Effects on bone mass of long term treatment with thyroid hormones: a meta-analysis.

Abstract

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.

Subclinical hyperthyroidism: clinical features and treatment options

“…Similar results were found in longitudinal studies with decreased or normal bone mineral density in pre-(92 -94) or postmenopausal women (72, 91, 92 -95) with exogenous subclinical hyperthyroidism. Indeed, in two meta-analyses, exogenous subclinical hyperthyroidism was associated with a significant bone loss in post-but not in premenopausal women (96,97).…”

Densidade mineral óssea de crianças e adolescentes com hipotireoidismo congênito

“…Poderse-ia especular que o tratamento com doses de l-T 4 discretamente maiores pudesse refletir nos valores de DMO dos pacientes em relação ao grupo controle, uma vez que, conforme a metanálise de Uzzan e cols. (30), o excesso de HT aumenta o turnover ósseo e diminui a massa óssea. Como, por questões éticas, não foi dosado TT 4 nas crianças do grupo controle, a relação entre DMO e valor de TT 4 no grupo A é hipotética, pois não se encontrou correlação entre as médias da dose de l-T 4 , TSH, TT 4 e FT 4 durante todo o seguimento e as médias de DMO e CMO dos pacientes.…”

Lack of deleterious effect on bone mineral density of long-term thyroxine suppressive therapy for differentiated thyroid carcinoma

“…Despite publication in the last decade of several studies (Franklyn et al 1992, Kung et al 1993, Giannini et al 1994, Marcocci et al 1994, McDermott et al 1995, Muller et al 1995, Rosen et al 1998) and meta-analyses on this topic (Faber & Galloe 1994, Uzzan et al 1996, evidence that subclinical hyperthyroidism affects skeletal integrity and is therefore a risk factor for osteoporosis, is inconclusive (Greenspan & Greenspan 1999, Toft 2001, Quan et al 2002, Murphy & Williams 2004. The meta-analyses and systematic reviews reported either a decrease in bone mineral density during prolonged subclinical hyperthyroidism, mainly in postmenopausal women, or no changes (Faber & Galloe 1994, Uzzan et al 1996, Greenspan & Greenspan 1999, Lau et al 2001, Toft 2001, Quan et al 2002, Murphy & Williams 2004. Among premenopausal women, the effect does not appear to be significant (Marcocci et al 1994).…”