The histopathological synovitis score is influenced by biopsy location in patients with knee osteoarthritis.

INTRODUCTION: Osteoarthritis (OA) and rheumatoid arthritis (RA) represent the most common forms of arthritis, which are mainly caused by mechanical and inflammatory components, respectively. Determination of synovial inflammation in synovial biopsies via the histopathological Krenn score may be crucial for correct diagnosis and treatment. Specifically, it remains unclear whether synovitis scores differ among multiple biopsy locations within a single joint. MATERIALS AND METHODS: Eighty synovial samples were taken from four standardized regions of the knee in 20 patients (ten primary OA, ten secondary OA) undergoing total knee arthroplasty (TKA) or total synovectomy. The Krenn synovitis score (grade 0-9) was determined in a blinded manner by two expert pathologists in all biopsies. Next to the inter-rater reliability, we evaluated the agreement of the determined scores among the four biopsy locations within each knee. RESULTS: The inter-rater reliability between the two pathologists was very high (Cohen's kappa = 0.712; r = 0.946; ICC = 0.972). The mean synovitis score was significantly higher in knees with secondary than in primary OA (p = 0.026). Importantly, we found clear differences between the scores of the four different biopsy locations within the individual knee joints, with an average deviation of 10.6%. These deviations were comparable in knees with primary and secondary OA (p = 0.64). CONCLUSIONS: While we confirmed the synovitis score as a reliable and reproducible parameter to assess the histopathological synovitis grade in the knee, the considerable variability within the joint indicates that multiple synovial biopsies from different regions should be obtained to enable reliable results of the synovitis score.

Th17 cell frequency is associated with low bone mass in primary sclerosing cholangitis.

BACKGROUND & AIMS: Osteoporotic fractures are a major cause of morbidity and reduced quality of life in patients with primary sclerosing cholangitis (PSC), a progressive bile duct disease of unknown origin. Although it is generally assumed that this pathology is a consequence of impaired calcium homeostasis and malabsorption, the cellular and molecular causes of PSC-associated osteoporosis are unknown. METHODS: We determined bone mineral density by dual-X-ray absorptiometry and assessed bone microstructure by high-resolution peripheral quantitative computed tomography in patients with PSC. Laboratory markers of liver and bone metabolism were measured, and liver stiffness was assessed by FibroScan. We determined the frequency of Th17 cells by the ex vivo stimulation of peripheral blood mononuclear cells in a subgroup of 40 patients with PSC. To investigate the potential involvement of IL-17 in PSC-associated bone loss, we analyzed the skeletal phenotype of mice lacking Abcb4 and/or Il-17. RESULTS: Unlike in patients with primary biliary cholangitis, bone loss in patients with PSC was not associated with disease duration or liver fibrosis. However, we observed a significant negative correlation between the bone resorption biomarker deoxypyridinoline and bone mineral density in the PSC cohort, indicating increased bone resorption. Importantly, the frequency of Th17 cells in peripheral blood was positively correlated with the urinary deoxypyridinoline level and negatively correlated with bone mass. We observed that Abcb4-deficient mice displayed a low-bone-mass phenotype, which was corrected by an additional Il-17 deficiency or anti-IL-17 treatment, whereas the liver pathology was unaffected. CONCLUSIONS: Our findings demonstrate that an increased frequency of Th17 cells is associated with bone resorption in PSC. Whether antibody-based IL-17 blockade is beneficial against bone loss in patients with PSC should be addressed in future studies. LAY SUMMARY: Primary sclerosing cholangitis (PSC) is a cholestatic liver disease characterized by progressive bile duct destruction. One serious complication of PSC is reduced bone mass resulting in increased fracture risk. Herein, we demonstrate that Th17 cells mediate bone loss in PSC by inducing bone resorption, which suggests that antibody-based IL-17 blockade might be beneficial for the treatment of bone loss in affected patients.

The impact of physical activity on serum levels of inflammatory markers in rheumatoid arthritis: a systematic literature review.

