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Idiopathic osteoporosis in premenopausal women

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Abstract

Although osteoporosis predominantly affects older postmenopausal women, low bone mineral density also occurs in men and younger women. In men, it is often unexplained by recognized secondary causes. These men with idiopathic osteoporosis have reductions in serum IGF-I as well as indices of reduced bone formation. Younger women also experience bone loss of unknown etiology (IOP). Whether premenopausal women with IOP have similar decreases in IGF-I levels and reduced indices of bone formation is unknown. We prospectively evaluated a group of premenopausal women with unexplained low bone mass and compared them to normal premenopausal women with respect to serum concentrations of IGF-I. Thirteen premenopausal women (34.2±2.3 years) with low bone density (mean lumbar spine T-score −2.26±0.20) were compared with 13 premenopausal women (35.7±1.7 years) with normal bone density of similar age, height and ethnic composition. Body mass index (BMI) was lower in subjects than controls (20.5±0.7 versus 25.2±1.1 kg/m2, P<0.01). A family history of osteoporosis and a history of fragility fractures were found more frequently in subjects than controls (P≤0.05). Calciotropic hormones did not differ between the two groups. In contrast to our observations in men with idiopathic osteoporosis, mean serum IGF-I concentrations did not differ between subjects and controls (subjects: 22.5±2.2 nmol/l versus controls: 20.8±1.6 nmol/l; NS). Moreover, serum IGF-I levels did not correlate significantly with serum estradiol or with BMD at either the lumbar spine or femoral neck. However, lower follicular phase serum estradiol levels among non-oral contraceptive users were found in subjects as compared to controls (subjects: 124.1±13 pmol/l versus controls 194.9±24 pmol/l, P=0.06). Calculated free, bioavailable estradiol levels were significantly lower overall in subjects than controls (0.6±0.1 versus 1.2±0.2 pmol/l, P<0.05). Total serum estradiol levels correlated with BMD at the femoral neck (r=+0.50; P<0.05). Free, bioavailable estradiol correlated with BMD and BMAD at the lumbar spine (r=+0.54, P<0.01 and r=+0.54, P<0.05, respectively) and femoral neck (r=+0.60 and r=+0.55 respectively, both P<0.01). Urinary NTX excretion, although within the normal premenopausal range, was 45% higher in subjects than controls (41.6±5.9 nmol BCE/l versus 28.3±2.4 nmol BCE/l; P<0.05). Bone-specific alkaline phosphatase activity was also higher (17.4±1.6 ng/ml versus 14.7±0.8 ng/ml), although the difference was not statistically significant. These results suggest differences in the pathogenesis of idiopathic osteoporosis in women as compared to men with IOP.

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References

  1. Orwoll ES, Klein RF (1995) Osteoporosis in men. Endocr Rev 16:87–116

    Article  CAS  PubMed  Google Scholar 

  2. Kelepouris N, Harper KD, Gannon F, Kaplan FS, Haddad JG (1995) Severe osteoporosis in men. Ann Int Med 123L452–460

  3. Kurland ES, Rosen CJ, Cosman F, McMahon D, Chan F, Shane E, Lindsay R, Dempster D, Bilezikian JP (1997) Insulin-like growth factor-I in men with idiopathic osteoporosis. J Clin Endocrinol Metab 82:2799–2805

    Article  CAS  PubMed  Google Scholar 

  4. Khosla S, Lufkin EG, Hodgson SF, Fitzpatrick LA, Melton LJ 3rd (1994) Epidemiology and clinical features of osteoporosis in young individuals. Bone 15:551–555

    Google Scholar 

  5. Moreira Kulak CA, Schussheim DH, McMahon DJ, Kurland E, Silverberg SJ, Siris ES, Bilezikian JP, Shane E (2000) Osteoporosis and low bone mass in premenopausal and perimenopausal women. Endocr Pract 6:296–304

    PubMed  Google Scholar 

  6. Peris P, Guanabens N, Martinez de Osaba MJ, Monegal A, Alvarez L, Pons F, Ros I, Cerda D, Munoz-Gomez J (2002) Clinical characteristics and etiologic factors of premenopausal osteoporosis in a group of Spanish women. Semin Arthr Rheum 32:64–70

