Calcified cartilage differs in patients with end-stage primary osteoarthritis and secondary osteoarthritis due to rheumatoid arthritis of the hip joint.

OBJECTIVES: Despite distinct aetiologies, the end-stages of primary osteoarthritis (OA) and secondary OA are described by common radiological features. However, the morphology of the bone-cartilage unit may differ depending on the pathogenesis. In this cross-sectional study, we aimed to investigate the histological differences in the bone-cartilage unit of the femoral head between patients with primary OA and secondary OA due to rheumatoid arthritis (RA). METHOD: Femoral heads were obtained from 12 patients with primary OA, six patients with secondary OA due to RA, and 12 control subjects. The femoral heads were investigated using stereological methods to ensure unbiased quantification. RESULTS: The volume (mean difference [95% confidence interval]) (2.1 [0.5;3.8] cm3, p = 0.016) and thickness (413 [78.9;747] µm, p = 0.029) of the articular cartilage and the thickness of the calcified cartilage (56.4 [0.4;113] µm, p = 0.017) were larger in patients with primary OA than in patients with secondary OA due to RA. Femoral head volume (1.2 [-3.6;6.1] cm3, p = 0.598), bone volume fraction (-1.1 [-2.8;5.1] cm3, p = 0.553), subchondral bone thickness (-2.5 [-212;207] µm, p = 0.980), and osteophyte area (25.3 [-53.6;104] cm2, p = 0.506) did not differ between patients. CONCLUSION: The thicker calcified cartilage in primary OA preceding the loss of articular cartilage can be attributed to endochondral ossification. Patients with secondary OA due to RA had severely thinner calcified cartilage as the pathogenesis is driven by inflammation and is characterized by a generalized and more severe loss of articular cartilage.

Local bone loss in patients with anti-citrullinated peptide antibody and arthralgia, evaluated with high-resolution peripheral quantitative computed tomography.

OBJECTIVE: To investigate bone changes in the metacarpophalangeal (MCP) joints of anti-citrullinated peptide antibody (ACPA)-positive patients with arthralgia, but not arthritis, compared to healthy controls. METHOD: Using a cross-sectional study design, patients were recruited from hospitals and private care rheumatologists, and controls from a test subject website. All subjects underwent medical history interview, clinical examination, and biochemical screening including ACPA. Patients with positive ACPA, arthralgia, and no rheumatic disease were included. Controls without a history or signs of rheumatological disease or positive ACPA were included. A 2.7-cm-long region around the second and third MCP joints was evaluated using high-resolution peripheral quantitative computed tomography with a voxel size of 82 µm. RESULTS: Twenty-nine ACPA-positive patients and 29 healthy controls were evaluated. Trabecular volumetric bone mineral density and bone volume fraction did not differ between the groups. In addition, the cortical bone was not affected in patients, as we found no difference in average cortical thickness and cortical bone area between the groups. In contrast, the trabeculae were significantly (p < 0.05) thinner in both second and third MCP heads compared with controls, whereas trabecular number and trabecular separation did not differ between the groups. No erosions were demonstrated and the number of non-specific breaks did not differ between the groups. CONCLUSION: Trabecular bone changes were observed in ACPA-positive patients with arthralgia compared with healthy controls. The results may reflect inflammatory up-regulated trabecular bone resorption leading to early bone loss before the onset of clinical arthritis.

Subchondral bone turnover, but not bone volume, is increased in early stage osteoarthritic lesions in the human hip joint.

OBJECTIVE: The pathogenesis of osteoarthritis (OA) is not fully understood, but bone changes are suggested to be important. Bone turnover and bone volume (BV) in human hip OA were investigated in relation to the overlying cartilage degeneration using design-based stereological estimators. MATERIALS AND METHODS: Femoral heads were obtained from 25 end-stage OA patients and 24 controls (CTL). Design-based stereological methods were used for sampling and quantification to obtain absolute estimates of volume and surface in the central trabecular and the subarticular bone region. The subarticular bone was further subdivided into regions according to the OARSI-score of the overlying articular cartilage in which erosion and osteoid surfaces were estimated. RESULTS: In the subarticular region, bone volume (BV/TV) was 15.0% higher in OA patients compared to CTL; The fraction of erosive (ES/BS) and osteoid surfaces (OS/BS) were 56.2% and 72.8% higher in OA compared to CTL. In subarticular regions with none to mild cartilage degeneration (OARSI grade 0-2), ES/BS and OS/BS were 48.6% and 59.9% higher in OA compared to CTL, whereas BV/TV did not differ between OA and CTL. CONCLUSION: In human end-stage hip OA, BV and bone turnover correlate with the degree of local cartilage degeneration. Subarticular bone sclerosis was only present in regions corresponding to end-stage OA. However, in regions with only none to mild cartilage degeneration the underlying bone had significantly higher turnover in OA patients compared to the control group, suggesting that high bone turnover may contribute to the early pathogenesis of OA.

Improving efficiency in stereology: a study applying the proportionator and the autodisector on virtual slides.

