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Bone disease with hyperthyroidism and thyroid hormone therapy

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

INTRODUCTION

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 demonstrate that bone loss is common in patients with overt hyperthyroidism and to a lesser extent in those with subclinical hyperthyroidism, whether caused by endogenous hyperthyroidism or excessive doses of thyroid hormone(s) (thyroxine [T4] or triiodothyronine [T3]).

This topic will review bone disease in patients with overt and subclinical hyperthyroidism. The clinical manifestations, diagnosis, and treatment of overt and subclinical hyperthyroidism are reviewed separately. (See "Overview of the clinical manifestations of hyperthyroidism in adults" and "Diagnosis of hyperthyroidism" and "Subclinical hyperthyroidism" and "Graves' hyperthyroidism in nonpregnant adults: Overview of treatment".)

PATHOGENESIS

Thyroid hormone directly stimulates bone resorption in organ culture [2]. This action is mediated by nuclear triiodothyronine (T3) receptors, predominantly thyroid receptor (TR)-alpha-1, which has been found in rat and human osteoblast cell lines [3-5] and in osteoclasts derived from an osteoclastoma [5]. 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 [6]. Thyroid-stimulating hormone (TSH) may also have a direct effect on bone formation and bone resorption, mediated via the TSH receptor on osteoblast and osteoclast precursors [7,8]; this putative effect is, however, controversial, since bone loss appeared independent of TSH levels in the experiments in mice with a loss-of-function TSH receptor [9].

Increased serum interleukin-6 (IL-6) concentrations in hyperthyroid patients may also play a role in thyroid hormone-stimulated bone loss [10]. IL-6 stimulates osteoclast production and may be an effector of the action of parathyroid hormone (PTH) on bone. (See "Hypercalcemia of malignancy: Mechanisms", section on 'Multiple myeloma'.)

OVERT HYPERTHYROIDISM

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.

                         

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Literature review current through: Jul 2016. | This topic last updated: Jun 21, 2016.
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