CHANGES IN BONE MASS DURING PROLONGED SUBCLINICAL HYPERTHYROIDISM DUETO L-THYROXINE TREATMENT - A METAANALYSIS

L-Thyroxine (L-T-4) in the treatment of thyroid disease resulting in r educed serum thyrotropin (TSH) has been associated with reduced bone m ass and thus the potential risk of premature development of osteoporos is. However, several recent studies have failed to show such a detrime ntal effect. These disagreements are probably due to only a small numb er of patients taking part in each study, decreasing the change of fin ding significant differences and increasing the risk of missing a real difference (type 1 and 2 errors, respectively). We therefore performe d 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-T- 4 treatment and in a control group. The women were divided according t o their pre- and postmenopausal state, because preserved estrogen prod uction plays a protective role against irreversible bone loss. Based o n the number of measurements performed on the different sites of the s keleton, a theoretical bone composed of 30.4% distal forearm, 28.8% fe moral neck and 40.8% lumbar spine could be constructed in premenopausa l women (441 measurements). A premenopausal woman at an average age of 39.6 years and treated with 164 mu g L-T-4/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. Similarly, a postmenop ausal woman with a bone consisting of 11.3% distal forearm, 42.0% femo ral neck and 46.7% lumbar spine (317 measurements) at an average age o f 61.2 years and treated with 171 mu g L-T-4/day for 9.9 years had 9.0 2% less bone mass than controls (2p < 0.007), corresponding to a signi ficant excess of annual loss of 0.91% after 9.9 years of treatment. Ei ghteen papers with a mean of 18 patients showing no difference between postmenopausal patients and controls would have to be published or fo und before this difference could turn into a nonsignificant finding (t he file drawer problem). In conclusion, the meta-analysis on the avail able cross-sectional studies did not find any significant reduction in bone mass during prolonged L-T-4 treatment resulting in reduced serum TSH in premenopausal women. The risk of the present meta-analysis mis sing a clinically relevant annual loss of at least 1% in premenopausal women was less than 15%. In contrast, L-T-4 treatment in postmenopaus al women in a dosis leading to reduced serum TSH resulted in a signifi cant excess of annual bone loss of 0.9l%/year after 9.9 years in compa rison to control women.