Contributing factors such as inflammation, low vitamin D, iron overload, delayed puberty, and bouts of inactivity in SCD result in decreased bone formation by osteoblasts and increased bone resorption by osteoclasts, leading to avascular necrosis, fractures, and pain. Osteoclast mediated resorption can be limited by bisphosphonates. FSH, follicle-stimulating hormone; GnRH, gonadotropin hormone-releasing hormone; IL, interleukin; LH, luteinizing hormone; ROS, reactive oxygen species. Created with Biorender.com