Periprosthetic Interface Research Articles

Water Jet Applicator for Interface Tissue Removal in Minimally Invasive Hip Refixation: Testing the Principle and Design of Prototype

Mechanical loosening of implants is in the majority accompanied with a periprosthetic interface membrane, which has to be removed during revision surgery. The same is true if a minimal invasive (percutaneous) refixation of a loose implant is done. We describe the requirements for a waterjet applicator for interface tissue removal for this percutaneous hip refixation technique. The technical requirements were either obtained from a literature review, a theoretical analysis, or by experimental setup. Based on the requirements, a waterjet applicator is designed which is basically a flexible tube (outer diameter 3 mm) with two channels. One channel for the water supply (diameter 0.9 mm) and one for suction to evacuate water and morcellated interface tissue from the periprosthetic cavity. The applicator has a rigid tip (length 6 mm), which directs the water flow to create two waterjets (diameter 0.2 mm), both focused into the suction channel. The functionality of this new applicator is demonstrated by testing a prototype of the applicator tip in an in vitro experimental setup. This testing has shown that the designed applicator for interface tissue removal will eliminate the risk of water pressure buildup; the ejected water was immediately evacuated from the periprosthetic cavity. Blocking of the suction opening was prevented because the jets cut through interface tissue that gets in front of the suction channel. Although further development of the water applicator is necessary, the presented design of the applicator is suitable for interface tissue removal in a minimally invasive hip refixation procedure.

Mechanical loading releases osteoclastogenesis-modulating factors through stimulation of the P2X7 receptor in hematopoietic progenitor cells.

Mechanical instability of bone implants stimulate osteoclast differentiation and peri-implant bone loss, leading to prosthetic loosening. It is unclear which cells at the periprosthetic interface transduce mechanical signals into a biochemical response, and subsequently facilitate bone loss. We hypothesized that mechanical overloading of hematopoietic bone marrow progenitor cells, which are located near to the inserted bone implants, stimulates the release of osteoclast-inducing soluble factors. Using a novel in vitro model to apply mechanical overloading, we found that hematopoietic progenitor cells released adenosine triphosphate (ATP) after only 2 min of mechanical loading. The released ATP interacts with its specific receptor P2X7 to stimulate the release of unknown soluble factors that inhibit (physiological loading) or promote (supraphysiological loading) the differentiation of multinucleated osteoclasts derived from bone marrow cultures. Inhibition of ATP-receptor P2X7 by Brilliant Blue G completely abolished the overloading-induced stimulation of osteoclast formation. Likewise, stimulation of P2X7 receptor on hematopoietic cells by BzATP enhanced the release of osteoclastogenesis-stimulating signaling molecules to a similar extent as supraphysiological loading. Supraphysiological loading affected neither gene expression of inflammatory markers involved in aseptic implant loosening (e.g., interleukin-1β (IL-1β), IL-6, tumor necrosis factor-α, and PTGES2) nor expression of the osteoclast modulators receptor activator of nuclear factor κ-Β ligandand osteoprotegerin. Our findings suggest that murine hematopoietic progenitor cells are a potential key player in local mechanical loading-induced bone implant loosening via the ATP/P2X7-axis. Our approach identifies potential therapeutic targets to prevent prosthetic loosening.

Protein phosphatase 2A as a new target for downregulating osteoclastogenesis and alleviating titanium particle-induced bone resorption

