EFFECTS ON BONE MASS OF LONG-TERM TREATMENT WITH THYROID-HORMONES - AMETAANALYSIS

Osteoporosis is the main cause of spine and hip fractures. Morbidity, mortality, and costs arising from hip fractures have been well documen ted. Thyroid hormones (TH) are widely prescribed, mainly in the elderl y. Some studies (but not all) found a deleterious effect of suppressiv e TH therapy on bone mass. These conflicting data raised a controversy as to the safety of current prescribing and follow-up habits, which, in turn, raised major health-care issues. To look for a detrimental ef fect on bone of TH therapy, we performed a meta-analysis (by pooling s tandardized differences, using a fixed effect model) of all published controlled cross-sectional studies (41, including about 1250 patients) concerning the impact of TH therapy on bone mineral density (BMD). St udies with women receiving estrogen therapy were excluded a priori, as were studies with a high percentage of patients with postoperative hy poparathyroidism, when no separate data were available. We decided to stratify the data according to anatomical site, menopausal status, and suppressive or replacement TH therapy, resulting in 25 meta-analyses on 138 homogeneous subsets of data. The main sources of heterogeneity between studies that we could identify were replacement or suppressive TH therapy, menopausal status, site (lumbar spine, femoral neck, Ward 's triangle,greater trochanter, midshaft and distal radius, with vario us percentages of cortical bone), and history of hyperthyroidism, whic h has recently been found to impair bone mass in a large epidemiologic al survey. To improve homogeneity, we excluded a posteriori 102 patien ts from 3 studies, who had a past history of hyperthyroidism and separ ate BEAD data, thus allowing assessment of the TH effect in almost all 25 subset mete-analyses. However, controls were usually not matched w ith cases for many factors influencing bone mass, such as body weight, age at menarche and at menopause, calcium dietary intake, smoking hab its, alcohol intake, exercise, etc. For lumbar spine and hip (as for a ll other sites), suppressive TH therapy was associated with significan t bone loss in postmenopausal women (but not in premenopausal women), whereas, conversely, replacement therapy was associated with bone loss in premenopausal women (spine and hip), but not in postmenopausal wom en. The detrimental effect of TH appeared more marked on cortical bone than on trabecular bone. Only a large long term prospective placebo-c ontrolled trial of TH therapy (e.g. in benign nodules) evaluating BMD (and ideally fracture rate) would provide further insight into these i ssues.