Bone Pain in Multiple Myeloma- a Translational Study

Overview

While the survival expectancy of myeloma patients continues increasing due to the discovery of novel treatments, bone pain remains one of the main symptoms of this patient population, impairing their mood and quality of life. The aim of this study is to characterize the subjective experience of pain in myeloma patients, and its correlation with disturbances in serum biomarkers and bone innervation. Primary research questions: How is the bone pain experienced by myeloma patients (intensity, location and type of pain) and how does it affect their quality of life? Do myeloma cells induce changes in the density and/or location of nerve fibres innervating the bone, and if so, are these correlated to the pain experience? Secondary research questions: Are the alterations in the bone innervation of myeloma patients similar to those of immunocompetent animal models of the disease (the 5TGM1 model)? Is serum paraprotein correlated with the subjective experience of myeloma-induced bone pain? Are the bone turnover biomarkers (C-terminal telopeptides Type 1 collagen, CTX, and procollagen type 1 N-terminal propeptide, P1NP) and inflammatory serum biomarkers correlated with the subjective experience of myeloma-induced bone pain? Do myeloma cells affect the location, number or density of bone cells (e.g. osteoblasts, osteoclasts)?

Patients undergoing diagnostic procedures (i.e. trephine bone biopsy) for suspected multiple myeloma will be invited to participate in the study, and provided with time to consider their participation. Patients who consent will be provided with a set of seven standardized questionnaires assessing their pain, quality of life and catastrophizing. Additionally, patients will be asked to fill in demographic information. Consenting patients will be asked to donate a fasting blood sample and give permission to the research team to retrieve their triphane bone biopsy, once the medical team has finished evaluating it. The presence, location and density of nerve fibres innervating the bone will be evaluated. Patients will also be consented to allow retrieval of medical information from their medical records, and correlations between serum biomarkers, disturbances in bone innervation, paraprotein levels, etc. and their self-reported experience of pain will be investigated. Patients with a negative diagnosis for multiple myeloma (expectably monoclonal gammopathy of undetermined significance (MGUS) patients) will be used as negative controls. Patients who receive a positive diagnosis for multiple myeloma will be asked to fill in the same set of questionnaires upon completion of the first-line treatment (approximately 7 to 8 months after baseline assessment). Fasting serum blood samples will be collected. To evaluate treatment´s success, it is common medical practice to extract a new trephine bone biopsy upon completion of first line treatment. The research team will access these biopsies and evaluate the presence, density and location of nerve fibres in bone. Changes in nerve fibre profiles, serum biomarkers and the self-reported experience of pain, quality of life and catastrophizing following first-line treatment will be evaluated.