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Objective: Monoclonal gammopathy of undetermined significance (MGUS) is the asymptomatic precursor of multiple myeloma (MM). Lytic bone lesions and fractures are hallmarks of MM and although there are no lytic lesions in MGUS, it has also been associated with fractures. The causes of fractures in MGUS are currently unclear but potential causes include inherent MGUS bone disease, undiagnosed MM, and peripheral neuropathy (PN). We therefore conducted a large population‐based study including 8395 individuals with MGUS and 30 851 matched controls from Sweden. Methods: Data on fractures, PN, and confounders were acquired from high‐quality registers in Sweden. Results: Monoclonal gammopathy of undetermined significance and PN were independently associated with fractures (hazard ratio [HR]: 1.29; 95% confidence interval [95% CI]: 1.21‐1.37; P <.001 and HR: 1.34; 95% CI: 1.16‐1.55; P <.001). Imminent MGUS progression increased the risk of fractures (odds ratio: 1.66; 95% CI: 1.27‐2.16; P <.001). Fractures were not associated with long‐term risk of MGUS progression (HR: 1.08; 95% CI: 0.77‐1.53; P =.64). Discussion: Based on these findings, we speculate that MGUS leads to fractures through at least 3 independent mechanisms: undetected MGUS progression to MM, MGUS inherent bone disease, and PN through falls. These findings highlight the need for further study of MGUS inherent bone disease and can inform further research into fracture prevention in MGUS. [ABSTRACT FROM AUTHOR]

Objectives and methods: We conducted a population‐based study including 19 303 individuals diagnosed with MGUS in Sweden from 1985 to 2013, with the aim to determine whether a prior history of autoimmune disease, a well‐described risk factor for MGUS is a risk factor for progression of MGUS to multiple myeloma (MM) or lymphoproliferative diseases (LPs). Using the nationwide Swedish Patient registry, we identified MGUS cases with versus without an autoimmune disease present at the time of MGUS diagnosis and estimated their risk of progression. Results: A total of 5612 (29.1%) MGUS cases had preceding autoimmune diseases. Using Cox proportional hazards models, we found the risk of progression from MGUS to MM (HR = 0.83, 95% CI 0.73‐0.94) and LPs (HR = 0.84, 95% CI 0.75‐0.94) to be significantly lower in MGUS cases with prior autoimmune disease (compared to MGUS cases without). Conclusions: In this large population‐based study, a history of autoimmune disease was associated with a reduced risk of progression from MGUS to MM/other LPs. Potential underlying reason is that MGUS caused by chronic antigen stimulation is biologically less likely to undergo the genetic events that trigger progression. Our results may have implications in clinical counseling for patients with MGUS and underlying autoimmune disease. [ABSTRACT FROM AUTHOR]