THU0470 Non-clonal elevation of serum immunoglobulin free light chains is predictive of hip fracture in both women and men
Authors: S. Amin, E.J. Atkinson, S.J. Achenbach, A. Dispenzieri, R.A. Kyle, S.V. Rajkumar
Journal: Annals of the Rheumatic Diseases (2018)

<h3>Background</h3> Proinflammatory cytokines favour uncoupling of bone turnover and decreased bone density and strength, leading to increased fracture risk. Non-clonal elevation of serum immunoglobulin free light chains (sum of kappa and lambda chains) (<b>∑FLC</b>) may be a global marker of generalised immune stimulation, and has been associated with chronic co-morbidities<sup>1</sup> as well as increased mortality<sup>2</sup>. <h3>Objectives</h3> We examined whether elevated ∑FLC is associated with an increased risk for hip fractures in a population-based cohort. <h3>Methods</h3> We studied Olmsted County, Minnesota, USA residents, age ≥50 years, in whom ∑FLC was measured between March 1995 and November 2003 and research authorisation was available. Anyone with a known plasma cell disorder was excluded. Using the Rochester Epidemiology Project, a unique medical records linkage system that allows access to all (inpatient and outpatient) community medical records for Olmsted County residents, we identified all hip fractures that occurred in subjects following their ∑FLC measurement to their last available follow-up or the end of 2015. All available medical records were reviewed by trained nurse abstractors to validate hip fractures identified and to determine their antecedent cause (pathological process [e.g., malignancy], severe trauma [e.g., motor vehicle accidents] and those due to no more than moderate trauma [by convention, equivalent to a fall from standing height or less]). Charlson comorbidity index (<b>CCI</b>) was determined at the time of baseline ∑FLC measurement. We used a Cox proportional hazards model, stratified by sex, adjusting for age, serum creatinine and CCI, to examine whether a ∑FLC ≥4.72 mg/dl (levels previously associated with increased mortality in this population<sup>1</sup>) is associated with an increased risk for hip fracture. <h3>Results</h3> We studied 15 814 residents [mean age (SD), 64<sup>10</sup> yrs; 8722 women, 7092 men] of whom 796 (9.1%) women and 781 (11.0%) men had a ∑FLC ≥4.72 mg/dl. Women and men with an elevated ∑FLC ≥4.72 mg/dl had higher CCI [median (IQR) 2 (0,4) vs 0 (0,2); same results for both sexes]. We identified 687 women and 255 men with a hip fracture from any cause (628 women and 220 men had a moderate trauma hip fracture), over 1 12 171 person-years (p-y) and 89 269 p-y of follow-up, respectively. We found that both women and men with ∑FLC ≥4.72 mg/dl had an increased risk for hip fracture due to any cause: hazard ratio (HR) [95% CI] 1.31 [1.00, 1.73] in women, HR 1.97 [1.37, 2.83] in men; as well as for moderate trauma hip fractures: HR 1.39 [1.05, 1.84] in women, HR 2.12 [1.46, 3.09] in men. <h3>Conclusions</h3> We found that ∑FLC ≥4.72 mg/dl is associated with an increased risk for hip fracture in both women and men, independent of age and chronic co-morbidities. Elevated ∑FLC may be a marker of proinflammatory cytokines detrimental to bone health and warrants further study. <h3>References</h3> [1] Nakano T, et al. Free Immunoglobulin Light Chain: Its Biology and Implications in Diseases. Clinica Chimica Acta. 2011;412(11–12):843–9. [2] Dispenzieri A, et al. Use of Nonclonal Serum Immunoglobulin Free Light Chains to Predict Overall Survival in the General Population. Mayo Clinic Proceedings 2012;87(6):517–523. <h3>Acknowledgements</h3> Supported by grant P01 AG04875, R01 CA107476 and R01 AG034676 from the National Institutes of Health, U.S. Public Health Service. <h3>Disclosure of Interest</h3> None declared