Osteoporosis, defined as an inappropriate decrease in bone mass, is a common disease. Osteoporosis is a silent disease. If bone pain is present, there may be associated conditions present such as osteoarthritis, or small fractures responsible for the pain. There is considerable misinformation regarding the relationship between osteoporosis susceptibility and thyroid hormone replacement. A brief review of the current medical facts is appropriate. First, patients taking thyroid hormone for prolonged periods of time, who maintain their TSH in the normal range, have no increased risk for the development of osteoporosis. It must be remembered that both thyroid disease and osteoporosis are both common diseases, especially in women, and hence many patients will have independently developed both osteoporosis and thyroid disease. This does not imply a causal relationship between the two.
Although bone loss does occur in patients with hyperthyroidism, it is generally reversible once the hyperthyroidism is treated and thyroid status returns to normal. A large study examining fracture risk in patients with hypothyroidism and hyperthyroidism detected a small but significant increase of fracture risk in patients with thyroid disease. This was not a cause and effect study, hence the influence of treatment of the thyroid disease on fracture risk cannot be ascertained. See Fractures in patients with hyperthyroidism and hypothyroidism: a nationwide follow-up study in 16,249 patients. Thyroid. 2002 May;12(5):411-9. In contrast, other studies have shown that three years after the resolution of the hyperthyroid state, bone density is essentially comparable in women with or without a previous history of hyperthyroidism, as shown in Bone mineral density in hyperthyroidism. Clin Endocrinol (Oxf). 2004 Oct;61(4):466-72. and Hyperthyroidism, bone mineral, and fracture risk--a meta-analysis. Thyroid. 2003 Jun;13(6):585-93. Review.
In older patients (greater than 65) not taking thyroid hormone, the detection of a low TSH may be associated with an increased risk of hip or vertebral fractures, however patients taking thyroid hormone with a normal TSH do not appear at increased risk for fractures as outlined in Risk for fracture in women with low serum levels of thyroid-stimulating hormone. Ann Intern Med. 2001 Apr 3;134(7):561-8. Similarly, in postmenopausal women, there does seem to be a modest correlation between levels of thyroid hormone, bone density, and an increased risk of non-vertebral fractures, even in subjects not taking thyroid hormone. However other correlations emerged as well, including changes in heart rate, grip strength, and balance. Thyroid Function within the Upper Normal Range Is Associated with Reduced Bone Mineral Density and an Increased Risk of Nonvertebral Fractures in Healthy Euthyroid Postmenopausal Women J Clin Endocrinol Metab. 2010 Apr 21. [Epub ahead of print]
In some studies, prolonged treatment with excessive doses of thyroid hormone results in a small but statistically significant increase in bone loss in a few but not all patients. It is important to remember that there are many risk factors for osteoporosis, including genetic predisposition, smoking, age at menopause, sedentary life style, and dietary intake of minerals and vitamins, to name a few. In some patients, excess thyroid hormone may slightly increase the risk of bone loss. In other studies, there has been non association between thyroid hormone use and hip fracture, as shown in Thyroid hormone use and the risk of hip fracture in women >/=65 years: a case-control study. J Womens Health (Larchmt). 2003 Jan-Feb;12(1):27-31.
A review on this subject, which addresses many of the limitations in the literature, is found in The effect of thyroid hormone on skeletal integrity. Ann Intern Med. 1999 May 4;130(9):750-8. Review.
There are recent studies in the literature, of younger patients with thyroid cancer taking suppressive doses of thyroxine, demonstrating no increased bone loss in these patients Randomized trial of pamidronate in patients with thyroid cancer: bone density is not reduced by suppressive doses of thyroxine, but is increased by cyclic intravenous pamidronate. J Clin Endocrinol Metab. 1998 Jul;83(7):2324-30 and Hip bone mineral density, bone turnover and risk of fracture in patients on long-term suppressive L-thyroxine therapy for differentiated thyroid carcinoma. Eur J Endocrinol. 2005 Jul;153(1):23-29. Furthermore, several larger studies have not shown any correlation between having a suppressed TSH (hyperthyroidism) and an increased risk of bone loss Low thyrotropin levels are not associated with bone loss in older women: a prospective study. J Clin Endocrinol Metab. 1997 Sep;82(9):2931-6. and Lack of deleterious effect on bone mineral density of long-term thyroxine suppressive therapy for differentiated thyroid carcinoma. Endocr Relat Cancer. 2005 Dec;12(4):973-81
Similar "negative results" were observed in a 2 year study of pre- and post-menopausal women treated with thyroxine to suppress TSH for nodular thyroid disease. No difference in bone mineral density was found in the group of patients with a borderline low TSH for 2 years. See Treatment of benign nodular goitre with mildly suppressive doses of L-thyroxine: effects on bone mineral density and on nodule size. J Intern Med. 2002 May;251(5):407-414.