This review aims to determine the specific effects of PA on systemic levels of interleukins and inflammatory markers. A systematic literature search was conducted in three computerized bibliographic databases (Medline, Embase, CENTRAL) to identify randomized controlled trials and matched case studies. Applied key words were: RA and PA including the terms exercise, exercise therapy, gymnastics and exercise movement techniques. Inclusion criteria were data on all types of proinflammatory interleukins (IL), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR). For data synthesis, the populations, interventions and outcomes were described according to the PRISMA statement. A total of 1289 publications were found. Fifteen papers, related to 14 different study populations, met the inclusion criteria. No study revealed a significant change regarding IL or CRP levels in response to the intervention (PA). In three study populations, a significant reduction of the ESR was identified, but the effect from PA was not discernible from effects of changes of the anti-rheumatic medication in these studies. The strong variability in study designs, cohort size and types of physical training programs remains an obstacle in the assessment of the measurable effects of PA on inflammatory markers in patients with RA. At present, there is no sufficient evidence to conclude that PA has a significant impact on systemic levels of inflammatory markers in RA.

Evaluation of bone microstructure in CRPS-affected upper limbs by HR-pQCT.

INTRODUCTION: Complex regional pain syndrome (CRPS) is a major complication after trauma, surgery, and/or immobilization of an extremity. The disease often starts with clinical signs of local inflammation and develops into a prolonged phase that is characterized by trophic changes and local osteoporosis and sometimes results in functional impairment of the affected limb. While the pathophysiology of CRPS remains poorly understood, increased local bone resorption plays an undisputed pivotal role. The aim of this retrospective clinical study was to assess the bone microstructure in patients with CRPS. METHODS: Patients with CRPS type I of the upper limb whose affected and unaffected distal radii were analyzed by high-resolution peripheral quantitative computed tomography (HR-pQCT) were identified retrospectively. The osteology laboratory data and dual-energy X-ray absorptiometry (DXA) images of the left femoral neck and lumbar spine, which were obtained on the same day as HR-pQCT, were extracted from the medical records. RESULTS: Five patients were identified. The CRPS-affected upper limbs had significantly lower trabecular numbers and higher trabecular thicknesses than the unaffected upper limbs. However, the trabecular bone volume to total bone volume and cortical thickness values of the affected and unaffected sides were similar. Trabecular thickness tended to increase with time since disease diagnosis. DISCUSSION: CRPS associated with significant alterations in the bone microstructure of the affected upper limb that may amplify as the duration of disease increases.

Sunitinib treatment reduces tumor growth and limits changes in microvascular properties after minor surgical intervention in an in vivo model of secondary breast cancer growth in bone.

BACKGROUND AND OBJECTIVES: Surgical interventions can alter the balance between pro- and anti-angiogenic growth factors and thereby modulate tumor growth. Since the microcirculatory properties of tumors underlie organ-specific differences, the microhemodynamic characteristics of bone metastasis have not yet been fully described. Angiogenesis inhibitors are increasingly being used to treat advanced stages of cancer. We hypothesized that the anti-angiogenic drug sunitinib abrogates alterations in microvascular properties following a minor surgical intervention in an in vivo model of secondary breast cancer growth in the bone. METHODS: Intravital microscopy was performed over 25 days using a xenograft model of breast cancer tumor growth in the bone to determine changes in microvascular properties during sunitinib treatment. Mastectomy was performed on day 5 to evaluate the effect of a minor surgical trauma on tumor growth and microvascular properties. RESULTS: Anti-angiogenic therapy resulted in reduced tumor growth, decreased vascular density, and increased vascular diameters. Blood flow velocity remained constant while microvascular permeability temporarily increased after the surgical intervention. CONCLUSIONS: Administration of sunitinib reduced tumor growth and altered microcirculatory properties in a time-dependent manner. The observed dramatic increase in microvascular permeability after the surgical intervention may have implications for local tumor growth, and metastatic dissemination. J. Surg. Oncol. 2016;113:515-521. © 2016 Wiley Periodicals, Inc.

