Using immunohistochemical methods we determined the presence of SP- and CGRP-immunopositive nerve fibers in the hip joint of patients with femoral neck fracture (controls, group 1), painful osteoarthritis (group 2), and painless failed total hip arthroplasties (group 3). Immunoreactive nerve fibers were found in the soft tissue of the fossa acetabuli as well as in the subintimal part of the synovial layer in the hip joint capsule of groups 1 and 2. In the capsule of controls the innervation density had a median of 5.7fibers/cm(2) for CGRP-ir and 3.2fibers/cm(2) for SP-ir afferents. In the osteoarthritic group, the density significantly increased to a median of 15.6fibers/cm(2) for CGRP-ir and 8.2fibers/cm(2) for SP-ir neurons (p=0.05). Patients with failed hip arthroplasties completely lacked these neuropeptide containing afferents. Innervation density in the fossa acetabuli of osteoarthritc patients showed a median of 14.1fibers/cm(2) for CGRP-ir and 5.9fibers/cm(2) for SP-ir afferents. From these data we assume that the hip joint capsule and the soft tissue of the fossa acetabuli are important triggers of nociception. This is supported by the fact, that patients with loosened total hip arthroplasties, where we failed to detect SP- and CGRP-immunoreactive fibers, did not feel pain. The upregulation of SP- and CGRP-positive neurons in response to arthritic stages suggests a mechanism involving neuropeptides in the maintenance of a painful degenerative joint disease and in mediating noxious stimuli from the periphery. Furthermore, these findings help to explain clinical observations, such as effectiveness of local therapy to control hip pain with intraarticular injection, synovectomy and denervation procedures.

Bearing surface wear and periprosthetic osteolysis due to wear particles are among the most common reasons for joint replacement failure. A murine calvarial model of wear particle-induced osteolysis has been used to identify different biologic factors associated with this problem and to test nonsurgical methods of modulating the host response to particulate debris. This model has utilized titanium particles, however, in clinical practice the most common source of particulate debris is polyethylene particles from bearing surface wear. We now report a calvarial model of wear particle-induced osteolysis based on commercially available polyethylene particles. We found that compared to sham surgery osteoclast recruitment and bone resorption can be induced by introduction of the titanium particles or polyethylene particles. However, bone resorption was significantly higher with polyethylene particles compared to titanium particles 0, = 0.02).We consider the polyethylene based murine calvarial model of wear particle-induced osteolysis a reliable and clinically relevant tool to understand the host factors and potential pharmacologic interventions that can influence wear debris generated osteolysis. This model might serve as an extension of the well-established titanium based bone resorption model.

Small-animal models are useful for the in vivo study of particle-induced osteolysis, the most frequent cause of aseptic loosening after total joint replacement. Microstructural changes associated with particle-induced osteolysis have been extensively explored using two-dimensional (2D) techniques. However, relatively little is known regarding the 3D dynamic microstructure of particle-induced osteolysis. Therefore, we tested micro-computed tomography (micro-CT) as a novel tool for 3D analysis of wear debris-mediated osteolysis in a small-animal model of particle-induced osteolysis. The murine calvarial model based on polyethylene particles was utilized in 14 C57BL/J6 mice randomly divided into two groups. Group 1 received sham surgery, and group 2 was treated with polyethylene particles. We performed 3D micro-CT analysis and histological assessment. Various bone morphometric parameters were assessed. Regression was used to examine the relation between the results achieved by the two methods. Micro-CT analysis provides a fully automated means to quantify bone destruction in a mouse model of particle-induced osteolysis. This method revealed that the osteolytic lesions in calvaria in the experimental group were affected irregularly compared to the rather even distribution of osteolysis in the control group. This is an observation which would have been missed if histomorphometric analysis only had been performed, leading to false assessment of the actual situation. These irregularities seen by micro-CT analysis provide new insight into individual bone changes which might otherwise be overlooked by histological analysis and can be used as baseline information on which future studies can be designed.

The action of the intersegmental agonist and antagonist muscles biomechanically increases the overall stiffness (stability) of the intervertebral joints in axial torque and lateral bending, whereas it may destabilize the segment in flexion.

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