Receptor activator of nuclear factor-кB ligand (RANKL)-induced osteoclastogenesis is believed to play a critical role in osteolytic diseases including peri-prosthetic osteolysis (PPO), the primary reason for implant failure and revision surgery. In this study, we observed that protein phosphatase 2A (PP2A), a major serine-threonine phosphatase, was highly expressed in human periprosthetic interface membranes with aseptic loosening and in a murine osteolysis model induced by titanium particle irritation. PP2A inhibition effectively alleviated titanium particle-induced bone destruction at osteolytic sites. In addition, PP2A downregulation significantly decreased osteoclast numbers and RANKL expression, compared with in animals treated with only titanium. Mechanistically, a PP2A selective inhibitor or PP2A siRNA suppressed osteoclastogenesis and alleviated osteoclastic resorption by inhibiting the RANKL-induced nuclear factor-кB and c-Jun N-terminal kinase signaling pathways. Downstream NFATc1 and c-Fos expression were also substantially suppressed by PP2A inhibition or knockdown. Our findings support the importance of PP2A during osteoclastogenesis, identifying PP2A as a novel target for treating particle-induced or other osteoclast-mediated bone resorption diseases. Statement of significanceExcessive osteoclast activation disrupts bone homeostasis and leads to osteoclast-mediated bone resorption diseases, such as peri-prosthetic osteolysis, regarded as the primary reason for implant failure and revision surgery. Here, we firstly demonstrated protein phosphatase 2A (PP2A), a major serine-threonine phosphatase, was highly expressed in human periprosthetic interface membranes with aseptic loosening and murine osteolysis model. Moreover, PP2A inhibition effectively alleviated titanium particle-induced bone destruction and decreased osteoclast numbers. Meanwhile, a PP2A selective inhibitor or PP2A siRNA suppressed osteoclastogenesis and alleviated osteoclastic resorption by inhibiting the nuclear factor-кB and c-Jun N-terminal kinase signaling pathways. Thus, PP2A is involved in osteoclastogenesis and could be a promising target for regulating bone homeostasis and osteolytic responses.

Supraphysiological loading induces osteocyte-mediated osteoclastogenesis in a novel in vitro model for bone implant loosening.

We aimed to develop an in vitro model for bone implant loosening, allowing analysis of biophysical and biological parameters contributing to mechanical instability-induced osteoclast differentiation and peri-implant bone loss. MLO-Y4-osteocytes were mechanically stimulated for 1 h by fluid shear stress using regimes simulating: (i) supraphysiological loading in the peri-prosthetic interface (2.9 ± 2.9 Pa, 1 Hz, square wave); (ii) physiologic loading in the cortical bone (0.7 ± 0.7 Pa, 5 Hz, sinusoidal wave); and (iii) stress shielding. Cellular morphological parameters, membrane-bound RANKL expression, gene expression influencing osteoclast differentiation, nitric oxide release and caspase 3/7-activity were determined. Either Mouse bone marrow cells were cultured on top of loaded osteocytes or osteocyte-conditioned medium was added to bone marrow cells. Osteoclast differentiation was assessed after 6 days. We found that osteocytes subjected to supraphysiological loading showed similar morphology and caspase 3/7-activity compared to simulated physiological loading or stress shielding. Supraphysiological stimulation of osteocytes enhanced osteoclast differentiation by 1.9-fold compared to physiological loading when cell-to-cell contact was permitted. In addition, it enhanced the number of osteoclasts using conditioned medium by 1.7-fold, membrane-bound RANKL by 3.3-fold, and nitric oxide production by 3.2-fold. The stimulatory effect of supraphysiological loading on membrane-bound RANKL and nitric oxide production was higher than that achieved by stress shielding. In conclusion, the in vitro model developed recapitulated the catabolic biological situation in the peri-prosthetic interface during instability that is associated with osteoclast differentiation and enhanced RANKL expression. The model thus provides a platform for pre-clinical testing of pharmacological interventions with potential to stop instability-induced bone implant loosening. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1425-1434, 2018.

Low sensitivity of implant sonication when screening for infection in revision surgery

Background and purpose — Prosthetic-joint infection (PJI) is the most serious complication of arthroplasty, and accurate identification of a potentially responsible microorganism is essential for successful antibiotic treatment. We therefore determined the diagnostic accuracy of sonication and compared it with tissue culture as a screening tool in detecting prosthetic joint infection in revision arthroplasty.Patients and methods — 252 consecutive revision arthroplasty cases were enrolled. These cases were determined as being suspected or unsuspected of having infection according to standard criteria. Perioperatively, 6 periprosthetic interface tissue biopsies were obtained from each patient and the implants removed were sonicated. The sensitivity and specificity of periprosthetic tissue culture and sonication fluid cultures were determined.Results — Preoperatively, 75 revision cases were classified as having PJI (33 early and 42 late) and 177 were unsuspected of having infection. Compared with tissue culture, the sensitivity of the sonication fluid analysis was low: 0.47 (95% CI: 0.35–0.59) for sonication as compared to 0.68 (95% CI: 0.56–0.78) for tissue culture. The specificity of the sonication fluid analysis was higher than that for tissue culture: 0.99 (95% CI: 0.96–1.0) as compared to 0.80 (95% CI: 0.74–0.86).Interpretation — Sonication is a highly specific test for diagnosis of PJI. However, due to the low sensitivity, a negative sonication result does not rule out the presence of PJI. Thus, sonication is not of value for screening of microorganisms during revision surgery.