Quality-Adjusted Life Years Gained by Hip and Knee Replacement Surgery and Its Aftercare.

OBJECTIVES: To determine the lifetime quality-adjusted life years (QALYs) gained by total joint arthroplasty (TJA), and assess the QALYs attributed to specific postoperative rehabilitation interventions. DESIGN: Secondary analysis of 2 multicenter, randomized controlled trials (RCTs) with 3-, 6-, 12-, and 24-month follow-up. SETTING: Two university hospitals, 2 municipal hospitals, and 1 rural hospital. PARTICIPANTS: Patients (N=827) who underwent total hip arthroplasty (THA) or total knee arthroplasty (TKA). INTERVENTIONS: RCT A: 465 patients were randomly assigned to receive aquatic therapy (pool exercises aimed at training of proprioception, coordination, and strengthening) 6 versus 14 days after THA or TKA. RCT B: 362 patients were randomly assigned to either perform or not perform ergometer cycling beginning 2 weeks after THA or TKA. MAIN OUTCOME MEASURE: QALYs, based on the Short Form-6 Dimensions utility, measured at baseline and 3, 6, 12, and 24 months' follow-up. RESULTS: After hip arthroplasty, the lifetime QALYs increased by 2.35 years in the nonergometer group, and by 2.30 years in the early aquatic therapy group. However, after knee arthroplasty, the lifetime QALYs increased by 1.81 years in the nonergometer group, and by 1.60 years in the early aquatic therapy group. By ergometer cycling, .55 additional QALYs could be gained after hip and .10 additional QALYs after knee arthroplasty, while the additional QALYs attributed to the timing of aquatic therapy were .12 years after hip and .01 years after knee arthroplasty. CONCLUSIONS: This analysis provides a sound estimate for the determination of the lifetime QALYs gained by THA and TKA. In addition, this analysis demonstrates that specific postoperative rehabilitation can result in an additional mean QALY gain of .55 years, which represents one fourth of the effect of surgery. Even if this is interpreted as a small effect at an individual level, it is important when extrapolated to all patients undergoing TJA. At a national level, these improvements appear to have a similar magnitude of QALY gain when compared with published data regarding medications to lower blood pressure in all persons with arterial hypertension.

Hyaline cartilage calcification of the first metatarsophalangeal joint is associated with osteoarthritis but independent of age and BMI.

BACKGROUND: Hyaline cartilage calcification (CC) is associated with osteoarthritis (OA) in hip and knee joints. The first metatarsophalangeal joint (1stMTPJ) is frequently affected by OA, but it is unclear if CC occurs in the 1stMTPJ. The aim of the present study was to analyze the prevalence of CC of the 1stMTPJ in the general population by high-resolution digital contact radiography (DCR) and to determine its association with histological OA severity, age and body mass index (BMI). METHODS: 168 metatarsal heads of 84 donors (n = 47 male, n = 37 female; mean age 62.73 years, SD ±18.8, range 20-93) were analyzed by DCR for the presence of CC. Histological OA grade (hOA) by OARSI was analyzed in the central load-bearing zone of the first metatarsal head (1st MH). Structural equation modeling (SEM) was performed to analyze the interrelationship between CC, hOA, age and BMI. RESULTS: The prevalence of CC of 1stMH was 48.8 % (41/84) (95 %-CI [37.7 %, 60.0 %]), independent of the affected side (p = 0.42), gender (p = 0.41) and BMI (p = 0.51). The mean amount of CC of one MH correlated significantly with that of the contralateral side (rs = 0.4, 95 %-CI [0.26, 0.52], p < 0.001). The mean amount of CC (in % of total cartilage area) of the MH correlated significantly with the severity of hOA (rs = 0.51, 95 %-CI [0.32, 0.65], p < 0.001). SEM revealed significant associations between CC and hOA (r = 0.74, p < 0.001) and between hOA and age (ß = 0.62, p = 0.001), but not between CC and age (p = 0.15). There was no significant influence of BMI on either CC (p = 0.37) or hOA (p = 0.16). CONCLUSION: The observation that CC of the 1stMH is significantly associated with the severity of OA but independent of age and BMI, suggests an intimate relationship between CC and the pathogenesis of OA, the exact nature of which will have to be explored by future studies.

