Steven R. Goldring

Background: The aim of the study was to examine the relationship among patients’ characteristics, intraoperative pathology and pre/post-operative symptoms in a cohort of patients undergoing arthroscopic partial meniscectomy for symptomatic meniscal tears. Methods: Clinical data were collected (age, sex, body mass index, time to surgery, trauma). Intraoperative cartilage pathology was assessed with Outerbridge score. Meniscal tears were graded with the ISAKOS classification. Synovial inflammation was scored using the Macro-score. Patient symptoms were assessed pre/post-operatively using the KOOS instrument. Results: In the series of 109 patients (median age 47 years), 50% of the meniscal tears were traumatic; 85% of patients showed mild to moderate synovitis; 52 (47.7%) patients had multiple cartilage defects and 31 (28.4%) exhibited a single focal chondral lesion. Outerbridge scores significantly correlated with patient age, BMI and synovial inflammation. There was a correlation between severity of chondral pathology and high-grade synovial hyperplasia. Pre-operative KOOS correlated with BMI, meniscal degenerative changes and symptom duration. Obesity, time to surgery, presence of high-grade synovial hyperplasia and high-grade cartilage lesions were independent predictors of worse post-operative pain and function. Conclusion: We demonstrated that pre-operative symptoms and post-operative outcomes correlate with synovitis severity and cartilage pathology, particularly in old and obese patients that underwent arthroscopic partial meniscectomy. Importantly, patients with a degenerative meniscal pattern and with longer time to surgery experienced more severe cartilage damage and, consequentially, pain and dysfunction. These findings are fundamental to identify patients suitable for earlier interventions.

The inflammatory arthropathies share in common their tendency to produce marked alterations in skeletal remodelling and architecture. This review will focus on RA and the seronegative spondyloarthopathies (SpA), which share common features with respect to their tendency to produce localized bone destruction at sites of articular and peri-articular inflammation. However, there are significant differences in the skeletal pathology in these conditions, which include the unique involvement of the axial skeleton and the presence of inflammation in the extra-articular entheses in SpA. There also are differences in the pattern of bone formation and repair associated with the articular and peri-articular inflammation. This review will highlight the molecular and cellular processes that are involved in the pathogenesis of the skeletal pathology in these two forms of inflammatory arthritis with specific focus on the pathogenic mechanisms underlying the differential patterns of bone formation and repair.

Adverse local tissue reaction (ALTR), characterized by a heterogeneous cellular inflammatory infiltrate and the presence of corrosion products in the periprosthetic soft tissues, has been recognized as a mechanism of failure in total hip replacement (THA). Different histological subtypes may have unique needs for longitudinal clinical follow-up and complication rates after revision arthroplasty. The purpose of this study was to describe the histological patterns observed in the periprosthetic tissue of failed THA in three different implant classes due to ALTR and their association with clinical features of implant failure. Consecutive patients presenting with ALTR from three major hip implant classes (N = 285 cases) were identified from our prospective Osteolysis Tissue Database and Repository. Clinical characteristics including age, sex, BMI, length of implantation, and serum metal ion levels were recorded. Retrieved synovial tissue morphology was graded using light microscopy. Clinical characteristics and features of synovial tissue analysis were compared between the three implant classes. Histological patterns of ALTR identified from our observations and the literature were used to classify each case. The association between implant class and histological patterns was compared. Our histological analysis demonstrates that ALTR encompasses three main histological patterns: 1) macrophage predominant, 2) mixed lymphocytic and macrophagic with or without features of associated with hypersensitivity/allergy or response to particle toxicity (eosinophils/mast cells and/or lymphocytic germinal centers), and 3) predominant sarcoid-like granulomas. Implant classification was associated with histological pattern of failure, and the macrophagic predominant pattern was more common in implants with metal-on-metal bearing surfaces (MoM HRA and MoM LHTHA groups). Duration of implantation and composition of periprosthetic cellular infiltrates was significantly different amongst the three implant types examined suggesting that histopathological features of ALTR may explain the variability of clinical implant performance in these cases. ALTR encompasses a diverse range of histological patterns, which are reflective of both the implant configuration independent of manufacturer and clinical features such as duration of implantation. The macrophagic predominant pattern and its mechanism of implant failure represent an important subgroup of ALTR which could become more prominent with increased length of implantation.

