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Changes in bone mass during prolonged subclinical hyperthyroidism due to l-thyroxine treatment: a meta-analysis
Abstract
L-Thyroxine (L-T4) in the treatment of thyroid disease resulting in reduced serum thyrotropin (TSH) has been associated with reduced bone mass and thus the potential risk of premature development of osteoporosis. However, several recent studies have failed to show such a detrimental effect. These disagreements are probably due to only a small number of patients taking part in each study, decreasing the change of finding significant differences and increasing the risk of missing a real difference (type 1 and 2 errors, respectively). We therefore performed a meta-analysis on the available papers (N = 13), in which bone mass was measured in the distal forearm, femoral neck or lumbar spine in a cross-sectional manner in women with suppressed serum TSH due to L-T4 treatment and in a control group. The women were divided according to their pre- and postmenopausal state, because preserved estrogen production plays a protective role against irreversible bone loss. Based on the number of measurements performed on the different sites of the skeleton, a theoretical bone composed of 30.4% distal forearm, 28.8% femoral neck and 40.8% lumbar spine could be constructed in premenopausal women (441 measurements). A premenopausal woman at an average age of 39.6 years and treated with 164 micrograms L-T4/day for 8.5 years, leading to suppressed serum TSH, had 2.67% less bone mass than controls (NS), corresponding to an excess annual bone loss of 0.31% after 8.5 years of treatment (NS). The risk…
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“The results of our meta-analysis reinforce the previous reports that levothyroxine treatment-induced subclinical hyperthyroidism affects BMD reduction in postmenopausal women (16,17,34) for various causes other than DTC were mixed, and the degree of TSH suppression varied considerably.”
From Effect of TSH Suppression Therapy on Bone Mineral Density in Differentiated Thyroid Cancer: A Systematic Review and Meta-analysis (2021) · cites this paper as [17]
In the citing paper
“A previous metaanalysis of 13 cross-sectional studies regarding the effect of induced subclinical hyperthyroidism during long-term levothyroxine treatment on BMD showed no significant differences in premenopausal women, unlike postmenopausal women who displayed significant bone loss compared with the control groups (17).”
From Effect of TSH Suppression Therapy on Bone Mineral Density in Differentiated Thyroid Cancer: A Systematic Review and Meta-analysis (2021) · cites this paper as [17]
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Levothyroxine treatment and occurrence of fracture of the hip
Sheppard, M. C., Holder, R., & Franklyn, J. A. (2002) · Archives of Internal Medicine · doi:10.1001/archinte.162.3.338 · Cited by 56
Changes in Body Composition in Women Following Treatment of Overt and Subclinical Hyperthyroidism
Greenlund, L. J. S., Nair, K. S., & Brennan, M. D. (2008) · Endocrine Practice · doi:10.4158/ep.14.8.973 · Cited by 56
Zingrillo, M., Torlontano, M., Ghiggi, M. R., Frusciante, V., Varraso, A., Liuzzi, A., & Trischitta, V. (2000) · Thyroid · doi:10.1089/thy.2000.10.985 · Cited by 54
Levothyroxine Dose and Fracture Risk According to the Osteoporosis Status in Elderly Women
Ko, Y.-J., Kim, J. Y., Lee, J., Song, H.-J., Kim, J.-Y., Choi, N.-K., & Park, B.-J. (2014) · Journal of Preventive Medicine & Public Health · doi:10.3961/jpmph.2014.47.1.36 · Cited by 47
An Analysis of the Natural Course of Subclinical Hyperthyroidism
Díez, J. J., & Iglesias, P. (2009) · The American Journal of the Medical Sciences · doi:10.1097/maj.0b013e318187e16d · Cited by 45
Papi, G., Pearce, E. N., Braverman, L. E., Betterle, C., & Roti, E. (2005) · The American Journal of Medicine · doi:10.1016/j.amjmed.2005.01.004 · Cited by 39
Schmidt, U., Nygaard, B., Jensen, E. W., Kvetny, J., Jarløv, A., & Faber, J. (2013) · Endocrine Connections · doi:10.1530/ec-12-0064 · Cited by 17
Self-citationHong, A. R., & Kang, H.-C. (2023) · Endocrinology and Metabolism · doi:10.3803/enm.2023.1701 · Cited by 15
Metadata
- Authors
- Faber, J., & Galløe, A. M.
- Affiliations
- Frederiksberg Hospital (DK)
- Corresponding author
- Faber, Jens
- ORCID
- Faber, Jens
- Venue
- European Journal of Endocrinology
- Publisher
- Oxford University Press (OUP)
- Published
- 1994-04
- Volume
- 130
- Issue
- 4
- Pages
- 350-356
- ISSN
- 0804-4643 (ISSN-L)
- 1479-683X
- OpenAlex
- W2159860352
- Cited by
- 377
- References
- 0
- Citations by year
- 2026: 3 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 2 · 2021: 6 · 2020: 7 · 2019: 6 · 2018: 7 · 2017: 9 · 2016: 8 · 2015: 10 · 2014: 12 · 2013: 10 · 2012: 18
- FWCI
- 13.50
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Endocrinology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Surgery › Thyroid and Parathyroid Surgery
- Keywords
- subclinical hyperthyroidism, levothyroxine, bone mass, bone loss, osteoporosis risk, TSH suppression, thyroid hormone replacement, postmenopausal women, premenopausal women, distal forearm, femoral neck, lumbar spine, type II error, power analysis
- MeSH terms
- Adult, Cross-Sectional Studies, Female, Femur, Humans, Hyperthyroidism, Hypothyroidism, Lumbar Vertebrae, Middle Aged, Osteoporosis, Radius, Thyroid Neoplasms, Thyrotropin, Thyroxine, Bone Density, Premenopause, Postmenopause
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