Objective  To explore the effect of denosumab and zoledronic acid on pain relief in patients with bone metastases from non-small cell lung cancer (NSCLC) and their impact on bone formation markers.

Methods  The clinical data of patients with NSCLC complicated with bone metastases admitted to the First People's Hospital of Tianmen from January 2022 to August 2024 were retrospectively collected. Patients were divided into the zoledronic acid group and the denosumab group according to their different treatment regimen, and received zoledronic acid injection or denosumab injection, respectively. The changes in pain numerical rating scale (NRS) before and after treatment, as well as serum alkaline phosphatase, serum calcium, serum phosphorus levels in the two groups of patients were compared. The incidence of skeletal-related events (SREs) and adverse drug reactions were evaluated in both groups.

Results  A total of 120 patients were included, with 60 in the zoledronic acid group and 60 in the denosumab group. After treatment, both groups showed significant improvement in NRS scores and bone metabolism indicators compared to before (P<0.05), and all indicators in the denosumab group were superior to those in the zoledronic acid group (P<0.05). There were no statistically significant differences in the incidence of SREs and the incidence of adverse drug reactions between the two groups (P>0.05).

Conclusion  Denosumab performs better than zoledronic acid in relieving cancer-related pain in patients with bone metastases from NSCLC and improving bone metabolism indicators. It also has good safety and high clinical application value.

1.Xue M, Ma L, Zhang P, et al. New insights into non-small cell lung cancer bone metastasis: mechanisms and therapies[J]. Int J Biol Sci, 2024, 20(14): 5747-5763. DOI: 10.7150/ijbs.100960.

2.Widyadharma IPE, Tertia C, Vania A, et al. The effect of denosumab vs. zoledronic acid in preventing skeletal-related events, including pain-related bone metastasis: a systematic review[J]. Postep Psychiatr Neurol, 2024, 33(3): 172-177. DOI: 10.5114/ppn.2024.144603.

3.支修益, 王洁, 刘伦旭, 等. 中国肺癌骨转移临床诊疗指南（2024版）[J]. 中国胸心血管外科临床杂志, 2024, 31(5): 643-653. [Zhi XY, Wang J, Liu LX, et al. Chinese clinical practice guidelines for bone metastasis of lung cancer (version 2024)[J]. Chinese Journal of Thoracic and Cardiovascular Surgery, 2024, 31(5): 643-653.] DOI: 10.7507/1007-4848.202402042.

4.Veszelyné Kotán E, Bartha-Lieb T, Parisek Z, et al. Database analysis of the risk factors of bisphosphonate-related osteonecrosis of the jaw in Hungarian patients[J]. BMJ Open, 2019, 9(5): e025600. DOI: 10.1136/bmjopen-2018-025600.

5.Lu J, Hu D, Zhang Y, et al. Current comprehensive understanding of denosumab (the RANKL neutralizing antibody) in the treatment of bone metastasis of malignant tumors, including pharmacological mechanism and clinical trials[J]. Front Oncol, 2023, 13: 1133828. DOI: 10.3389/fonc.2023.1133828.

6.Zheng Y, Wang PP, Fu Y, et al. Zoledronic acid enhances the efficacy of immunotherapy in non-small cell lung cancer[J]. Int Immunopharmacol, 2022, 110: 109030. DOI: 10.1016/j.intimp.2022.109030.

7.Asano Y, Yamamoto N, Demura S, et al. Combination therapy with immune checkpoint inhibitors and denosumab improves clinical outcomes in non-small cell lung cancer with bone metastases[J]. Lung Cancer, 2024, 193: 107858. DOI: 10.1016/j.lungcan.2024.107858.

8.Hofbauer LC, Neubauer A, Heufelder AE. Receptor activator of nuclear factor-kappaB ligand and osteoprotegerin: potential implications for the pathogenesis and treatment of malignant bone diseases[J]. Cancer, 2001, 92(3): 460-470.DOI: 10.1002/1097-0142(20010801)92:3<460::aid-cncr1344>3.0.co;2-d.

