High Prevalence of Radiological Vertebral Fractures in Women on Thyroid-Stimulating Hormone–Suppressive Therapy for Thyroid Carcinoma
Open accessAbstract
Context: Bone loss and nonvertebral fractures have been reported in patients with differentiated thyroid carcinoma (DTC) undergoing thyroid-stimulating hormone (TSH) suppressive therapy. Radiological vertebral fractures (VFs) are an early and clinically crucial marker of bone fragility. Objective and Design: A cross-sectional study to evaluate the prevalence and determinants of radiological VFs in women receiving l-thyroxine (L-T4) therapy for DTC. Patients and Interventions: A total of 179 consecutive women (median age, 59 years; n = 178 postmenopausal) who had undergone thyroidectomy for DTC and were currently receiving L-T4 were evaluated for radiological VFs and bone mineral density (BMD). There were three TSH target levels [<0.5 mU/L, group 1 (n = 83); 0.5 to 1.0 mU/L, group 2 (n = 50); >1.0 mU/L, group 3 (n = 46)]. Results: VFs were found in 51 patients (28.5%), with significantly (P < 0.001) higher prevalence in group 1 (44.6%) as compared with group 2 (24.0%) and group 3 (4.3%). VF prevalence was not significantly different among patients in group 1 with normal BMD, osteopenia, or osteoporosis, whereas in groups 2 and 3, VFs were more frequent in patients with osteoporosis than in those with either osteopenia or normal BMD. In the whole population, VFs were significantly and independently associated with TSH level <1.0 mU/L; densitometric diagnosis of osteoporosis at lumbar spine, femoral neck, or total hip; age of patients; and duration of L-T4 therapy. Conclusion: The prevalence of VFs was high in women with DTC who were undergoing long-term, suppressive L-T4 therapy.
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Overtreatment of LT4 is associated with adverse effects on bone.
“And overtreatment of LT4 is associated with adverse effects on bone [14, 15].”
From Effects of levothyroxine therapy on bone and mineral metabolism in hypothyroidism: a systematic review and meta-analysis (2025) · cites this paper as [14]
Women with differentiated thyroid carcinoma treated with long-term LT4 suppression therapy have a higher prevalence of vertebral fractures.
“Mazziotti et al. [14] demonstrated that women with differentiated thyroid carcinoma treated with long-term LT4 suppression therapy have a higher prevalence of vertebral fractures.”
From Effects of levothyroxine therapy on bone and mineral metabolism in hypothyroidism: a systematic review and meta-analysis (2025) · cites this paper as [14]
Radiological vertebral fractures in women with differentiated thyroid carcinoma receiving post-surgical levothyroxine treatment are significantly and independently associated with duration of L-T4 therapy.
“fractures in women with differentiated thyroid carcinoma receiving post-surgical levothyroxine treatment were significantly and independently associated with TSH <1.0 mU/l, age of patients, duration of L-T4 therapy and densitometric diagnosis of osteoporosis at any skeletal site (109).”
From Levothyroxine therapy in elderly patients with hypothyroidism (2021) · cites this paper as [109]
Radiological vertebral fractures in women with differentiated thyroid carcinoma receiving post-surgical levothyroxine treatment are significantly and independently associated with TSH <1.0 mU/l.
“fractures in women with differentiated thyroid carcinoma receiving post-surgical levothyroxine treatment were significantly and independently associated with TSH <1.0 mU/l, age of patients, duration of L-T4 therapy and densitometric diagnosis of osteoporosis at any skeletal site (109).”
From Levothyroxine therapy in elderly patients with hypothyroidism (2021) · cites this paper as [109]
Radiological vertebral fractures in women with differentiated thyroid carcinoma receiving post-surgical levothyroxine treatment are significantly and independently associated with age of patients.
“fractures in women with differentiated thyroid carcinoma receiving post-surgical levothyroxine treatment were significantly and independently associated with TSH <1.0 mU/l, age of patients, duration of L-T4 therapy and densitometric diagnosis of osteoporosis at any skeletal site (109).”
From Levothyroxine therapy in elderly patients with hypothyroidism (2021) · cites this paper as [109]
Radiological vertebral fractures in women with differentiated thyroid carcinoma receiving post-surgical levothyroxine treatment are significantly and independently associated with densitometric diagnosis of osteoporosis at any skeletal site.
“fractures in women with differentiated thyroid carcinoma receiving post-surgical levothyroxine treatment were significantly and independently associated with TSH <1.0 mU/l, age of patients, duration of L-T4 therapy and densitometric diagnosis of osteoporosis at any skeletal site (109).”
