Periprosthetic joint infection (PJI) is a potentially devastating complication of joint replacement surgery. Osteocytes comprise 90–95% of all cells in hard bone tissue, are long-lived and are becoming increasingly recognised as a critical cell type in the regulation of bone and systemic physiology. The purpose of this study was to examine role of these cells in PJI pathophysiology and aetiology, with the rationale that their involvement could contribute to the difficulty in detecting and clearing PJI. This study examined the ability of human osteocytes to become infected by Staphylococcus aureus and the responses of both the host cell and pathogen in this scenario.

Several S. aureus (MRSA) strains were tested for their ability to infect human primary osteocyte-like cells in vitro and human bone samples ex vivo. Bone biopsies were retrieved from patients undergoing revision total hip arthroplasty for either aseptic loosening associated with osteolysis, or for PJI. Retrieved bacterial colony number from cell lysates and colony morphology were determined. Gene expression was measured by microarray/bioinformatics analysis and/or real-time RT-PCR.

Exposure to planktonic S. aureus (approx. 100 CFU/cell) resulted in intracellular infection of human osteocyte-like cells. We found no evidence of increased rates of osteocyte cell death in bacteria exposed cultures. Microarray analysis of osteocyte gene expression 24h following exposure revealed more than 1,500 differentially expressed genes (fold-change more than 2, false discovery rate p < 0.01). The gene expression patterns were consistent with a strong innate immune response and altered functionality of the osteocytes. Consistent patterns of host gene expression were observed between experimentally infected osteocyte-like cultures and human bone, and in PJI patient bone samples. Internalised bacteria switched to the quasi-dormant small colony variant (SCV) form over a period of 5d, and the ensuing infection appeared to reach a stable state. S. aureus infection of viable osteocytes was also identified in bone taken from PJI patients.

We have demonstrated [1] that human osteocytes can become infected by S. aureus and respond robustly by producing immune mediators. The bony location of the infected osteocyte may render them refractory to clearance by immune cells, and osteocytes may therefore be an immune-privileged cell type. The phenotypic switch of S. aureus to SCV, a form less sensitive to most antibiotics and one associated with intracellular survival, suggests that infection of osteocytes may contribute to a chronic disease state. The osteocyte may therefore serve as a reservoir of bacteria for reinfection, perhaps explaining the high prevalence of infections that only become apparent after long periods of time or recur following surgical/medical treatment. Our findings also provide a biological rationale for the recognised need for aggressive bone debridement in the surgical management of PJI.

Osteocytes (OCY) are the end stage differentiation cells of the osteoblast lineage, and are incorporated in the bone matrix during bone formation. In doing so, OCY control the mineralisation of osteoid. OCY form a dense inter-connected network of cell bodies and cell processes throughout the mineralised matrix of bone.

OCY viability depends on interstitial fluid flow along the OCY canaliculi, driven by pulsatile blood flow and loading of the skeleton. Maintenance of the density and viability of OCY are essential for bone health because OCY perform many important functions in bone. Firstly, OCY appear to initiate bone repair of bone microdamage. Secondly, OCY are almost certainly the cells, which initiate new bone formation in response to increased loading of bone. Thirdly, OCY are able to regulate the amount of new bone formation in bone remodelling cycles, at least in part by the production of a molecule called sclerostin (SCL).

Mutations in the SCL gene, or deletion of the SCL gene in transgenic mice, are associated with particularly dense, fracture resistant bones. This information has led to development of anti-SCL antibodies as a potential anabolic therapy for bones. Bone loss in ovariectomised aged rats was shown recently to be reversed by treatment with neutralising SCL antibodies. There is also some data to suggest that these antibodies may promote fracture healing. Reduced OCY viability and/or density have been reported in association with osteoporotic fracture. OCY viability seems to be dependent on skeletal loading, adequate skeletal blood flow and estrogen in females. OCY viability is adversely affected by hypoxia, unloading of the skeleton and pharmacobiology, such as chronic exposure to glucocorticoids. Both micro and macro-fractures result in disruption of the OCY network, as do procedures such as drilling and cutting of bone.

Because of the important roles of OCY in bone, new approaches to bone health may require the identification of agents to protect these cells from harmful influences in disease and ageing.

The aim of this study was to examine the progression of osteolytic lesions following liner exchange surgery and relate this to the size of the lesion prior to surgery, and whether the defect underwent curettage and bone grafting during surgery.

Six patients with well-fixed Harris-Galante-1 acetabular components underwent liner exchange surgery for excessive polyethylene wear and osteolysis. The mean interval from primary arthroplasty to revision was 14 years (range 11–17 years). All patients underwent a CT scan pre-operatively to identify the location and size of the osteolytic lesions and during surgery, accessible lesions were curetted and bone grafted. One patient had recurrent dislocations and the acetabular component was revised one year following liner exchange surgery. The remaining five patients had CT scans taken at a mean of five months (range 3–5 months) and 5 years (range 3.4–8.2 years) following surgery. Osteolytic lesion volume with or without bone grafting was measured.

Of the 19 osteolytic lesions detected pre-operatively, the first post-operative CT scan showed that four lesions were fully bone-grafted, ten lesions were partially bone-grafted and five lesions had no bone grafting during surgery. At a minimum of three years following surgery, all fully bone-grafted lesions remained full of bone- graft. Of the ten partially bone-grafted lesions, the osteolytic non-grafted zone decreased in volume in five lesions and five lesions remained unchanged. Of the five osteolytic lesions with no bone grafting, one lesion increased in volume, one lesion decreased in volume and three lesions remained unchanged. No new lesions were detected in any of the hips.

These preliminary results suggest that liner exchange surgery is effective in treating periacetabular osteolysis. Although bone grafting appears to aid in restoring bone stock, it is not essential in halting the progression of osteolysis, which likely results from the ongoing production of polyethylene particles in the joint.

Sensitive and accurate measures of osteolysis around TKR are needed to enhance clinical management and assist in planning revision surgery. Therefore, our aim was to examine, in a cadaver model of osteolysis around TKR, the sensitivity of detection and the accuracy of measuring osteolysis using Xray, CT and MRI.

Fifty-four simulated osteolytic lesions were created around six cadaver knees implanted with either a cemented or cementless TKR. Twenty-four lesions were created in the femur and thirty in the tibia ranging in size from 0.7 cm3 to 14 cm3. Standard anteroposterior and lateral fluoroscopically guided radiographs, CT and MRI scans with metal reduction protocols were taken of the knees prior to the creation of lesions and at every stage as the lesion sizes were enlarged. The location, number and size of the lesions from images obtained by each method were recorded.

The sensitivity of osteolytic lesion detection was 44% for plain radiographs, 92% for CT and 94% for MRI. On plain radiographs, 54% of lesions in the femur and 37% of lesions in the tibia were detected. None of the six posterior lesions created in the tibia were detected on the AP radiographs; however, three of these six lesions were detected on the lateral radiographs. CT was able to detect lesions of all sizes, except for four lesions in the posterior tibia (mean volume of 1.2 cm3, range 1.06–1.47 cm3). Likewise, MRI was very sensitive in detecting lesions of all sizes, with the exception of three lesions, two of which were in the femur and one was in the medial condyle of the tibia (mean volume of 1.9 cm3, range 1.09–3.14 cm3). Notably, all six posterior tibial lesions, which could not be detected using AP radiographs, were detected by MRI.

This study demonstrates the high sensitivity of both CT and MRI (which uses no ionising radiation) to detect simulated knee osteolysis and can therefore be used to detect and monitor progression of osteolysis around TKR. The study also shows the limitations of plain radiographs to assess osteolysis.