    Article  Google Scholar 

  7. Sowers MR, Clark MK, Hollis B, Wallace RB, Jannausch M (1992) Radial bone mineral density in pre- and perimenopausal women: a prospective study of rates and risk factors for loss. J Bone Miner Res 7:647–657

    CAS  PubMed  Google Scholar 

  8. Heshmati HM, Khosla S (1998) Idiopathic osteoporosis: a heterogeneous entity. Ann Med Int (Paris) 149:77–81

    Google Scholar 

  9. Marie PJ, de Vernejoul MC, Connes D, Hott M (1991) Decreased DNA synthesis by cultured osteoblastic cells in eugonadal osteoporotic men with defective bone formation. J Clin Invest 88:1167–1172

    CAS  PubMed  Google Scholar 

  10. Zerwekh JE, Sakhaee K, Breslau NA, Gottschalk F, Pak CY (1992) Impaired bone formation in male idiopathic osteoporosis: further reduction in the presence of concomitant hypercalciuria. Osteoporos Int 2:128–134

    CAS  PubMed  Google Scholar 

  11. Khosla S (1997) Idiopathic osteoporosis—is the osteoblast to blame? J Clin Endocrinol Metab 82:2792–2794

    Article  CAS  PubMed  Google Scholar 

  12. Ljunghall S, Johansson AG, Burman P, Kampe O, Lindh E, Karlsson FA (1992) Low plasma levels of insulin-like growth factor 1 (IGF-1) in male patients with idiopathic osteoporosis. J Int Med 232:59–64

    CAS  Google Scholar 

  13. Reed BY, Zerwekh JE, Sakhaee K, Breslau NA, Gottschalk F, Pak CY (1995) Serum IGF 1 is low and correlated with osteoblastic surface in idiopathic osteoporosis. J Bone Miner Res 10:1218–1224

    CAS  PubMed  Google Scholar 

  14. Rosen CJ, Kurland ES, Vereault D, Adler RA, Rackoff PJ, Craig WY, Witte S, Rogers J, Bilezikian JP (1998) Association between serum insulin growth factor-I (IGF-I) and a simple sequence repeat in IGF-I gene: implications for genetic studies of bone mineral density. J Clin Endocrinol Metab 83:2286–2290

    Article  CAS  PubMed  Google Scholar 

  15. Carter DR, Bouxsein ML, Marcus R (1992) New approaches for interpreting projected bone densitometry data. J Bone Miner Res 7:137–145

    CAS  PubMed  Google Scholar 

  16. Katzman DK, Bachrach LK,. Carter DR, Marcus R (1991) Clinical and anthropometric correlates of bone mineral acquisition in healthy adolescent girls. J Clin Endocrinol Metab 73:1332–1339

    CAS  PubMed  Google Scholar 

  17. Garner DM, Garfinkel PE (1979) The Eating Attitudes Test: an index of the symptoms of anorexia nervosa. Psychol Med 9:273–279

    CAS  PubMed  Google Scholar 

  18. Nussbaum SR, Zahradnik RJ, Lavigne JR, Brennan GL, Nozawa-Ung K, Kim LY, Keutmann HT, Wang CA, Potts JT Jr, Segre GV (1987) Highly sensitive two-site immunoradiometric assay of parathyrin, and its clinical utility in evaluating patients with hypercalcemia. Clin Chem 33:1364–1367

    CAS  PubMed  Google Scholar 

  19. Breier BH, Gallaher BW, Gluckman PD (1991) Radioimmunoassay for insulin-like growth factor-I: solutions to some potential problems and pitfalls. J Endocrinol 128:347–357

    CAS  PubMed  Google Scholar 

  20. Grogean T, Verault D, Millalrd P (1997) A comparative analysis of methods to measure IGF-1 in human serum. Endocrinol Metab 4:109–114

    Google Scholar 

  21. Hanson DA, Weis MA, Bollen AM, Maslan SL, Singer FR, Eyre DR (1992) A specific immunoassay for monitoring human bone resorption: quantitation of type I collagen cross-linked N-telopeptides in urine. J Bone Miner Res 7:1251–1258

    CAS  PubMed  Google Scholar 

  22. Kowalski A, Paul W (1976) Clin Chem 25:1152

    Google Scholar 

  23. 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 16:801–810

    Article  CAS  PubMed  Google Scholar 

  24. Darby AJ, Meunier PJ (1981) Mean wall thickness and formation periods of trabecular bone packets in idiopathic osteoporosis. Calcif Tissue Int 33:199–204

