A new approach to comprehensively evaluate the morphological properties of the human femoral head : example of application to osteoarthritic joint

Osteoarthritis affects the morphological properties of the femoral head. The goal of this study was to develop a method to elucidate whether these changes are localised to discrete regions, or if the reported trends in microstructural changes may be identified throughout the subchondral bone of the human femoral head. Whole femoral heads extracted from osteoarthritic (n = 5) and healthy controls (n = 5) underwent microCT imaging 39 μm voxel size. The subchondral bone plate was virtually isolated to evaluate the plate thickness and plate porosity. The trabecular bone region was divided into 37 volumes of interest spatially distributed in the femoral head, and bone morphometric properties were determined in each region. The study showed how the developed approach can be used to study the heterogeneous properties of the human femoral head affected by a disease such as osteoarthritis. As example, in the superior femoral head osteoarthritic specimens exhibited a more heterogeneous micro-architecture, with trends towards thicker cortical bone plate, higher trabecular connectivity density, higher trabecular bone density and thicker structures, something that could only be observed with the newly developed approach. Bone cysts were mostly confined to the postero-lateral quadrants extending from the subchondral region into the mid trabecular region. Nevertheless, in order to generalise these findings, a larger sample size should be analysed in the future. This novel method allowed a comprehensive evaluation of the heterogeneous micro-architectural properties of the human femoral head, highlighting effects of OA in the superior subchondral cortical and trabecular bone. Further investigations on different stages of OA would be needed to identify early changes in the bone

Glycation marker glucosepane increases with the progression of osteoarthritis and correlates with morphological and functional changes of cartilage in vivo

Background: Changes of serum concentrations of glycated, oxidized, and nitrated amino acids and hydroxyproline and anticyclic citrullinated peptide antibody status combined by machine learning techniques in algorithms have recently been found to provide improved diagnosis and typing of early-stage arthritis of the knee, including osteoarthritis (OA), in patients. The association of glycated, oxidized, and nitrated amino acids released from the joint with development and progression of knee OA is unknown. We studied this in an OA animal model as well as interleukin-1β-activated human chondrocytes in vitro and translated key findings to patients with OA. Methods: Sixty male 3-week-old Dunkin-Hartley guinea pigs were studied. Separate groups of 12 animals were killed at age 4, 12, 20, 28 and 36 weeks, and histological severity of knee OA was evaluated, and cartilage rheological properties were assessed. Human chondrocytes cultured in multilayers were treated for 10 days with interleukin-1β. Human patients with early and advanced OA and healthy controls were recruited, blood samples were collected, and serum or plasma was prepared. Serum, plasma, and culture medium were analyzed for glycated, oxidized, and nitrated amino acids. Results: Severity of OA increased progressively in guinea pigs with age. Glycated, oxidized, and nitrated amino acids were increased markedly at week 36, with glucosepane and dityrosine increasing progressively from weeks 20 and 28, respectively. Glucosepane correlated positively with OA histological severity (r = 0.58, p < 0.0001) and instantaneous modulus (r = 0.52–0.56; p < 0.0001), oxidation free adducts correlated positively with OA severity (p < 0.0009–0.0062), and hydroxyproline correlated positively with cartilage thickness (p < 0.0003–0.003). Interleukin-1β increased the release of glycated and nitrated amino acids from chondrocytes in vitro. In clinical translation, plasma glucosepane was increased 38% in early-stage OA (p < 0.05) and sixfold in patients with advanced OA (p < 0.001) compared with healthy controls. Conclusions: These studies further advance the prospective role of glycated, oxidized, and nitrated amino acids as serum biomarkers in diagnostic algorithms for early-stage detection of OA and other arthritic disease. Plasma glucosepane, reported here for the first time to our knowledge, may improve early-stage diagnosis and progression of clinical OA

Fundamental subchondral bone changes in spontaneous knee osteoarthritis

Osteoarthritis has an unknown aetiology, and tissue samples from early stage human osteoarthritis tissue cannot be reliably obtained. Therefore understanding the development of OA relies on using animal models: such as the spontaneous changes seen in the Dunkin-Hartley guinea pig strain, which are biochemically, histologically and radiologically similar to human OA. We investigated the role of bone change in early OA development using the non-OA developing Bristol strain-2 as control from 3 to 36 weeks by standard microfocal X-ray imaging and histological techniques. The patella, tibia and femur epiphyseal region and immediate subchondral area were analysed for bone density at all ages. We found that both radiological and histological osteoarthritis scores increased progressively for the Dunkin-Hartley, but not for the BS2 demonstrating its value as a control. The Dunkin-Hartley had a higher bone density and greater subchondral bone thickness from 24 weeks of age. We conclude that prior to any gross osteoarthritis pathology the Dunkin-Hartley are undergoing subchondral bone remodelling, thus demonstrating the fundamental role of early bone remodelling in the development of osteoarthritis