Disrupted radial and tibial microarchitecture in patients with monoclonal gammopathy of undetermined significance
Patients with monoclonal gammopathy of undetermined significance (MGUS) had abnormalities in volumetric BMD (vBMD), microarchitecture, and stiffness at both the radius and tibia by high-resolution peripheral quantitative CT compared to matched controls. This is the first report demonstrating that patients with MGUS have microarchitectural deficits at multiple skeletal sites.
Fracture risk is elevated in patients with monoclonal gammopathy of undetermined significance (MGUS). However, the pathogenesis of bone disease in these patients is poorly understood. Prior work using high-resolution peripheral CT (HRpQCT) demonstrated abnormal microarchitecture at the radius, with predominantly cortical abnormalities. We hypothesized that patients with MGUS have abnormal microarchitecture at both radius and tibia compared to controls, reflecting global skeletal effects of the disease.
This case-control study enrolled 36 subjects; patients with MGUS (n = 12) were matched 1:2 by age, sex, and race to controls (n = 24). Areal BMD (aBMD) was measured by DXA, vBMD, and microarchitecture by HRpQCT, and whole bone stiffness by finite element analysis. Serum was drawn for markers of bone metabolism and inflammation.
By DXA, MGUS patients had lower aBMD at the lumbar spine, femoral neck, and 1/3 radius. Markers of bone metabolism and inflammation did not differ. By HRpQCT at the radius, MGUS patients had lower total, trabecular and cortical density, lower trabecular number, and greater trabecular separation and heterogeneity. At the tibia, MGUS patients had lower total and trabecular density, lower trabecular number, greater separation and heterogeneity, and lower whole bone stiffness.
Patients with MGUS had lower vBMD, cortical, and trabecular abnormalities at the radius compared to matched controls. At the tibia, trabecular abnormalities predominated. These results suggest that in addition to previously described cortical deficits, deterioration of trabecular bone may contribute to a generalized skeletal fragility in patients with MGUS.
KeywordsBone quality Microarchitecture Monoclonal gammopathy of undetermined significance Osteoporosis
This work was supported by NIH K23 DK084337 (Stein), NIH U01 AR055968 (Shane), and a gift from the Linden Trust.
Compliance with ethical standards
Conflict of interest
Emily Stein, Alexander Dash, Sanchita Agarwal, Mariana Bucovsky, Jing Fu, Elizabeth Lentzsch, and Elizabeth Shane declare that they have no conflict of interest. Dr. Lentzsch is chief scientific advisor and shareholder of Caelum Biosciences and advisor for Janssen, Bayer, and Karyopharm.
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