Tenosynovial giant cell tumour (pigmented villonodular synovitis-)-like changes in periprosthetic interface membranes.

Tenosynovial giant cell tumour (TSGCT; synonym, pigmented villonodular synovitis (PVNS)) is a rare low-grade mesenchymal neoplasm of either intra-articular or extra-articular origin. The etiopathogenesis of TSGCT is still uncertain, but recent studies showed a translocation involving colony-stimulating factor 1 (CSF-1) gene in a subset of cases. Histological features mimicking TSGCT can sometimes be encountered in periprosthetic interface membranes. To investigate the frequency and morphologic spectrum of this phenomenon, we conducted a systematic analysis of 477 periprosthetic interface membranes and performed immunohistochemical analysis on a subset of lesions compared to genuine TSGCT. In 26 of 477 periprosthetic membrane samples (5 %), at least some TSGCT-like features were found and 18 cases (4 %) strongly resembled it. Wear particles were detected in 100 % of the TSGCT-like lesions but only in 63.3 % of the whole cohort of periprosthetic membranes (p value <0.001). Immunohistochemistry comparing true TSGCT and TSGCT-like membranes showed similar inflammatory infiltrates with slightly elevated CD3+/CD8+ T lymphocytes and a slightly higher proliferation index in TSGCT samples. In conclusion, TSGCT-like changes in periprosthetic membranes likely represent exuberant fibrohistiocytic inflammatory response induced by wear particles and should be distinguished from genuine (neoplastic) TSGCT. Although TSGCT and TSGCT-like periprosthetic membranes represent different entities, their comparable morphology might reflect analogous morphogenesis.

Waterjet cutting of periprosthetic interface tissue in loosened hip prostheses: An in vitro feasibility study

Waterjet cutting technology is considered a promising technology to be used for minimally invasive removal of interface tissue surrounding aseptically loose hip prostheses. The goal of this study was to investigate the feasibility of waterjet cutting of interface tissue membrane. Waterjets with 0.2 mm and 0.6 mm diameter, a stand-off distance of 5 mm, and a traverse speed of 0.5 mm/s were used to cut interface tissue samples in half. The water flow through the nozzle was controlled by means of a valve. By changing the flow, the resulting waterjet pressure was regulated. Tissue sample thickness and the required waterjet pressures were measured. Mean thickness of the samples tested within the 0.2 mm nozzle group was 2.3 mm (SD 0.7 mm) and within the 0.6 mm nozzle group 2.6 mm (SD 0.9 mm). The required waterjet pressure to cut samples was between 10 and 12 MPa for the 0.2 mm nozzle and between 5 and 10 MPa for the 0.6 mm nozzle. Cutting bone or bone cement requires about 3 times higher waterjet pressure (30–50 MPa, depending on used nozzle diameter) and therefore we consider waterjet cutting as a safe technique to be used for minimally invasive interface tissue removal.

Investigation of neutrophilic peptides in periprosthetic tissue by matrix-assisted laser desorption ionisation time-of-flight imaging mass spectrometry.

