Updated March 08, 2014.

The effects of thyroid hormone on bone density and bone strength, as well as risk of osteoporosis, are still being debated, even after many studies have been conducted that attempt to resolve this question. Since levothyroxine (i.e., Synthroid, Unithroid, Levoxyl, etc.) is the most frequently-prescribed drug to treat hypothyroidism, the effect of levothyroxine on the bones is an important issue.

A 2003 medical journal review article conducted a systematic review of the effects of TSH-suppressive (higher doses given to thyroid cancer patients) and replacement doses of levothyroxine therapy on bone mineral density.

The goal of the review was to provide guidance for patient management and to recommend the directions that future studies of this question should take.

Included in the review were 63 separate English-language studies published from 1990-2001 that were identified by a Medline search. Many of these studies were designed to determine whether the patients taking thyroid hormone replacement had a reduction in bone mineral density.

What the reviewers found was of interest to patients and practitioners: All studies provided results that were considered by the reviewers to be either limited and/or controversial. Of the 63 studies reviewed:

• 31 reported no effects of levothyroxine on bone mineral density
• 23 studies found partial beneficial or adverse effects, and
• 9 studies showed overall adverse effects.

The studies involved a total of 3279 patients but the sample size only varied from 9 to 202. Only five studies had more than 100 subjects included. Adults were the subjects examined in almost all of the studies.

In addition, most studies included only women with postmenopausal women being included twice as often as premenopausal. Most studies included patients with the same diagnosis yet 17 studies included patients with different thyroid diseases. Both the techniques used and the sites examined for changes in bone mineral density varied among the studies.

The dose of levothyroxine for patients involved in 53 of these studies averaged 148 mcg/day with a range of 72-259 mcg/day. The mean treatment duration in 52 studies was 8.7 years, ranging from ½ to 20 years. The follow-up period averaged 27 months, ranging from 12 to 72 months.

No association seems to exist between the duration of levothyroxine therapy and the associated reduction of bone mineral density if it occurs. There was no conclusive evidence of a dose-effect relationship when all studies were considered. 

It was not clear from these studies whether underlying thyroid diseases and/or their treatments are independent or additional risk factors for reduced bone mineral density. Further, these was disagreement among the studies as to whether a potential negative effect of levothyroxine on bone mineral density is reversible, preventable, or helped by drug treatments for osteoporosis.

The reviewers note that the findings of these studies are complex and confusing and no definitive conclusion can be made about whether levothyroxine therapy has an adverse effect on bone mineral density.