Deterioration of teeth and alveolar bone loss due to chronic environmental high-level fluoride and low calcium exposure.

OBJECTIVES: Health risks due to chronic exposure to highly fluoridated groundwater could be underestimated because fluoride might not only influence the teeth in an aesthetic manner but also seems to led to dentoalveolar structure changes. Therefore, we studied the tooth and alveolar bone structures of Dorper sheep chronically exposed to very highly fluoridated and low calcium groundwater in the Kalahari Desert in comparison to controls consuming groundwater with low fluoride and normal calcium levels within the World Health Organization (WHO) recommended range. MATERIALS AND METHODS: Two flocks of Dorper ewes in Namibia were studied. Chemical analyses of water, blood and urine were performed. Mineralized tissue investigations included radiography, HR-pQCT analyses, histomorphometry, energy-dispersive X-ray spectroscopy and X-ray diffraction-analyses. RESULTS: Fluoride levels were significantly elevated in water, blood and urine samples in the Kalahari group compared to the low fluoride control samples. In addition to high fluoride, low calcium levels were detected in the Kalahari water. Tooth height and mandibular bone quality were significantly decreased in sheep, exposed to very high levels of fluoride and low levels of calcium in drinking water. Particularly, bone volume and cortical thickness of the mandibular bone were significantly reduced in these sheep. CONCLUSIONS: The current study suggests that chronic environmental fluoride exposure with levels above the recommended limits in combination with low calcium uptake can cause significant attrition of teeth and a significant impaired mandibular bone quality. CLINICAL RELEVANCE: In the presence of high fluoride and low calcium-associated dental changes, deterioration of the mandibular bone and a potential alveolar bone loss needs to be considered regardless whether other signs of systemic skeletal fluorosis are observed or not.

Angiogenic growth factors in rheumatoid arthritis.

We investigated whether the angiogenic profile, which is based on the local expression and systemic levels of angiogenic growth factors (VEGF, Ang-1, Ang-2, and the corresponding receptors), differs between rheumatoid arthritis (RA) and osteoarthritis (OA) patients. We determined the expression of VEGF, Ang-1, and Ang-2 together with its receptors (VEGFR-1/-2 and Tie2) in synovium tissue (ST) and muscular tissue (MT) from patients with RA and OA using quantitative PCR. Tissue samples were obtained from 15 RA and 19 OA patients during total knee arthroplasty. Control MT samples (n = 10) were obtained during spinal surgery. Results are correlated to VEGF and angiopoietin serum levels via ELISA measurements. The VEGF expressions in ST and serum levels were significantly higher in RA patients than in OA patients (P < 0.05). Furthermore, the VEGFR-1 and VEGFR-2 expression in ST from RA patients were significantly higher than in OA patients (P < 0.001 and P < 0.05). The relative concentration of angiopoietins (Ang-1/Ang-2 ratio) was significantly increased in RA (P < 0.01). Serum levels for Ang-2 showed no significant differences. Statistical analysis showed a significant higher level of Tie2 in RA patients (P < 0.001). Analysis of local levels of VEGF, VEGFR-1, VEGFR-2, Ang-1, Ang-2, and Tie2 in the muscular tissue showed no significant difference between RA and OA patients. These results underline the importance of pro-angiogenic growth factor levels for RA corroborating the assumption that VEGF and angiopoietins play an important role in the pathogenesis of RA.

Loose Bodies Found in the Human Intra-Articular Space Showed Characteristics Similar to Endochondral Bone Formation.

