Thyroid-stimulating Hormone Suppressive Therapy and Osteoporosis: A Review and Meta-analysis
Keywords:
TSH suppression, differentiated thyroid carcinoma, osteoporosis
Abstract
Background: Osteoporosis is a common morbid and mortal disease; thyroidstimulating hormone (TSH) suppression is the state-of-the-art for postoperative
differentiated thyroid carcinoma (DTC). However, its association with osteoporosis
remains controversial. The current meta-analysis assessed the relationship between
TSH suppressive therapy and osteoporosis among patients with DTC.
Methods: We systematically searched PubMed, Cochrane Library, EBSCO, and the
first 100 articles in Google Scholar for relevant articles published in English during
the period from 2008 to November 2020. The keywords differentiated thyroid cancer,
TSH suppression, osteoporosis, low bone mineral density, osteopenia; fracture risk,
disturbed bone micro-architecture, bone loss, and trabecular bone were used. One
hundred and eighty-four articles were retrieved; of them, fourteen were eligible and
met the inclusion and exclusion criteria. The RevMan system was used for data analysis.
Results: We included 36 cohorts from 15 studies, the studies showed higher
osteoporosis and osteopenia among TSH-suppressed women, odd ratio, 2.64, 1.48–
4.68 and 2.23, 0.33–14.96, respectively. High heterogeneity was observed, I2 = 68%
and 96%, respectively). The sub-analysis showed a lower bone mineral density among
postmenopausal women at both femoral neck and lumbar spines, odds ratio, –0.02,
–0.07 to 0.04, and –0.03, –0.06 to 0.01, I2 for heterogeneity, 69%, and 51% in contrast
to men and premenopausal women who showed normal or higher bone density.
Conclusion: TSH suppression for DTC was associated with osteoporosis and
osteopenia among postmenopausal women but not premenopausal women or men.
Studies focusing on trabecular bone scores are needed.
References
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and fractures in patients with thyroid cancer: A case-control study in U.S. veterans.
Oncologist, vol. 24, no. 9, pp. 1166–1173.
[29] Biondi, B. and Cooper, D. S. (2010). Benefits of thyrotropin suppression versus the
risks of adverse effects in differentiated thyroid cancer. Thyroid, vol. 20, no. 2, pp.
135–146.
[30] Soydal, Ç., Özkan, E., Nak, D., et al. (2019). Risk factors for predicting osteoporosis
in patients who receive thyrotropin suppressive levothyroxine treatment for
differentiated thyroid carcinoma. Molecular Imaging And Radionuclide Therapy, vol.
28, no. 2, pp. 69–75.
[31] Hawkins Carranza, F., Guadalix Iglesias, S., Luisa De Mingo Domínguez, M., et al.
(2020).Trabecular bone deterioration in differentiated thyroid cancer: Impact of longterm TSH suppressive therapy. Cancer Medicine, vol. 9, no. 16, pp. 5746–5755.
prognosis of thyroid carcinoma. Nuklearmedizin, vol. 58, no. 2, pp. 86–92.
[2] Sekkath Veedu, J., Wang, K., Lei, F., et al. (2018). Trends in thyroid cancer incidence
in India. Journal of Clinical Oncology, vol. 36, no. 15, pp. 18095–18095.
[3] Krishnaja, K. S., Rallapeta, R. P., Shaik, M., et al. (2019). Papillary carcinoma thyroid metastases presenting as thyrotoxicosis post thyroidectomy - A case report.
Indian Journal of Nuclear Medicine, vol. 34, no. 2, pp.134–136.
[4] Papaleontiou, M., Chen, D. W., Banerjee, M., et al. (2022). Thyrotropin suppression
for papillary thyroid cancer: A physician survey study. Thyroid, vol. 31, no. 9, pp.
1383–1390.
[5] Soydal, Ç., Özkan, E., Nak, D., et al. (2019). Risk factors for predicting osteoporosis in
patients who receive thyrotropin suppressive levothyroxine treatment for differentiated thyroid carcinoma. Molecular Imaging and Radionuclide Therapy, vol. 28, no.
2, pp. 69–75.
[6] Bai, Y., Huo, Y., Yu, F., et al. (2017). Effect of hypoparathyroid on bone mineral density
of lumber spine in postmenopausal women with differentiated thyroid cancinoma.
Hellenic Journal of Nuclear Medicine, vol. 20, pp.7–13.
[7] Freudenthal, B. and Williams, G. R. (2017). Thyroid stimulating hormone suppression in the long-term follow-up of differentiated thyroid cancer. Clinical Oncology
(Royal College of Radiologists), vol. 29, no.5, pp. 325–328.
[8] Ku, E. J., Yoo, W. S., Lee, E. K., et al. (2022). Effect of TSH suppression therapy
on bone mineral density in differentiated thyroid cancer: A systematic review and
meta-analysis. Journal of Clinical Endocrinology and Metabolism, vol. 106, no. 12,
pp. 3655–3667.
[9] Müller, C. G., Bayley, T. A., Harrison, J. E., et al. (1995). Possible limited bone loss with
suppressive thyroxine therapy is unlikely to have clinical relevance. Thyroid, vol. 5,
no. 2, pp. 81–87.
[10] Wang, L. Y., Smith, A. W., Palmer, F. L., et al. (2015). Thyrotropin suppression increases
the risk of osteoporosis without decreasing recurrence in ATA low- and intermediaterisk patients with differentiated thyroid carcinoma. Thyroid, vol. 25, no. 3, pp. 300–
307.
