Immune and stem cell compartments of acetabular and femoral bone marrow in hip osteoarthritis patients.

OBJECTIVE: Hip osteoarthritis (OA) affects all components of the osteochondral unit, leading to bone marrow (BM) lesions, and unknown consequences on BM cell functionality. We analyzed the cellular composition in OA-affected acetabula compared to proximal femur shafts obtained of hip OA patients to reveal yet not explored immune and stem cell compartments. DESIGN: Combining flow cytometry, cellular assays and transcription analyses, we performed extensive ex vivo phenotyping of acetabular BM cells from 18 hip OA patients, comparing them with their counterparts from patient-matched femoral shaft BM samples. Findings were related to differences in skeletal sites and age. RESULTS: Acetabular BM had a greater frequency of T-lymphocytes, non-hematopoietic cells and colony-forming units fibroblastic potential than femoral BM. The incidence of acetabular CD45+CD3+ T-lymphocytes increased (95% CI: 0.1770 to 0.0.8416), while clonogenic hematopoietic progenitors declined (95% CI: -0.9023 to -0.2399) with age of patients. On the other side, in femoral BM, we observed higher B-lymphocyte, myeloid and erythroid cell frequencies. Acetabular mesenchymal stromal cells (MSCs) showed a senescent profile associated with the expression of survival and inflammation-related genes. Efficient osteogenic and chondrogenic differentiation was detected in acetabular MSCs, while adipogenesis was more pronounced in their femoral counterparts. CONCLUSION: Our results suggest that distinctions in BM cellular compartments and MSCs may be due to the influence of the OA-stressed microenvironment, but also acetabular vs femoral shaft-specific peculiarities cannot be excluded. These results bring new knowledge on acetabular BM cell populations and may be addressed as novel pathogenic mechanisms and therapeutic targets in OA.

[Mega-prostheses in revision knee arthroplasty]. / Megaprothesen in der Knierevision.

BACKGROUND: Due to a predicted increase in primary total knee arthroplasty (TKA), revision TKA will gain importance over the following years. Because the average age of patients receiving a TKA is decreasing the possible need for multiple revisions might increase as well. Despite efforts to minimize bone and soft tissue damage, the resulting bone and soft-tissue loss increases with each revision and will make the use of megaprostheses indispensable in the future. COMPLICATIONS: The implantation of a mega-prosthesis must be carefully considered and planned, since mega-prostheses in particular are associated with an increased risk of infection and loosening. Mechanical complications, patient-specific problems and periprosthetic infections can be either the cause for or the result of revision surgery of a mega-prosthesis. In the case of a complication, only a salvage procedure, namely an arthrodesis, amputation or-if necessary-the installation of a permanent fistula is commonly recommended.

[Diagnosis of periprosthetic joint infection : Development of an evidence-based algorithm by the work group of implant-associated infection of the AE-(German Society for Arthroplasty)]. / Diagnostik der periprothetischen Infektion : Entwicklung eines evidenzbasierten Algorithmus der Arbeitsgruppe implantatassoziierte Infektion der Arbeitsgemeinschaft Endoprothetik.

BACKGROUND: Prosthetic joint infections (PPI) will challenge orthopaedic surgeons and the health care system in the coming years. Evidence-based and reliable preoperative diagnostics are necessary for success in the field of revision arthroplasty. Especially the preoperative detection of PPI is important with respect to the treatment strategy. AIM: The aim of this study was to develop a detailed and structured standard operating procedure (SOP) to detect PPI preoperatively. METHODS: A systematic literature research was performed and relevant articles identified. After extracting the data, statistical calculations of sensitivity, specificity, positive/negative predictive value and positive/negative likelihood ratio were performed. The results were discussed and evaluated in four meetings analogously to standard Delphi rounds by the workgroup of implant-associated infections of the German AE (Arbeitsgemeinschaft Endoprothetik). An algorithm for the diagnostic approach according to ISO 5807 was made. RESULTS: The standardized algorithm combines a sequence of evidence-based procedures with detailed and structured main and additional criteria to every critical step in the diagnostic approach. CONCLUSION: The detection of PPI is of tremendous importance prior to revision arthroplasty and determines its success or failure. The diagnosis "prosthetic joint infection" requires a substantial change with respect to treatment concepts. The algorithm summarizes current literature and specialized expert opinions in a modern standardized format for a transparent diagnostic approach.

Customised bi-compartmental knee arthroplasty shows encouraging 3-year results: findings of a prospective, multicenter study.