We previously showed that repetitive cyclic loading of the mouse knee joint causes changes that recapitulate the features of osteoarthritis (OA) in humans. By applying a single loading session, we characterized the temporal progression of the structural and compositional changes in subchondral bone and articular cartilage. We applied loading during a single 5‐minute session to the left tibia of adult (26‐week‐old) C57Bl/6 male mice at a peak load of 9.0N for 1,200 cycles. Knee joints were collected at times 0, 1, and 2 weeks after loading. The changes in articular cartilage and subchondral bone were analyzed by histology, immunohistochemistry (caspase‐3 and cathepsin K), and microcomputed tomography. At time 0, no change was evident in chondrocyte viability or cartilage or subchondral bone integrity. However, cartilage pathology demonstrated by localized thinning and proteoglycan loss occurred at 1 and 2 weeks after the single session of loading. Transient cancellous bone loss was evident at 1 week, associated with increased osteoclast number. Bone loss was reversed to control levels at 2 weeks. We observed formation of fibrous and cartilaginous tissues at the joint margins at 1 and 2 weeks. Our findings demonstrate that a single session of noninvasive loading leads to the development of OA—like morphological and cellular alterations in articular cartilage and subchondral bone. The loss in subchondral trabecular bone mass and thickness returns to control levels at 2 weeks, whereas the cartilage thinning and proteoglycan loss persist. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:1941–1949, 2016.

Osteocytes are the most abundant cell type in bone and are distributed throughout the mineralised bone matrix forming an interconnected network that ideally positions them to sense and to respond to local biomechanical and systemic stimuli to regulate bone remodelling and adaptation. The adaptive process is dependent on the coordinated activity of osteoclasts and osteoblasts that form a so called bone multicellular unit that remodels cortical and trabecular bone through a process of osteoclast-mediated bone resorption, followed by a phase of bone formation mediated by osteoblasts. Osteocytes mediate their effects on bone remodelling via both cell–cell interactions with osteoclasts and osteoblasts, but also via signaling through the release of soluble mediators. The remodelling process provides a mechanism for adapting the skeleton to local biomechanical factors and systemic hormonal influences and for replacing bone that has undergone damage from repetitive mechanical loading.

Adverse local tissue reaction (ALTR) is characterized by periprosthetic soft tissue inflammation composed of a mixed inflammatory cell infiltrate, extensive soft tissue necrosis, and vascular changes. Multiple hip implant classes have been reported to result in ALTR, and clinical differences may represent variation in the soft tissue response at the cellular and tissue levels. The purpose of this study was to describe similarities and differences in periprosthetic tissue structure, organization, and cellular composition by conventional histology and immunohistochemistry in ALTR resulting from two common total hip arthroplasty (THA) implant classes.

The seronegative spondyloarthopathies (SpA) share certain common articular and peri-articular features that differ from rheumatoid arthritis (RA) and other forms of inflammatory arthritis. These include the tendency of the SpAs to involve the axial skeleton in addition to the diarthrodial joints, and the prominent involvement of the extra-articular entheses (sites of ligamentous and tendon insertion), which are not common sites of primary pathology in RA and other inflammatory arthropathies. The differential anatomic sites of bone pathology in the SpAs in comparison to the other forms of arthritis suggest that the underlying pathogenic processes and cellular and molecular mechanisms that account for the peri-articular bone pathology involve different underlying disease mechanisms. This review will highlight the molecular and cellular processes that are involved in the pathogenesis of the skeletal pathology in the SpAs, and provide evidence that many of the factors involved in regulation of bone cell function exhibit potent immune-regulatory activity, providing support for the general concept of osteoimmunology.