Skip to main content

Advertisement

SpringerLink
Log in

Negative correlation between bone mineral density and TSH receptor antibodies in male patients with untreated Graves’ disease

  • Original Article
  • Published:
Osteoporosis International Aims and scope Submit manuscript

Abstract

Introduction

Although it has been established that hyperthyroidism leads to reduced bone mineral density (BMD), with accelerated bone turnover promoting bone resorption in female patients, there is a dearth of data for male patients with hyperthyroidism. This study evaluated BMD and bone metabolism in male patients with Graves’ disease.

Methods

The study included 56 Japanese male patients with newly diagnosed Graves’ disease and 34 normal Japanese male control subjects of similar age and body mass index. We used dual energy x-ray absorptiometry to measure BMD at sites with different cortical/cancellous bone ratios (lumbar spine, femoral neck, and distal radius).

Results

At the lumbar spine and the distal radius, BMD and T-scores were significantly lower for patients than for controls. At the femoral neck, on the other hand, the same values were relatively, but not significantly, lower in patients than in controls. However, Z-scores at all three sites were significantly lower for patients than for controls. The Z -score at the distal radius of patients was significantly lower than that at their lumbar spine and femoral neck. In addition, Z-score at the distal radius correlated negatively with age, free thyroxine, thyroid stimulating hormone receptor antibodies, thyroid stimulating antibody, and urinary N-terminal telopeptide of type I collagen normalized by creatinine.

Conclusions

These results indicate a high prevalence of cortical bone loss in male patients with Graves’ disease, especially elderly patients. We conclude that BMD measurement is crucial in all Graves’ disease patients regardless of their gender and that the radial BMD as well as BMD at the lumbar spine and femoral neck should be monitored to effectively prevent bone loss and subsequent fracture.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Campos-Pastor MM, Munoz-Torres M, Escobar-Jimenez F, Ruiz de Almodovar M, Jodar Gimeno E (1993) Bone mass in females with different thyroid disorders: influence of menopausal status. Bone Miner 21:1–8

    Article  PubMed  CAS  Google Scholar 

  2. Diamond T, Vine J, Smart R, Butler P (1994) Thyrotoxic bone disease in women: a potentially reversible disorder. Ann Intern Med 120:8–11

    PubMed  CAS  Google Scholar 

  3. Gomez Acotto C, Schott AM, Hans D, Niepomniszcze H, Mautalen CA, Meunier PJ (1998) Hyperthyroidism influences ultrasound bone measurement on the Os calcis. Osteoporos Int 8:455–459

    Article  PubMed  CAS  Google Scholar 

  4. Olkawa M, Kushida K, Takahashi M, Ohishi T, Hoshino H, Suzuki M, Ogihara H, Ishigaki J, Inoue T (1999) Bone turnover and cortical bone mineral density in the distal radius in patients with hyperthyroidism being treated with antithyroid drugs for various periods of time. Clin Endocrinol (Oxf) 50:171–176

    Article  CAS  Google Scholar 

  5. Mora S, Pitukcheewanont P, Kaufman FR, Nelson JC, Gilsanz V (1999) Biochemical markers of bone turnover and the volume and the density of bone in children at different stages of sexual development. J Bone Miner Res 14:1664–1671

    Article  PubMed  CAS  Google Scholar 

  6. Ben-Shlomo A, Hagag P, Evans S, Weiss M (2001) Early postmenopausal bone loss in hyperthyroidism. Maturitas 39:19–27

    Article  PubMed  CAS  Google Scholar 

  7. Karga H, Papapetrou PD, Korakovouni A, Papandroulaki F, Polymeris A, Pampouras G (2004) Bone mineral density in hyperthyroidism. Clin Endocrinol (Oxf) 61:466–472

    Article  Google Scholar 

  8. Greenspan SL, Greenspan FS (1999) The effect of thyroid hormone on skeletal integrity. Ann Intern Med 130:750–758

    PubMed  CAS  Google Scholar 

  9. Marcocci C, Golia F, Vignali E, Pinchera A (1997) Skeletal integrity in men chronically treated with suppressive doses of L-thyroxine. J Bone Miner Res 12:72–77

    Article  PubMed  CAS  Google Scholar 

  10. Rosen HN, Moses AC, Garber J, Ross DS, Lee SL, Ferguson L, Chen V, Lee K, Greenspan SL (1998) Randomized trial of pamidronate in patients with thyroid cancer: bone density is not reduced by suppressive doses of thyroxine, but is increased by cyclic intravenous pamidronate. J Clin Endocrinol Metab 83:2324–2330

