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Restoration of euthyroidism in women with Hashimoto’s thyroiditis changes bone microarchitecture but not estimated bone strength

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Abstract

Purpose

Fracture risk in hypothyroid patients is debated, and since the effects of hypothyroidism on bone microarchitecture and strength are unclarified, we investigated these characteristics by high-resolution peripheral quantitative computed tomography (HR-pQCT).

Methods

Two approaches were used: a cross-sectional control study, comparing 32 hypothyroid women (mean age; 47 ± 12 years) suffering from Hashimoto’s thyroiditis with 32 sex-, age-, and menopause-matched healthy controls; a prospective study, where 27 of the women were reexamined 1 year after restoration of euthyroidism. HR-pQCT of the distal radius and tibia, and dual-energy X-ray absorptiometry (DXA) of the spine and hip were performed. Bone strength was estimated using a finite element analysis (FEA).

Results

Cross-sectional control study: in the radius, total (mean 14.6 ± 29.3% (SD); p = 0.04) and trabecular bone areas (19.8 ± 37.1%, p = 0.04) were higher, and cortical volumetric bone mineral density (vBMD) lower (−2.2 ± 6.5%, p = 0.032) in hypothyroid patients than in controls. All indices of tibia cortical and trabecular vBMD, microarchitecture, and estimated bone strength were similar between groups, as was hip and spine areal BMD (aBMD). Prospective study: in the radius, mean cortical (−0.9 ± 1.8%, p = 0.02) and trabecular (−1.5 ± 4.6%, p = 0.02) vBMD decreased, and cortical porosity increased (18.9 ± 32.7%, p = 0.02). In the tibia, mean total vBMD (−1.1 ± 1.9%, p = 0.01) and cortical vBMD (−0.8 ± 1.4%, p = 0.01) decreased, while cortical porosity (8.2 ± 11.5%, p = 0.002) and trabecular area (0.2 ± 0.6%, p = 0.047) increased. No changes in FEA were detected. Lumbar spine aBMD decreased (−1.3 ± 3.0%, p = 0.04).

Conclusions

Hypothyroidism was associated with an increased trabecular bone area and a lower mineral density of cortical bone in the radius, as assessed by HR-pQCT. Restoration of euthyroidism mainly increased cortical porosity, while estimated bone strength was unaffected.

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References

  1. A. Carle, P. Laurberg, I.B. Pedersen, N. Knudsen, H. Perrild, L. Ovesen, L.B. Rasmussen, T. Jorgensen, Epidemiology of subtypes of hypothyroidism in Denmark. Eur. J. Endocrinol. 154, 21–28 (2006)

    Article  CAS  Google Scholar 

  2. M. Thvilum, F. Brandt, D. Almind, K. Christensen, T.H. Brix, L. Hegedus, Type and extent of somatic morbidity before and after the diagnosis of hypothyroidism. a nationwide register study. PLoS ONE 8, e75789 (2013)

    Article  CAS  Google Scholar 

  3. M. Thvilum, F. Brandt, D. Almind, K. Christensen, T.H. Brix, L. Hegedus, Increased psychiatric morbidity before and after the diagnosis of hypothyroidism: a nationwide register study. Thyroid 24, 802–808 (2014)

    Article  Google Scholar 

  4. T.H. Brix, C. Ferlov-Schwensen, M. Thvilum, L. Hegedus, Death by unnatural causes, mainly suicide, is increased in patients with Hashimoto’s thyroiditis. A nationwide Danish register study. Endocrine 65, 616–622 (2019)

    Article  Google Scholar 

  5. M. Lillevang-Johansen, B. Abrahamsen, H.L. Jorgensen, T.H. Brix, L. Hegedus, Over- and under-treatment of hypothyroidism is associated with excess mortality: a register-based cohort study. Thyroid 28, 566–574 (2018)