9.Fisch MJ, Lee JW, Weiss M, et al. Prospective, observational study of pain and analgesic prescribing in medical oncology outpatients with breast, colorectal, lung, or prostate cancer[J]. J Clin Oncol, 2012, 30(16): 1980-1988. DOI: 10.1200/jco.2011.39.2381.

10.王凯元, 孙姗, 张霄蓓, 等. 转移性癌性骨痛的分子机制及临床治疗研究进展[J]. 中国肿瘤临床, 2020, 47(8): 418-422. [Wang KY, Sun S, Zhang XB, et al. Molecular mechanisms and clinical treatment research progress of metastatic cancer bone pain[J]. Chinese Journal of Clinical Oncology, 2020, 47(8): 418-422.] DOI: 10.3969/j.issn.1000-8179.2020.08.093.

11.Cleeland CS, Body JJ, Stopeck A, et al. Pain outcomes in patients with advanced breast cancer and bone metastases: results from a randomized, double-blind study of denosumab and zoledronic acid[J]. Cancer, 2013, 119(4): 832-838. DOI: 10.1002/cncr.27789.

12.Brown JE, Cook RJ, Major P, et al. Bone turnover markers as predictors of skeletal complications in prostate cancer, lung cancer, and other solid tumors[J]. J Natl Cancer Inst, 2005, 97(1): 59-69. DOI: 10.1093/jnci/dji002.

13.Zhang L, Gong Z. Clinical characteristics and prognostic factors in bone metastases from lung cancer[J]. Med Sci Monit, 2017, 23: 4087-4094. DOI: 10.12659/msm.902971.

14.吴冬灵, 王杰斌, 陈阔. 比较地舒单抗与唑来膦酸对恶性肿瘤骨转移患者骨形成标志物及癌痛程度的影响[J]. 天津药学, 2025, 37(6): 682-686. [Wu DL, Wang JB, Chen K. Comparison of the effects of denosumab and zoledronic acid on bone formation markers and cancer pain in patients with bone metastases from malignant tumors[J]. Tianjin Pharmacy, 2025, 37(6): 682-686.] DOI: 10.20283/j.cnki.1006-5687.2025.06.09.

15.Eremkina A, Krupinova J, Dobreva E, et al. Denosumab for management of severe hypercalcemia in primary hyperparathyroidism[J]. Endocr Connect, 2020, 9(10): 1019-1027. DOI: 10.1530/ec-20-0380.

16.Body JJ, Bone HG, de Boer RH, et al. Hypocalcaemia in patients with metastatic bone disease treated with denosumab[J]. Eur J Cancer, 2015, 51(13): 1812-1821. DOI: 10.1016/j.ejca.2015. 05.016.

17.Kong P, Yan J, Liu D, et al. Skeletal-related events and overall survival of patients with bone metastasis from nonsmall cell lung cancer - a retrospective analysis[J]. Medicine (Baltimore), 2017, 96(51): e9327. DOI: 10.1097/md.0000000000009327.

18.Stopeck AT, Lipton A, Body JJ, et al. Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer: a randomized, double-blind study[J]. J Clin Oncol, 2010, 28(35): 5132-5139. DOI: 10.1200/jco.2010.29.7101.

19.Aliyev V, Guliyev M, Günaltılı M, et al. Comparative efficacy and cost-effectiveness of denosumab versus zoledronic acid in cancer patients with bone metastases[J]. J Clin Med, 2025, 14(18): 6469. DOI: 10.3390/jcm14186469.

20.甄路路, 刘学峁, 陈建琦, 等. 地舒单抗与唑来膦酸在实体肿瘤骨转移和多发性骨髓瘤患者中应用效果和安全性的Meta分析[J]. 药物流行病学杂志, 2024, 33(2): 194-202. [Zhen LL, Liu XM, Chen JQ, et al. Meta-analysis of the efficacy and safety of denosumab versus zoledronic acid in patients with bone metastases from solid tumors and multiple myeloma[J]. Chinese Journal of Pharmacoepidemiology, 2024, 33(2): 194-202.] DOI: 10.12173/j.issn.1005-0698.202311036.