# Risk factors for skeletal-related events in patients with stage IV lung adenocarcinoma and bone metastases receiving denosumab: a retrospective cohort analysis

## TL;DR

The study identifies risk factors for bone-related complications in lung cancer patients treated with denosumab, highlighting the protective role of bisphosphonate use and risks from low blood calcium and smoking.

## Contribution

First study to show bisphosphonate use protects against skeletal events during denosumab treatment in lung cancer patients with bone metastases.

## Key findings

- A prior history of bisphosphonate use reduces the risk of skeletal-related events during denosumab treatment.
- Pretreatment hypocalcemia and smoking are significant risk factors for skeletal-related events.
- 24.3% of patients experienced skeletal-related events during follow-up.

## Abstract

This study aimed to identify independent risk factors for skeletal-related events(SREs) during denosumab treatment in patients with bone-metastatic stage IV lung adenocarcinoma by integrating multidimensional clinical parameters, thereby providing an evidence-based foundation for risk stratification and targeted management.

In this retrospective cohort study, patients with stage IV lung adenocarcinoma and radiologically confirmed bone metastases diagnosed at Xuanhan County People's Hospital between July 2021 and December 2023 were enrolled. All patients received standardized denosumab therapy (120 mg subcutaneously every 4 weeks ± 7 days). Baseline demographic, laboratory, and treatment response data were extracted from the electronic medical record system. Univariate analyses were used to screen candidate variables, followed by multivariate logistic regression to identify independent predictors. Model fit was assessed using the Hosmer–Lemeshow test.

A total of 111 patients were included (median age, 65.5 years; 50.45% male). During follow-up, 27 patients (24.3%) experienced SREs. Multivariate analysis identified a prior history of bisphosphonate use as an independent protective factor against SREs (odds ratio [OR], 0.191; 95% confidence interval [CI], 0.049–0.741 P = 0.017), while Pretreatment hypocalcemia and smoking were both significantly associated with increased risk.

This study is the first to demonstrate in a county-level hospital cohort that a history of bisphosphonate use serves as an independent protective factor against SREs during denosumab treatment, while Pretreatment hypocalcemia and smoking history significantly increase SREs risk. These findings provide critical evidence for individualized management of stage IV lung adenocarcinoma patients with bone metastases.