Impact of polyethylene glenoid cementation technique on cement mantle integrity and stability after cyclic loading: a computed tomography and biomechanical study.

BACKGROUND: There are no generally accepted guidelines for polyethylene (PE) glenoid component cementation techniques. In particular, it is not known whether the backside of a PE glenoid should be fully or partially cemented-or not cemented at all. We hypothesized that cementing techniques would have an impact on cement mantle volume and integrity, as well as biomechanical stability, measured as micromotion under cyclic loading. METHODS: To address our hypothesis, 3 different cementation techniques using a single 2-peg PE glenoid design with polyurethane foam were compared regarding (1) the quality and quantity of the cement mantle and (2) biomechanical stability after cyclic loading in vitro. Eight identically cemented glenoids per group were used. Group A underwent cement application only into the peg holes, group B received additional complete cement mantle application on the backside of the glenoid, and group C received the same treatment as group B but with additional standardized drill holes in the surface of the glenoid bone for extra cement interdigitation. All glenoids underwent cyclic edge loading by 105 cycles according to ASTM F2028-14. Before and after loading, cement mantle evaluation was performed by XtremeCT and biomechanical strength and loosening were evaluated by measuring the relative motion of the implants. RESULTS: The cement mantle at the back of the implant was incomplete in group A as compared with groups B and C, in which the complete PE backside was covered with a homogeneous cement mantle. The cement mantle was thickest in group C, followed by group B (P = .006) and group A (P < .001). We did not detect any breakage of the cement mantle in any of the 3 groups after testing. Primary stability during cyclic loading was similar in all groups after the "running-in" phase (up to 4000 cycles). Gross loosening did not occur in any implant. CONCLUSIONS: Coverage of the PE glenoid with cement was reproducible in the fully cemented groups (ie, groups B and C) as compared with relevant cement defects in group A. The addition of cement to the back of the PE glenoid and additional drill holes in the glenoid surface did not improve primary stability in the tested setting.

Chronic pain in osteoarthritis of the hip is associated with selective cognitive impairment.

INTRODUCTION: Chronic pain of various origin is known to be associated with selective cognitive impairment. Osteoarthritis (OA) of the hip is one of the leading causes of chronic pain in the adult population, but its association with cognitive performance has not been evaluated. Here, we investigate the effect of chronic pain due to unilateral OA of one hip and no further source of chronic pain on cognitive performance. MATERIALS AND METHODS: A neuropsychological test battery, consisting of the Mini-Mental State Examination, Rey-Osterrieth complex figure test, Rivermead behavioural memory test, d2 test of attention, and F-A-S test was applied in 148 patients and 82 healthy pain-free control individuals. The influence of potentially confounding factors such as depression and anxiety was examined. RESULTS: Patients with OA of the hip showed decreased performance in specific neuropsychological tests. Performance in verbal and visual short-term and long-term memory and selective attention tests was significantly poorer compared to healthy controls. Whereas the executive functions "updating", "set shifting", "response inhibition" and "reflection" appear intact, "problem solving" and "planning" were impaired. None of the confounders showed any influence on cognitive performance in both study groups. CONCLUSION: We conclude that chronic pain secondary to end-stage hip OA is associated with selective cognitive impairment. Future studies are required to investigate the effect of total hip arthroplasty on cognitive performance.

Diagnostic value of open incisional biopsies in suspected, difficult-to-diagnose periprosthetic hip joint infection prior to revision surgery.

