Bone Microstructure and Regional Distribution of Osteoblast and Osteoclast Activity in the Osteonecrotic Femoral Head

Abstract

ObjectiveTo detect and compare the bone microstructure and osteoblast and osteoclast activity in different regions of human osteonecrotic femoral heads.MethodsOsteonecrotic femoral heads were obtained from 10 patients (6 males, 4 females; Ficat IV) undergoing total hip arthroplasty between 2011 and 2013. The samples were divided into subchondral bone, necrotic, sclerotic, and healthy regions based on micro-computed tomography (CT) images. The bone microstructure, micromechanics, and osteoblast and osteoclast activity were assessed using micro-CT, pathology, immunohistochemistry, nanoindentation, reverse transcription polymerase chain reaction (RT-PCR), tartrate-resistant acid phosphatase staining and Western blotting.Results(1) The spatial structure of the bone trabeculae differed markedly in the various regions of the osteonecrotic femoral heads. (2) The elastic modulus and hardness of the bone trabeculae in the healthy and necrotic regions did not differ significantly (P >0.05). (3) The subchondral bone and necrotic region were positive on TRAP staining, while the other regions were negative. (4) On immunohistochemical staining, RANK and RANKL staining intensities were increased significantly in the subchondral bone and necrotic region compared with the healthy region, while RUNX2 and BMP2 staining intensities were increased significantly in the sclerotic region compared with the necrotic region. (5) OPG, RANK, RANKL, RUNX2, BMP2, and BMP7 protein levels were greater in the necrotic and sclerotic region than in subchondral bone and the healthy region.ConclusionThe micromechanical properties of bone trabeculae in the necrotic region did not differ significantly from the healthy region. During the progress of osteonecrosis, the bone structure changed markedly. Osteoclast activity increased in subchondral bone and the necrotic region while osteoblast activity increased in the sclerotic region. We speculate that the altered osteoblast and osteoclast activity leads to a reduction in macroscopic mechanical strength.

Effects of sclerotic changes on stress concentration in early‐stage osteonecrosis: A patient‐specific, 3D finite element analysis

“…Regarding the pathogenesis of the femoral head collapse in ONFH, Bullough and DiCarlo proposed that it might result from the focal concentration of stress at the junction between the thin trabeculae of the necrotic zone and the thickened trabeculae of the reparative zone. Similar to previous reports, micro‐CT evaluations in this study showed that in the reparative zone with sclerotic changes, the trabecular thickness was significantly increased compared to that in the necrotic zone. In addition, collapse has been found to consistently involve subchondral fractures at the lateral boundary .…”

“…Several authors have conducted experiments using resected femoral heads with end‐stage ONFH to explore the mechanism of femoral head collapse. Wang et al showed that the micromechanical properties of bone trabeculae in collapsed femoral heads with ONFH did not differ significantly between the necrotic zone and the healthy zone. Using Raman spectroscopy analyses, Pascart et al also demonstrated that the molecular composition and structure of the trabecular bone were not modified in end‐stage ONFH.…”

“…The elastic modulus of bone in collapsed ONFH has been reported to be markedly lower (72%) than in samples from normal femoral heads . However, the biomechanical properties of femoral heads with osteonecrosis have been reported to be similar in the necrotic and viable zones in both nanoindentation testing and Raman spectroscopy analyses . Since this study used CT data from cases of early‐stage osteonecrosis, the elastic moduli of both the necrotic and viable zones were determined based on CT density values.…”

“…First, the apparent bone mineral density (p in g/cm 3 ) of each element was determined using Hounsfield units. The elastic modulus (E [MPa]) of each element was then determined from the apparent bone density value using the equations proposed by Keyak et al Since the biomechanical properties of ONFH have been reported to be similar in necrotic and viable zones, the elastic modulus of necrotic zones was also determined from CT density values. The Poisson's ratio of the pelvis, the femur, and necrotic zones was 0.40 .…”

Efficacy of teriparatide in the treatment of nontraumatic osteonecrosis of the femoral head: a retrospective comparative study with alendronate

“…The precise mechanism of collapse in NOFH has not been clarified; however, excessive bone resorption by osteoclast in necrotic regions is thought to induce collapse of the femoral head [7]. The disease is progressive and once collapse of the femoral head occurs, osteoarthritis of the hip joint is developed in few years.…”