title: Monoclonal gammopathy of undetermined significance and risk of skeletal fractures: a population-based study.
abstract: Patients with multiple myeloma (MM) have an increased risk of fractures. On the basis of small numbers, patients with monoclonal gammopathy of undetermined significance (MGUS) have been reported to have an increased fracture risk. Using population-based data from Sweden, we assessed the risks of fractures in 5326 MGUS patients diagnosed from 1958 to 2006, compared with 20 161 matched controls. MGUS patients had an increased risk of any fracture at 5 (hazard ratio [HR] = 1.74; 95% confidence interval [CI], 1.58-1.92) and 10 (HR = 1.61; 95% CI, 1.49-1.74) years. The risk was significantly higher for axial (skull, vertebral/pelvis, and sternum/costae) compared with distal (arm and leg) fractures (P < .001). On the basis of 10 years of follow-up, there was an increased risk of vertebral/pelvic (HR = 2.37; 95% CI, 2.02-2.78), sternal/costae (HR = 1.93; 95% CI, 1.5-2.48), arm (HR = 1.23; 95% CI, 1.06-1.43), leg (HR = 1.40; 95% CI, 1.26-1.56), and other/multiple fractures (HR = 4.25; 95% CI, 3.29-5.51). Risks for fractures did not differ by isotype or M protein concentration at diagnosis. MGUS patients with (versus without) fractures had no excess risk of MM or Waldenström macroglobulinemia. Our results suggest that bone alterations are present in early myelomagenesis. Our findings may have implications for the development of better prophylaxis for bone disease in MGUS, and they provide novel clues on pathogenesis of MM bone disease.
authors.affiliation: Department of Medicine, Division of Hematology, Karolinska University Hospital Solna and Karolinska Institutet, Stockholm, Sweden. sigurdur.kristinsson@karolinska.se
authors.forename: Sigurdur Y
authors.initials: SY
authors.lastname: Kristinsson
authors.forename: Min
authors.initials: M
authors.lastname: Tang
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Pfeiffer
authors.forename: Magnus
authors.initials: M
authors.lastname: Björkholm
authors.forename: Cecilie
authors.initials: C
authors.lastname: Blimark
authors.forename: Ulf-Henrik
authors.initials: UH
authors.lastname: Mellqvist
authors.forename: Anders
authors.initials: A
authors.lastname: Wahlin
authors.forename: Ingemar
authors.initials: I
authors.lastname: Turesson
authors.forename: Ola
authors.initials: O
authors.lastname: Landgren
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D016001:Confidence Intervals; D005260:Female; D005500:Follow-Up Studies; D050723:Fractures, Bone / Q000209:etiology*; D006801:Humans; D007132:Immunoglobulin Isotypes; D008297:Male; D008875:Middle Aged; D008998:Monoclonal Gammopathy of Undetermined Significance / Q000150:complications* / Q000276:immunology; D009101:Multiple Myeloma / Q000150:complications; D016016:Proportional Hazards Models; D012307:Risk Factors; D013548:Sweden; D055815:Young Adult
chemical_list: D007132:Immunoglobulin Isotypes