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Osteoporosis International

, Volume 17, Issue 9, pp 1329–1336 | Cite as

Endogenous sex steroids, weight change and rates of hip bone loss in older men: the MrOS study

  • K. E. EnsrudEmail author
  • C. E. Lewis
  • L. C. Lambert
  • B. C. Taylor
  • H. A. Fink
  • E. Barrett-Connor
  • J. A. Cauley
  • M. L. Stefanick
  • E. Orwoll
  • Osteoporotic Fractures in Men (MrOS) Study Research Group
Original Article

Abstract

Introduction

Lower levels of endogenous sex steroids or declines in these hormones may contribute to the increased rates of bone loss observed in older adults experiencing weight loss. We hypothesized that among older men with weight loss, higher rates of bone loss at the hip would be observed in men with lower baseline bioavailable sex steroids or those with greater declines in these hormones.

Methods

To test this hypothesis, body weight, hip bone mineral density (BMD) using dual energy x-ray absorptiometry and endogenous sex steroids in paired serum samples by sensitive immunoassays were measured at a baseline and at a second examination that was held an average of 1.8 years later in 1267 older men enrolled in the Osteoporotic Fractures in Men (MrOS) study.

Results

Men experiencing weight loss had higher rates of hip bone loss than those with stable weight or weight gain within each quartile of baseline sex steroid level [p values for test of trend across weight change categories <0.010 within each quartile of bioavailable estradiol and testosterone and <0.060 within each quartile of sex hormone-binding globulin (SHBG)]. Results were similar when a change in sex steroids was substituted for baseline sex steroids in the analyses. Among men with weight loss, the rate of decline in total hip BMD showed a stepwise increase in magnitude with decreasing baseline bioavailable estradiol (p value for trend <0.040), with increasing baseline SHBG (p value for trend<0.030) and with greater decreases in bioavailable testosterone from baseline (p value for trend <0.001).

Conclusions

These findings support the hypothesis that the impact of weight loss in older men on rates of hip bone loss may be increased by the presence of a sex steroid insufficiency.

Keywords

Bone density Estrogen Men Osteoporosis Testosterone Weight loss 

Notes

Acknowledgements

Investigators in the Osteoporotic Fractures in Men (MrOS) Research Group: Coordinating Center (University of California, San Francisco and California Pacific Medical Center Research Institute): S.R. Cummings (principal investigator), M.C. Nevitt (co-investigator), D.C. Bauer (co-investigator), K.L. Stone (co-investigator), D.M. Black (co-investigator), P.M. Cawthon (project director), R. Fullman (research associate), R. Benard, T. Blackwell, J. Diehl, S. Ewing, C. Fox, M. Jaime-Chavez, E. Kwan, S. Litwack, L.Y. Lui, A. Mills, L. Palermo, J. Schneider, R. Scott, D. Tanaka, C. Yeung; Administrative Center) (Oregon Health and Sciences University: E. Orwoll (principal investigator), L. Marshall (co-investigator), J. Babich Blank (project director), L. Lambert, B. Chan, D. Neevel, J. Mougey, L. Press; University of Alabama, Birmingham: C.E. Lewis (principal investigator), J. Shikany (co-investigator), P. Johnson (project director), E. Clavino, C. Oden, N. Webb, K. Hardy, S. Felder, P. Grayson, J. Wilkoff, J. King, T. Johnsey, J. Thompson; University of Minnesota: K. Ensrud (principal investigator), H. Fink (co-investigator), D. King (program manager), N. Michaels (asst. program manager), N. Nelson (clinic coordinator), C. Bird, D. Blanks, F. Imker-Witte, K. Moen, M. Paudel, M. Slindee; Stanford University: M. Stefanick (principal investigator), A. Hoffman (co-investigator), E. Moore (project director), K. Kent, B. Malig, S. Wong; University of Pittsburgh: J. Cauley (principal investigator), J. Zmuda (co-investigator), M. Danielson, L. Harper (project director), L. Buck (clinic coordinator), M. Nasim, D. Cusick, D. Moore, M. Gorecki, D. Lee, N. Watson, C. Bashada, C. Newman, G. Engleka; University of California, San Diego: E. Barrett-Connor (principal investigator), T. Dam (co-investigator), ML Carrion-Petersen (project director), P. Miller, N. Kamantigue, S. Szerdi, G. Reno.