PURPOSE: The purpose of this study was to assess the clinical and patient-reported outcomes of a customised, individually made (CIM) bi-compartmental knee arthroplasty (BKA). METHODS: A prospectively recruited cohort of 79 patients was implanted with a CIM-BKA (patello-femoral plus either medial or lateral tibio-femoral, iDuo G2 system, Conformis, Billerica MA) at eight centres in the US and Germany. Patients were assessed for the 2011 KSS, KOOS, and ROM pre-operatively and at 2 weeks, 6 weeks, 12 weeks, 1 year, and 2 years post-operatively. RESULTS: The objective KSS score significantly improved from 69 at the pre-operative visit, to 94 at the 2-year post-operative time-point. Similar improvements were observed for the KSS function and satisfaction domains. Significant improvements from pre-operative levels were observed across all five domains of the KOOS. Two patients have undergone surgery to revise their CIM-BKA implant to total knees, resulting in a survivorship rate of 97.5% at an average follow-up of 2.6 years. CONCLUSIONS: CIM-BKA compares favourably to published scores as well as revision rates for previously available monolithic OTS-BKA implants. CIM-BKA implants provide surgeons with a viable and patient-specific monolithic implant solution as an option for patients presenting with bi-compartmental disease, who might, otherwise, be treated by performing uni-condylar + patello-femoral joint or bicruciate sparing TKA surgeries. Longer follow-up and higher numbers have to be awaited for further validation of these encouraging early results. LEVEL OF EVIDENCE: 3b (individual case-controlled study).

Screw fixation of the syndesmosis alters joint contact characteristics in an axially loaded cadaveric model.

BACKGROUND: The purpose of this study was to quantify the effects of rigid syndesmotic fixation on functional talar position and cartilage contact mechanics. METHODS: Twelve below-knee cadaveric specimens with an intact distal syndesmosis were mechanically loaded in four flexion positions (20° plantar flexion, 10° plantar flexion, neutral, 10° dorsiflexion) with zero, one, or two 3.5-mm syndesmotic screws. Rigid clusters of reflective markers were used to track bony movement and ankle-specific pressure sensors were used to measure talar dome and medial/lateral gutter contact mechanics. RESULTS: Screw fixation caused negligible anterior and inferior shifts of the talus within the mortise. Relative to no fixation, mean peak contact pressure decreased by 6%-32% on the talar dome and increased 2.4- to 6.6-fold in the medial and lateral gutters, respectively, depending on ankle position and number of screws. CONCLUSIONS: Two-way ANOVA indicated syndesmotic screw fixation significantly increased contact pressure in the medial/lateral gutters and decreased talar dome contact pressure while minimally altering talar position.

Periprosthetic infection is the major indication for TKA revision - experiences from a university referral arthroplasty center.

BACKGROUND: We hypothesized, that periprosthetic joint infection (PJI) accounts for the major proportion of first (primary) and repeated (secondary) Total Knee Arthroplasty revisions at our university referral arthroplasty center. METHODS: One thousand one hundred forty-three revisions, performed between 2008 and 2016 were grouped into primary (55%) and secondary (45%) revisions. The rate of revision indications was calculated and indications were categorized by time after index operation. The odds ratios of the indications for primary versus secondary revision were calculated. RESULTS: In the primary revision group PJI accounted for 22.3%, instability for 20.0%, aseptic loosening for 14.9% and retropatellar arthrosis for 14.2%. PJI (25.6%) was the most common indication up to 1 year after implantation, retropatellar arthrosis (26.8%) 1-3 years and aseptic loosening (25.6%) more than 3 years after implantation. In the secondary revision group PJI accounted for 39.7%, aseptic loosening for 16.2% and instability for 13.2%. PJI was the most common indication at any time of revision with 43.8% up to one, 35.4% 1-3 years and 39.4% more the 3 years after index operation. The odds ratios in repeated revision were 2.32 times higher (p = 0.000) for PJI. For instability and retropatellar arthrosis the odds ratios were 0.60 times (p = 0.006) and 0.22 times (p = 0.000) lower. CONCLUSIONS: PJI is the most common indication for secondary TKA revision and within one year after primary TKA. Aseptical failures such as instability, retropatellar arthrosis and aseptical loosening are the predominant reasons for revision more than one year after primary TKA.

Changes in Joint Contact Mechanics in a Large Quadrupedal Animal Model After Partial Meniscectomy and a Focal Cartilage Injury.