The accurate diagnosis of periprosthetic joint infection (PJI) relies on clinical investigation, laboratory parameters, radiological methods, sterile joint aspiration for synovial fluid leucocyte count and microbiological analysis and tissue sampling for histopathology. Due to the limits in specificity and sensitivity of these methods, molecular techniques and new biomarkers were introduced into the diagnostic procedure. Histological examination is related to the amount of neutrophils in the periprosthetic tissue in frozen sections and formalin-fixed paraffin embedded material (FFPE). However, the threshold of neutrophils per defined area of tissue among various studies is very inconsistent. We have applied matrix-assisted laser desorption ionisation time-of-flight imaging mass spectrometry (MALDI IMS) to a total of 32 periprosthetic tissue samples of patients with PJI to detect peptides associated with areas of neutrophil infiltration. Specific peaks associated with a high amount of neutrophils were detected. Of these m/z peaks, four could be assigned to predictive neutrophil molecules. These peptides include annexin A1, calgizzarin (S100A11), calgranulin C (S100A12) and histone H2A. By MALDI IMS, these peptides could be shown to be co-localised with the infiltration of neutrophils in the immediate vicinity of the periprosthetic interface, whereas more distant areas did not show neutrophil invasion or infection-related peptides. MALDI IMS is a new method allowing identification of neutrophil peptides in periprosthetic tissues and may be a surrogate for counting neutrophils as an objective parameter for PJI.

Tumor necrosis factor-like weak inducer of apoptosis regulates particle-induced inflammatory osteolysis via the p38 mitogen-activated protein kinase signaling pathway.

Periprosthetic osteolysis is the predominant cause of artificial joint loosening. Previous studies have demonstrated that p38 mitogen-activated protein kinase (p38 MAPK) may be involved in periprosthetic osteolysis. Tumor necrosis factor (TNF)-like weak inducer of apoptosis (TWEAK) is a member of the TNF family and is a multifunctional cytokine, which regulates cellular proliferation, angiogenesis, inflammation and apoptosis via the p38 MAPK signaling pathway. The present study investigated the expression levels of TWEAK and p38 MAPK in periprosthetic interface membranes and in RAW264.7 monocyte/macrophage cells, which were treated with titanium (Ti) particle stimulation, with or without a p38 inhibitor (SB203580). This was performed to determine whether TWEAK was involved in the particle-induced inflammatory osteolysis via the p38 MAPK signaling pathway. The expression levels of TWEAK, p38 MAPK and phosphorylated (p-)p38 MAPK were evaluated in the periprosthetic interface membrane tissues and the RAW cells by reverse transcription-quantitative polymerase chain reaction and western blotting. The contents of interleukin-6 and monocyte chemoattractant protein-1 in the supernatant were measured by ELISA. The results demonstrated that the expression levels of TWEAK and p-p38 MAPK increased in the periprosthetic interface membrane tissues and the RAW cells stimulated with Ti particles, suggesting that TWEAK was involved in particle-induced inflammatory osteolysis via the p38 MAPK signaling pathway.

Percutaneous interface biopsy in dry-aspiration cases of chronic periprosthetic joint infections: A technique for preoperative isolation of the infecting organism

Preoperative identification of the infecting micro-organism is of paramount importance in the treatment protocol for chronic periprosthetic joint infections, as it enables selection of the most appropriate antibiotic treatment. Preoperative joint aspiration, the most commonly used sampling technique, has proven to have a broad range of sensitivity values and the frequency of dry aspirations has not been well assessed. In such dry-tap cases a biopsy sample could be an option. The purpose of this study was to assess the diagnostic accuracy of percutaneous interface biopsy (PIB) in isolating the infecting organism in cases of chronic Periprosthetic Joint Infection (PJI) and dry-tap event. The basic technique is to harvest and culture a sample from the periprosthetic interface membrane by a percutaneous technique in the preoperative period. A retrospective study was done involving 24 consecutive patients suspected of PJI and where no fluid was obtained from the joint. Culture results from a percutaneous interface biopsy (PIB) were compared with intraoperative tissue cultures at the time of revision surgery. In all cases, a two-stage replacement was done. The sensitivity was 88.2%; specificity was 100%. Positive predictive value was 100%, while negative predictive value was 77.9%. Accuracy was 91.6%. No technique-related complication was observed. We conclude that PIB is a useful test for preoperative isolation of the infecting organism and could play a role in cases with dry-tap joint aspirations.