References

  1. 1.
    Khosla S, Melton LJ, III, Riggs BL (2002) Clinical review 144: estrogen and the male skeleton. J Clin Endocrinol Metab 87(4):1443–1450PubMedCrossRefGoogle Scholar
  2. 2.
    Riggs BL, Khosla S, Melton LJ III (1998) A unitary model for involutional osteoporosis: estrogen deficiency causes both type I and type II osteoporosis in postmenopausal women and contributes to bone loss in aging men. J Bone Miner Res 13(5):763–773PubMedCrossRefGoogle Scholar
  3. 3.
    Khosla S, Melton LJ III, Atkinson EJ, O’Fallon WM, Klee GG, Riggs BL (1998) Relationship of serum sex steroid levels and bone turnover markers with bone mineral density in men and women: a key role for bioavailable estrogen. J Clin Endocrinol Metab 83(7):2266–2274PubMedCrossRefGoogle Scholar
  4. 4.
    Ferrini RL, Barrett-Connor E (1998) Sex hormones and age: a cross-sectional study of testosterone and estradiol and their bioavailable fractions in community-dwelling men. Am J Epidemiol 147(8):750–754PubMedGoogle Scholar
  5. 5.
    Harman SM, Metter EJ, Tobin JD, Pearson J, Blackman MR (2001) Longitudinal effects of aging on serum total and free testosterone levels in healthy men. Baltimore Longitudinal Study of Aging. J Clin Endocrinol Metab 86(2):724–731PubMedCrossRefGoogle Scholar
  6. 6.
    Feldman HA, Longcope C, Derby CA, Johannes CB, Araujo AB, Coviello AD, Bremner WJ, McKinlay JB (2002) Age trends in the level of serum testosterone and other hormones in middle-aged men: longitudinal results from the Massachusetts male aging study. J Clin Endocrinol Metab 87(2):589–598PubMedCrossRefGoogle Scholar
  7. 7.
    van den Beld AW, de Jong FH, Grobbee DE, Pols HA, Lamberts SW (2000) 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 85(9):3276–3282PubMedCrossRefGoogle Scholar
  8. 8.
    Slemenda CW, Longcope C, Zhou L, Hui SL, Peacock M, Johnston CC (1997) Sex steroids and bone mass in older men. Positive associations with serum estrogens and negative associations with androgens. J Clin Invest 100(7):1755–1759PubMedCrossRefGoogle Scholar
  9. 9.
    Amin S, Zhang Y, Sawin CT, Evans SR, Hannan MT, Kiel DP, Wilson PW, Felson DT (2000) Association of hypogonadism and estradiol levels with bone mineral density in elderly men from the Framingham study. Ann Intern Med 133(12):951–963PubMedGoogle Scholar
  10. 10.
    Greendale GA, Edelstein S, Barrett-Connor E (1997) Endogenous sex steroids and bone mineral density in older women and men: the Rancho Bernardo Study. J Bone Miner Res 12(11):1833–1843PubMedCrossRefGoogle Scholar
  11. 11.
    Szulc P, Munoz F, Claustrat B, Garnero P, Marchand F, Duboeuf F, Delmas PD (2001) Bioavailable estradiol may be an important determinant of osteoporosis in men: the MINOS study. J Clin Endocrinol Metab 86(1):192–199PubMedCrossRefGoogle Scholar
  12. 12.
    Center JR, Nguyen TV, Sambrook PN, Eisman JA (1999) Hormonal and biochemical parameters in the determination of osteoporosis in elderly men. J Clin Endocrinol Metab 84(10):3626–3635PubMedCrossRefGoogle Scholar
  13. 13.
    Khosla S, Melton LJ III, Atkinson EJ, O’Fallon WM (2001) Relationship of serum sex steroid levels to longitudinal changes in bone density in young versus elderly men. J Clin Endocrinol Metab 86(8):3555–3561PubMedCrossRefGoogle Scholar
  14. 14.
    Gennari L, Merlotti D, Martini G, Gonnelli S, Franci B, Campagna S, Lucani B, Dal Canto N, Valenti R, Gennari C, Nuti R (2003) Longitudinal association between sex hormone levels, bone loss, and bone turnover in elderly men. J Clin Endocrinol Metab 88(11):5327–5333PubMedCrossRefGoogle Scholar
  15. 15.
    Cauley J, Taylor B, Fink H, Ensrud K, Bauer D, Barrett-Connor E, Marshall L, Nevitt M, Stefanick M, Orwoll E. Sex steroid hormones in older men: cross-sectional and longitudinal associations with bone mineral density (BMD). The Osteoporotic Fracture in Men Study (MrOS). J Bone Miner Res 19[Suppl 1]:S16. 2004. Ref Type: AbstractGoogle Scholar
  16. 16.
    Edelstein SL, Barrett-Connor E (1993) Relation between body size and bone mineral density in elderly men and women. Am J Epidemiol 138(3):160–169PubMedGoogle Scholar
  17. 17.
    Hannan MT, Felson DT, Anderson JJ (1992) Bone mineral density in elderly men and women: results from the Framingham osteoporosis study. J Bone Miner Res 7(5):547–553PubMedGoogle Scholar
  18. 18.