From Levothyroxine therapy in elderly patients with hypothyroidism (2021) · cites this paper as [109]
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Sousa, B. É. C. A., Silva, B. C. C., Guidotti, T. D. O., Pires, M. C., Soares, M. M. S., & Kakehasi, A. M. (2021) · Journal of Endocrinological Investigation · doi:10.1007/s40618-021-01537-0 · Cited by 12 · see citing works
Li, X., Zhang, T., Zhang, H., Liu, S., & Tian, L. (2025) · BMC Endocrine Disorders · doi:10.1186/s12902-024-01819-7 · Cited by 10 · see citing works
Update on vertebral fractures in pituitary diseases: from research to clinical practice
Carrone, F., Ariano, S. A., Piccini, S., Milani, D., Mirani, M., Balzarini, L., Lania, A. G., & Mazziotti, G. (2021) · HORMONES · doi:10.1007/s42000-021-00275-5 · Cited by 10 · see citing works
Kim, J., Han, K., Jung, J., Ha, J., Jeong, C., Heu, J.-Y., Lee, S., Lee, J., Lim, Y., Kim, M. K., et al. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1173781 · Cited by 9 · see citing works
Cellini, M., Piccini, S., Ferrante, G., Carrone, F., Olivetti, R., Cicorella, N., Aroldi, M., Pini, D., Centanni, M., Lania, A. G., et al. (2020) · Journal of Endocrinological Investigation · doi:10.1007/s40618-020-01237-1 · Cited by 8 · see citing works
CACA guidelines for holistic integrative management of thyroid cancer
Ge, M., Gao, M., Cheng, R., Chen, X., Guan, H., Lin, Y., Liu, S., Wang, Y., Zheng, C., & Zheng, X. (2022) · Holistic Integrative Oncology · doi:10.1007/s44178-022-00015-8 · Cited by 7 · see citing works
Frara, S., Uygur, M. M., Bolamperti, F. M., di Filippo, L., Doga, M., Ferrari, F., Losa, M., Mortini, P., & Giustina, A. (2024) · Pituitary · doi:10.1007/s11102-024-01394-z · Cited by 7 · see citing works
Vitamin D and hip protectors in osteosarcopenia: a combined hip fracture preventing approach
Giustina, A., & Giustina, A. (2024) · Reviews in Endocrine and Metabolic Disorders · doi:10.1007/s11154-024-09907-8 · Cited by 7 · see citing works
Thewjitcharoen, Y., Chatchomchuan, W., Wanothayaroj, E., Butadej, S., Nakasatien, S., Krittiyawong, S., Rajatanavin, R., & Himathongkam, T. (2024) · Medicine · doi:10.1097/md.0000000000038290 · Cited by 6 · see citing works
Hong, A. R., Ahn, H. Y., Kim, B. K., Ahn, S. H., Park, S. Y., Kim, M., Lee, J., Cho, S. W., & Kang, H. (2022) · International Journal of Thyroidology · doi:10.11106/ijt.2022.15.1.1 · Cited by 5 · see citing works
Carranza, F. H., Arroba, C. M., Álvarez, M. B. L., Librizzi, S., & Diaz‐Guerra, G. M. (2024) · Diagnostics · doi:10.3390/diagnostics14090868 · Cited by 4 · see citing works
TSH-secreting pituitary adenomas and bone
Losa, M., Vassallo, A., Frara, S., Mortini, P., & Giustina, A. (2024) · Pituitary · doi:10.1007/s11102-024-01467-z · Cited by 4 · see citing works
Clinical Implementation of Bone Regeneration and Maintenance
Barbeck, M., Rosenberg, N., Kačarević, Ž. P., Jung, O., & Rider, P. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.85328 · Cited by 4 · see citing works
Teng, W. (2021) · Springer eBooks · doi:10.1007/978-3-030-63277-9_8 · Cited by 3 · see citing works
Gender, FT4 levels, T stage, and BMI as predictors of TSH levels in thyroid cancer patients
Zhang, S., Niu, S., & Zhou, L. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1422464 · Cited by 3 · see citing works
Song, X., Zhi, X., & Qian, L. (2025) · Endocrine · doi:10.1007/s12020-025-04223-w · Cited by 2 · see citing works
Jin, M., & Yoo, W. S. (2025) · Journal of Bone Metabolism · doi:10.11005/jbm.25.869 · Cited by 1 · see citing works
Subclinical thyrotoxicosis and bone
Doga, M., Formenti, A. M., Frara, S., Memo, M., Giustina, A., & Mazziotti, G. (2018) · Current Opinion in Endocrine and Metabolic Research · doi:10.1016/j.coemr.2018.03.002 · Cited by 1 · see citing works
Thyroid Disorders and Osteoporosis
Ale, A. O. (2019) · IntechOpen eBooks · doi:10.5772/intechopen.87129 · Cited by 1 · see citing works
Osteoporosis and arthropathy in functioning pituitary tumors
Claessen, K. M. J. A., Appelman‐Dijkstra, N. M., & Biermasz, N. R. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-819949-7.00019-6 · Cited by 1 · see citing works
Tournis, S., Trovas, G., Triantafyllopoulos, I. Κ., & Balanika, A. P. (2018) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2018-01638 · Cited by 1 · see citing works
Risks of Thyroid Hormone Suppression for Differentiated Thyroid Cancer in the Elderly
Yalamanchi, S., & Cooper, D. K. C. (2015) · Springer eBooks · doi:10.1007/978-3-319-22401-5_18
Primary hyperparathyroidism in prostate cancer: guilty or not guilty?
