Muscle Deficits in Rheumatoid Arthritis Contribute to Inferior Cortical Bone Structure and Trabecular Bone Mineral Density

Abstract

Objective Rheumatoid arthritis (RA) is associated with muscle loss, osteoporosis, and fracture. We examined associations between skeletal muscle mass, strength, and quality and trabecular and cortical bone deficits in patients with RA and healthy controls. Methods Participants, ages 18–75 years, completed whole-body DXA and peripheral quantitative CT of the tibia to quantify appendicular lean mass and fat mass indices (ALMI, FMI),, muscle density at the lower leg, trabecular bone density, and cortical bone thickness. Age-, sex-, and race-specific Z-Scores were calculated based on distributions in controls. Associations between body composition and pQCT bone outcomes were assessed in RA and controls. Linear regression analyses assessed differences in bone outcomes after considering differences in body mass index (BMI) and body composition. Results The sample consisted of 112 RA patients (55 men) and 412 controls (194 men). Compared to controls, RA patients had greater BMI (p=0.004), lower ALMI after adjustment for FMI (p=0.02), lower muscle strength (p=0.006), and lower muscle density (p<0.0001). Among RA, ALMI Z-Scores were positively associated with trabecular density [β: 0.29 (0.062,0.52) p=0.01] and cortical thickness [β: 0.32 (0.13,0.53) p=0.002]. Associations were similar in controls. Bone outcomes were inferior in RA patients after adjusting for BMI but similar to controls when adjusting for body composition. Radiographic damage and higher adiponectin levels were independently associated with inferior bone outcomes. Conclusions Patients with RA exhibit deficits in cortical bone structure and trabecular density at the tibia and a preserved functional muscle-bone unit. A loss of mechanical loading may contribute to bone deficits.

Intramuscular Fat Accumulation and Associations With Body Composition, Strength, and Physical Functioning in Patients With Rheumatoid Arthritis

“…Characteristics of the RA study population are described in Table 1. Comparisons between RA patients and the reference population have been previously published from this cohort (19). Patients with RA had substantially lower muscle density compared to the reference group as evidenced by low (negative) muscle density Z-Scores, consistent with greater intramuscular fat (Table 1).…”

“…Patients with RA also had excessive visceral adiposity, with 32% of patients being characterized as having a “high” VAT area (>160 cm) (42). The characteristics of the reference population have been previously described elsewhere (15, 19, 20).…”

“…Low muscle density has been observed in patients with rheumatoid arthritis (RA) and is associated with greater disease activity and Interleukin(IL)-6 levels (19–21). Two previous studies demonstrated that low muscle density was correlated with poorer physical functioning in RA (21, 22).…”

Association of Low Muscle Density With Deteriorations in Muscle Strength and Physical Functioning in Rheumatoid Arthritis

“…In rheumatoid arthritis (RA), adverse changes to body composition, including obesity, excess adiposity, and low muscle mass, have been linked to poor physical function in cross‐sectional studies (12–15). Low muscle density has also recently been observed in patients with RA and is independently associated with greater disease activity, high interleukin‐6 (IL‐6) levels, and worse physical function in several cross‐sectional studies (16–19).…”

Myostatin induces tumor necrosis factor‐α expression in rheumatoid arthritis synovial fibroblasts through the PI3K–Akt signaling pathway

“…Observations of altered body composition in patients with rheumatoid arthritis (RA) describe deficits in muscle mass, quality, and strength, as well as poorly adapted cortical bone structure and trabecular volumetric bone mineral density, compared to what would be expected for their body mass index (Baker et al, ). RA pathogenesis is marked by joint swelling, cartilage, and bone erosion, as well as the exponential proliferation of RA synovial fibroblasts (RASFs) in the superficial layer of the synovium, due to secreted and accumulated proinflammatory cytokines situated near the inflamed joint (Hirota et al, ).…”