Bone Changes in Pre- and Postmenopausal Women with Thyroid Cancer on Levothyroxine Therapy: Evolution of Axial and Appendicular Bone Mass

Abstract

The effects of suppressive doses of levothyroxine (LT4) on bone mass are controversial. Our aim was to evaluate the effects on axial and appendicular bone mineral density (BMD) and bone metabolism of long-term LT4 suppressive therapy in women by means of cross-sectional and longitudinal studies, and also to assess the potential influence of menopausal status and LT4 dose. Seventy-six women (aged 47 +/- 13 years, 37 pre- and 39 postmenopausal) on suppressive therapy (67 +/- 34 months duration, mean LT4 dose 168 +/- 41 micrograms/day) from our Thyroid Cancer Unit without previous hyperthyroidism or concomitant hypoparathyroidism were studied. Serum TSH, T3 free T4, calcium, phosphorus, alkaline phosphatase, BGP, iPTH and urinary calcium (uCA) were measured. BMD was measured by dual-energy X-ray absorptiometry (DXA) at lumbar spine, femoral neck, Ward's triangle, ultradistal and distal third radius and expressed as a Z-score. In a subset of 27 women aged 46 +/- 15 years (14 pre- and 13 postmenopausal) a second densitometry scan was performed 27 +/- 5 months later. Patients on suppressive therapy showed a small reduction in BMD at the distal third radius (Z-score: -0.77 +/- 0.98; 95% confidence interval: -1.11, -0.44) without differences between pre- and postmenopausal women. Significant relations with the regimen of suppressive therapy and bone turnover markers were detected except at the lumbar spine. In the longitudinal study a significant although mild reduction in femoral neck BMD was found that correlated with prior T3 and iPTH. In conclusion, our data show a small detrimental effect of cautious LT4 suppressive therapy on bone mass assessed by DXA; it remains to be established whether this increases the prevalence of fractures.