INTRODUCTION: Prior to revision of total hip arthroplasty (THA), low-grade chronic periprosthetic joint infection (PJI) is often difficult to diagnose. We aimed to determine the diagnostic accuracy of open incisional tissue biopsy for the prediction of PJI prior to THA revision in cases with culture-negative or dry tap joint aspirates. MATERIALS AND METHODS: This retrospective single-center study includes 32 consecutive THA revision cases with high clinical suspicion of low-grade chronic PJI of the hip with culture-negative or dry tap joint aspirates and without systemic signs of infection. Open incisional biopsy (OIB) was performed prior to revision surgery. Periprosthetic tissue samples were analyzed by microbiology and histopathology for PJI. During definitive revision arthroplasty, identical diagnostics were repeated. Results from both procedures were compared and sensitivity, specificity, positive and negative predictive values of OIB for the final diagnosis were calculated. RESULTS: Average age at revision was 69.3 ± 13.5 years. The sensitivity of the OIB procedure was 80% (microbiology), 69% (histology) and 82% for combined analyses (microbiology and histology). Specificity of OIB was 80% (microbiology), 94% (histology) and 60% for combined analyses. CONCLUSIONS: Open tissue biopsy performed in cases with culture-negative or inconclusive synovial fluid aspirates prior to revision of THA has limited diagnostic accuracy for the prediction of PJI. The procedure does not reliably close the diagnostic gap in a substantial number of cases. In this difficult patient population, risk of an open procedure may outweigh benefits and alternative less invasive methods should be considered for the preoperative diagnosis of PJI.

[Gout (ICD 10: M10): a retrospective analysis of the data from the histopathological arthritis register of the DGORh]. / Gicht (ICD-10: M10): Eine retrospektive Analyse der Daten des histopathologischen Arthritisregisters der DGORh.

BACKGROUND: Gout is considered to be the most common inflammatory arthritis worldwide. The histopathological arthritis register of the German Society for Orthopedic Rheumatology (DGORh) was founded in 2018. The aim of this register is a systematic collection of histopathological data on joint pathologies. As part of a master's thesis in medicine at the Sigmund Freud Private University (Vienna, Austria) the data on gout cases were retrospectively analyzed. OBJECTIVE: The objective of this analysis was to determine the prevalence of gout, the localizations of gout in the musculoskeletal system and the sensitivity of clinical gout diagnostics. MATERIAL AND METHODS: In cooperation with the Medical Treatment Center for Histology, Cytology and Molecular Diagnostics in Trier, Germany (MVZ-HZMD-Trier GmbH; Germany), tissue samples from 190 different orthopedic clinics and practices were analyzed and 7595 datasets were collected and stored in an arthritis register created by the DGORh. All gout cases stored between 1 January 2018 and 20 January 2020 were eligible for retrospective analysis (N = 102). RESULTS: The prevalence of gout was calculated at 1.34%. Of 108 histopathologically confirmed urate crystal depositions and gout granulomas, 76 were found in the lower extremities (70.37%), 30 in the upper extremities (27.78%) and 2 in the spinal joints (1.85%). The sensitivity of clinical gout diagnostics could be determined at 73.53%. CONCLUSION: Gout affects different anatomical regions with the first metatarsophalangeal joint being the main localization site. The sensitivity of clinical gout diagnostics was determined at 73.53%. These results emphasize the importance of histopathology in gout diagnostics.

Hip abductor tendon pathology visualized by 1.5 versus 3. 0 Tesla MRIs.

INTRODUCTION: Hip abductor tendinopathies are becoming increasingly recognized as clinically relevant disorders. However, knowledge about prevalence of abductor tendinopathies and associated disorders of adjacent hip articular and periarticular structures is limited. In this context, the relative diagnostic value of 1.5-T vs. 3.0-T MRI magnets has not been studied yet. MATERIALS AND METHODS: Pelvic MRI scans of 1000 hips from 500 consecutive unselected patients (341 in 3.0-T/159 in 1.5-T magnets, with standardized scanning protocols over the entire study period) were analysed for the detection of abductor tendinosis, calcifying tendinitis, partial or full-thickness tears of the M. gluteus medius (GMed) and/or -minimus (GMin) and trochanteric bursitis (TB). The occurrence of these lesions was correlated to the presence of muscle atrophy (MA) of GMed/GMin, hip joint effusion (JE) and osteoarthritis (OA). RESULTS: Peritrochanteric lesions were observed with a prevalence of 31.4% of all patients (22.3% of all hips). TB occurred almost exclusively in the presence of GMed/GMin tendinopathies. Compared to overall prevalence, patients with MA displayed lesions of GMed/GMin or TB in 70%, patients, with OA in 30% and with JE in 23%. These lesions occurred significantly more often ipsilateral to MA and OA than contralateral (MA: 76.8% vs. 23.2%, p < 0.001; OA: 64.4% vs. 35.6%, p = 0.03; JE: 62.7% vs. 37.3%, p = 0.08). Significantly more tendon lesions, in particular specific radiological diagnoses like partial/full-thickness tears, were detected by 3.0-T MRI than by 1.5 T (p = 0.019). CONCLUSIONS: Peritrochanteric lesions are a prevalent pathology that should specifically be looked for, preferably by 3.0-T MRI, independent of concomitant hip joint pathology.

