Clinical value of serum bone resorption markers for predicting clinical outcomes after use of bone modifying agents in metastatic bone tumors: A prospective cohort study

Abstract

Bone modifying agents (BMAs) have become a standard treatment to prevent skeletal-related events (SREs) in bone metastases (BMs). The aim of our study is to determine the clinical value of serum bone resorption markers for predicting clinical outcomes after using BMAs in patients with BM. Patients were enrolled between May 2013 and October 2017 at the Nagoya University Hospital, Japan. We prospectively observed changes in pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and tartrate-resistant acid phosphatase 5b (TRACP-5b) during treatment with BMAs. The relationship between serum markers before and after treatment and clinical outcomes such as progression of bone disease (BD), SREs and overall survival (OS) were evaluated. Pearson chi-square test and Kaplan-Meier product limit methods were used for analysis. Sixty-seven patients were analyzed. The primary tumor sites were 21 lung, 16 breast and 30 others. Forty and 27 patients were treated with Denosumab and Zoledronic acid, respectively. Progression of BDs, SREs and death were observed in 10, 16 and 31 cases, respectively. The median follow-up period after using BMAs was 12.3 (range 0.3-66.3) months. ICTP at 3-4 weeks was significantly correlated with increasing BD progression, SREs and death after treatment in both the whole and lung cancer cohorts. Base line ICTP and TRACP-5b were also associated with increasing BD progression in the whole cohort. Our study showed that early posttreatment ICTP is useful for predicting BD progression, SREs and OS after use of BMAs in patients with BM and even in patients with lung cancer BM.Additional Supporting Information may be found in the online version of this article.

Analysis of the Mechanism and Safety of Bisphosphonates in Patients with Lung Cancer and Bone Metastases

“…Tumor cells will degrade the bad bone apoptotic component, osteoclasts will be activated, osteolysis will be seen, and bone metastases will damage bone, resulting in an increase in blood calcium levels [ 24 ]. The study evaluated the therapeutic effectiveness of bisphosphonate medicines in eligible individuals with lung cancer and bone metastases.…”

Acid-Induced Inflammatory Cytokines in Osteoblasts: A Guided Path to Osteolysis in Bone Metastasis

“…In this study, we showed the very strong correlation between osteolysis, as detected by circulating concentration of TRACP5b and IL-8 in BM patients. TRACP5b is a specific index of bone resorption, and an accurate marker of OC number since it is released from OC into the blood circulation, together with matrix degradation products, during the bone resorption process through the basolateral membrane (Avnet et al, 2008;Savarino et al, 2010;Urakawa et al, 2020). However, in these patients, we could not directly prove that the release of these inflammatory mediators is derived from the cancer-induced bone lesion or from intratumoral acidosis.…”

Comparison of the efficacy and safety of a proposed biosimilar QL1206 with reference denosumab in patients with bone metastasis from breast cancer: a subgroup analysis of a randomized, double-blinded phase III study

“…In this phase III trial, the surrogate endpoint of Week 13 uNTx/Cr was used as the primary endpoint, which was widely used as an indicator of bone resorption [22,27]. The uNTx/Cr serves as a highly speci c biomarker for bone osteolysis and proves to be a valuable predictor for the treatment of BM [27][28][29][30]. Regulatory guidelines from the NMPA, the U.S. Food and Drug Administration (FDA), and the European Medicines Agency (EMA) support the use of biomarkers as primary endpoints in biosimilar clinical trials against their reference products [31 -33].…”