    Glynn NW, Meilahn EN, Charron M, Anderson SJ, Kuller LH, Cauley JA (1995) Determinants of bone mineral density in older men. J Bone Miner Res 10(11):1769–1777PubMedCrossRefGoogle Scholar
  19. 19.
    Orwoll ES, Bevan L, Phipps KR (2000) Determinants of bone mineral density in older men. Osteoporos Int 11(10):815–821PubMedCrossRefGoogle Scholar
  20. 20.
    Cauley JA, Fullman RL, Stone KL, Zmuda JM, Bauer DC, Barrett-Connor E, Ensrud K, Lau EM, Orwoll ES (2005) Factors associated with the lumbar spine and proximal femur bone mineral density in older men. Osteoporos Int (in press)Google Scholar
  21. 21.
    Dennison E, Eastell R, Fall CH, Kellingray S, Wood PJ, Cooper C (1999) Determinants of bone loss in elderly men and women: a prospective population-based study. Osteoporos Int 10(5):384–391PubMedCrossRefGoogle Scholar
  22. 22.
    Hannan MT, Felson DT, Dawson-Hughes B, Tucker KL, Cupples LA, Wilson PW, Kiel DP (2000) Risk factors for longitudinal bone loss in elderly men and women: the Framingham Osteoporosis Study. J Bone Miner Res 15(4):710–720PubMedCrossRefGoogle Scholar
  23. 23.
    Knoke JD, Barrett-Connor E (2003) Weight loss: a determinant of hip bone loss in older men and women. The Rancho Bernardo Study. Am J Epidemiol 158(12):1132–1138PubMedCrossRefGoogle Scholar
  24. 24.
    Ensrud KE, Fullman RL, Barrett-Connor E, Cauley JA, Stefanick ML, Fink HA, Lewis CE, Orwoll E (2005) Voluntary weight reduction in older men increases hip bone loss: the osteoporotic fractures in men study. J Clin Endocrinol Metab 90(4):1998–2004PubMedCrossRefGoogle Scholar
  25. 25.
    Orwoll E, Blank JB, Barrett-Connor E, Cauley J, Cummings S, Ensrud K, Lewis C, Cawthon PM, Marcus R, Marshall LM, McGowan J, Phipps K, Sherman S, Stefanick ML, Stone K (2005) Design and baseline characteristics of the osteoporotic fractures in men (MrOS) study-a large observational study of the determinants of fracture in older men. Contemp Clin Trials 26(5):569–585PubMedCrossRefGoogle Scholar
  26. 26.
    Blank JB, Cawthon PM, Carrion-Petersen ML, Harper L, Johnson JP, Mitson E, Delay RR (2005) Overview of recruitment for the osteoporotic fractures in men study (MrOS). Contemp Clin Trials 26(5):557–568PubMedCrossRefGoogle Scholar
  27. 27.
    Sodergard R, Backstrom T, Shanbhag V, Carstensen H (1982) Calculation of free and bound fractions of testosterone and estradiol-17 beta to human plasma proteins at body temperature. J Steroid Biochem 16(6):801–810PubMedCrossRefGoogle Scholar
  28. 28.
    Vermeulen A, Verdonck L, Kaufman JM (1999) A critical evaluation of simple methods for the estimation of free testosterone in serum. J Clin Endocrinol Metab 84(10):3666–3672PubMedCrossRefGoogle Scholar
  29. 29.
    Frost HM (1997) On our age-related bone loss: insights from a new paradigm. J Bone Miner Res 12(10):1539–1546PubMedCrossRefGoogle Scholar
  30. 30.
    Orwoll E, Lambert L, Marshall L, Phipps K, Blank J, Barrett-Connor E, Cauley J, Ensrud K, Cummings S (2005) Sex steroids in older men: The MrOS Study. Submitted to J Clin Endocrinol MetabGoogle Scholar
  31. 31.
    Langlois JA, Visser M, Davidovic LS, Maggi S, Li G, Harris TB (1998) Hip fracture risk in older white men is associated with change in body weight from age 50 years to old age. Arch Intern Med 158(9):990–996PubMedCrossRefGoogle Scholar
  32. 32.
    Ensrud KE, Ewing SK, Stone KL, Cauley JA, Bowman PJ, Cummings SR (2003) Intentional and unintentional weight loss increase bone loss and hip fracture risk in older women. J Am Geriatr Soc 51(12):1740–1747PubMedCrossRefGoogle Scholar

Copyright information

© International Osteoporosis Foundation and National Osteoporosis Foundation 2006

Authors and Affiliations

  • K. E. Ensrud
    • 1
    Email author
  • C. E. Lewis
    • 2
  • L. C. Lambert
    • 3
  • B. C. Taylor
    • 1
  • H. A. Fink
    • 1
  • E. Barrett-Connor
    • 4
  • J. A. Cauley
    • 5
  • M. L. Stefanick
    • 6
  • E. Orwoll
    • 3
  • Osteoporotic Fractures in Men (MrOS) Study Research Group
    • 1
  1. 1.Department of Medicine (111–0)VA Medical CenterMinneapolisUSA
  2. 2.University of AlabamaBirminghamUSA
  3. 3.Oregon Health and Science UniversityPortlandUSA
  4. 4.University of CaliforniaSan DiegoUSA
  5. 5.University of PittsburghPittsburghUSA
  6. 6.Stanford UniversityStanfordUSA

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