osteoprotegerin and Musculoskeletal-Pain

Paget's disease of bone is a common disorder characterized by increased but disorganized bone remodelling. Some patients are asymptomatic but others present with bone pain or other complications such as fracture and deformity. Major advances have been made in understanding the pathophysiology of Paget's disease in recent years and highly effective agents are now available with which to suppress the abnormal bone turnover that causes the disease. Here we review recent advances in the epidemiology, pathogenesis, clinical features and management of Paget's disease. We also reflect upon the future challenges that remain to be overcome to explain the unusual distribution of the disease and to favourably alter the natural history and prevent the development of complications.

Topics: Adaptor Proteins, Signal Transducing; Bone Density Conservation Agents; Bone Remodeling; Environmental Exposure; Forecasting; Fractures, Spontaneous; Genetic Predisposition to Disease; Humans; Musculoskeletal Pain; Mutation; Osteitis Deformans; Osteoprotegerin; Practice Guidelines as Topic; Receptor Activator of Nuclear Factor-kappa B; Sequestosome-1 Protein

Aromatase inhibitor (AI) therapy is associated with musculoskeletal (MS) toxicity, which adversely affects quality of life and therapy adherence. Our objective was to evaluate whether genetic variants may predict endocrine therapy-related MS pain and hot flashes in a prospective observational cohort study.. 254 early breast cancer patients starting AI (n = 159) or tamoxifen therapy (n = 95) were included in this genetic biomarker study. MS and vasomotor symptoms were assessed at baseline and after 3, 6 and 12 months of therapy. AI-induced MS pain was defined as an increase in arthralgia or myalgia relative to baseline. Single nucleotide polymorphisms (SNP) in candidate genes involved in oestrogen signalling or previously associated with AI-related MS pain or oestrogen levels were selected.. Overall, 13 SNPs in CYP19, CYP17, osteoprotegerin (OPG) and oestrogen receptor 1 exhibited an allele frequency >0.05 and were included in the analysis. Patients carrying the G allele of rs2073618 in OPG experienced significantly more AI-induced MS toxicity compared to the wildtype allele, after correction for multiple testing (P = 0.046). Furthermore, this SNP was associated with severity of pain (P = 0.018). No association was found with regard to the other SNPs, both in AI and tamoxifen-treated patients. Neither could an association with vasomotor symptoms be demonstrated.. The SNP rs2073618 in OPG is associated with an increased risk of MS symptoms and pain with AI therapy, which has not been reported previously. Validation of this finding in larger cohorts and further functional studies are required.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents, Hormonal; Aromatase Inhibitors; Arthralgia; Breast Neoplasms; Female; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Longitudinal Studies; Middle Aged; Musculoskeletal Pain; Myalgia; Osteoprotegerin; Pain Measurement; Phenotype; Polymorphism, Single Nucleotide; Prospective Studies; Risk Factors; Time Factors