Cigarette Smoke Induced Alterations in Bone Microarchitecture: Regional Differences in a Mouse Model

Background Oxidative stress from prolonged exposure to tobacco smoke plays a major role in the pathogenic process leading to COPD. An increased respiratory load due to altered lung and airway mechanics increases the demand on respiratory muscles and contributes to difficulties in maintaining body weight. Theoretically, the increased muscle demand, by imposing additional stress on the muscular‐skeletal insertion, may alter bone characteristics of the rib cage and contribute to rib fracture in patients with respiratory disease. There is growing evidence that smoking delays or inhibits vertebral and long bone healing after surgery or trauma. Finally, the incidence of osteoporosis is increased in humans with poor nutrition as well as a history of current smoking, with female gender an additional risk factor in developing osteoporosis. However, direct linkage between CS exposure and bone health has proven elusive due to co‐morbidities and/or therapeutics. Here, we sought to test the hypothesis that CS smoke‐exposure alone, in the absence of glucocorticoid use, will cause alterations in bone structure. Methods Female C57BL/6J mice (17–21 g;12–14 weeks) were randomly assigned to either whole body exposure to filtered room air (n=15) or cigarette smoke (CS; n =15, SciReq; In‐Expose; 3R4F University of Kentucky reference cigarettes; ISO 1991 standard exposure; 1 hr/2× daily, 5 days/week; total particulate matter was 100 mg/m 3 for the first 3 days then 300 mg/m 3 for a total of 6 weeks). Mouse carcasses were imaged with microCT (Skyscan 1176; 9 um). Reconstruction with volume rendering and 3D model creation was performed. Morphometric analyses were performed on cortical bone of the 1st, 6th, and 10th ribs and sternum, and on trabecular bone of the sternum, femur and 6th lumbar vertebrae (LV6). Results Cortical bone thickness was significantly (p < 0.05) reduced in the 1st and 10th rib in CS‐exposed relative to RA‐exposed mice, but was unchanged in the sternum and 6 th rib. Percent trabecular bone/tissue volume, a reflection of bone mass, was significantly reduced in femurs of CS‐exposed animals (p< 0.05) but comparable in sternum and LV6 between exposure groups. Conclusions These data demonstrate in a mouse model, that chronic CS exposure alone results in thinning of the ribs that experience the greatest torque, and reduced trabecular bone mass in the femur. This profile is likely to predispose to fracture and impaired bone healing, consistent with observations in actively smoking humans. Support or Funding Information N0014‐10‐0761; N00014‐13‐1‐0742