    Article  PubMed  CAS  Google Scholar 

  11. Jodar E, Martinez-Diaz-Guerra G, Azriel S, Hawkins F (2001) Bone mineral density in male patients with L-thyroxine suppressive therapy and Graves disease. Calcif Tissue Int 69:84–87

    Article  PubMed  CAS  Google Scholar 

  12. Riggs BL, Melton LJ 3rd (1986) Involutional osteoporosis. N Engl J Med 26:1676–1686

    Article  Google Scholar 

  13. Mosekilde L, Eriksen EF, Charles P (1990) Effects of thyroid hormones on bone and mineral metabolism. Endocrinol Metab Clin North Am 19:35–63

    Google Scholar 

  14. Lee MS, Kim SY, Lee MC, Cho BY, Lee HK, Koh CS, Min HK (1990) Negative correlation between the change in bone mineral density and serum osteocalcin in patients with hyperthyroidism. J Clin Endocrinol Metab 70:766–770

    Article  PubMed  CAS  Google Scholar 

  15. Wakasugi M, Wakao R, Tawata M, Gan N, Koizumi K, Onaya T (1993) Bone mineral density in patients with hyperthyroidism measured by dual energy X-ray absorptiometry. Clin Endocrinol (Oxf) 38:283–286

    CAS  Google Scholar 

  16. Jodar E, Munoz-Torres M, Escobar-Jimenez F, Quesada-Charneco M, Lund del Castillo JD (1997) Bone loss in hyperthyroid patients and in former hyperthyroid patients controlled on medical therapy: influence of aetiology and menopause. Clin Endocrinol (Oxf) 47:279–285

    Article  CAS  Google Scholar 

  17. Mudde AH, Reijnders FJ, Kruseman AC (1992) Peripheral bone density in women with untreated multinodular goitre. Clin Endocrinol (Oxf) 37:35–39

    CAS  Google Scholar 

  18. Fraser SA, Anderson JB, Smith DA, Wilson GM (1971) Osteoporosis and fractures following thyrotoxicosis. Lancet 1:981–983

    Article  PubMed  CAS  Google Scholar 

  19. Kumeda Y, Inaba M, Tahara H, Kurioka Y, Ishikawa T, Morii H, Nishizawa Y (2000) Persistent increase in bone turnover in Graves’ patients with subclinical hyperthyroidism. J Clin Endocrinol Metab 85:4157–4161

    Article  PubMed  CAS  Google Scholar 

  20. Siddiqi A, Burrin JM, Noonan K, James I, Wood DF, Price CP, Monson JP (1997) A longitudinal study of markers of bone turnover in Graves’ disease and their value in predicting bone mineral density. J Clin Endocrinol Metab 82:753–759

    Article  PubMed  CAS  Google Scholar 

  21. Lucidarme N, Ruiz JC, Czernichow P, Leger J (2000) Reduced bone mineral density at diagnosis and bone mineral recovery during treatment in children with Graves’ disease. J Pediatr 137:56–62

    Article  PubMed  CAS  Google Scholar 

  22. Ugur-Altun B, Altun A, Arikan E, Guldiken S, Tugrul A (2003) Relationships existing between the serum cytokine levels and bone mineral density in women in the premenopausal period affected by Graves’ disease with subclinical hyperthyroidism. Endocr Res 29:389–398

    Article  PubMed  CAS  Google Scholar 

  23. Fittipaldi MR, Fonderico F, Vitale G, Ciccarelli A, Lupoli GA, Cascella T, Panico A, Lupoli G (2002) Osteoporosis treatment in elderly hyperthyroid male patients. J Endocrinol Invest 25:98–100

    PubMed  CAS  Google Scholar 

  24. Toh SH, Claunch BC, Brown PH (1985) Effect of hyperthyroidism and its treatment on bone mineral content. Arch Intern Med 145:883–886

    Article  PubMed  CAS  Google Scholar 

  25. Bilezikian JP (1999) Osteoporosis in men. J Clin Endocrinol Metab 84:3431–3434

    Article  PubMed  CAS  Google Scholar 

  26. Milne M, Kang MI, Quail JM, Baran DT (1998) Thyroid hormone excess increases insulin-like growth factor I transcripts in bone marrow cell cultures: divergent effects on vertebral and femoral cell cultures. Endocrinology 139:2527–2534

    Article  PubMed  CAS  Google Scholar 

  27. Vestergaard P, Rejnmark L, Weeke J, Mosekilde L (2000) Fracture risk in patients treated for hyperthyroidism. Thyroid 10:341–348

