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Bone disease with hyperthyroidism and thyroid hormone therapy

Douglas S Ross, MD
Section Editors
David S Cooper, MD
Marc K Drezner, MD
Deputy Editor
Jean E Mulder, MD


The adverse effects of hyperthyroidism on the skeleton were known before the advent of satisfactory treatment for hyperthyroidism. One of the first reports of hyperthyroid bone disease was in 1891 when von Recklinghausen described the "worm eaten" appearance of the long bones of a young woman who died from hyperthyroidism [1]. With the introduction of antithyroid drugs and radioiodine in the 1940s, clinically apparent hyperthyroid bone disease became less common.

However, bone density measurements during the last decade have demonstrated that bone loss is common in patients with overt hyperthyroidism and to a lesser extent in those with subclinical hyperthyroidism, whether caused by nodular goiter or excessive doses of thyroid hormone (TR).

Thyroid hormone directly stimulates bone resorption in organ culture [2]. This action may be mediated by a nuclear triiodothyronine (T3) receptor which has been found in rat and human osteoblast cell lines [3-5] and in osteoclasts derived from an osteoclastoma [5]. Experimental studies in mice lacking either the TR-alpha or TR-beta receptor suggest bone loss is mediated by TR-alpha [6]. Thus, thyroid hormone may affect bone calcium metabolism either by a direct action on osteoclasts, or by acting on osteoblasts which in turn mediate osteoclastic bone resorption [7]. Thyroid-stimulating hormone (TSH) may also appear to have a direct effect on bone formation and bone resorption, mediated via the TSH receptor on osteoblast and osteoclast precursors [8]; however, bone loss appeared independent of TSH levels in the experiments with mice lacking specific TR isoforms [6].

Increased serum interleukin-6 (IL-6) concentrations in hyperthyroid patients may also play a role in thyroid hormone-stimulated bone loss [9]. IL-6 stimulates osteoclast production and may be an effector of the action of parathyroid hormone (PTH) on bone. (See "Hypercalcemia of malignancy", section on 'Multiple myeloma'.)


Overt hyperthyroidism is associated with accelerated bone remodeling, reduced bone density, osteoporosis, and an increase in fracture rate. The bone density changes may or may not be reversible with therapy. These changes in bone metabolism are associated with negative calcium balance, hypercalciuria and, rarely, hypercalcemia (see below).


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Literature review current through: Apr 2016. | This topic last updated: Jul 6, 2015.
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