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Does levothyroxine therapy during the treatment of subclinical hypothyroidism affect bone density?

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Hypothyroidism is very common. Overt hypothyroidism occurs when both the thyroid hormone level (usually FT4) is low and the TSH level is high. Subclinical hypothyroidism is defined as having an only an increased TSH level while the FT4 is in the normal range. As opposed to overt hypothyroidism, treatment with thyroid hormone in subclinical hypothyroidism is controversial. Most experts recommend treatment for subclinical hypothyroidism when TSH levels are above 7-10 mIU/ml. However, in practice, the majority of adults with TSH levels above the normal range receive thyroid hormone treatment.

Thyroid hormone has a direct effect on bone. High levels of thyroid hormone (either from having an overactive thyroid or from taking too much thyroid hormone) cause increased bone turnover leading to bone loss and a decrease in bone density. High thyroid hormone levels also have been linked to fracture. Thyroid hormone therapy treating overt hypothyroidism that causes suppressed TSH levels has been associated with bone loss and osteoporosis. This study addresses the question of whether treatment with thyroid hormone for subclinical hypothyroidism can also lead to bone loss.

Büchi AE et al. 2022 Bone geometry in older adults with subclinical hypothyroidism upon levothyroxine therapy: A nested study within a randomized placebo controlled trial. Bone 161:116404. PMID: 35381390.

Study participants from the TRUST trial were examined. A total of 162 individuals, all over 65 years of age with subclinical hypothyroidism, were divided in 2 groups. One group received levothyroxine and the other group received placebo pills. Doses of levothyroxine given to the first group were increased as needed to maintain a normal TSH level. A year later, 98 participants were studied for their bone structure by measuring it with a specific bone density test, called peripheral quantitative computed tomography (pQCT). Measurement of bone structure by pQCT may allow for a better determination of the strength of the bone as compared with the traditional bone mineral density test.

The average age of the participants was 74 years old and 46% were women. Before receiving levothyroxine treatment (50 individuals) or placebo (48 individuals) their pQCT results were similar. After 1 year of treatment, the bone volume or density measured by pQCT was remained unchanged in the treatment group as compared to the placebo group.

This study confirms that treatment with levothyroxine in patients with subclinical hypothyroidism does not have a negative impact on bone mass. It is reassuring to know that treatment of subclinical hypothyroidism does not affect the bones, as long as levothyroxine doses are tailored to keep a normal TSH level. As with patients with overt hypothyroidism, clinicians who treat subclinical hypothyroidism should be cautious to avoid over treatment. Whether treatment of subclinical hypothyroidism is needed or helpful is another question.

— Susana Ebner MD


Subclinical Hypothyroidism: a mild form of hypothyroidism where the only abnormal hormone level is an increased TSH. There is controversy as to whether this should be treated or not

Overt Hypothyroidism: clear hypothyroidism an increased TSH and a decreased T4 level. All patients with overt hypothyroidism are usually treated with thyroid hormone pills.

Levothyroxine (T4): the major hormone produced by the thyroid gland and available in pill form as Synthroid™, Levoxyl™, Tyrosint™ and generic preparations.

Thyroid hormone therapy: patients with hypothyroidism are most often treated with Levothyroxine in order to return their thyroid hormone levels to normal. Replacement therapy means the goal is a TSH in the normal range and is the usual therapy. Suppressive therapy means that the goal is a TSH below the normal range and is used in thyroid cancer patients to prevent growth of any remaining cancer cells.

TSH: thyroid stimulating hormone — produced by the pituitary gland that regulates thyroid function; also the best screening test to determine if the thyroid is functioning normally

Bone Mineral Density (BMD): this is usually measured in the lumbar (lower) spine and the hip and the results give information as to the strength of the bone and the risk of fractures. The results are expressed as T scores, which as standard deviations from the average bone density in a person in their 20s, when bone mass is the highest. A T score of -1 to -2.5 is termed Osteopenia and a T score >2.5 is termed Osteoporosis.