In some studies of older women, hyperthyroidism does seem to be an independent risk factor for osteoporosis. A prospective study of 686 women over the age of 65 found that hyperthyroidism, as detected using the TSH assay, was an independent risk factor for fracture risk. In other observational studies , women taking thyroid hormone with levels of TSH in the normal range did not have an increased risk of hip fracture. These findings emphasize the importance of monitoring TSH levels in patients on thyroid hormone replacement. In the Clalit Health Services population, analysis of a historical cohort of 14,325 subjects revealed an increased incidence of hip fractures in women, but not men with low levels of TSH (0.35-1.6). Thyrotropin levels within the lower normal range are associated with an increased risk of hip fractures in euthyroid women, but not men, over the age of 65 years J Clin Endocrinol Metab. 2014 Aug;99(8):2665-73
Unless the patient has thyroid cancer, it seems prudent to avoid excess levels of thyroid hormone in similar patient populations. See Risk for fracture in women with low serum levels of thyroid-stimulating hormone. Ann Intern Med. 2001 Apr 3;134(7):561-8.
Conversely, a cross sectional study of subclinical thyroid dysfunction in 4,936 individuals age 65 or older enrolled in the Cardiovscular Health study did not reveal any association between subclinical hyperthyrodism or subclinical hypothyroidism and hip fracture in men or women. For subjects with available bone mineral density determnations, there was no association between biochemical (subclinical) thyroid dysfunction ans bone mineral density. Subclinical thyroid dysfunction and hip fracture and bone mineral density in older adults: the cardiovascular health study J Clin Endocrinol Metab. 2014 Aug;99(8):2657-64
Giving the rapidly evolving body of evidence linking osteoporosis with excess thyroid hormone, it seems reasonable to keep an open mind about the possible but not invariable link between osteoporosis and thyroid status in individual patients. Even in patients with thyroid cancer who need to take higher than normal doses of thyroxine for decades, there is little convincing evidence that the risk of osteoporosis is significantly increased. See Bone mineral density in well-differentiated thyroid cancer patients treated with suppressive thyroxine: A systematic overview of the literature. J Surg Oncol. 2002 Jan;79(1):62-70.
Furthermore, large epidemiological studies of hip fracture that have examined the use of L-thyroxine as a potential independent risk factor have failed to show conclusive links between use of thyroid hormone and an increased risk of hip fracture in women. See Levothyroxine treatment and occurrence of fracture of the hip. Arch Intern Med. 2002 Feb 11;162(3):338-43.
However, analysis of levels of TSH and bone and mineral status in the
NHANEs (National Health and Nutrition Examination Survey) study did
demonstrate a correlation between levels of TSH in the normal range and
bone mineral density in postmenopausal American women, as described in The
association between serum thyroid-stimulating hormone in its reference
range and bone status in postmenopausal American women. Bone.
2007 Jan 19; [Epub ahead of print]. Similarly, analysis of thyroid
hormone levels in 2374 postmenopausal women followed for 6 years
demonstrated a correlation between bone loss, thyroid hormone levels, and
an increased risk of non-vertebral fractures Thyroid
Function within the Upper Normal Range Is Associated with Reduced Bone
Mineral Density and an Increased Risk of Nonvertebral Fractures in Healthy
Euthyroid Postmenopausal Women. J
Clin Endocrinol Metab. 2010 Apr 21. [Epub ahead of print]
- Patients taking thyroid hormone for treatment of hypothyroidism should maintain their TSH in the normal but not suppressed range.
- Patients taking thyroid hormone to suppress further growth of thyroid nodules should maintain their TSH in the low normal range
- Patients taking thyroid hormone for the treatment of thyroid cancer should maintain their TSH in the suppressed range, using the minimal dose of thyroxine required to achieve TSH suppression
- If osteoporosis is a concern, attention should be paid to risk factors, exercise, diet, calcium and vitamin D supplementation, and if necessary, additional medications for the treatment of osteoporosis can be considered.
- Patients with thyroid cancer who face lifelong excess thyroid hormone replacement should consider a baseline bone density to establish parameters for sequential monitoring of bone density over time.