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.

Quantification of Bone Fatty Acid Metabolism and Its Regulation by Adipocyte Lipoprotein Lipase.

Adipocytes are master regulators of energy homeostasis. Although the contributions of classical brown and white adipose tissue (BAT and WAT, respectively) to glucose and fatty acid metabolism are well characterized, the metabolic role of adipocytes in bone marrow remains largely unclear. Here, we quantify bone fatty acid metabolism and its contribution to systemic nutrient handling in mice. Whereas in parts of the skeleton the specific amount of nutrients taken-up from the circulation was lower than in other metabolically active tissues such as BAT or liver, the overall contribution of the skeleton as a whole organ was remarkable, placing it among the top organs involved in systemic glucose as well as fatty acid clearance. We show that there are considerable site-specific variations in bone marrow fatty acid composition throughout the skeleton and that, especially in the tibia, marrow fatty acid profiles resemble classical BAT and WAT. Using a mouse model lacking lipoprotein lipase (LPL), a master regulator of plasma lipid turnover specifically in adipocytes, we show that impaired fatty acid flux leads to reduced amounts of dietary essential fatty acids while there was a profound increase in de novo produced fatty acids in both bone marrow and cortical bone. Notably, these changes in fatty acid profiles were not associated with any gross skeletal phenotype. These results identify LPL as an important regulator of fatty acid transport to skeletal compartments and demonstrate an intricate functional link between systemic and skeletal fatty acid and glucose metabolism.

Agrin mediates chondrocyte homeostasis and requires both LRP4 and α-dystroglycan to enhance cartilage formation in vitro and in vivo.

OBJECTIVES: Osteoarthritis (OA) is a leading cause of disability for which there is no cure. The identification of molecules supporting cartilage homeostasis and regeneration is therefore a major pursuit in musculoskeletal medicine. Agrin is a heparan sulfate proteoglycan which, through binding to low-density lipoprotein receptor-related protein 4 (LRP4), is required for neuromuscular synapse formation. In other tissues, it connects the cytoskeleton to the basement membrane through binding to α-dystroglycan. Prompted by an unexpected expression pattern, we investigated the role and receptor usage of agrin in cartilage. METHODS: Agrin expression pattern was investigated in human osteoarthritic cartilage and following destabilisation of the medial meniscus in mice. Extracellular matrix (ECM) formation and chondrocyte differentiation was studied in gain and loss of function experiments in vitro in three-dimensional cultures and gain of function in vivo, using an ectopic cartilage formation assay in nude mice. Receptor usage was investigated by disrupting LRP4 and α-dystroglycan by siRNA and blocking antibodies respectively. RESULTS: Agrin was detected in normal cartilage but was progressively lost in OA. In vitro, agrin knockdown resulted in reduced glycosaminoglycan content, downregulation of the cartilage transcription factor SOX9 and other cartilage-specific ECM molecules. Conversely, exogenous agrin supported cartilage differentiation in vitro and ectopic cartilage formation in vivo. In the context of cartilage differentiation, agrin used an unusual receptor repertoire requiring both LRP4 and α-dystroglycan. CONCLUSIONS: We have discovered that agrin strongly promotes chondrocyte differentiation and cartilage formation in vivo. Our results identify agrin as a novel potent anabolic growth factor with strong therapeutic potential in cartilage regeneration.

