Bone remodeling markers and bone metastases: From cancer research to clinical implications

Abstract

Bone metastasis is a frequent finding in the natural history of several types of cancers. However, its anticipated risk, diagnosis and response to therapy are still challenging to assess in clinical practice. Markers of bone metabolism are biochemical by-products that provide insight into the tumor-bone interaction, with potential to enhance the clinical management of patients with bone metastases. In fact, these markers had a cornerstone role in the development of bone-targeted agents; however, its translation to routine practice is still unclear, as reflected by current international guidelines. In this review, we aimed to capture several of the research and clinical translational challenges regarding the use of bone metabolism markers that we consider relevant for future research in bone metastasis.

Targeting collagen for diagnostic imaging and therapeutic delivery

“…US is typically used as a diagnostic tool in chest diseases, and as a guide for transthoracic needle biopsies [51]. Biochemical assays are non-invasive and suitable for high-throughput screening either in preclinical or clinical settings for estimating the safety and efficacy of certain therapies [52, 53], but they are neither site-specific nor disease-specific [55]. Scientists and engineers are addressing limitations of early stage detection (e.g., for MRI [56]) and inadequate correlation between the disease and serum markers [52].…”

“…There is a wealth of research on identifying biochemical markers associated with degradation of bone and cartilage [52, 55, 92–93]. In general, these biochemical markers, or neoepitopes, are by-products of enzymatic processes which are involved in the formation and degradation of bone and cartilage.…”

“…There are several methods to detect these biomarkers including ELISA, radioimmunoassay (RIA), electrochemical luminescence, and HPLC analysis. Two notable epitopes for analyzing bone quality are serum C-telopeptide of type I collagen (CTX-I) and serum N-propeptide of type I collagen (PINP), which correlates with bone resorption and bone formation, respectively [55]. In contrast, cartilage quality can be measured by detecting the level of serum C-telopeptide of type II collagen (CTX-II).…”

“…55); (C) In vivo molecular imaging of pulmonary (top panel) and liver fibrosis (bottom panel) using EP-3533 (reprinted with permission from Ref. 59 and 60).…”

Bone regenerative effect of aqueous Cynanchum wilfordii extract in receptor activator of nuclear factor-κB ligand-induced osteoclast differentiation and estrogen deficiency-induced osteoporosis

“…In addition, several regulators of bone cell activity and, therefore, bone turnover may also be used as biomarkers. Bone turnover biomarkers used in preclinical and clinical research of bone metastasis are serum bone-specific alkaline phosphatase (BALP), osteocalcin (OCN), and procollagen type I N propeptide (P1NP), as well as pyridinoline (PYD), deoxypyridinoline (DPD), aminoterminal crosslinked telopeptide of type I collagen (NTX-I), and carboxy-terminal crosslinked telopeptides of collagen type I (CTx-I and ICTP) [8]. A menopause-triggered decrease in BMD and high turnover bone metabolism is associated with the occurrence of post-menopausal osteoporosis [9].…”