Pathways of macrophage apoptosis within the interface membrane in aseptic loosening of prostheses

Aseptic loosening is a major cause of failure of total hip arthroplasty (THA). Macrophage apoptosis in interface membrane has been proved to play an important role in the pathogenesis of aseptic loosening. The purpose of current study was to identify the apoptotic mechanism of macrophages in the interface membrane of aseptic loosening. We collected periprosthetic interface membrane from 23 patients undergoing the revision operations for aseptic loosening of hip joint prostheses. To serve as the control group, samples of capsule were collected from 18 patients undergoing the primary hip arthroplasties for osteoarthritis (OA). The ultrastructure of interface membrane was examined by transmission electron microscopy (TEM), and in situ apoptotic macrophage identification was performed by TUNEL staining. Furthermore, using immunohistochemical methods we investigated the expression of some apoptosis-related markers such as inducible nitric oxide synthase (iNOS), peroxynitrite (ONOO −), cleaved caspase-3/4/8/9, cytochrome c, glucose regulated protein 78 (GRP78), and growth arrest and DNA damage-inducible gene 153 (GADD153) in macrophages. These markers were regarded as apoptotic inducers or specific indicators of different apoptotic pathways such as death receptor pathway, mitochondrial pathway and endoplasmic reticulum (ER) stress pathway. TEM showed that a great deal of wear debris was phagocytosed by macrophages, which displayed morphological changes characteristic of apoptosis. The results of TUNEL staining demonstrated that there were more apoptotic macrophages in interface membrane. The expression levels of iNOS, ONOO −, cleaved caspase-3/4/8/9, cytochrome c, GRP78 and GADD153 in macrophages in interface membrane were significantly higher than those in the control samples ( p < 0.05). Our results suggest that death receptor pathway, mitochondria/cytochrosome c caspase-dependent pathway and ER stress pathway are involved in the process of macrophage apoptosis. A therapeutic target to modulate the apoptotic pathways in macrophages may be a strategy to prevent and treat aseptic loosening.

Interface membrane is the best sample for histological study to diagnose prosthetic joint infection

The objective of our study was to study which is the most accurate specimen for histological diagnosis of prosthetic joint infections (pseudocapsule or interface membrane). This is a prospective study including hip revision arthroplasties performed from January 2007 to June 2009. Specimens from pseudocapsule and from interface membrane were obtained from each patient. The histology was considered positive for infection when ≥5 neutrophils per high-power field ( × 40) were found. Definitive diagnosis of infection was considered when ≥2 cultures were positive for the same microorganism. According to the definition of infection, patients were classified in two groups: (A) patients with aseptic loosening in whom cultures obtained during surgery were negative and (B) patients with prosthetic joint infection. A total of 69 revisions were included in the study; 57 were classified in group A and 12 in group B. In group B, the percentage of positive interface membrane histology was significantly higher than the percentage of positive pseudocapsule histology (83 vs 42%, P=0.04, Fisher's exact test). The results suggest that periprosthetic interface membrane is the best specimen for the histological diagnosis of prosthetic joint infection.

Immunologic Adverse Reaction Associated with Low-carbide Metal-on-metal Bearings in Total Hip Arthroplasty

An increased incidence of periprosthetic osteolysis, resulting in loss of biologic fixation, has been reported in contemporary THAs with low-carbide metal-on-metal compared with metal-on-polyethylene couple bearings. Although a hypersensitivity reaction attributable to Co and Cr debris is reportedly a potential cause for failure of THAs with high-carbide bearings, there are no evidence-based data for this reaction in low-carbide metal-on-metal bearings, although such hypersensitivity might be related to osteolysis. We investigated whether there were differences in immunologic hypersensitivity reactions in retrievals from revised THAs with ceramic-on-polyethylene versus metal-on-metal bearing couples. We compared newly formed capsule and periprosthetic interface membranes from revision surgery for aseptic failure from 20 patients with low-carbide bearings and 13 patients with ceramic-on-polyethylene bearings. For control tissue, we obtained samples from the hip capsule during the primary THA implantation in 13 patients with low-carbide bearings and seven with ceramic-on-polyethylene bearings. We examined the tissues with conventional histologic and immunohistochemical methods. Compared with tissue from the control subjects and patients with ceramic-on-polyethylene bearings, the tissues from patients with low-carbide metal-on-metal bearings were associated with (1) extensive necrosis and fibrin exudation in the newly formed hip capsule and (2) diffuse and perivascular lymphocytic infiltration of a higher degree than in the hips with ceramic-on-polyethylene bearings in conventional histologic examination, and (3) more T than B cells. The conventional histologic and immunohistochemical findings in tissues retrieved from failed THAs with low-carbide metal-on-metal bearings are consistent with a link between hypersensitivity and osteolysis with low-carbide bearing couples.

