Radiation Decreases Bone Density while Diabetes Increases Osteoarthritis in Non-Human Primates.

Abstract

Total-body irradiation has long-term effects and may cause joint damage, especially in individuals with diabetes. Lowered bone mineral density and arthropathy related to radiation can contribute to the development of osteoarthritis. Monitoring these conditions in humans is challenging, but non-human primate models allow for longitudinal tracking of metabolic and degenerative changes. This study investigated the effect of radiation on joint health in non-human primates, including bone mineral density, and examined how diabetes influences the development of osteoarthritis. We hypothesized that joint health would be worse in diabetic and irradiated primates. Our group evaluated 163 irradiated rhesus macaques and 38 unexposed controls (total n = 201). Diabetes was present in 24 animals. Osteoarthritis was assessed in the knees, hips, shoulders, and spine, with overall osteoarthritis defined as osteoarthritis in at least one joint. Two sub-cohorts of 134 irradiated and 32 nonirradiated animals, and nine diabetic and 77 non-diabetic animals, were selected to analyze proximal humeral length and bone mineralization. The prevalence of diabetes was similar between irradiated and control groups. No link was observed between radiation exposure and overall osteoarthritis, but osteoarthritis was significantly more common in nonirradiated animals across the knee, hip, shoulder, and spine. Diabetic animals showed higher rates of osteoarthritis in all joints and overall. Irradiated non-human primates had reduced cortical volume, lower cortical and trabecular bone mineral densities, and shorter humeral length. Diabetic primates exhibited higher cortical volume and bone mineral density, while trabecular bone mineral density and humeral length remained similar. Osteoarthritis in all joints was more prevalent among diabetic and obese non-human primates. Radiation exposure decreased cortical volume and mineralization, whereas diabetes increased both cortical volume and mineralization. Overall, diabetes appears to contribute to joint degeneration and increased bone mineralization, while radiation decreases bone mineralization without increasing osteoarthritis. These findings lay the groundwork for future studies to investigate the pathways that may contribute to these conditions.