Acute mechanical damage and the resulting joint contact abnormalities are central to the initiation and progression of post-traumatic osteoarthritis (PTOA). Study of PTOA is typically performed in vivo with replicate animals using artificially induced injury features. The goal of this work was to measure changes in a joint contact stress in the knee of a large quadruped after creation of a clinically realistic overload injury and a focal cartilage defect. Whole-joint overload was achieved by excising a 5-mm wedge of the anterior medial meniscus. Focal cartilage defects were created using a custom pneumatic impact gun specifically developed and mechanically characterized for this work. To evaluate the effect of these injuries on joint contact mechanics, Tekscan (Tekscan, Inc., South Boston, MA) measurements were obtained pre-operatively, postmeniscectomy, and postimpact (1.2-J) in a nonrandomized group of axially loaded cadaveric sheep knees. Postmeniscectomy, peak contact stress in the medial compartment is increased by 71% (p = 0.03) and contact area is decreased by 35% (p = 0.001); the center of pressure (CoP) shifted toward the cruciate ligaments in both the medial (p = 0.004) and lateral (p = 0.03) compartments. The creation of a cartilage defect did not significantly change any aspect of contact mechanics measured in the meniscectomized knee. This work characterizes the mechanical environment present in a quadrupedal animal knee joint after two methods to reproducibly induce joint injury features that lead to PTOA.

[Scaffold-based Bone Tissue Engineering]. / Gerüstträgerbasiertes Knochen-Tissue-Engineering.

Tissue engineering provides the possibility of regenerating damaged or lost osseous structures without the need for permanent implants. Within this context, biodegradable and bioresorbable scaffolds can provide structural and biomechanical stability until the body's own tissue can take over their function. Additive biomanufacturing makes it possible to design the scaffold's architectural characteristics to specifically guide tissue formation and regeneration. Its nano-, micro-, and macro-architectural properties can be tailored to ensure vascularization, oxygenation, nutrient supply, waste exchange, and eventually ossification not only in its periphery but also in its center, which is not in direct contact with osteogenic elements of the surrounding healthy tissue. In this article we provide an overview about our conceptual design and process of the clinical translation of scaffold-based bone tissue engineering applications.

[Treatment of acetabular bone defects in revision hip arthroplasty using the Revisio-System]. / Defektadaptierte Versorgung azetabulärer Knochendefekte mit dem Revisio-System.

BACKGROUND: Many different systems for the management of primary and secondary acetabular defects are available, each with its inherent advantages and disadvantages. The Revisio-System is a press-fit oval mono-block implant that makes a defect-oriented reconstruction and restoration of the center of rotation possible. MATERIAL AND METHODS: In this study, we retrospectively reviewed the outcome of 92 consecutive patients treated with this oval press-fit cup due to periacetabular bone loss. The average follow-up was 58.2 months. Defects were classified according to D'Antonio. There were 39 type II, 38 Type III, and 15 type IV defects. After an average of 4.9 years, the implant survival rate was 94.6% with cup revision as the end point and 89.1% with revision for any reason as the end point. The Harris Hip Score increased from 41.1 preoperatively to 62.3 postoperatively. The mean level of pain measured with the Visual Analogue Scale (VSA) was reduced from 6.9 preoperatively to 3.8 postoperatively. RESULTS: The Revisio-System represents a promising toolbox for defect-orientated reconstruction of acetabular bone loss in revision hip arthroplasty. Our results demonstrate that the implantation of the Revisio-System can result in a good mid-term clinical outcome.

Acetabular defect classification in times of 3D imaging and patient-specific treatment protocols.

Parallel to the rising number of revision hip procedures, an increasing number of complex periprosthetic osseous defects can be expected. Stable long-term fixation of the revision implant remains the ultimate goal of the surgical protocol. Within this context, an elaborate preoperative planning process including anticipation of the periacetabular defect form and size and analysis of the remaining supporting osseous elements are essential. However, detection and evaluation of periacetabular bone defects using an unsystematic analysis of plain anteroposterior radiographs of the pelvis is in many cases difficult. Therefore, periacetabular bone defect classification schemes such as the Paprosky system have been introduced that use standardized radiographic criteria to better anticipate the intraoperative reality. Recent studies were able to demonstrate that larger defects are often underestimated when using the Paprosky classification and that the intra- and interobserver reliability of the system is low. This makes it hard to compare results in terms of defects being studied. Novel software tools that are based on the analysis of CT data may provide an opportunity to overcome the limitations of native radiographic defect analysis. In the following article we discuss potential benefits of these novel instruments against the background of the obvious limitations of the currently used native radiographic defect analysis.