Cell counting in stereology is time-consuming. The proportionator is a new stereological sampling method combining automatic image analysis and non-uniform sampling. The autodisector on virtual slides combines automatic generation of disector pairs with the use of digital images. The aim of the study was to investigate the time efficiency of the proportionator and the autodisector on virtual slides compared with traditional methods in a practical application, namely the estimation of osteoclast numbers in paws from mice with experimental arthritis and control mice. Tissue slides were scanned in a digital slide scanner and the autodisector was applied on the obtained virtual tissue slides. Every slide was partitioned into fields of view, and cells were counted in all of them. Based on the original exhaustive data set comprising 100% of fields of view and covering the total section area, a proportionator sampling and a systematic, uniform random sampling were simulated. We found that the proportionator was 50% to 90% more time efficient than systematic, uniform random sampling. The time efficiency of the autodisector on virtual slides was 60% to 100% better than the disector on tissue slides. We conclude that both the proportionator and the autodisector on virtual slides may improve efficiency of cell counting in stereology.

Early referral of patients with suspected polymyalgia rheumatica - A systematic review.

INTRODUCTION: Prompt diagnosis and treatment of polymyalgia rheumatica (PMR) is crucial to prevent long-term complications and improve patient outcomes. However, there is currently no standardized approach to referral of suspected PMR patients to rheumatologists, leading to inconsistent management practices. The objective of this systematic review was to clarify the existing evidence regarding the following aspects of early management strategies in patients with suspected PMR: diagnostic strategies, GCA screening, glucocorticoid initiation prior to referral, value of shared care and value of fast track clinic. METHODS: Two authors performed a systematic literature search, data extraction and risk of bias assessment independently. The literature search was conducted in Embase, MEDLINE (PubMed) and Cochrane. Studies were included if they contained cohorts of suspected PMR patients and evaluated the efficacy of different diagnostic strategies for PMR, screening for giant cell arteritis (GCA), starting glucocorticoids before referral to secondary care, shared care, or fast-track clinics. RESULTS: From 2,437 records excluding duplicates, 14 studies met the inclusion criteria. Among these, 10 studies investigated the diagnostic accuracy of various diagnostic strategies with the majority evaluating different clinical approaches, but none of them showed consistently high performance. However, 4 studies on shared care and fast-track clinics showed promising results, including reduced hospitalization rates, lower starting doses of glucocorticoids, and faster PMR diagnosis. CONCLUSION: This review emphasizes the sparse evidence of early management and referral strategies for patients with suspected PMR. Additionally, screening and diagnostic strategies for differentiating PMR from other diseases, including concurrent GCA, require clarification. Fast-track clinics may have potential to aid patients with PMR in the future, but studies will be needed to determine the appropriate pre-referral work-up.

Histological changes in chronic autoimmune SKG-arthritis evaluated by quantitative three-dimensional stereological estimators.

OBJECTIVES: To investigate the quantitative arthritic and bone erosive changes, including the number of osteoclasts and osteoclast precursors in the new SKG-model of inflammatory polyarthritis using three-dimensional (3D) stereological methods. METHODS: Arthritis was induced in female SKG-mice with Zymosan A. Quantitative histology was made in four control mice and four mice with arthritis euthanised after 6 and 12 weeks. The right hind paw was embedded undecalcified in methylmethacrylate and cut exhaustively generating vertical uniform random sections. A computer controlled microscope and stereological software was used for histological quantification. Total volumes were estimated according to the Cavalieri principle, total surfaces were estimated using the vertical sections design, and the number of osteoclasts was counted in a physical fractionator. RESULTS: The arthritis score increased during the 12-week period and was paralleled by an increase in the volume of inflammatory tissue (r=0.96, p<0.001). The number of osteoclasts on bone (r=0.77, p<0.05) and osteoclast-covered bone surface (r=0.62, p<0.05) increased resulting in a decrease in the volume of bone (r=-0.65, p<0.05). However, the number of osteoclast precursors declined between week 6 and 12 (p<0.05). Furthermore, the total cartilage surface (r=-0.74, p<0.05) and cartilage volume (r=-0.74, p<0.05) decreased during the 12 weeks of arthritis. CONCLUSIONS: In this study we demonstrated changes in 3D stereological parameters of inflammatory tissue, bone erosion, osteoclasts, and cartilage in mouse paws during the course of arthritis in the SKG mouse. This is the first time 3D quantitative histology has been applied in a mouse model of rheumatoid arthritis.

Vascular channels in metacarpophalangeal joints: a comparative histologic and high-resolution imaging study.

We evaluated whether cortical interruptions classified as vascular channel (VC) on high-resolution peripheral quantitative computed tomography (HR-pQCT) could be confirmed by histology. We subsequently evaluated the image characteristics of histologically identified VCs on matched single and multiplane HR-pQCT images. Four 3-mm thick portions in three anatomic metacarpophalangeal joint specimens were selected for histologic sectioning. First, VCs identified with HR-pQCT were examined for confirmation on histology. Second and independently, VCs identified by histology were matched to single and multiplane HR-pQCT images to assess for presence of cortical interruptions. Only one out of five cortical interruptions suggestive for VC on HR-pQCT could be confirmed on histology. In contrast, 52 VCs were identified by histology of which 39 (75%) could be classified as cortical interruption or periosteal excavation on matched single HR-pQCT slices. On multiplane HR-pQCT images, 11 (21%) showed a cortical interruption in at least two consecutive slices in two planes, 36 (69%) in at least one slice in two planes and five (10%) showed no cortical interruption. Substantially more VCs were present in histology sections than initially suggested by HR-pQCT. The small size and heterogeneous presentation, limit the identification as VC on HR-pQCT.