Bone mineral density during maintenance treatment with supraphysiological doses of levothyroxine in affective disorders: a longitudinal study.

Background: This prospective study was designed to determine whether patients with prophylaxis-resistant affective disorders, receiving adjunctive maintenance therapy with supraphysiological doses of levothyroxine (L-T4), show evidence of accelerated bone loss compared to the reference population database.

Methods: In 21 patients, bone mineral density (BMD) of the spine (lumbar vertebrae L1-L4) and femur (femoral neck, trochanter, and Ward's triangle) was measured by dual energy X-ray absorptiometry (DXA). BMD measurement was performed first after patients had been on thyroid-stimulating hormone (TSH)-suppressive therapy with L-T4 (mean dose=411 mcg/d) for an average of 16.4 months and again after 33.6 months of L-T4 (mean dose=416 mcg/d) therapy.

Results: There was no statistically significant difference between the actual percentage decline in bone mineral density and the expected percentage decline in any of the measured bone regions. In a stepwise linear regression analysis, age was identified as a predictor of percentage change in BMD. After controlling for age, the only other variable that showed a consistent trend was the dose of L-T4, with higher doses being positively correlated with the percentage decline of BMD.

Limitations: Relatively small sample size, no bone density assessment prior to treatment with L-T4, no patient control group with mood disorders who did not receive L-T4 treatment, and bone density follow-up intervals were variable.

Conclusions: This study did not demonstrate evidence that long-term treatment of affectively ill patients with supraphysiological doses of L-T4 significantly accelerates loss of bone mineral density compared to the age-matched reference population. However, the decline of BMD in one individual patient underscores that caution is indicated and that regular assessment of BMD during longer-term supraphysiological thyroid hormone treatment is needed.