It is relatively well established that thyroid hormone has a clinically significant effect on bone. Although some aspects, such as the bone mineral loss associated with overt thyrotoxicosis have been relatively well described, others remain much less clear. A major focus of this review is on the effects of chronic exogenous thyroid hormone administration on bone physiology. When thyroid hormone dosage is supraphysiologic, an iatrogenic clinical model is produced comparable to endogenous “subclinical hyperthyroidism.” Indeed, literature on bone mineral changes in the latter entity may be analyzed as representative of effects of excessive circulating thyroid hormone. At the molecular level, thyroid hormone receptors as well as thyroid-stimulating hormone (TSH) receptors have been identified on osteoblasts and osteoclasts, and have been shown to mediate significant effects on bone physiology.
In reviewing the literature extant on this subject, an important clinical distinction has to be made between the effects on bone of thyroid hormone given in “suppressive” dosage vs “replacement” dosage. Some, albeit rare, earlier studies reported or implied a potentially harmful effect of physiologic replacement dosage of thyroid hormone on bone. Retrospective analysis indicates that these studies were plagued with a number of problems. Insensitive TSH assays hampered the ability to accurately determine if the replacement dosage was truly physiological, and other problems were related to patient population selection and the techniques used to assess bone mineral density. Data on fracture risk is particularly scant with most studies failing to identify thyroid hormone therapy as a risk factor for fracture. Rather, it would appear that when bone mineral loss is seen in men or premenopausal women on replacement dosage of thyroid hormone, there will be some other confounding element playing the dominant etiologic role. In post-menopausal women, the most important contributing factor to osteoporosis is estrogen deficiency, and bone loss in estrogen-deficient women will be clearly accelerated by concomitant suppressive dosage of thyroid hormone. Availability of sensitive TSH assays allows us to carefully titrate thyroid hormone dosage and avoid excesses. The risks of even slight thyroid hormone excess on the heart have been recognized for the past decade, and those risks taken together with the risk of bone loss should cause us to re-examine the indications for suppressive dosage of thyroid hormone. When suppressive dosage is necessary (e.g., for patients with residual or recurrent thyroid cancer), the bone-resorptive effects of thyroid hormone should be tempered by eliminating all other factors contributing to bone loss and considering the addition of a bone-enhancing therapeutic agent such as a bisphosphonate.