The effect of levothyroxine therapy on bone mineral density: a systematic review of the literature.

BACKGROUND Currently debate still exists about the effects of thyroid hormone therapy on skeletal integrity, that is the safety of levothyroxine use with respect to bone mineral density. OBJECTIVE A systematic review of the effects of TSH-suppressive and replacement levothyroxine therapy on bone mineral density evaluated main causes of conflicting results and its implications for clinical practice, and suggested directions of future research. DATA SOURCE AND STUDY SELECTION A MEDLINE search identified English-language studies assessing bone mineral density under levothyroxine therapy published from 1990 to 2001. DATA EXTRACTION The studies were grouped by design and type of intervention. Outcomes were qualitatively analysed. Subgroup analysis assessed heterogeneity between studies. DATA SYNTHESIS Of 63 identified studies, 31 studies reported no effects of levothyroxine on bone mineral density, 23 studies showed partial beneficial or adverse, and 9 studies overall adverse effects. A significant dose-response was not found. There was a tendency towards peripheral cortical bone loss, suggesting a site-specific effect. In adolescents, men, and premenopausal women evidence for levothyroxine influence was weaker than in postmenopausal women. However, also findings in postmenopausal women remained unclear. The extent and etiology of underlying thyroid diseases also contributed to inconsistent results. Further, controversial results were due to substantial heterogeneity of studies. Above all, studies were limited by moderate quality, small size, and inadequate control for confounders. CONCLUSIONS Based on current studies there is insufficient evidence about effectiveness of levothyroxine on bone mineral density. All conclusions, however, must take into account the important methodical drawbacks. Present data may only be proved by longitudinal, high quality studies in homogeneous patients with sufficient sample size, clinical implication of future research remains questionable, though.