Bone Loss in Premenopausal Women on Long-term Suppressive Therapy With Thyroid Hormone

Sinisa Sijanovi, MD, Prof. Ivan Karner MD, PhD

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Abstract and Introduction

Background: The effects on bone metabolism of long-term treatment with thyroid hormone given at suppressive doses have been debated.

Objective: To determine whether long-term thyroxine therapy in the premenopausal period is a risk factor for the development of secondary osteoporosis and whether women receiving this therapy have increased bone loss during the premenopausal period.
Patients and Methods: The study enrolled a select group of 19 premenopausal women of mean ages 39 +/- 8 years suffering from differentiated thyroid gland carcinoma. All subjects had undergone total thyroidectomy and subsequently initiated thyroxine suppressive therapy. At the beginning of our study, the women had been on suppressive therapy for 9.4 +/- 6.4 years. Laboratory results were performed to exclud other possible factors for secondary osteoporosis. This prospective study of bone mineral density (BMD) was conducted over a 4-year period on all subjects using the method of dual photon x-ray absorptiometry (DXA) of the spine and the femoral neck and also by the method of single-photon absorptiometry (SPA) of the distal radius.
Results: At the beginning of this study, 2 subjects had osteopenia in the spine and 2 had osteopenia in the femoral neck; they had been on suppressive thyroxine therapy for 10 years. Osteopenia in the distal radius was found in 4 subjects . Overall, 8 of the 19 women had osteopenia at the beginning of the study. One year later, after the second BMD measurement, no statistically significant loss of bone mass occurred in any region of the skeleton in any of the patients. However, a review of the individual scores revealed osteopenia in 6 patients at the distal radius; bone loss also occurred at the spine and the femoral neck in several women, but not to the extent that would establish osteopenia. After the 4 years, BMD measurements indicated significant bone loss.
Conclusion: Our results suggest that women who begin long-term ( ˜ 10 years) thyroxine therapy in the premenopausal period can develop osteopenia by the beginning of menopause.

Bone remodeling is enhanced by thyroid hormones. Although both osteoclastic and osteoblastic activities increase with elevated concentrations of thyroid hormones, the osteoclastic activity with consequential bone mass loss prevails.[1] Thyrotoxicosis is associated with elevated serum concentrations of osteocalcin and alkaline phosphatase.[1,2,3] Increased bone resorption is accompanied by elevated urine concentrations of hydroxyproline and type I collagen cross linkages. Elevated concentrations of these biochemical markers of bone turnover seem to correlate with serum concentrations of thyroid hormones.

Decreased bone density in patients with thyrotoxicosis is reversible with efficient treatment. The administration of high doses of thyroid hormones to suppress the secretion of thyroid-stimulating hormone (TSH) in patients subjected to radical treatment for differentiated carcinoma of the thyroid is considered the appropriate therapy. In patients prone to osteoporosis, however, this therapy may increase the risk of fractures. Suppressive doses of thyroid hormones have been reported to reduce or to have no effect on bone mineral density (BMD) in women. Meta-analysis of published reports has indicated that a 1% BMD loss occurs during the postmenopausal period in women who were administered suppressive doses of thyroxine. In contrast, substitution therapy with thyroid hormone shows no harmful effect on BMD.[1]

Suppressive therapy may accelerate the development of osteoporosis.[4,5,6,7,8,9,10] There is increasing interest in the studies of the effects of thyroid hormone therapy on the development of osteoporosis. Cvijetic and associates[11] point out that substitution therapy with thyroxine in hypothyroidism is also a risk factor, while others belive that suppressive doses of thyroxine have no major impact on bone mineral loss.[12,13,14,15,16,17,18]

In this prospective study, the effects of suppressive therapy with levothyroxine in premenopausal women who had undergone total sugical thyroidectomy for differentiated thyroid carcinoma were investigated. A number of longitudinal and prospective studies have been conducted worldwide to assess the effects of suppressive therapy with thyroid hormones on bone mass.

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