    Article  CAS  Google Scholar 

  6. M. Thvilum, F. Brandt, D. Almind, K. Christensen, L. Hegedus, T.H. Brix, Excess mortality in patients diagnosed with hypothyroidism: a nationwide cohort study of singletons and twins. J. Clin. Endocrinol. Metab. 98, 1069–1075 (2013)

    Article  CAS  Google Scholar 

  7. G.R. Williams, J.H.D. Bassett, Thyroid diseases and bone health. J. Endocrinol. Investig. 41, 99–109 (2018)

    Article  CAS  Google Scholar 

  8. B. Abrahamsen, H.L. Jorgensen, A.S. Laulund, M. Nybo, T.H. Brix, L. Hegedus, Low serum thyrotropin level and duration of suppression as a predictor of major osteoporotic fractures-the OPENTHYRO register cohort. J. Bone Miner. Res. 29, 2040–2050 (2014)

    Article  CAS  Google Scholar 

  9. E.F. Eriksen, L. Mosekilde, F. Melsen, Kinetics of trabecular bone resorption and formation in hypothyroidism: evidence for a positive balance per remodeling cycle. Bone 7, 101–108 (1986)

    Article  CAS  Google Scholar 

  10. L. Mosekilde, F. Melsen, Morphometric and dynamic studies of bone changes in hypothyroidism. Acta Pathol. Microbiol. Scand. A 86, 56–62 (1978)

    CAS  PubMed  Google Scholar 

  11. J.M. Coindre, J.P. David, L. Riviere, J.F. Goussot, P. Roger, A. de Mascarel, P.J. Meunier, Bone loss in hypothyroidism with hormone replacement. A histomorphometric study. Arch. Intern. Med. 146, 48–53 (1986)

    Article  CAS  Google Scholar 

  12. J.H. Bassett, G.R. Williams, Role of thyroid hormones in skeletal development and bone maintenance. Endocr. Rev. 37, 135–187 (2016)

    Article  CAS  Google Scholar 

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

    Article  Google Scholar 

  14. P. Vestergaard, J. Weeke, H.C. Hoeck, H.K. Nielsen, J. Rungby, L. Rejnmark, P. Laurberg, L. Mosekilde, Fractures in patients with primary idiopathic hypothyroidism. Thyroid 10, 335–340 (2000)

    Article  CAS  Google Scholar 

  15. B. Abrahamsen, H.L. Jorgensen, A.S. Laulund, M. Nybo, D.C. Bauer, T.H. Brix, L. Hegedus, The excess risk of major osteoporotic fractures in hypothyroidism is driven by cumulative hyperthyroid as opposed to hypothyroid time: an observational register-based time-resolved cohort analysis. J. Bone Miner. Res. 30, 898–905 (2015)

    Article  CAS  Google Scholar 

  16. E.J. Samelson, K.E. Broe, H. Xu, L. Yang, S. Boyd, E. Biver, P. Szulc, J. Adachi, S. Amin, E. Atkinson, C. Berger, L. Burt, R. Chapurlat, T. Chevalley, S. Ferrari, D. Goltzman, D.A. Hanley, M.T. Hannan, S. Khosla, C.T. Liu, M. Lorentzon, D. Mellstrom, B. Merle, M. Nethander, R. Rizzoli, E. Sornay-Rendu, B. Van Rietbergen, D. Sundh, A.K.O. Wong, C. Ohlsson, S. Demissie, D.P. Kiel, M.L. Bouxsein, Cortical and trabecular bone microarchitecture as an independent predictor of incident fracture risk in older women and men in the Bone Microarchitecture International Consortium (BoMIC): a prospective study. Lancet Diabetes Endocrinol. 7, 34–43 (2019)

    Article  Google Scholar 

  17. V.V. Shanbhogue, K. Brixen, S. Hansen, Age- and sex-related changes in bone microarchitecture and estimated strength: a three-year prospective study using HRpQCT. J. Bone Miner. Res. 31, 1541–1549 (2016)

