]
  14. Hreshchyshyn M. M., Hopkins A., Zylstra S., Anbar M. Associations of parity, breast-feeding, and birth control pills with lumbar spine and femoral neck bone densities. Am J Obstet Gynecol. 1988 Aug;159(2):318–322. doi: 10.1016/s0002-9378(88)80075-9. [DOI] [PubMed] [Google Scholar]
  15. Hümpel M., Nieuweboer B., Wendt H., Speck U. Investigations of pharmacokinetics of ethinyloestradiol to specific consideration of a possible first-pass effect in women. Contraception. 1979 Apr;19(4):421–432. doi: 10.1016/0010-7824(79)90036-2. [DOI] [PubMed] [Google Scholar]
  16. Liel Y., Edwards J., Shary J., Spicer K. M., Gordon L., Bell N. H. The effects of race and body habitus on bone mineral density of the radius, hip, and spine in premenopausal women. J Clin Endocrinol Metab. 1988 Jun;66(6):1247–1250. doi: 10.1210/jcem-66-6-1247. [DOI] [PubMed] [Google Scholar]
  17. Lindsay R. Estrogens, bone mass, and osteoporotic fracture. Am J Med. 1991 Nov 25;91(5B):10S–13S. doi: 10.1016/0002-9343(91)90240-x. [DOI] [PubMed] [Google Scholar]
  18. 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]
  19. Lindsay R., Tohme J., Kanders B. The effect of oral contraceptive use on vertebral bone mass in pre- and post-menopausal women. Contraception. 1986 Oct;34(4):333–340. doi: 10.1016/0010-7824(86)90086-7. [DOI] [PubMed] [Google Scholar]
  20. Lloyd T., Buchanan J. R., Ursino G. R., Myers C., Woodward G., Halbert D. R. Long-term oral contraceptive use does not affect trabecular bone density. Am J Obstet Gynecol. 1989 Feb;160(2):402–404. doi: 10.1016/0002-9378(89)90457-2. [DOI] [PubMed] [Google Scholar]
  21. Matkovic V., Fontana D., Tominac C., Goel P., Chesnut C. H., 3rd Factors that influence peak bone mass formation: a study of calcium balance and the inheritance of bone mass in adolescent females. Am J Clin Nutr. 1990 Nov;52(5):878–888. doi: 10.1093/ajcn/52.5.878. [DOI] [PubMed] [Google Scholar]
  22. Mazess R. B., Barden H. S. Bone density in premenopausal women: effects of age, dietary intake, physical activity, smoking, and birth-control pills. Am J Clin Nutr. 1991 Jan;53(1):132–142. doi: 10.1093/ajcn/53.1.132. [DOI] [PubMed] [Google Scholar]
  23. Mishell D. R., Jr, Thorneycroft I. H., Nakamura R. M., Nagata Y., Stone S. C. Serum estradiol in women ingesting combination oral contraceptive steroids. Am J Obstet Gynecol. 1972 Dec 1;114(7):923–928. doi: 10.1016/0002-9378(72)90098-1. [DOI] [PubMed] [Google Scholar]
  24. Ott S. M. Attainment of peak bone mass. J Clin Endocrinol Metab. 1990 Nov;71(5):1082A–1082C. doi: 10.1210/jcem-71-5-1082. [DOI] [PubMed] [Google Scholar]
  25. Pacifici R., Rupich R. C., Avioli L. V. Vertebral cortical bone mass measurement by a new quantitative computer tomography method: correlations with vertebral trabecular bone measurements. Calcif Tissue Int. 1990 Oct;47(4):215–220. doi: 10.1007/BF02555922. [DOI] [PubMed] [Google Scholar]
  26. Pocock N. A., Eisman J. A., Hopper J. L., Yeates M. G., Sambrook P. N., Eberl S. Genetic determinants of bone mass in adults. A twin study. J Clin Invest. 1987 Sep;80(3):706–710. doi: 10.1172/JCI113125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Prior J. C., Vigna Y. M., Schechter M. T., Burgess A. E. Spinal bone loss and ovulatory disturbances. N Engl J Med. 1990 Nov 1;323(18):1221–1227. doi: 10.1056/NEJM199011013231801. [DOI] [PubMed] [Google Scholar]
  28. Rosenthal D. I., Mayo-Smith W., Hayes C. W., Khurana J. S., Biller B. M., Neer R. M., Klibanski A. Age and bone mass in premenopausal women. J Bone Miner Res. 1989 Aug;4(4):533–538. doi: 10.1002/jbmr.5650040412. [DOI] [PubMed] [Google Scholar]
  29. Seeman E., Hopper J. L., Bach L. A., Cooper M. E., Parkinson E., McKay J., Jerums G. Reduced bone mass in daughters of women with osteoporosis. N Engl J Med. 1989 Mar 2;320(9):554–558. doi: 10.1056/NEJM198903023200903. [DOI] [PubMed] [Google Scholar]
  30. 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]
  31. Sowers M. R., Shapiro B., Gilbraith M. A., Jannausch M. Health and hormonal characteristics of premenopausal women with lower bone mass. Calcif Tissue Int. 1990 Sep;47(3):130–135. doi: 10.1007/BF02555976. [DOI] [PubMed] [Google Scholar]
  32. Steinberg K. K., Freni-Titulaer L. W., DePuey E. G., Miller D. T., Sgoutas D. S., Coralli C. H., Phillips D. L., Rogers T. N., Clark R. V. Sex steroids and bone density in premenopausal and perimenopausal women. J Clin Endocrinol Metab. 1989 Sep;69(3):533–539. doi: 10.1210/jcem-69-3-533. [DOI] [PubMed] [Google Scholar]
  33. Tylavsky F. A., Bortz A. D., Hancock R. L., Anderson J. J. Familial resemblance of radial bone mass between premenopausal mothers and their college-age daughters. Calcif Tissue Int. 1989 Nov;45(5):265–272. doi: 10.1007/BF02556017. [DOI] [PubMed] [Google Scholar]
  34. Villareal D. T., Civitelli R., Chines A., Avioli L. V. Subclinical vitamin D deficiency in postmenopausal women with low vertebral bone mass. J Clin Endocrinol Metab. 1991 Mar;72(3):628–634. doi: 10.1210/jcem-72-3-628. [DOI] [PubMed] [Google Scholar]
  35. Watts N. B., Harris S. T., Genant H. K., Wasnich R. D., Miller P. D., Jackson R. D., Licata A. A., Ross P., Woodson G. C., 3rd, Yanover M. J. Intermittent cyclical etidronate treatment of postmenopausal osteoporosis. N Engl J Med. 1990 Jul 12;323(2):73–79. doi: 10.1056/NEJM199007123230201. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES