dinsdag 3 april 2012

Dosis levothyroxine en de kans op botbreuken bij ouderen

Levothyroxine dose is linked to fracture risk in older adults, according to the results of a nested case-control study reported online April 28, 2011 in the BMJ.

'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
BMJ 2011;342:d2238

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 study

The 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 use

Case 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.

Comparison with other studies

Previous studies examining the association between levothyroxine replacement and fracture risk have yielded inconsistent conclusions and have not tackled the role of levothyroxine dose in this relation. Studies largely in younger people and postmenopausal women have not found a relation between any fracture or hip fractures and levothyroxine use. Secondary analyses of other studies have only found associations between levothyroxine replacement and hip fractures in men and forearm fractures in older adults within the first two years of treatment. Recently a population based cohort study of people aged over 18 years found an increased risk of fractures only in those taking excess levothyroxine replacement based on suppression of serum thyroid stimulating hormone levels. Our study specifically focused on older adults, who have a higher baseline risk of fracture and are more vulnerable to excessive levothyroxine replacement.

Leese and Flynn

In an accompanying editorial, Graham P. Leese and Robert V. Flynn at Ninewells Hospital in Dundee, United Kingdom, caution that ideal thyroxine doses may be surprisingly low in the elderly population: 'The increased risk of fracture for patients taking long term thyroxine is small, with the main risk likely to be in elderly patients with a suppressed serum TSH [thyroid-stimulating hormone] concentration', Drs. Leese and Flynn write. 'Current guidelines of aiming for a TSH value within the reference range should be adhered to ... It is 120 years since the effect of excess thyroid hormone on bone was first described, yet research in this area still lacks funding.' (BMJ; Medscape).




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