[Endoprosthetic tumor replacement : Reconstruction of the extensor mechanism and complications]. / Tumorendoprothetik : Rekonstruktion des Streckapparates und Komplikationen.

BACKGROUND: The reconstruction of the extensor mechanism around the knee is an essential part of tumorresection and tumor arthroplasty in orthopaedic oncology for functional rehabilitation of quality of life and daily activities. OBJECTIVES: Operative procedures, treatment options and management of complications with reconstruction of the extensor mechanism after tumor resection around the knee depend on the type of arthroplasty. MATERIALS AND METHODS: Description of the different treatment option for extensor deficiency divided into infra- and suprapatellar modalities. RESULTS: The operative procedure is always an individual decision depending on the size of the tumor and its localisation. The extensor mechanism is reconstructed with autogenic, allogenic or synthetic material in combination with tumor arthroplasty. CONCLUSIONS: Extensor reconstruction (supra-/infrapatellar) is an essential part of tumor resection and tumor arthroplasty around the knee. Often, low functional results and high levels of complications (arthrofibrosis, rerupture extensor mechanism, periprosthetic joint infection) are seen in these highly demanding cases in orthopaedic oncology.

Direct bone morphogenetic protein 2 and Indian hedgehog gene transfer for articular cartilage repair using bone marrow coagulates.

OBJECTIVE: Bone morphogenetic protein 2 (BMP-2, encoded by BMP2) and Indian hedgehog protein (IHH, encoded by IHH) are well known regulators of chondrogenesis and chondrogenic hypertrophy. Despite being a potent chondrogenic factor BMP-2 was observed to induce chondrocyte hypertrophy in osteoarthritis (OA), growth plate cartilage and adult mesenchymal stem cells (MSCs). IHH might induce chondrogenic differentiation through different intracellular signalling pathways without inducing subsequent chondrocyte hypertrophy. The primary objective of this study is to test the efficacy of direct BMP2 and IHH gene delivery via bone marrow coagulates to influence histological repair cartilage quality in vivo. METHOD: Vector-laden autologous bone marrow coagulates with 10(11) adenoviral vector particles encoding BMP2, IHH or the Green fluorescent protein (GFP) were delivered to 3.2 mm osteochondral defects in the trochlea of rabbit knees. After 13 weeks the histological repair cartilage quality was assessed using the ICRS II scoring system and the type II collagen positive area. RESULTS: IHH treatment resulted in superior histological repair cartilage quality than GFP controls in all of the assessed parameters (with P < 0.05 in five of 14 assessed parameters). Results of BMP2 treatment varied substantially, including severe intralesional bone formation in two of six joints after 13 weeks. CONCLUSION: IHH gene transfer is effective to improve repair cartilage quality in vivo, whereas BMP2 treatment, carried the risk intralesional bone formation. Therefore IHH protein can be considered as an attractive alternative candidate growth factor for further preclinical research and development towards improved treatments for articular cartilage defects.

A clinically realistic large animal model of intra-articular fracture that progresses to post-traumatic osteoarthritis.

OBJECTIVE: Translation of promising treatments for post-traumatic osteoarthritis (PTOA) to patients with intra-articular fracture (IAF) has been limited by the lack of a realistic large animal model. To address this issue we developed a large animal model of IAF in the distal tibia of Yucatan minipigs and documented the natural progression of this injury. DESIGN: Twenty-two fractures were treated using open reduction and internal fixation with either an anatomic reduction or an intentional 2-mm step-off. Pre-operatively, and 3 days, 1, 2, 4, 8, and 12 weeks post-operatively, animals were sedated for synovial fluid draws and radiographs. Limb loading was monitored at the same time points using a Tekscan Walkway. Animals were sacrificed at 12 weeks and the limbs were harvested for histological evaluation. RESULTS: All animals achieved bony union by 12 weeks, facilitating nearly complete recovery of the initial 60% decrease in limb loading. TNFα, IL1ß, IL6, and IL8 concentrations in the fractured limbs were elevated (P < 0.05) at specific times during the 2 weeks after fracture. Histological cartilage degeneration was more severe in the step-off group (0.0001 < P < 0.27 compared to normal) than in the anatomic reconstruction group (0.27 < P < 0.99 compared to normal). CONCLUSIONS: This model replicated key features of a human IAF, including surgical stabilization, inflammatory responses, and progression to osteoarthritic cartilage degeneration, thereby providing a potentially useful model for translating promising treatment options to clinical practice.

