'Chronic hyperthyroidism may increase the risk of fractures, particularly in older people and postmenopausal women who already have a higher risk of osteoporosis and fractures', write Marci R. Turner, from the Department of Medicine, University of Toronto, Toronto, Ontario, Canada, and colleagues. 'Studies have found that higher compared with lower doses of levothyroxine replacement and subclinical hyperthyroidism are associated with a lower bone density and bone quality, as measured by ultrasonography. An excess of thyroid hormone can also affect neuromuscular function and muscle strength and increase the risk of arrhythmias and falls, which can raise the risk of fractures independent of bone density.'
Levothyroxine dose and risk of fractures in older adults: nested case-control study
Marci R Turner, Ximena Camacho, Hadas D Fischer, Peter C Austin, Geoff M Anderson, Paula A Rochon, Lorraine L Lipscombe
Is it safe for patients taking thyroxine to have a low but not suppressed serum TSH concentration?
Graham Leese & Robert Flynn
Dundee, United Kingdom
Scherp ingestelde thyroxinesubstitutie bij hypothyreoïdie leidt niet tot verhoogde comorbiditeit
Maarten R. Soeters en Marcel T. Twickler, Academisch Medische Centrum Amsterdam
Ned Tijdschr Geneeskd. 2010;154:A1654
Goal of the studyThe goal of the study was to quantify the effect of levothyroxine dose on fracture risk in older adults. Using population-based health databases in Ontario, Canada, the investigators identified 213,511 adults 70 years or older who were prescribed levothyroxine between April 1, 2002, and March 31, 2007. Follow-up for fractures of the wrist or forearm, shoulder or upper arm, thoracic spine, lumbar spine and pelvis, hip or femur, or lower leg or ankle, continued until March 31, 2008 (mean duration of follow-up, 3.8 years).
Main endpoint was fracture risk as a function of levothyroxine useCase patients, defined as cohort members who were hospitalized for any fracture, were matched with up to 5 control patients within the cohort who had not yet had a fracture. The main study endpoint was fracture risk as a function of levothyroxine use, characterized as current, recent, past, or remote. For current levothyroxine users, the risk was compared among those prescribed high, medium, and low cumulative doses of levothyroxine in the year before fracture. Of 22,236 cohort members (10.4%) who had a fracture during follow-up, 18,108 (88%) were women.
The risk for fracture was significantly higher for current vs remote levothyroxine use, even after adjustment for numerous risk factors. Compared with low cumulative doses, high and medium cumulative doses were associated with a significantly increased fracture risk among current users).
Strong dose-response relation'Among adults aged 70 or more, current levothyroxine treatment was associated with a significantly increased risk of fracture, with a strong dose-response relation', the study authors write. 'Ongoing monitoring of levothyroxine dose is important to avoid overtreatment in this population.'
Limitations of this study include lack of laboratory and radiologic data, such as serum thyroid stimulating hormone levels and radiology reports, inability to verify the indication for levothyroxine treatment, and possible misclassification and selection bias.