Material changes of bone following ishcemia of the immature femoral head

Abstract

Legg-Calvé-Perthes disease (LCPD) is a childhood hip disorder resulting from the loss of blood flow to the femoral head. In severe cases of the disease, the femoral head can develop a flattening deformity; additionally, if the disease is diagnosed at a later stage, it leaves most patients to develop early osteoarthritis of the hip. Due to a lack of pathological specimen from patients, an experimental piglet model of femoral head ischemia was developed. The model closely follows the radiographic changes seen in LCPD patients, where there is subchondral fracture, resorption, and a flattening deformity of the femoral head. After ischemia, the trabecular bone tissue in the femoral head is hypothesized to undergo material changes that predispose it to possible subchondral fracture and increased resorption. The increased resorption outpaces new bone formation resulting in overall bone loss. Successful treatment is largely dependent on maintaining sphericity while the femoral head is revascularized with new blood supply and reossified with new bone. In order to elucidate the pathological events from femoral head ischemia, the material (i.e. nanomechanical and mineral) changes in trabecular bone were investigated. This study consists of three parts: 1) the avascular stage where there is no resorption or revascularization and prior to any fracture, 2) the revascular stage where there is extensive resorption of the bone, and 3) the revascular stage where the femoral head has been treated with anabolic and anti-resorptive agents to restore the balance of bone resorption and bone formation. The bone was characterized using optical and fluorescence microscopy, nanoindentation, scanning electron microscopy, Raman spectroscopy, and X-ray absorbance near edge structure spectroscopy. Results show the nanoindentation properties of the trabecular bone are increased in the early stage of ischemic osteonecrosis of the immature femoral head and make it more susceptible to microcrack formation, while balanced repair aided by anabolic and anti-resorptive treatments help normalize the material properties. This study provides a greater understanding of ischemia of the developing femoral head and the role of treatment on the material properties of bone. It identifies microstructural damage and compositional variance in ischemic bone that has been previously unavailable. In addition, it provides valuable insight on the quality of bone after treatment, and potentially provides further evidence for the use of anabolic and anti-resorptive treatments in LCPD patients.