    Article  PubMed  CAS  Google Scholar 

  28. Vestergaard P, Mosekilde L (2002) Fractures in patients with hyperthyroidism and hypothyroidism: a nationwide follow-up study in 16,249 patients. Thyroid 12:411–419

    Google Scholar 

  29. Vestergaard P, Mosekilde L (2003) Hyperthyroidism, bone mineral, and fracture risk-a meta-analysis. Thyroid 13:585–593

    Article  PubMed  Google Scholar 

  30. Cummings SR, Nevitt MC, Browner WS, Stone K, Fox KM, Ensrud KE, Cauley J, Black D, Vogt TM (1995) Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group. N Engl J Med 332:767–773

    Article  PubMed  CAS  Google Scholar 

  31. Wejda B, Hintze G, Katschinski B, Olbricht T, Benker G (1995) Hip fractures and the thyroid: a case-control study. J Intern Med 237:241–247

    Google Scholar 

  32. Abe E, Marians RC, Yu W, Wu XB, Ando T, Li Y, Iqbal J, Eldeiry L, Rajendren G, Blair HC, Davies TF, Zaidi M (2003) TSH is a negative regulator of skeletal remodeling. Cell 115:151–162

    Article  PubMed  CAS  Google Scholar 

  33. Morimura T, Tsunekawa K, Kasahara T, Seki K, Ogiwara T, Mori M, Murakami M (2005) Expression of type 2 iodothyronine deiodinase in human osteoblast is stimulated by thyrotropin. Endocrinology 146:2077–2084

    Google Scholar 

  34. Greenspan SL, Greenspan FS, Resnick NM, Block JE, Friedlander AL, Genant HK (1991) Skeletal integrity in premenopausal and postmenopausal women receiving long-term L-thyroxine therapy. Am J Med 91:5–14

    Article  PubMed  CAS  Google Scholar 

  35. Torring O, Tallstedt L, Wallin G, Lundell G, Ljunggren JG, Taube A, Saaf M, Hamberger B (1996) Graves’ hyperthyroidism: treatment with antithyroid drugs, surgery, or radioiodine–a prospective, randomized study. Thyroid Study Group. J Clin Endocrinol Metab 81:2986–2993

    Article  PubMed  CAS  Google Scholar 

  36. Brokken LJ, Wiersinga WM, Prummel MF (2003) Thyrotropin receptor autoantibodies are associated with continued thyrotropin suppression in treated euthyroid Graves’ disease patients. J Clin Endocrinol Metab 88:4135–4138

    Article  PubMed  CAS  Google Scholar 

  37. Schneider R, Reiners C (2003) The effect of levothyroxine therapy on bone mineral density: a systematic review of the literature. Exp Clin Endocrinol Diabetes 111:455–470

    Article  PubMed  CAS  Google Scholar 

  38. Fitts JM, Klein RM, Powers CA (2001) Estrogen and tamoxifen interplay with T(3) in male rats: pharmacologically distinct classes of estrogen responses affecting growth, bone, and lipid metabolism, and their relation to serum GH and IGF-I. Endocrinology 142:4223–4235

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported in part by a Grant-in-Aid from the Japanese Ministry of Health, Labour and Welfare (#H17-Saisei-003), the Japanese Ministry of Education, Science, Sports, and Culture (#17590958), the Smoking Research Foundation, and the Foundation of Growth Science.

Author information

Authors and Affiliations

  1. Department of Endocrinology and Metabolism, Rakuwakai Otowa Hospital, Kyoto, Japan

    T. Majima, K. Doi, C. Takagi & M. Shigemoto

  2. Department of Medicine and Clinical Science, Kyoto University Graduate School of Medicine, 54 Shogoin Kawahara-cho Sakyo-ku, Kyoto, 606-8507, Japan

    Y. Komatsu & K. Nakao

  3. Department of Psychosomatic Medicine, Rakuwakai Otowa Hospital, Kyoto, Japan

    A. Fukao

  4. Department of General Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan

    T. Morimoto

  5. Rakuwakai Otowa Hospital, Kyoto, Japan

    J. Corners

Authors
  1. T. Majima
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y. Komatsu
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. K. Doi
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. C. Takagi
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. M. Shigemoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. A. Fukao
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. T. Morimoto
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. J. Corners
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. K. Nakao
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Y. Komatsu.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Majima, T., Komatsu, Y., Doi, K. et al. Negative correlation between bone mineral density and TSH receptor antibodies in male patients with untreated Graves’ disease. Osteoporos Int 17, 1103–1110 (2006). https://doi.org/10.1007/s00198-006-0091-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00198-006-0091-4

Keywords

Search

Navigation