Mazziotti, G., Frara, S., & Mosca, A. (2018) · Endocrine · doi:10.1007/s12020-018-1632-2
Fragilità scheletrica nel paziente con carcinoma differenziato della tiroide
Cellini, M., Ariano, S. A., Vescini, F., Grimaldi, F., Lania, A. G., & Mazziotti, G. (2021) · L Endocrinologo · doi:10.1007/s40619-021-00866-9
Research Activities Calendar - Research Division
shecanip (2011)
Thyroid Disorders and Bone Disease
Watts, L. M., Freudenthal, B., Bassett, J. H. D., & Williams, G. R. (2022) · doi:10.1093/med/9780198870197.003.0089
Clinical Assessment and Systemic Manifestations of Thyrotoxicosis
Marcocci, C., & Cetani, F. (2022) · doi:10.1093/med/9780198870197.003.0054
Risks of Thyroid Hormone Suppression for Differentiated Thyroid Cancer in the Elderly
Yalamanchi, S., & Cooper, D. S. (2020) · Springer eBooks · doi:10.1007/978-3-030-61919-0_17
Thyroid-stimulating Hormone Suppressive Therapy and Osteoporosis: A Review and Meta-analysis
Mirghani, H. O., & Altowigri, A. (2022) · Sudan Journal of Medical Sciences · doi:10.18502/sjms.v17i2.11460
Yavuz, D. G., Yazan, C. D., Hekimsoy, Z., Aydın, K., Gökkaya, N., Ersoy, C., Aydoğan, B. İ., Akalın, A., Topaloğlu, Ö., DİLEKÇİ, E. N. A., et al. (2026) · Endocrine Connections · doi:10.1530/ec-26-0103
Deng, T., Zhang, W., Zhang, Y., Zhang, M., Huan, Z., Yu, C., Zhang, X., Wang, Y., & Xu, J. (2021) · Figshare · doi:10.6084/m9.figshare.14228503
TSH suppression attenuates the early efficacy of zoledronic acid in osteoporosis
Liu, Y., Zhang, Y., Li, M., Qian, Y., Zhang, Z., Jiang, Z., & Qu, W. (2026) · Archives of Osteoporosis · doi:10.1007/s11657-026-01672-2
Candemir, B., Akın, Ş., Candemir, M., & Gülçelik, N. E. (2026) · Thyroid · doi:10.1177/10507256261442839
Jay, M., Esttaifo, F., Reszetnik, G., GOENS, C., WILSON, E., Lipscombe, L. L., & Eskander, A. (2026) · Thyroid · doi:10.1177/10507256261499041
- Authors
- Mazziotti, G., Formenti, A. M., Frara, S., Olivetti, R., Banfi, G., Memo, M., Maroldi, R., Giubbini, R., & Giustina, A.
- Affiliations
- Endocrine Unit, Azienda Socio-Sanitaria Territoriale, Mantua, Italy
- University of Brescia (IT)
- Vita-Salute San Raffaele University (IT)
- Corresponding author
- Giustina, Andrea
- ORCID
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2017-11-07
- Volume
- 103
- Issue
- 3
- Pages
- 956-964
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2767543492
- Cited by
- 57
- References
- 54
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 5 · 2023: 4 · 2022: 5 · 2021: 12 · 2020: 6 · 2019: 5 · 2018: 9 · 2015: 1
- FWCI
- 6.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Institutional Research Information System (Università degli Studi di Brescia) (submittedVersion)
- Archivio Istituzionale della Ricerca - Università Vita-Salute San Raffaele (submittedVersion)
- Funders
- Abbott Diagnostics
- Topics
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Cancer Diagnosis and Treatment
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Keywords
- vertebral fractures, differentiated thyroid cancer, L-thyroxine therapy, bone loss, osteoporosis, bone mineral density, postmenopausal women, fracture prevalence, fracture risk factors
- MeSH terms
- Adult, Aged, Aged, 80 and over, Cross-Sectional Studies, Drug Administration Schedule, Humans, Male, Middle Aged, Radiography, Thyroid Neoplasms, Thyroidectomy, Thyrotropin, Thyroxine, Bone Density, Osteoporosis, Postmenopausal, Spinal Fractures, Chemotherapy, Adjuvant, Osteoporotic Fractures
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