Changes in bone mass during prolonged subclinical hyperthyroidism due to L-thyroxine treatment: a meta-analysis

L-Thyroxine (L-T4) in the treatment of thyroid disease resulting in reduced serum thyrotropin (TSH) has been associated with reduced bone mass and thus the potential risk of premature development of osteoporosis. However, several recent studies have failed to show such a detrimental effect. These disagreements are probably due to only a small number of patients taking part in each study, decreasing the change of finding significant differences and increasing the risk of missing a real difference (type 1 and 2 errors, respectively). We therefore performed a meta-analysis on the available papers (N = 13), in which bone mass was measured in the distal forearm, femoral neck or lumbar spine in a cross-sectional manner in women with suppressed serum TSH due to L-T4 treatment and in a control group. The women were divided according to their pre- and postmenopausal state, because preserved estrogen production plays a protective role against irreversible bone loss. Based on the number of measurements performed on the different sites of the skeleton, a theoretical bone composed of 30.4% distal forearm, 28.8% femoral neck and 40.8% lumbar spine could be constructed in premenopausal women (441 measurements). A premenopausal woman at an average age of 39.6 years and treated with 164 micrograms L-T4/day for 8.5 years, leading to suppressed serum TSH, had 2.67% less bone mass than controls (NS), corresponding to an excess annual bone loss of 0.31% after 8.5 years of treatment (NS). The risk of not detecting an excess bone loss of at least 1% per year (type 2 error) was p < 0.15.(ABSTRACT TRUNCATED AT 250 WORDS)