OBJECTIVE: Loose bodies are free-floating tissues of cartilage and bone that can cause pain, swelling, the inability to straighten the knee, or intermittent locking of the knee. Loose bodies can arise from degenerative joint disease, flake fractures, osteochondritis dissecans, or chondromatosis. We hypothesized that loose bodies can be classified in stages with tissue characteristics similar to endochondral ossification. DESIGN: Loose bodies were harvested from patients undergoing joint replacement. Samples were processed for histology, gene expression analysis, and micro-computed tomography (µCT). Cartilage- and bone-related genes and proteins were selected for immunofluorescence stainings (collagen type I, II, and X, SOX9 [SRY-box transcription factor 9], and MMP13 [matrix metalloproteinase 13]) and gene expression analysis (FN [fibronectin], COL1A1, COL2A1, COL10A1, SOX9, MMP13, and aggrecan [ACAN]). RESULTS: Loose bodies were grouped in 4 stages: fibrous, (mineralized) cartilaginous, cartilage and bone, and bone. Hyaline-like cartilage tissue with Benninghoff arcades was present in stages 2 and 3. A transition from cartilaginous to mineralized tissue and bone trabecula was defined by an increase in COL1A1 and COL10A1 (stage 3 vs. 4: p = 0.047) positive area. Stage 4 showed typical trabecular bone tissue. The relative volume of calcified tissue (mineralized cartilage and bone tissue) decreased with stages (stages 1-2 vs. 3: p = 0.002; stage 1-2 vs. 4: p = 0.012). COL2A1 expression and stained area decreased from stages 1-2 to 4 (p = 0.010 and p = 0.004). ACAN expression decreased from stage 1-2 to stage 3 (p = 0.049) and stage 4 (p = 0.002). CONCLUSION: Loose bodies show tissue characteristics similar to endochondral ossification. They are probably a relevant substrate for regenerative therapeutic interventions in joint disease.

Multicenter randomized controlled trial comparing early versus late aquatic therapy after total hip or knee arthroplasty.

OBJECTIVE: To evaluate if the timing of aquatic therapy influences clinical outcomes after total knee arthroplasty (TKA) or total hip arthroplasty (THA). DESIGN: Multicenter randomized controlled trial with 3-, 6-, 12-, and 24-month follow-up. SETTING: Two university hospitals, 1 municipal hospital, and 1 rural hospital. PARTICIPANTS: Patients (N=465) undergoing primary THA (n=280) or TKA (n=185): 156 men, 309 women. INTERVENTION: Patients were randomly assigned to receive aquatic therapy (pool exercises aimed at training of proprioception, coordination, and strengthening) after 6 versus 14 days after THA or TKA. MAIN OUTCOME MEASURES: Primary outcome was self-reported physical function as measured by the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at 3-, 6-, 12-, and 24-months postoperatively. Results were compared with published thresholds for minimal clinically important improvements. Secondary outcomes included the Medical Outcomes Study 36-Item Short-Form Health Survey, Lequesne-Hip/Knee-Score, WOMAC-pain and stiffness scores, and patient satisfaction. RESULTS: Baseline characteristics of the 2 groups were similar. Analyzing the total study population did not result in statistically significant differences at all follow-ups. However, when performing subanalysis for THA and TKA, opposite effects of early aquatic therapy were seen between TKA and THA. After TKA all WOMAC subscales were superior in the early aquatic therapy group, with effect sizes of WOMAC physical function ranging from .22 to .39. After THA, however, all outcomes were superior in the late aquatic therapy group, with WOMAC effect sizes ranging from .01 to .19. However, the differences between treatment groups of these subanalyses were not statistically significant. CONCLUSIONS: Early start of aquatic therapy had contrary effects after TKA when compared with THA and it influenced clinical outcomes after TKA. Although the treatment differences did not achieve statistically significance, the effect size for early aquatic therapy after TKA had the same magnitude as the effect size of nonsteroidal anti-inflammatory drugs in the treatment of osteoarthritis of the knee. However, the results of this study do not support the use of early aquatic therapy after THA. The timing of physiotherapeutic interventions has to be clearly defined when conducting studies to evaluate the effect of physiotherapeutic interventions after TKA and THA.

Amyloid deposition in rheumatoid arthritis of the hip.