    Article  Google Scholar 

  18. S. Boutroy, M.L. Bouxsein, F. Munoz, P.D. Delmas, In vivo assessment of trabecular bone microarchitecture by high-resolution peripheral quantitative computed tomography. J. Clin. Endocrinol. Metab. 90, 6508–6515 (2005)

    Article  CAS  Google Scholar 

  19. A.J. Burghardt, H.R. Buie, A. Laib, S. Majumdar, S.K. Boyd, Reproducibility of direct quantitative measures of cortical bone microarchitecture of the distal radius and tibia by HR-pQCT. Bone 47, 519–528 (2010)

    Article  Google Scholar 

  20. S. Hansen, E.M. Hauge, J.E. Beck Jensen, K. Brixen, Differing effects of PTH 1-34, PTH 1-84, and zoledronic acid on bone microarchitecture and estimated strength in postmenopausal women with osteoporosis: an 18-month open-labeled observational study using HR-pQCT. J. Bone Miner. Res. 28, 736–745 (2013)

    Article  CAS  Google Scholar 

  21. L. Mosekilde, M.S. Christensen, F. Melsen, N.S. Sorensen, Effect of antithyroid treatment on calcium-phosphorus metabolism in hyperthyroidism. I: chemical quantities in serum and urine. Acta Endocrinol. 87, 743–750 (1978)

    Article  CAS  Google Scholar 

  22. S.P. Polovina, D. Miljic, S. Zivojinovic, N. Milic, D. Micic, V.P. Brkic, The impact of thyroid autoimmunity (TPOAb) on bone density and fracture risk in postmenopausal women. Hormones 16, 54–61 (2017)

    PubMed  Google Scholar 

  23. C. Meier, M. Beat, M. Guglielmetti, M. Christ-Crain, J.J. Staub, M. Kraenzlin, Restoration of euthyroidism accelerates bone turnover in patients with subclinical hypothyroidism: a randomized controlled trial. Osteoporos. Int. 15, 209–216 (2004)

    Article  Google Scholar 

  24. E. Moser, T. Sikjaer, L. Mosekilde, L. Rejnmark, Bone Indices in thyroidectomized patients on long-term substitution therapy with levothyroxine assessed by DXA and HR-pQCT. J. Thyroid Res. 2015, 796871 (2015)

    Article  Google Scholar 

  25. J.D. Pedrera-Zamorano, R. Roncero-Martin, J.F. Calderon-Garcia, M. Santos-Vivas, V. Vera, M. Martinez-Alvarez, P. Rey-Sanchez, Treatment of subclinical hypothyroidism does not affect bone mass as determined by dual-energy X-ray absorptiometry, peripheral quantitative computed tomography and quantitative bone ultrasound in Spanish women. Arch. Med. Sci. 11, 1008–1014 (2015)

    CAS  PubMed  PubMed Central  Google Scholar 

  26. R.P. Babu, A. Christy, A. Hegde, P. Manjrekar, V. D’Souza, Do premenopausal hypothyroid women on levothyroxine therapy need bone status monitoring? Clin. Med. Insights Womens Health 8, 1–6 (2015)

    CAS  PubMed  PubMed Central  Google Scholar 

  27. M. Karimifar, F. Esmaili, A. Salari, A. Kachuei, Z. Faragzadegan, M. Karimifar, Effects of Levothyroxine and thyroid stimulating hormone on bone loss in patients with primary hypothyroidism. J. Res. Pharm. Pract. 3, 83–87 (2014)

    Article  Google Scholar 

  28. R. Balena, M.S. Shih, A.M. Parfitt, Bone resorption and formation on the periosteal envelope of the ilium: a histomorphometric study in healthy women. J. Bone Miner. Res. 7, 1475–1482 (1992)

