Fracture risk in monoclonal gammopathy of undetermined significance.
To assess fractures in monoclonal gammopathy of undetermined significance (MGUS), the precursor of multiple myeloma, we followed 488 Olmsted County, MN, residents with MGUS in a retrospective cohort study. There was a 2.7-fold increase in the risk of axial fractures but no increase in limb fractures. The pathophysiologic basis for the increased axial fractures should be determined.


BACKGROUND
Multiple myeloma is often preceded by monoclonal gammopathy of undetermined significance (MGUS). Fractures are common in myeloma as a result of lytic bone lesions, generalized bone loss, and elevated bone turnover from excessive cytokine production. Whether fractures are also increased in MGUS is unknown.


METHODS
In a population-based retrospective cohort study, 488 Olmsted County, MN, residents with MGUS first diagnosed in 1960-1994 (52% men; mean age, 71.4 +/- 12.8 years) were followed for 3901 person-years; follow-up was censored at progression to myeloma. The relative risk of fractures was assessed by standardized incidence ratios (SIRs), and risk factors were evaluated in proportional hazards models.


CONCLUSIONS
Altogether, 200 patients experienced 385 fractures. Compared with expected rates in the community, statistically significant increases were seen for fractures at most axial sites, for example, vertebrae (SIR, 6.3; 95% CI, 5.2-7.5). There was a slight increase in hip (SIR, 1.6; 95% CI, 1.2-2.2) but not distal forearm fractures (SIR, 0.8; 95% CI, 0.4-1.5). The relative risk (SIR) of any axial fracture was 2.7 (95% CI, 2.3-3.1) compared with only 1.1 (95% CI, 0.9-1.4) for all limb fractures combined. In a multivariate analysis, the independent predictors of any subsequent fracture were age (hazard ratio [HR] per 10-year increase, 1.4; 95% CI, 1.2-1.6) and corticosteroid use (HR, 1.8; 95% CI, 1.2-2.6); greater weight at diagnosis (HR per 10 kg, 0.8; 95% CI, 0.8-0.9), and IgG monoclonal protein (HR, 0.7; 95% CI, 0.5-0.97) were protective. Baseline monoclonal protein level, a determinant of myeloma progression, did not predict fracture risk. Thus, the risk of axial, but not peripheral, fractures is increased among MGUS patients even before progression to myeloma. The pathophysiologic basis for this should be determined because elevated bone turnover, for example, might be treatable.
Melton
L Joseph
LJ
Division of Epidemiology, Department of Health Sciences Research, Mayo Clinic and Mayo Foundation, Rochester, Minnesota 55905, USA.
Rajkumar
S Vincent
SV
Khosla
Sundeep
S
Achenbach
Sara J
SJ
Oberg
Ann L
AL
Kyle
Robert A
RA
D000058:Accidental Falls; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D001827:Body Height; D015992:Body Mass Index; D001835:Body Weight; D015331:Cohort Studies; D005260:Female; D050723:Fractures, Bone / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology; D005598:Fractures, Spontaneous / Q000453:epidemiology / Q000209:etiology / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D008910:Minnesota / Q000453:epidemiology; D015999:Multivariate Analysis; D010265:Paraproteinemias / Q000150:complications*; D016016:Proportional Hazards Models; D012189:Retrospective Studies; D012307:Risk Factors; D013124:Spinal Injuries / Q000453:epidemiology / Q000209:etiology / Q000473:pathology; D014947:Wounds and Injuries / Q000453:epidemiology / Q000209:etiology / Q000473:pathology
D000305:Adrenal Cortex Hormones