# TSH suppression attenuates the early efficacy of zoledronic acid in osteoporosis

**Authors:** Yujuan Liu, Yilei Zhang, Meiye Li, Ying Qian, Zongjing Zhang, Zhaoshun Jiang, Wei Qu

PMC · DOI: 10.1007/s11657-026-01672-2 · Archives of Osteoporosis · 2026-02-24

## TL;DR

TSH suppression reduces the early effectiveness of zoledronic acid for treating osteoporosis in thyroid cancer patients.

## Contribution

This study shows that TSH suppression therapy diminishes the early skeletal response to zoledronic acid in postoperative thyroid cancer patients with osteoporosis.

## Key findings

- TSH suppression was linked to less bone mineral density improvement at 9 months.
- Bone turnover markers remained elevated in the TSH suppression group.
- The effect was more pronounced in postmenopausal women.

## Abstract

TSH suppression was associated with an attenuated early skeletal response to zoledronic acid in postoperative DTC patients with osteoporosis.

This prospective study aimed to evaluate the impact of TSH suppression therapy on the early skeletal efficacy of zoledronic acid in patients with differentiated thyroid cancer (DTC), and to explore whether this response differs across subgroups.

Patients were divided into two groups: the osteoporosis with TSH suppression group (TSH + OP, n = 42) and the osteoporosis without TSH suppression group (TSH − OP, n = 67). Both groups received a single infusion of zoledronic acid (5 mg) along with daily calcium and calcitriol supplementation. Primary analyses compared changes in bone mineral density (BMD) and bone turnover markers(BTMs) at 6 and 9 months post-treatment. After propensity score matching (PSM), 36 patients from each group were included in the primary analyses. Exploratory subgroup analyses were conducted according to age and sex.

After PSM, the TSH + OP group showed significantly less BMD improvement compared to the TSH − OP group. At 9 months, the intergroup differences in BMD change were -7.08 mg/cm2 (lumbar, P = 0.02), -12.03 mg/cm2 (left hip, P < 0.001) and -6.12 mg/cm2 (femoral neck, P < 0.001). BTMs (PINP and β-CTX) remained higher in the TSH + OP group at all time points (all P < 0.01). Subgroup analyses suggested that these differences were primarily observed in postmenopausal patients.

TSH suppression therapy was associated with an attenuated early skeletal response to zoledronic acid in postoperative DTC patients with osteoporosis, with this attenuation being more pronounced at the hip and femoral neck. Exploratory subgroup analyses suggested that this attenuation was primarily observed in postmenopausal women. In patients undergoing TSH suppression, serum PINP and β-CTX are useful monitoring biomarkers.

## Linked entities

- **Chemicals:** zoledronic acid (PubChem CID 68740), calcium (PubChem CID 5460341), calcitriol (PubChem CID 5280453), β-CTX (PubChem CID 9571035)
- **Diseases:** osteoporosis (MONDO:0005298), differentiated thyroid cancer (MONDO:0015447)

## Full-text entities

- **Genes:** ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, MCF2L (MCF.2 cell line derived transforming sequence like) [NCBI Gene 23263] {aka ARHGEF14, DBS, OST}, BGLAP (bone gamma-carboxyglutamate protein) [NCBI Gene 632] {aka BGP, OC, OCN}, MAPK14 (mitogen-activated protein kinase 14) [NCBI Gene 1432] {aka CSBP, CSBP1, CSBP2, CSPB1, EXIP, Mxi2}, GDF2 (growth differentiation factor 2) [NCBI Gene 2658] {aka BMP-9, BMP9, HHT5}, ALPP (alkaline phosphatase, placental) [NCBI Gene 250] {aka ALP, PALP, PLAP, PLAP-1}, RUNX2 (RUNX family transcription factor 2) [NCBI Gene 860] {aka AML3, CBF-alpha-1, CBFA1, CCD, CCD1, CLCD}, TSHR (thyroid stimulating hormone receptor) [NCBI Gene 7253] {aka CHNG1, LGR3, hTSHR-I}, COL1A2 (collagen type I alpha 2 chain) [NCBI Gene 1278] {aka EDSARTH2, EDSCV, OI4}, GPT (glutamic--pyruvic transaminase) [NCBI Gene 2875] {aka AAT1, ALT, ALT1, GPT1, SGPT}, PRKAB1 (protein kinase AMP-activated non-catalytic subunit beta 1) [NCBI Gene 5564] {aka AMPK, HAMPKb}, BMP2 (bone morphogenetic protein 2) [NCBI Gene 650] {aka BDA2, BMP2A, SSFSC, SSFSC1}
- **Diseases:** atrial fibrillation (MESH:D001281), endocrine/metabolic disorders (MESH:D004700), Osteoporosis (MESH:D010024), bone loss (MESH:D001847), metastases (MESH:D009362), hip fractures (MESH:D006620), hypopituitarism (MESH:D007018), DTC (MESH:D013964), TSH (MESH:D007037), kidney disease (MESH:D007674), estrogen deficiency (MESH:D056828), type 1 diabetes (MESH:D003922), Cancer (MESH:D009369), osteoporotic (MESH:D058866), fracture (MESH:D050723), parathyroid dysfunction (MESH:D010279), Cushing's syndrome (MESH:D003480), fragility fracture (MESH:D005600), thyroid (MESH:D013966), autoimmune diseases (MESH:D001327), BMD (MESH:D001851), hyperthyroidism (MESH:D006980)
- **Chemicals:** TSH (MESH:D013972), 25(OH)D (-), levothyroxine (MESH:D013974), 25-hydroxyvitamin D (MESH:C104450), alcohol (MESH:D000438), T3 (MESH:D014284), calcitriol (MESH:D002117), Ca calcium (MESH:D002118), creatinine (MESH:D003404), bisphosphonate (MESH:D004164), OP (MESH:C572232), iodine (MESH:D007455), alendronate sodium (MESH:D019386), vitamin D (MESH:D014807), calcium carbonate (MESH:D002119), OPE (MESH:C005448), zoledronic acid (MESH:D000077211)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

1 references — full list in the complete paper: https://tomesphere.com/paper/PMC12932301/full.md

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Source: https://tomesphere.com/paper/PMC12932301