Douglas C. Bauer, MD
What is the relation between levothyroxine dose and risk for fractures in older adults?
Population-based, nested case–control study, with linkage of a provincial drug benefits database, a national ambulatory care reporting system, and discharge abstract databases. Mean follow-up was 3.8 years.
Cases and controls were identified from a cohort of 213 511 Ontario residents 70 to 105 years of age (mean age 82 y) with ≥ 1 prescription for levothyroxine between 1 Apr 2002 and 31 Mar 2007. Exclusion criteria were dialysis or palliative care ≤ 6 months before study entry and a history of thyroid cancer or previous hyperthyroidism. Cases (n = 22 236) had ≥ 1 relevant fracture during follow-up. Each index case was matched with ≤ 5 control patients who were still at risk for fracture on the index date (n = 109 373).
Current (prescription included index date plus 14 d), recent (prescription ended 15 to 180 d before index date), or remote levothyroxine use (prescription ended > 180 d before index date). Current users were categorized by cumulative daily dose in the year before the index date: low dose (< 0.044 mg/d), medium dose (0.044 to 0.093 mg/d), or high dose (> 0.093 mg/d).
Any fracture (first visit to an emergency department or hospitalization for any fracture of the wrist, forearm, shoulder, upper arm, thoracic spine, lumbar spine and pelvis, hip, femur, lower leg, or ankle) except those resulting from seizure, trauma, bone cancer, multiple myeloma, or disease.
10% of persons (n = 22 236) had ≥ 1 fracture; 27% (n = 58 063) died during follow-up. Current and recent levothyroxine use was associated with greater risk for fracture than remote use (Table). In current users, higher levothyroxine doses were associated with higher risk for fractures (Table).
In older patients, current and recent use of levothyroxine was associated with increased risk for fractures, with a strong dose–response relation.
Association between levothyroxine use and fractures in older patients*
*CI defined in Glossary.
†Current use = prescription included index date plus 14 d; recent use = prescription ended 15 to 180 d before index date; remote use = prescription ended > 180 d before index date.
‡Adjusted for fifth of neighborhood income, Charlson comorbidity index, history of health service use at index date, previous fractures, risk factors for fracture, comorbid conditions ≤ 5 y before index date, and use of other prescription drugs ≤ 1 y before index date.
Bauer DC. Current use of levothyroxine was associated with increased risk for fractures in patients ≥ 70 years of age. Ann Intern Med. ;155:JC3–5. doi: 10.7326/0003-4819-155-6-201109200-02005
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Published: Ann Intern Med. 2011;155(6):JC3-5.
Endocrine and Metabolism, Geriatric Medicine, Metabolic Bone Disorders, Thyroid Disorders.
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Print ISSN: 0003-4819 | Online ISSN: 1539-3704
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