The aim of this study was to examine the frequency of amyloid deposition in patients with end-stage rheumatoid arthritis (RA) of the hip. The impact on the clinical situation and the RA severity regarding the inflammation was analyzed. Fifty patients with RA who consecutively underwent total hip replacement were prospectively evaluated. X-rays of the patients were analyzed radiologically (Larsen score) to quantify the radiological changes. A clinical score (Harris Hip Score) was preoperatively calculated from every patient. A laboratory set of inflammation markers (erythrocyte sedimentation rate, CRP, serum amyloid A-SAA, electrophoresis) was measured in every patient the day before the operation. Specimens of bone and cartilage from the femoral head and of the capsule were obtained from every patient intraoperatively for histological evaluation. A histological grading was performed. In patients with amyloid deposits, the subtypes were characterized immunohistologically. Ninety-two percent of the patients had raised SAA in the blood samples, but the only amyloid subtype was ATTR. No correlation was found for any other measured item, such as inflammation signs in the blood samples, the histological grading, the radiological or the clinical score. Amyloid plays a role in inflammatory joint destruction processes in RA with raised SAA values, but the amyloid deposits in the joint are of a different subtype. Thus, these amyloid deposits can be considered as minor pathologic significance. A correlation to the radiological and histological changes was ruled out by our study. As in degenerative arthritis, ATTR amyloid deposits may be an incidental finding in aged joints.

Cementation and interface analysis of early failure cases after hip-resurfacing arthroplasty.

PURPOSE: The use of inappropriate cementation techniques has been suggested as an adverse factor for the long-term survival of hip-resurfacing arthroplasty. Inadequate initial fixation, thermal osteonecrosis and interface biological reactions are possible causes of failure. We analysed morphological changes associated with the cementation technique in a large collection of retrieved femoral components. METHODS: One hundred and fifty femoral components (mean time to failure of 8.3 months±11.0) obtained at revision surgery were analysed morphometrically and histopathologically. Cement mantle and penetration were quantified in six different regions of interest. Histopathological analysis of the bone-cement interface was performed on undecalcified processed bone tissue. RESULTS: The vast majority of the cases differed substantially from laboratory-based cement-penetration depth recommendations. Fifty-nine cases had a fibrous membrane at the cement-bone interface. This membrane was significantly thicker in cases with osteonecrosis compared to cases viable bone. CONCLUSIONS: Our results demonstrate that most failures were cemented inappropriately. We suggest that poor cementation was an important adverse factor; however, the cause of the failures was obviously multifactorial. The thickness of the fibrous membrane at the cement-bone interface differed significantly between cases with osteonecrosis and specimens with viable bone tissue.

Sex differences in the morphological failure patterns following hip resurfacing arthroplasty.

BACKGROUND: Metal-on-metal hybrid hip resurfacing arthroplasty (with a cementless acetabular component and a cemented femoral component) is offered as an alternative to traditional total hip arthroplasty for the young and active adult with advanced osteoarthritis. Although it has been suggested that women are less appropriate candidates for metal-on-metal arthroplasty, the mechanisms of prosthesis failure has not been fully explained. While specific failure patterns, particularly osteonecrosis and delayed type hypersensitivity reactions have been suggested to be specifically linked to the sex of the patient, we wished to examine the potential influence of sex, clinical diagnosis, age of the patient and the size of the femoral component on morphological failure patterns in a large cohort of retrieved specimens following aseptic failure of hip resurfacing arthroplasty. METHODS: Femoral remnants retrieved from 173 hips with known patient's sex were morphologically analyzed for the cause of failure. The results were compared with the control group of the remaining 31 failures from patients of unknown sex. The odds ratios (OR) and 95% confidence intervals (CI) of the following morphologically defined variables were calculated using logistic regression analysis: periprosthetic fractures (n=133), osteonecrosis (n=151), the presence of excessive intraosseous lymphocyte infiltration (n=11), and interface hyperosteoidosis (n=30). Logistic regression analysis was performed both unadjusted and after adjustment for sex, age, the size of the femoral component, and preoperative clinical diagnosis. RESULTS: Femoral remnants from female patients had a smaller OR for fracture (adjusted OR: 0.29, 95% CI 0.11, 0.80, P for difference=0.02) and for the presence of osteonecrosis (adjusted OR: 0.16, 95% CI 0.04, 0.63, P for difference=0.01). However, women had a higher OR for both the presence of excessive intraosseous lymphocyte infiltration (adjusted OR: 10.22, 95% CI 0.79, 132.57, P for difference=0.08) and interface hyperosteoidosis (adjusted OR: 4.19, 95% CI 1.14, 15.38, P for difference=0.03). CONCLUSIONS: Within the limitations of this study, we demonstrated substantial sex differences in distinct failure patterns of metal-on-metal hip resurfacing. Recognition of pathogenically distinct failure modes will enable further stratification of risk factors for certain failure mechanisms and thus affect future therapeutic options for selected patient groups.

