# Evaluation of Osteonecrosis Risk Using Serum C-Terminal Cross-Linked Telopeptide of Type 1 Collagen (CTX-1) Levels in Osteoporotic Patients: Effects of Drug Holidays and Risk Factors

**Authors:** Emine Esra Ergül, Oğuzhan Laçin, Hamide Özge Kılıçaslan, Fahrettin Bostancı, Elif Can Özdemir, Ayşegül Kılıç, Serhat Hayme, Hilal Büşra Ayçiçek

PMC · DOI: 10.5152/eurasianjmed.2026.251104 · The Eurasian Journal of Medicine · 2026-01-15

## TL;DR

This study examines how CTX-1 levels relate to osteonecrosis risk in osteoporosis patients and finds drug holidays and bisphosphonate types affect CTX-1 levels.

## Contribution

The study introduces a novel approach to evaluating osteonecrosis risk using CTX-1 levels and drug holiday effects in osteoporosis treatment.

## Key findings

- Patients on drug holidays had significantly higher CTX-1 levels compared to those without drug holidays.
- Denosumab-treated patients showed the lowest CTX-1 levels compared to bisphosphonate treatments.
- Vitamin D levels did not significantly affect CTX-1 levels in the studied population.

## Abstract

The aim of this study is to evaluate the risk of osteonecrosis of the jaw in patients receiving osteoporosis treatment using C-terminal cross-linked telopeptide of type 1 collagen (CTX-1) values, to analyze follow-ups after drug holidays, and to compare treatment agents and other risk factors to determine the association with CTX-1 results.

A total of 273 patients (266 female and 7 male) who received bisphosphonate and denosumab treatment for osteoporosis were included in this retrospective study. Sociodemographic characteristics, vitamin D levels, serum CTX-1 level, presence of diseases affecting CTX-1 levels, type of bisphosphonate, duration of use, presence of drug holidays, and duration of denosumab use (if any) were recorded. The effects of bisphosphonates and denosumab on CTX-1 levels were compared, and differences in the risk of osteonecrosis between them were evaluated.

In this study, a meaningful association was not identified between serum CTX-1 levels and the measured vitamin D values (P = .232). Patients who underwent a drug holiday had significantly higher mean serum CTX-1 levels (266.2 ± 175.1 pg/mL) compared to those without a drug holiday (199.9 ± 138.5 pg/mL; P = .009). Higher CTX-1 levels were observed in individuals receiving ibandronate and alendronate, whereas the lowest values were detected in patients treated with denosumab.

Serum CTX-1 levels appeared unaffected by vitamin D. Although the denosumab group exhibited the highest risk of osteonecrosis, the difference compared to zoledronic acid was not statistically significant. These results suggest caution during jaw-related procedures and consideration of drug holidays when necessary.

## Linked entities

- **Chemicals:** CTX-1 (PubChem CID 435038), bisphosphonate (PubChem CID 2088), ibandronate (PubChem CID 60852), alendronate (PubChem CID 2088), zoledronic acid (PubChem CID 68740)
- **Diseases:** osteoporosis (MONDO:0005298), osteonecrosis of the jaw (MONDO:0018378)

## Full-text entities

- **Diseases:** Osteoporotic (MESH:D058866), osteonecrosis of the jaw (MESH:D059266), osteoporosis (MESH:D010024), Osteonecrosis (MESH:D010020)
- **Chemicals:** denosumab (MESH:D000069448), alendronate (MESH:D019386), CTX-1 (-), ibandronate (MESH:D000077557), bisphosphonate (MESH:D004164), zoledronic acid (MESH:D000077211), vitamin D (MESH:D014807)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Full text

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## Figures

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## References

31 references — full list in the complete paper: https://tomesphere.com/paper/PMC12884653/full.md

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Source: https://tomesphere.com/paper/PMC12884653