[Individualized total knee arthroplasty]. / Individualendoprothetik am Kniegelenk.

This article describes the rationale and the surgical technique of patient-specific uni-, bi-, or three-compartmental knee arthroplasty using the second generation (G2) of ConforMIS™ technology. The patient-individual implants and instruments are designed and fabricated based on data from a preoperative computed tomography of the lower limb. The disposable patient-specific drill guides and cutting-jigs are manufactured under consideration of the anatomical and biomechanical axes of the knee joint and mediate efficient pre-navigation of the saw-cuts on the femoral and tibial bone without the need for an additional navigation or balancing device. The surgical technique for all types of knee resurfacement comprises the steps of cartilage removal, knee balancing in extension and flexion, sparing bony cuts, final preparation of femur and tibia, trialling, cementing of components and final choice of tibial insert. The use of individualized three-dimensional image-derived resurfacing implants, as well as personalized single-use instrumentation, facilitates the surgeon to perform an almost anatomical knee resurfacement that has the potential to restore almost normal knee kinematics. The limited data on this novel technology is promising, however long-term clinical data is needed for final evaluation of this technology.

[Regulation of bone metabolism in osteoporosis : novel drugs for osteoporosis in development]. / Regulation des Knochenstoffwechsels bei Osteoporose : Neuartige Osteoporosemedikamente in der Entwicklung.

Bone is continuously regenerated and remodeled as an adaptation to mechanical load. Bone mass and fracture resistance are maintained by a balanced equilibrium between bone formation and bone resorption. Regeneration and response to mechanical load are, however, impaired in osteoporosis and during aging. Bone resorption is enhanced by chronic inflammation while bone formation is altered by rising levels of inhibitors in the aging organism. Core molecular principles of the regulation of bone metabolism in health and disease have been characterized and developed as therapeutic targets. The receptor activator of nuclear factor kappaB ligand (RANKL) and osteoclast-derived protease cathepsin K are important regulators and effectors of osteoclast differentiation and bone resorption. Bone formation is stimulated by bone morphogenetic proteins (BMP) and via the parathyroid hormone receptor and the Wnt signaling pathway. The principles of osteoclast inhibition using bisphosphonates have now been known for almost three decades. Based on more recent knowledge RANKL and cathepsin K have been developed as new therapeutic targets to inhibit bone resorption. While denosumab, a RANKL antibody, has already been introduced into routine treatment strategies, the cathepsin K antagonist odanacatib is currently in the licensing process. Bone formation can also be stimulated by local administration of BMPs, by systemic treatment with the parathyroid hormone fragment teriparatide and by using antibodies targeting the Wnt inhibitor sclerostin. The latter are presently being tested in phase III clinical studies. In the near future a panel of traditional and novel treatment strategies will be available that will enable us to meet the individual clinical needs during aging and for the treatment of osteoporosis.

An instrumented pendulum system for measuring energy absorption during fracture insult to large animal joints in vivo.

For systematic laboratory studies of bone fractures in general and intra-articular fractures in particular, it is often necessary to control for injury severity. Quantitatively, a parameter of primary interest in that regard is the energy absorbed during the injury event. For this purpose, a novel technique has been developed to measure energy absorption in experimental impaction. The specific application is for fracture insult to porcine hock (tibiotalar) joints in vivo, for which illustrative intra-operative data are reported. The instrumentation allowed for the measurement of the delivered kinetic energy and of the energy passed through the specimen during impaction. The energy absorbed by the specimen was calculated as the difference between those two values. A foam specimen validation study was first performed to compare the energy absorption measurements from the pendulum instrumentation versus the work of indentation performed by an MTS machine. Following validation, the pendulum apparatus was used to measure the energy absorbed during intra-articular fractures created in 14 minipig hock joints in vivo. The foam validation study showed close correspondence between the pendulum-measured energy absorption and MTS-performed work of indentation. In the survival animal series, the energy delivered ranged from 31.5 to 48.3 Js (41.3±4.0, mean±s.d.) and the proportion of energy absorbed to energy delivered ranged from 44.2% to 64.7% (53.6%±4.5%). The foam validation results support the reliability of the energy absorption measure provided by the instrumented pendulum system. Given that a very substantial proportion of delivered energy passed--unabsorbed--through the specimens, the energy absorption measure provided by this novel technique arguably provides better characterization of injury severity than is provided simply by energy delivery.