[11] de Melo, T. G., da Assumpção, L. V., Santos Ade, O., et al. (2015). Low BMI and low
TSH value as risk factors related to lower bone mineral density in postmenospausal
women under levothyroxine therapy for differentiated thyroid carcinoma. Thyroid
Research, vol. 2, no. 8, p. 7.
[12] Mazziotti, G., Formenti, A. M., Frara, S., et al. (2018). High prevalence of radiological
vertebral fractures in women on thyroid-stimulating hormone-suppressive therapy
for thyroid carcinoma. Journal of Clinical Endocrinology and Metabolism, vol. 103,
no. 3, pp. 956–964.
[13] Zhang, P., Xi, H., and Yan, R. (2018). Effects of thyrotropin suppression on lumbar bone
mineral density in postmenopausal women with differentiated thyroid carcinoma.
OncoTargets and Therapy, vol. 9, no. 11, pp. 6687–6692
[14] Vera, L., Gay, S., Campomenosi, C., et al. (2016). Ten-year estimated risk of
bone fracture in women with differentiated thyroid cancer under TSH-suppressive
levothyroxine therapy. Endokrynologia Polska, vol. 67, no. 4, pp. 350–358.
[15] De Mingo Dominguez, M. L., Guadalix Iglesias, S., Martin-Arriscado Arroba, C., et al.
(2018). Low trabecular bone score in postmenopausal women with differentiated thyroid carcinoma after long-term TSH suppressive therapy. Endocrine, vol. 62, no. 1,
pp. 166–173.
[16] Franklyn, J. A., Betteridge, J., Daykin, J., et al. (1992). Long-term thyroxine treatment
and bone mineral density. Lancet, vol. 340, no. 8810, pp. 9–13.
[17] Fujiyama, K., Kiriyama, T., Ito, M., et al. (1995). Suppressive doses of thyroxine do not
accelerate age-related bone loss in late postmenopausal women. Thyroid, vol. 5,
no. 1, pp. 13–17.
[18] Kung, A. W., Lorentz, T., and Tam, S. C. (1993). Thyroxine suppressive therapy
decreases bone mineral density in post-menopausal women. Clinical Endocrinology,
vol. 39, no. 5, pp. 535–540.
[19] Moon, J. H., Jung, K. Y., Kim, K. M., et al. (2016). The effect of thyroid stimulating
hormone suppressive therapy on bone geometry in the hip area of patients
with differentiated thyroid carcinoma. Bone, vol. 83, pp. 104–110.
[20] Reverter, J. L., Holgado, S., Alonso, N., et al. (2005). Lack of deleterious effect on
bone mineral density of long-term thyroxine suppressive therapy for differentiated
thyroid carcinoma. Endocrine-Related Cancer, vol. 12, no. 4, pp. 973–981.
[21] Tournis, S., Antoniou, J. D., Liakou, C. G., et al. (2015). Volumetric bone mineral
density and bone geometry assessed by peripheral quantitative computed
tomography in women with differentiated thyroid cancer under TSH suppression.
Clinical Endocrinology, vol. 82, no. 2, pp. 197–204.
[22] Goerres, G., Theiler, R., and Müller-Brand, J. (1998). Interfemur variation of bone
mineral density in patients receiving high-dose thyroxin therapy. Calcified Tissue
International, vol. 63, no. 2, pp. 98–101.
[23] Rozenberg, S., Bruyère, O., Bergmann, P., et al. (2020). How to manage osteoporosis
before the age of 50. Maturitas, vol. 138, pp. 14–25.
[24] Langdahl, B. L. (2017). Osteoporosis in premenopausal women. Current Opinion in
Rheumatology, vol. 29, no. 4, pp. 410–415.
[25] Ku, E. J., Yoo, W. S., Lee, E. K., et al. (2022). Effect of TSH suppression therapy
on bone mineral density in differentiated thyroid cancer: A systematic review and
meta-analysis. Journal of Clinical Endocrinology and Metabolism, vol. 106, no. 12,
pp. 3655–3667.
[26] Kwak, D., Ha, J., Won, Y., et al. Effects of thyroid-stimulating hormone suppression
after thyroidectomy for thyroid cancer on bone mineral density in postmenopausal
women: a systematic review and meta-analysis. BMJ Open, vol. 11, no. 5, p. 043007.
[27] Haymart, M. R., Reyes-Gastelum, D., Caoili, E., et al. (2020). The relationship between
imaging and thyroid cancer diagnosis and survival. Oncologist, vol. 25, no. 9, pp.
765–771.
[28] Papaleontiou, M., Banerjee, M., Reyes-Gastelum, D., et al. (2019). Risk of osteoporosis
and fractures in patients with thyroid cancer: A case-control study in U.S. veterans.
Oncologist, vol. 24, no. 9, pp. 1166–1173.
[29] Biondi, B. and Cooper, D. S. (2010). Benefits of thyrotropin suppression versus the
risks of adverse effects in differentiated thyroid cancer. Thyroid, vol. 20, no. 2, pp.
135–146.
[30] Soydal, Ç., Özkan, E., Nak, D., et al. (2019). Risk factors for predicting osteoporosis
in patients who receive thyrotropin suppressive levothyroxine treatment for
differentiated thyroid carcinoma. Molecular Imaging And Radionuclide Therapy, vol.
28, no. 2, pp. 69–75.
[31] Hawkins Carranza, F., Guadalix Iglesias, S., Luisa De Mingo Domínguez, M., et al.
(2020).Trabecular bone deterioration in differentiated thyroid cancer: Impact of longterm TSH suppressive therapy. Cancer Medicine, vol. 9, no. 16, pp. 5746–5755.
