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Risk for Fracture in Women with Low Serum Levels of Thyroid-Stimulating Hormone
Abstract
BACKGROUND: Biochemical evidence of hyperthyroidism may be associated with low bone mass, particularly in older postmenopausal women, but no prospective studies of thyroid function and subsequent fracture risk have been done. OBJECTIVE: To examine the association between low levels of thyroid-stimulating hormone (TSH) and fracture in older women. DESIGN: Prospective cohort study with case-cohort sampling. SETTING: Four clinical centers in the United States. PATIENTS: 686 women older than 65 years of age from a cohort of 9704 women recruited from population-based listings between 1986 and 1988. MEASUREMENTS: Baseline assessment of calcaneal bone mass, spine radiography, and history of thyroid disease. Spine radiography was repeated after a mean follow-up of 3.7 years; nonspine fractures were centrally adjudicated. Thyroid-stimulating hormone was measured in sera obtained at baseline from 148 women with new hip fractures, 149 women with new vertebral fractures, and a subsample of 398 women randomly selected from the cohort. RESULTS: After adjustment for age, history of previous hyperthyroidism, self-rated health, and use of estrogen and thyroid hormone, women with a low TSH level (0.1 mU/L) had a threefold increased risk for hip fracture (relative hazard, 3.6 [95% CI, 1.0 to 12.9]) and a fourfold increased risk for vertebral fracture (odds ratio, 4.5 [CI, 1.3 to 15.6]) compared with women who had normal TSH levels (0.5 to 5.5 mU/L). After adjustment for TSH level, a history of hyperthyroidism was associated with a twofold increase in hip fracture (relative hazard, 2.2 [CI, 1.0 to 4.4]), but use of thyroid hormone itself was not associated with increased risk for hip fracture (relative hazard, 0.5 [CI, 0.2 to 1.3]). CONCLUSIONS: Women older than 65 years of age who have low serum TSH levels, indicating physiologic hyperthyroidism, are at increased risk for new hip and vertebral fractures. Use of thyroid hormone itself does not increase risk for fracture if TSH levels are normal.
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“Conflicting results have also been reported regarding the risk of fractures [63,105,106] .”
From The 2015 European Thyroid Association Guidelines on Diagnosis and Treatment of Endogenous Subclinical Hyperthyroidism (2015) · cites this paper as [105]
In the citing paper
“If TH levels are elevated in the long term, patients will have a higher risk of atrial fibrillation, osteoporosis, and fracture (169, 170).”
From Levothyroxine: conventional and novel drug delivery formulations. (2023) · cites this paper as [169]
In the citing paper
“Evidence in the clinical literature suggests that there is an increased risk of bone fracture in individuals who are exposed to supratherapeutic doses of exogenous thyroid hormone for extended periods of time.”
From Diagnosis and management of treatment-refractory hypothyroidism: an expert consensus report (2017) · cites this paper as [96]
In the citing paper
“Increased bone loss and risk of fracture was also found in euthyroid postmenopausal women with fT4 and/or fT3 levels within the upper normal range and in older adults with low TSH (104–106).”
From Levothyroxine therapy in elderly patients with hypothyroidism (2021) · cites this paper as [105]
In the citing paper
“A number of population-based studies have reported that certain groups of subjects with SH have increased fracture rates, including all adults (407), postmenopausal women (408), men (409), or subjects who progress to overt hyperthyroidism over time (391).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [408]
In the citing paper
“Some of these studies re-ported increased risks of overall mortality in older subjects (380,429), cardiovascular events (391), heart failure (381), and atrial fibrillation in all subjects (401) or in older subjects (384), and vertebral fractures in older women (408).”
From 2016 American Thyroid Association Guidelines for Diagnosis and Management of Hyperthyroidism and Other Causes of Thyrotoxicosis (2016) · cites this paper as [408]
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Metadata
- Authors
- Bauer, D. C., Ettinger, B., Nevitt, M. C., Stone, K. L., & for the Study of Osteoporotic Fractures Research Group
- Affiliations
- University of Minnesota (US)
- Venue
- Annals of Internal Medicine
- Publisher
- American College of Physicians
- Published
- 2001-04-03
- Volume
- 134
- Issue
- 7
- Pages
- 561-568
- ISSN
- 0003-4819 (ISSN-L)
- 1539-3704
- OpenAlex
- W1992692011
- Cited by
- 467
- References
- 53
- Citations by year
- 2026: 7 · 2025: 8 · 2024: 9 · 2023: 16 · 2022: 15 · 2021: 17 · 2020: 15 · 2019: 12 · 2018: 22 · 2017: 19 · 2016: 23 · 2015: 16 · 2014: 30 · 2013: 23 · 2012: 35
- FWCI
- 14.33
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Annals of Internal Medicine (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5k08ag000629-03)
- National Institute on Aging (K08-AG-00629)
- Topics
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Thyroid Disorders and Treatments
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Menopause: Health Impacts and Treatments
- Keywords
- thyroid-stimulating hormone, fracture risk, hyperthyroidism, hip fracture, vertebral fractures, postmenopausal women, older women, bone mass, thyroid hormone replacement, osteoporosis
- MeSH terms
- Aged, Follow-Up Studies, Hip Fractures, Humans, Hyperthyroidism, Male, Prospective Studies, Risk Factors, Thyroid Hormones, Thyrotropin, Bone Density, Estrogen Replacement Therapy, Case-Control Studies, Spinal Fractures, Postmenopause, Fractures, Bone
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