    Article  CAS  Google Scholar 

  29. E.F. Eriksen, Cellular mechanisms of bone remodeling. Rev. Endocr. Metab. Disord. 11, 219–227 (2010)

    Article  Google Scholar 

  30. G. Mendonca Monteiro de Barros, M. Madeira, L. Vieira Neto, F. de Paula Paranhos Neto, L.M. Carvalho Mendonca, I. Correa Barbosa Lima, R. Corbo, M.L. Fleiuss Farias, Bone mineral density and bone microarchitecture after long-term suppressive levothyroxine treatment of differentiated thyroid carcinoma in young adult patients. J. Bone Miner. Metab. 34, 417–421 (2016)

    Article  Google Scholar 

  31. J. Frolich, S. Hansen, L.A. Winkler, A.K. Andresen, A.P. Hermann, R.K. Stoving, The role of body weight on bone in anorexia nervosa: a HR-pQCT study. Calcif. Tissue Int. 101, 24–33 (2017)

    Article  Google Scholar 

  32. K.D. Frederiksen, S. Hanson, S. Hansen, K. Brixen, J. Gram, N.R. Jorgensen, R.K. Stoving, Bone structural changes and estimated strength after gastric bypass surgery evaluated by HR-pQCT. Calcif. Tissue Int. 98, 253–262 (2016)

    Article  CAS  Google Scholar 

  33. L.J. Melton 3rd, E. Ardila, C.S. Crowson, W.M. O’Fallon, S. Khosla, Fractures following thyroidectomy in women: a population-based cohort study. Bone 27, 695–700 (2000)

    Article  Google Scholar 

  34. M.R. Blum, D.C. Bauer, T.H. Collet, H.A. Fink, A.R. Cappola, B.R. da Costa, C.D. Wirth, R.P. Peeters, B.O. Asvold, W.P. den Elzen, R.N. Luben, M. Imaizumi, A.P. Bremner, A. Gogakos, R. Eastell, P.M. Kearney, E.S. Strotmeyer, E.R. Wallace, M. Hoff, G. Ceresini, F. Rivadeneira, A.G. Uitterlinden, D.J. Stott, R.G. Westendorp, K.T. Khaw, A. Langhammer, L. Ferrucci, J. Gussekloo, G.R. Williams, J.P. Walsh, P. Juni, D. Aujesky, N. Rodondi, C. Thyroid Studies, Subclinical thyroid dysfunction and fracture risk: a meta-analysis. JAMA 313, 2055–2065 (2015)

    Article  Google Scholar 

  35. Z. Stark, R. Savarirayan, Osteopetrosis. Orphanet J. Rare Dis. 4, 5 (2009)

    Article  Google Scholar 

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Acknowledgements

We wish to thank technicians at the Osteoporosis clinic for performing bone scans and in particular Steffanie Christensen for her help in study coordination.

Funding

This study received funding from “The Music Publishers Agnes and Knut Mørk’s Foundation”, from the “Danish Thyroid Federation”, and from research grants at Odense University Hospital.

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Authors and Affiliations

  1. Department of Endocrinology, Odense University Hospital, Odense, Denmark

    Maria Lohman Obling, Pia Nicolaisen, Thomas Heiberg Brix, Kristian Hillert Winther, Laszlo Hegedüs, Anne Pernille Hermann & Steen Joop Bonnema

  2. Department of Clinical Research, University of Southern Denmark, Odense, Denmark

    Maria Lohman Obling, Pia Nicolaisen & Steen Joop Bonnema

  3. Department of Medicine, Hospital of South West Jutland, Esbjerg, Denmark

    Stinus Hansen

  4. Department of Regional Health Research, University of Southern Denmark, Odense, Denmark

    Stinus Hansen

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  1. Maria Lohman Obling
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Correspondence to Steen Joop Bonnema.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the Regional Research Ethics Committee of Southern Denmark (S-2011–0018) and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Obling, M.L., Nicolaisen, P., Brix, T.H. et al. Restoration of euthyroidism in women with Hashimoto’s thyroiditis changes bone microarchitecture but not estimated bone strength. Endocrine 71, 397–406 (2021). https://doi.org/10.1007/s12020-020-02398-y

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