Cellular alterations in trabecular bone following monocrotaline-induced right heart failure in rats

Heart failure is associated with bone deterioration, consequently increasing the risk of fractures. Fractures occurring in patients with heart failure are associated with increased hospitalization and mortality rates, making the prevention of bone deterioration a critical clinical concern. The cellular alterations associated with heart failure-related bone deterioration remain largely unexplored. This study aimed to investigate histological changes in trabecular bone following heart failure, with a focus on characterizing cellular alterations associated with bone deterioration. Male Wistar rats were assigned to either a control or heart failure group. The heart failure group was administered monocrotaline intraperitoneally, while the control group received a vehicle injection. Twenty-eight days post-injection, histological analyses were conducted on the proximal humerus, proximal femur, distal femur, and proximal tibia. Compared to controls, rats in the heart failure group exhibited a significant reduction in trabecular bone volume at all examined sites. In parallel, they showed a significant increase in the number of osteoclasts, an increased empty lacuna ratio (indicative of osteocyte loss), and a greater proportion of caspase-3-positive osteocytes (a marker of apoptosis). These changes were consistently observed across all anatomical locations. These findings suggest that heart failure induces osteocyte apoptosis, which may drive osteoclastogenesis and lead to trabecular bone loss. The fact that similar changes were observed consistently across all anatomical sites suggests that systemic factors associated with heart failure, rather than localized influences, are likely the primary contributors to bone deterioration. Understanding these processes could inform novel therapeutic strategies to prevent bone loss following heart failure.