# Longitudinal Bone Density During TSH Suppression in Differentiated Thyroid Cancer: A Paired PET/CT Analysis

## TL;DR

This study shows that long-term TSH suppression in thyroid cancer patients leads to reduced bone density, especially in women, suggesting the need for regular bone health monitoring.

## Contribution

The study provides longitudinal evidence of bone density decline during TSH suppression using PET/CT scans in both male and female patients.

## Key findings

- Bone density significantly decreased over time in all lumbar vertebrae for the entire cohort.
- Women showed significant declines in bone density at multiple vertebral levels, while men showed non-significant trends.
- Age was a stronger baseline determinant of bone density than sex.

## Abstract

Many patients treated for differentiated thyroid cancer receive long-term levothyroxine therapy to suppress thyroid-stimulating hormone (TSH) and lower the risk of recurrence. This hormone state can affect several organs, including the skeleton. We examined whether bone density in the lumbar spine declines during suppression. Using routinely performed CT scans, we measured Hounsfield units in each lumbar vertebra at two timepoints with a mean interval of four years. Bone density decreased significantly over time in the entire cohort. In sex-stratified analyses, women showed significant declines at several vertebral levels, whereas men showed a smaller, non-significant downward trend. Age, rather than sex alone, was the stronger baseline determinant of bone density. These findings support regular bone-health monitoring during long-term levothyroxine-induced TSH suppression.

Background: While TSH suppression is essential in patients with differentiated thyroid cancer (DTC) to reduce the risk of recurrence, it has also been linked to side effects, particularly a reduction in bone mineral density that may contribute to osteoporosis. However, previous studies investigating this association have yielded inconsistent results. This study aimed to evaluate bone density using Hounsfield units from PET/CT scans in a longitudinal analysis including both sexes. Methods: Patients with DTC under continuous TSH suppression who underwent two PET/CT scans were included. Hounsfield units were measured for each lumbar vertebra (L1–L5) in the CT by placing an elliptical region of interest (ROI) in the center of the vertebra, avoiding hyperdense edges. Laboratory parameters were also collected. Results: A total of 50 patients were included in the study (25 male, 25 female), with a mean age of 57.2 (±15.3) years at the time of the first scan. The mean duration of TSH suppression before the first scan was 3.7 ± 3.9 years, and the mean interval between both scans was 4.4 ± 4.0 years. At the follow-up scan, bone density was significantly lower compared with baseline for all lumbar vertebrae (L1–L5 combined and individually) (all p < 0.05). Subgroup analysis revealed a significant decline in women at L1, L2, L4, and L5 and for overall lumbar bone density, while men showed nonsignificant trends. Conclusions: Our study suggests a sustained reduction in vertebral bone density during TSH suppression. The results support routine monitoring in both sexes, risk stratification by age and duration of suppression, and, when oncologically appropriate, consideration of lower suppression intensity or initiation of bone-protective therapy in high-risk patients.