Phenotypic diversity in chondromyxoid fibroma reveals differentiation pattern of tumor mimicking fetal cartilage canals development: an immunohistochemical study.

Chondromyxoid fibroma represents a rare benign cartilaginous tumor of young patients occurring in a subcortical metaphyseal location. The histogenesis of chondromyxoid fibroma has not yet been postulated, even though the conventional histology and recent immunohistochemical studies on phenotype of the mesenchymal cells and extracellular matrix components suggested its origin in immature cartilage. Therefore, we wished to compare the morphological pattern of immature cartilage tissue with chondromyxoid fibroma to investigate a possible developmental counterpart of chondromyxoid fibroma. Archival paraffin-embedded tissues from 4 fetal femora and 10 cases of chondromyxoid fibroma were analyzed simultaneously using histochemistry (safranin O) and established immunohistochemical antibodies (CD34, CD163, and smooth muscle actin). Vascularized cartilage canals growing into the fetal cartilage from the perichondrium displayed characteristic glomeruloid structures with central arterioles within the immature mesenchymal stroma and numerous superficial sinusoidal blood vessels accompanied by macrophage infiltration. Similarly, each case of chondromyxoid fibroma demonstrated admixture of two characteristic components: immature fibrous tissue of vascularized stroma with accumulation of macrophages in areas of superficial sinusoidal proliferation, and variable amounts of lobulated chondroid tissue. Based on the observed substantial morphological similarity between the cartilage canals and chondromyxoid fibroma, we suggest that the chondromyxoid fibroma represents a neoplasm originating from or mimicking the fetal cartilage canals within the immature cartilage.

Women recover faster than men after standard knee arthroplasty.

BACKGROUND: Specific anatomic differences are believed to account for gender-specific function and health-related quality of life after TKA. However, there are conflicting data in the literature regarding these gender-specific outcomes, especially as woman appear to have surgery later in the course of the disease compared with men. QUESTIONS/PURPOSES: We asked whether (1) women had worse knee function and health-related quality of life after TKA compared with men, (2) lower improvements in scores, and (3) slower recovery after surgery. METHODS: Using a cohort study design, we retrospectively analyzed prospectively collected data from three multicenter randomized controlled trials evaluating rehabilitation measures after standard unisex knee arthroplasty in 494 patients (141 men and 353 women). The primary outcome was self-reported physical function as measured by the WOMAC at 3, 6, 12, and 24 months after surgery. Secondary outcomes included the pain and stiffness scales of the WOMAC and the physical and mental component summaries of the SF-36. At the time of surgery, the women were on average older (70.8 versus 67.8 years), had lower mean physical function (55 versus 47), higher mean pain scores (54 versus 48), and greater stiffness (54 versus 46) as measured by the WOMAC. RESULTS: At the 3-, 6-, 12-, and 24-month followups, men and women had similar WOMAC scores. Improvements were greater for women compared with men for WOMAC function and pain subscale scores at the 3-month (function, 28 versus 23; pain, 32 versus 25) and 6-month followups (function, 32 versus 27; pain, 36 versus 31). At the 12- and 24-month followups we noted no differences in improvement between men and women. CONCLUSION: Although women had greater functional limitations at the time of surgery than men, they recover faster early after standard TKA although function is similar at 12 and 24 months. Women also had greater improvement of WOMAC scores after standard TKA than men. LEVEL OF EVIDENCE: Level II, prognostic study. See the guidelines for authors for a complete description of levels of evidence.