    CAS  PubMed  Google Scholar 

  25. Sowers MR, Shapiro B, Gilbraith MA, Jannausch M (1990) Health and hormonal characteristics of premenopausal women with lower bone mass. Calcif Tissue Int 47:130–135

    CAS  PubMed  Google Scholar 

  26. Sowers M, Randolph JF Jr, Crutchfield M, Jannausch ML, Shapiro B, Zhang B, La Pietra M (1998) Urinary ovarian and gonadotropin hormone levels in premenopausal women with low bone mass. J Bone Miner Res 13:1191–1202

    CAS  PubMed  Google Scholar 

  27. Ackerman GE, Smith ME, Mendelson CR, MacDonald PC, Simpson ER (1981) Aromatization of androstenedione by human adipose tissue stromal cells in monolayer culture. J Clin Endocrinol Metab 53:412–417

    CAS  PubMed  Google Scholar 

  28. Longcope C, Baker S (1993) Androgen and estrogen dynamics: relationships with age, weight, and menopausal status. J Clin Endocrinol Metab 76:601–604

    Article  CAS  PubMed  Google Scholar 

  29. Bakker I, Twisk JW, Van Mechelen W, Kemper HC (2003) Fat-free body mass is the most important body composition determinant of 10-yr longitudinal development of lumbar bone in adult men and women. J Clin Endocrinol Metab 88:2607–2613

    Article  CAS  PubMed  Google Scholar 

  30. Hui SL, Perkins AJ, Zhou L, Longcope C, Econs MJ, Peacock M, McClintock C, Johnston CC Jr (2002) Bone loss at the femoral neck in premenopausal white women: effects of weight change and sex-hormone levels. J Clin Endocrinol Metab 87:1539–1543

    Article  CAS  PubMed  Google Scholar 

  31. Slemenda C, Longcope C, Peacock M, Hui S, Johnston CC (1996) Sex steroids, bone mass, and bone loss. A prospective study of pre-, peri-, and postmenopausal women. J Clin Invest 97:14–21

    CAS  PubMed  Google Scholar 

  32. Licata AA (2000) “Does she or doesn’t she...have osteoporosis?” The use and abuse of bone densitometry. Endocr Pract 6:336–337

    CAS  PubMed  Google Scholar 

  33. Lindsay R (1994) Bone mass measurement for premenopausal women. Osteoporos Int 4:39–41

    Google Scholar 

  34. Kanis JA, Melton LJ 3rd, Christiansen C, Johnston CC, Khaltaev N (1994) The diagnosis of osteoporosis. J Bone Miner Res 9:1137–1141

    CAS  PubMed  Google Scholar 

  35. Osteoporosis prevention, diagnosis, and therapy (2000) NIH Consensus Statement 17:1–45

    Google Scholar 

  36. Dempster DW (2000) The contribution of trabecular architecture to cancellous bone quality. J Bone Miner Res 15:20–23

    CAS  PubMed  Google Scholar 

  37. Melton LJ 3rd, Eddy DM, Johnston CC Jr (1990) Screening for osteoporosis. Ann Int Med 112:516–528

    PubMed  Google Scholar 

  38. Horowitz M, Wishart JM, Bochner M, Need AG, Chatterton BE, Nordin BE (1988) Mineral density of bone in the forearm in premenopausal women with fractured wrists. BMJ 297:1314–1315

    CAS  PubMed  Google Scholar 

  39. Honkanen R, Tuppurainen M, Kroger H, Alhava E, Puntila E (1997) Associations of early premenopausal fractures with subsequent fractures vary by sites and mechanisms of fractures. Calcif Tissue Int 60:327–331

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

This work was supported by a grant from the Endocrine Fellows Foundation and Grant RR-006645 from the National Institutes of Health.

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Correspondence to Elizabeth Shane.

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Rubin, M.R., Schussheim, D.H., Kulak, C.A.M. et al. Idiopathic osteoporosis in premenopausal women. Osteoporos Int 16, 526–533 (2005). https://doi.org/10.1007/s00198-004-1716-0

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  • DOI: https://doi.org/10.1007/s00198-004-1716-0

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