Cortical Bone Loss in a Spontaneous Murine Model of Systemic Lupus Erythematosus.

Abstract

Patients with systemic lupus erythematosus (SLE), a chronic inflammatory disease characterized by loss of T- and B-cell tolerance to autoantigens, are at increased risk for osteoporosis and fractures. Mice deficient in Fc gamma receptor IIb (FcγRIIB) exhibit spontaneous SLE and its restoration rescues the disease. To determine whether deleting FcγRIIB affects cortical bone mass and mechanical properties, we analyzed cortical bone phenotype of FcγRIIB knockouts at different ages. FACS analysis revealed that 6-month-old FcγRIIB-/- mice had increased B220lowCD138+ cells, markers of plasma cells, indicating active SLE disease. In contrast, 3-month-old FcγRIIB-/- mice did not develop the active SLE disease. µCT analysis indicated that FcγRIIB deletion did not affect cortical bone in 3-month-old mutants. However, 6- and 10-month-old FcγRIIB-/- males and females had osteopenic cortical bone and the severity of bone loss increased with disease duration. FcγRIIB deletion decreased cross-sectional area, cortical area, and marrow area in 6-month-old males. Cortical area and cortical thickness were decreased in 10-month-old FcγRIIB-/- males. Lack of FcγRIIB decreased cortical thickness without affecting cortical area in females. However, deletion of a single FcγRIIB allele was insufficient to induce cortical bone loss. The bending strength was decreased in 6- and 10-month-old FcγRIIB-deficient males compared to WT controls. A microindentation analysis demonstrated significantly decreased hardness in both 10-month-old FcγRIIB-/- males and females. Our data indicate that FcγRIIB contributes to the regulation of cortical bone homeostasis subsequent to SLE development and that deletion of FcγRIIB in mice leads to SLE-like disease associated with cortical bone loss and decreased bending strength and hardness.