Amyloid deposition in osteoarthritis of the hip.

PURPOSE: The aim of this study was to examine the frequency of amyloid deposition in patients with end-stage hip osteoarthritis (OA). Further, their impact on the clinical situation and the OA severity were analyzed. METHODS: Fifty patients with OA who consecutively underwent total hip replacement were prospectively evaluated. The X-rays of the patients were analyzed using a radiological score (Kellgren-Lawrence) to quantify the amount of radiological changes. A clinical score [Harris hip score (HHS)] was preoperatively calculated for every patient. Specimens from the femoral head of bone and cartilage, and additionally 1 cm(2) of the capsule, were obtained from every patient intraoperatively for analyzing the amyloid deposition histologically. A histological grading was also performed. On a subset of patients with amyloid deposits, the subtypes were characterized immunohistologically. RESULTS: The only subtype of amyloid was ATTR. There was a high, significant correlation between articular amyloid deposition and the age of the patient at the time of the operation. No correlation was found for any other measured item, such as signs of inflammation in the blood samples, histological grading, radiological score or clinical score. CONCLUSIONS: The frequency of amyloid deposits in the joint increases with age, and it can generally be considered to be of no pathologic significance, since a correlation with the radiological and histological changes was ruled out by our study. Thus, the presence of ATTR amyloid may simply be an incidental finding in aged joints.

Necrobiosis and T-lymphocyte infiltration in retrieved aseptically loosened metal-on-polyethylene arthroplasties.

BACKGROUND AND PURPOSE: Soft tissue necrobiosis and T-lymphocyte infiltration within the periprosthetic soft tissue have been linked to a suggested hypersensitivity reaction of the delayed-type following the metal-on-metal arthroplasty. While we observed both synovial necrobiosis and lymphocyte infiltrates in synovial tissues with failed metal-on-polyethylene prostheses, we hypothesized that both findings are unspecific for metal-on-metal bearing coupes. Thus, we wished to quantify the extent of necrobiosis and the amount of T-lymphocyte infiltration in aseptically loosened metal-on-polyethylene prostheses. MATERIALS AND METHODS: We analyzed 28 consecutive synovial biopsy specimens obtained at revision surgery of aseptically loosened metal-on-polyethylene prostheses (19 hips and 9 knees) and quantified both the extent of necrobiosis vertically and the density of CD3+, CD4+, and CD8+ lymphocytes within the joint capsular tissue. We excluded patients with inflammatory skeletal disease or with a history of metal hypersensitivity. RESULTS: We found necrobiosis in 23 of 28 cases and it was most often connected with the superficial portions of the synovium. Necrobiosis of deeper tissues was seen in 8 specimens and it was strongly associated with superficial necrobiosis. While CD3+ lymphocytes were detected in each biopsy, 4 cases with more than 300 CD3+ lymphocytes were identified in the group of 26 cases that presented with more than 100 CD3+ lymphocytes within one high-power field. 16 cases with more than 100 CD3+ lymphocytes also showed concomitant superficial necrobiosis of the synovium. In the inflammatory infiltration of periprosthetic synovium, CD8+ lymphocytes predominated over CD4+ cells. INTERPRETATION: Synovial necrobiosis and infiltration of T-lymphocytes are common findings in tissues around aseptically loosened metal-on-polyethylene arthroplasty in patients without a clinically suspected metal hypersensitivity reaction. Thus, neither necrobiosis nor infiltration of T-lymphocytes should be considered to be specific for failed metal-on-metal bearings or metal hypersensitivity reaction.