Proposal for a histopathological consensus classification of the periprosthetic interface membrane

Aims: The introduction of clearly defined histopathological criteria for a standardised evaluation of the periprosthetic membrane, which can appear in cases of total joint arthroplasty revision surgery. Methods: Based on...

Simultaneous labeling of mast cell proteases and protease mRNAs at the bone–implant interface of aseptically loosened hip implants

Human mast cells (MC) exhibit two distinct phenotypes based on the protease content of their secretory granules. MC TC cells express tryptase, chymase, cathepsin G, and mast cell carboxypeptidase, while MC T cells express only tryptase. Both mast cell phenotypes were assessed near regions of osteolysis in uninfected failed joint implants by immunohistochemistry with antibodies to tryptase and chymase, and by in situ hybridization with anti-sense RNA probes for the respective mRNA molecules. Specimens from the interface membrane of 32 aseptically loosened total hip implants were studied, 28 of which had mast cells of the MC TC type. Most of these mast cells were aligned along the bone–prosthesis interface adjacent to loosened implants, suggesting involvement in the chronic inflammatory response that leads to bone resorption. Further ultrastructural evidence of mast cells in tissues from failed joint interface membranes was shown by transmission electron microscopy, and detection by staining after magnetic activated cell sorting. The presence of MC at the periprosthetic interface of eroded bone suggests MC degranulation and activity are associated with osteolysis in failed joint prostheses.

Insulin-like growth factors I and II in the aseptic loosening of total hip implants

Periprosthetic interface tissue and pseudocapsule samples surrounding aseptically loosened hip implants and control knee synovium were studied by reverse transcriptase polymerase chain reaction (RT-PCR) and immunohistochemistry. Endothelial cells, fibroblasts, and monocyte/macrophages contained bone formation-enhancing insulin-like growth factors (IGFs). In interface tissue we found fewer IGF-I and IGF-II positive cells than in control tissue. In pseudocapsular tissue we found fewer IGF-I positive cells and an equal amount of IGF-II positive cells compared to control tissues. Decreased bone formation may contribute to net loss of bone around aseptically loosened hip implants.

Protein expression of MMP-13, uPA, and PAI-1 in pseudocapsular and interface tissue around implants of loose artificial hip joints and in osteoarthritis

Matrix metalloproteinase 13 (MMP-13), urokinase type plasminogen activator (uPA), and plasminogen activator inhibitor type-1 (PAI-1) have been reported to be involved in aseptic loosening of artificial hip joints. This study for the first time presents the protein levels of all of these factors in synovial-like interfaces between bone and prosthesis and in pseudocapsular tissues surrounding the artificial joint in patients with aseptic loosening (n=17) measured by ELISA. No differences were observed in the antigen expression of MMP-13, uPA, and PAI-1, comparing interface and pseudocapsular tissue. Also, no significant correlation between the protein expression of these factors and years from arthroplasty to revision or to type of fixation (cemented vs. cementless) was observed. As control, MMP-13, uPA, and PAI-1 antigen levels were also determined in the synovium of patients with osteoarthritis (n=10). Yet, the antigen levels of MMP-13, uPA, and PAI-1 in tissue specimens from patients with aseptic loosening of artificial hip joints were significantly higher compared to their expression in synovial capsular tissues obtained from patients with osteoarthritis. In conclusion, this study shows that elevated protein levels of uPA, PAI-1, and MMP-13 in periprosthetic pseudocapsular and interface tissues from patients after total hip replacement due to aseptic loosening seem not to be associated with the patient outcome.

