Effects on bone mass of long term treatment with thyroid hormones: a meta-analysis
B Uzzan, J Campos, M Cucherat, P Nony, JP Boissel and GY Perret
Hopital Avicenne, Centre Hospitale Universitaire Paris Nord, France.
Osteoporosis is the main cause of spine and hip fractures. Morbidity,
mortality, and costs arising from hip fractures have been well documented.
Thyroid hormones (TH) are widely prescribed, mainly in the elderly. Some
studies (but not all) found a deleterious effect of suppressive 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 effect on bone of TH therapy,
we performed a meta-analysis (by pooling standardized 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). Studies with women receiving estrogen therapy
were excluded a priori, as were studies with a high percentage of patients
with postoperative hypoparathyroidism, 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-analysis on 138 homogeneous subsets of data. The main sources of
heterogensity 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
various percentages of cortical bone), and history of hyperthyroidism,
which has recently been found to impair bone mass in a large
epidemiological survey. To improve homogeneity, we excluded a posteriori
102 patients from 3 studies, who had a past history of hyperthyroidism and
separate BMD data, thus allowing assessment of the TH effect in almost all
25 subset meta-analyses. However, controls were usually not matched with
cases for many factors influencing bone mass, such as body weight, age at
menarche and at menopause, calcium dietary intake, smoking habits, alcohol
intake, exercise, etc. For lumbar spine and hip (as for all other sites),
suppressive TH therapy was associated with significant 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 women. The detrimental effect of
TH appeared more marked on cortical bone than on trabecular bone. Only a
large long term prospective placebo- controlled trial of TH therapy (e.g.
in benign nodules) evaluating BMD (and ideally fracture rate) would provide
further insight into these issues.
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