A new sensor for measurement of dynamic contact stress in the hip.

Various techniques exist for quantifying articular contact stress distributions, an important class of measurements in the field of orthopaedic biomechanics. In situations where the need for dynamic recording has been paramount, the approach of preference has involved thin-sheet multiplexed grid-array transducers. To date, these sensors have been used to study contact stresses in the knee, shoulder, ankle, wrist, and spinal facet joints. Until now, however, no such sensor had been available for the human hip joint due to difficulties posed by the deep, bi-curvilinear geometry of the acetabulum. We report here the design and development of a novel sensor capable of measuring dynamic contact stress in human cadaveric hip joints (maximum contact stress of 20 MPa and maximum sampling rate 100 readings/s). Particular emphasis is placed on issues concerning calibration, and on the effect of joint curvature on the sensor's performance. The active pressure-sensing regions of the sensors have the shape of a segment of an annulus with a 150-deg circumferential span, and employ a polar/circumferential "ring-and-spoke" sensel grid layout. There are two sensor sizes, having outside radii of 44 and 48 mm, respectively. The new design was evaluated in human cadaver hip joints using two methods. The stress magnitudes and spatial distribution measured by the sensor were compared to contact stresses measured by pressure sensitive film during static loading conditions that simulated heel strike during walking and stair climbing. Additionally, the forces obtained by spatial integration of the sensor contact stresses were compared to the forces measured by load cells during the static simulations and for loading applied by a dynamic hip simulator. Stress magnitudes and spatial distribution patterns obtained from the sensor versus from pressure sensitive film exhibited good agreement. The joint forces obtained during both static and dynamic loading were within ±10% and ±26%, respectively, of the forces measured by the load cells. These results provide confidence in the measurements obtained by the sensor. The new sensor's real-time output and dynamic measurement capabilities hold significant advantages over static measurements from pressure sensitive film.

[Damage to implants due to high-frequency electrocautery : analysis of four fractured hip endoprostheses shafts]. / Implantatschädigung durch Einsatz eines Hochfrequenzmessers : Analyse von vier Hüftendoprothesenschaftbrüchen.

In revision surgery of joints, high-frequency electrocauterization instruments are used for homeostasis and dissection of soft tissue. If there is contact of these instruments with the metal implants, flashover can occur. This can lead to thermal microstructural changes in the material and as a consequence may reduce the fatigue strength of the implant. Four cases of hip revision surgeries were analysed. In all cases flashovers occurred and secondarily, the titanium hip endoprosthesis stem broke in the neck section of the prosthesis. The conducted investigations showed that contact between the high-frequency instrument and the anterolateral aspect of the endoprosthesis neck had occurred. Electrothermal implant damage was found in the broken area. If in hip revision surgery the stem is not to be replaced, contact between high-frequency instruments and the metal implant should be avoided.

A novel impaction technique to create experimental articular fractures in large animal joints.

OBJECTIVE: A novel impaction fracture insult technique, developed for modeling post-traumatic osteoarthritis in porcine hocks in vivo, was tested to determine the extent to which it could replicate the cell-level cartilage pathology in human clinical intra-articular fractures. DESIGN: Eight fresh porcine hocks (whole-joint specimens with fully viable chondrocytes) were subjected to fracture insult. From the fractured distal tibial surfaces, osteoarticular fragments were immediately sampled and cultured in vitro for 48 h. These samples were analyzed for the distribution and progression of chondrocyte death, using the Live/Dead assay. Five control joints, in which "fractures" were simulated by means of surgical osteotomy, were also similarly analyzed. RESULTS: In the impaction-fractured joints, chondrocyte death was concentrated in regions adjacent to fracture lines (near-fracture regions), as evidenced by fractional cell death significantly higher (P < 0.0001) than in central non-fracture (control) regions. Although nominally similar spatial distribution patterns were identified in the osteotomized joints, fractional cell death in the near-osteotomy regions was nine-fold lower (P < 0.0001) than in the near-fracture regions. Cell death in the near-fracture regions increased monotonically during 48 h after impaction, dominantly within 1 mm from the fracture lines. CONCLUSION: The impaction-fractured joints exhibited chondrocyte death characteristics reasonably consistent with those in human intra-articular fractures, but were strikingly different from those in "fractures" simulated by surgical osteotomy. These observations support promise of this new impaction fracture technique as a mechanical insult modality to replicate the pathophysiology of human intra-articular fractures in large animal joints in vivo.