Receptor activator of nuclear factor κB ligand is expressed in resident and inflammatory cells in aseptic and septic prosthesis loosening

Objective: The pathogenesis of periprosthetic bone loss in aseptic and septic prosthesis loosening is unclear. There is considerable evidence that macrophages and osteoclasts play a key role in focal bone erosion and osteolysis around the prosthesis. RANKL (receptor activator of nuclear factor κB ligand) was shown to be a potent osteoclastogenic factor, and to be involved in bone destruction of myeloma and rheumatoid arthritis patients. Osteoprotegerin (OPG) is the natural RANKL inhibitor and may prevent periprosthetic bone loss.Methods: The presence and distribution of RANKL, its receptor RANK and OPG in the periprosthetic interface of septically (n=5) and aseptically (n=6) loosened prostheses was examined by immunohistochemistry and immunoblotting. Additionally, the immunophenotype of the inflammatory infiltrate was determined [CD3, CD68, Ki‐67, tartrate‐resistant acid posphatase (TRAP)].Results: Aseptic and septic cases revealed a different histopathologic pattern. However, in all cases RANKL and RANK could be demonstrated in macrophages and giant cells. In addition, RANKL detected by immunoblot analysis proved to have the same molecular weight as a recombinant RANKL used as a control (31 kD and approximately 48 kD). OPG was detected in aseptic loosening, where macrophages showed a strong staining, but multinucleated giant cells were only weakly stained. A weak OPG staining was also observed in septic loosening.Conclusion: The pathogenesis of bone loss in septic loosening remains unclear, because the septic membrane bears few macrophages and giant cells, and half of them express OPG. In aseptic loosening, macrophages might not be stimulated by RANKL as a result of OPG expression. But multinucleated giant cells may be activated, as they hardly express OPG. They might be responsible for periprosthetic bone loss in aseptic loosening as a result of their RANKL and RANK expression.

Differential gene expression in the periprosthetic membrane: lubricin as a new possible pathogenetic factor in prosthesis loosening.

About 10% of hip endoprostheses will loosen after 10 years. Prosthesis loosening is caused by two different pathomechanisms: aseptic loosening (AL) and septic loosening (SL). This study evaluated differences in gene expression in AL and SL. Eight hybridizations were performed on PIQOR cDNA arrays. Objects of the study were periprosthetic interface tissue samples from two patients with SL and three patients with AL. Tissue parts directly adjacent to the site of RNA isolation were analyzed immuno/histopathologically in order to overcome the problem of tissue heterogeneity. Thirty-three genes were found constantly differentially expressed, among which were cd11b, cd18, cd68, osteopontin and ferritin heavy-chain upregulated in AL and collagen types 1alpha-1, 3alpha-1, integrin alpha-1, thrombospondin2 and nidogen upregulated in SL. The most striking finding was the strong upregulation (from 20-fold to 323-fold) of megakaryocyte stimulating factor (msf) in all aseptic cases and one of the two septic cases, which was confirmed by real-time reverse transcription-polymerase chain reaction. In this study, msf is linked to prosthesis loosening for the first time. The upregulation in AL suggests an important pathogenetic role: the msf splice product lubricin is responsible for the lubrication of healthy joints, but its excellent lubrication ability may disturb the tight interaction between bone and prosthesis and thereby contribute to prosthesis loosening.

Longitudinal change in periprosthetic, peripheral, and axial bone mineral density after total hip arthroplasty

To determine the bone mineral changes after total hip arthroplasty, bone mineral densities (BMD) at the periprosthetic interface, lumbar spine, radius, and calcaneus were measured in a prospective and longitudinal observation. Twenty-four patients (24 joints) who had received a total hip arthroplasty and were followed longitudinally were enrolled in this study. The subjects comprised 2 men and 22 women with a mean age of 69.2 years at the time of surgery. Bone mineral measurements were performed at 1, 3, 6, 12, 18, 24, 30, and 36 months after surgery. The periprosthetic BMD after total hip arthroplasty continued to decrease for 6–12 months after surgery, and then recovered, except in Gruen zone 7 (the calcar region). The calcaneal BMD decreased rapidly for 3 months after surgery before increasing. The lumbar BMD showed a decreasing trend for 12 months after surgery, and then increased gradually. The radial BMD was not affected by surgery. We conclude that changes in the periprosthetic BMD after total hip arthroplasty show an apparent difference between zones, and also differ between the weight-bearing bones and the nonweight-bearing bones.