Bone disease in Monoclonal Gammopathy of Undetermined Significance: Results from a Screened Population-Based Study S. Thorsteinsdottir 1, 2, S. Lund2, E. Lindqvist3, G. Sigurdsson4, R. Costello5, D. Burton5, H. Steingrimsdottir1, L. Launer6, V. Gudnason2, 4, G. Eiriksdottir4, K. Siggeirsdottir4, T. Harris6, O. Landgren7, S. Kristinsson1, 2 1Department of Internal Medicine, Landspitali - The National University Hospital of Iceland, 2Faculty of Medicine, University of Iceland, Reykjavik, Iceland, 3Department of Medicine, Division of Hematology, Karolinska University Hospital and Karolinska Institutet, Stockholm, Sweden, 4Icelandic Heart Association, Kopavogur, Iceland, 5Center for Cancer Research, National Cancer Institute, National Institutes of Health, United States, 6National Institute on Aging, National Institutes of Health, Bethesda, United States, 7Myeloma Service, Division of Hematologic Oncology, Memorial Sloan-Kettering Cancer Center, New York, United States Institutes of Health, Bethesda, 7Myeloma Service, Division of Hematologic Oncology, Memorial Sloan-Kettering Cancer Center, New York, United States Introduction Results Monoclonal gammopathy of undetermined significance (MGUS) is a precursor condition that precedes multiple myeloma (MM). Bone disease is a major manifestation of MM, and includes osteolytic lesions, fractures, and osteoporosis. Previous population-based studies based on clinical cohorts have shown that individuals with MGUS have an increased risk of fractures, although the mechanism behind this increased risk remains unknown. No difference was found in BMD between subjects with MGUS and others at the spine or total hip (Table 1). Volumetric measurements showed that individuals with MGUS had statistically significant increased bone volume compared to others in the lumbar spine (p<0.001) and in total hip (p<0.001). A significant difference was found in bone volume in total hip in MGUS men, compared to other men (p=0.04). Overall, the risk of fractures was not increased in individuals with MGUS as compared to others (Table 2). Men with MGUS had a significantly increased risk of fractures, compared to other men (p=0.046). Aims Our aim was to analyze bone mineral density (BMD), bone volume, and risk of fractures among individuals with MGUS in a screened population. METHODS We performed a screening for MGUS in the Age Gene/Environment Susceptibility Reykjavik study (AGES- Reykjavik) cohort, consisting of 5,764 elderly Icelandic men and women. Through serum protein electrophoresis and free light chain analyses, 300 individuals with MGUS (159 men and 141 women) and 52 individuals with light chain MGUS (LC- MGUS; 35 men and 18 women) were identified. Quantitative computerized tomography (QCT) was performed in the lumbar spine (L1/L2), hip and mid-femoral shaft to evaluate BMD as well as bone geometry in all individuals. Analysis of variance and Tukey's honest significance test were used to compare the groups. Hospital records were used to record fractures from the individuals’ enrollment into the study with a mean follow up time of 6.9 years. Cox proportional hazard models were used to compare risk of fractures in MGUS and others. Results were adjusted for age and sex. Conclusion Our results from a screened population show that induviduals with MGUS do not have a decreased BMD at the lumbar spine, hip or femur. Surprisingly, however, we find that bone volume is increased in individuals with MGUS, especially in men, who also have an increased risk of fractures. This suggests an effect of MGUS on bone metabolism in men that is not noted in women, probably as a results of other stronger risk factors in women. Further reaserch is needed to explain the increased bone volume in men with MGUS. CONTACT INFORMATION Sigrun Thorsteinsdottir, MD, Department of Internal Medicine Landspitali - The National University Hospital of Iceland sigrunt@landspitali.is