Assessment of bone turnover markers and DXA parameters to predict bone metastasis progression during zoledronate treatment: a single-center experience

Abstract

Bone metastases (BM) are a serious cancer complication, potentially causing substantial morbidity. Among the clinical issues related to BM, there is the lack of specific tools for early diagnosis and prognosis. We explored whether combining bone turnover markers (BTM) with dual-energy X-ray absorptiometry (DXA) assessment could identify early BM progression and risk of skeletal-related events (SREs) during zoledronate treatment. Before the initiation of zoledronate (T0) and after six months of treatment (T1), serum levels of five BTM were measured, and patients (N = 47) underwent DXA evaluation. Standard radiological imaging was performed to assess bone tumor response to medical anti-cancer treatment. High tumor burden in bone correlated with higher serum CTX (p = 0.007) and NTX (p = 0.005) at baseline. Low concentrations of OPG at T0 predicted BM progression with a sensitivity and specificity of 63% and 77%, respectively, when a cutoff of 5.2 pmol/l was used; such a predictive meaning was stronger in patients with lytic BM (sensitivity: 88%, specificity: 80%; p = 0.0006). As for the risk of SREs, we observed an association between low baseline OC (p = 0.04) and OPG (p = 0.08) and the onset of any-time SREs, whereas an increase in OPG over time was associated with reduced risk of on-study events (p = 0.03). Moreover, a statistically significant correlation emerged between low baseline lumbar T-score and femur BMD and on-study SREs (p < 0.001 in both instances). These findings suggest that addition of DXA to BTM dosage could help stratifying the risk of SREs at the time of BM diagnosis but does not enhance our capability of detecting bone progression, during zoledronate treatment.

Retrospective Evaluation of Bone Turnover Markers in Serum for the Prediction of Metastases Development in Breast Cancer Patients: A Cohort Study

“…An interesting aspect, which is suggested by these findings, is the potential of BTMs to stratify patients at a high risk of (bone) metastatic disease and govern further treatments in the adjuvant setting to increase bone-metastasis-free survival; a comprehensive list of biomarkers is provided by Wang et al [ 28 ]. Interestingly, stronger evidence of this notion has arisen in the context of advanced disease [ 29 , 30 , 31 ]. D’Oronzo and colleagues recently studied 47 patients with bone metastatic BC who underwent BTM measurements and dual-energy X-ray absorptiometry (DXA) before bisphosphonate treatment.…”

“…The authors showed that OPG levels < 5.2 pmol/L were associated with an increased risk of progression. Skeletal-related events were also significantly associated with lower concentrations of osteocalcin, OPG, lower lumbar T-Score, and femur bone mineral density at baseline [ 30 ]. Another prospective study of patients with bone metastases (various tumors including BC) by Ibrahim et al demonstrated that RANKL transcription levels were the best marker of the response of bone metastases during treatment with zoledronic acid [ 31 ].…”