Inhibition of Notch1 promotes hedgehog signalling in a HES1-dependent manner in chondrocytes and exacerbates experimental osteoarthritis.

OBJECTIVES: Notch ligands and receptors have recently been shown to be differentially expressed in osteoarthritis (OA). We aim to further elucidate the functional role of Notch signalling in OA using Notch1 antisense transgenic (Notch1 AS) mice. METHODS: Notch and hedgehog signalling were analysed by real-time PCR and immunohistochemistry. Notch-1 AS mice were employed as a model of impaired Notch signalling in vivo. Experimental OA was induced by destabilisation of the medial meniscus (DMM). The extent of cartilage destruction and osteophyte formation was analysed by safranin-O staining with subsequent assessment of the Osteoarthritis Research Society International (OARSI) and Mankin scores and µCT scanning. Collagen X staining was used as a marker of chondrocyte hypertrophy. The role of hairy/enhancer of split 1 (Hes-1) was investigated with knockdown and overexpression experiments. RESULTS: Notch signalling was activated in human and murine OA with increased expression of Jagged1, Notch-1, accumulation of the Notch intracellular domain 1 and increased transcription of Hes-1. Notch1 AS mice showed exacerbated OA with increases in OARSI scores, osteophyte formation, increased subchondral bone plate density, collagen X and osteocalcin expression and elevated levels of Epas1 and ADAM-TS5 mRNA. Inhibition of the Notch pathway induced activation of hedgehog signalling with induction of Gli-1 and Gli-2 and increased transcription of hedgehog target genes. The regulatory effects of Notch signalling on Gli-expression were mimicked by Hes-1. CONCLUSIONS: Inhibition of Notch signalling activates hedgehog signalling, enhances chondrocyte hypertrophy and exacerbates experimental OA including osteophyte formation. These data suggest that the activation of the Notch pathway may limit aberrant hedgehog signalling in OA.

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.

Signature of circulating microRNAs in osteoarthritis.

BACKGROUND: Osteoarthritis is the most common form of arthritis and a major socioeconomic burden. Our study is the first to explore the association between serum microRNA levels and the development of severe osteoarthritis of the knee and hip joint in the general population. METHODS: We followed 816 Caucasian individuals from 1995 to 2010 and assessed joint arthroplasty as a definitive outcome of severe osteoarthritis of the knee and hip. After a microarray screen, we validated 12 microRNAs by real-time PCR in the entire cohort at baseline. RESULTS: In Cox regression analysis, three microRNAs were associated with severe knee and hip osteoarthritis. let-7e was a negative predictor for total joint arthroplasty with an adjusted HR of 0.75 (95% CI 0.58 to 0.96; p=0.021) when normalised to U6, and 0.76 (95% CI 0.6 to 0.97; p=0.026) after normalisation to the Ct average. miRNA-454 was inversely correlated with severe knee or hip osteoarthritis with an adjusted HR of 0.77 (95% CI 0.61 to 0.97; p=0.028) when normalised to U6. This correlation was lost when data were normalised to Ct average (p=0.118). Finally, miRNA-885-5p showed a trend towards a positive relationship with arthroplasty when normalised to U6 (HR 1.24; 95% CI 0.95 to 1.62; p=0.107) or to Ct average (HR 1.30; 95% CI 0.99 to 1.70; p=0.056). CONCLUSIONS: Our study is the first to identify differentially expressed circulating microRNAs in osteoarthritis patients necessitating arthroplasty in a large, population-based cohort. Among these microRNAs, let-7e emerged as potential predictor for severe knee or hip osteoarthritis.

Effects of adipocyte lipoprotein lipase on de novo lipogenesis and white adipose tissue browning.

Efficient storage of dietary and endogenous fatty acids is a prerequisite for a healthy adipose tissue function. Lipoprotein lipase (LPL) is the master regulator of fatty acid uptake from triglyceride-rich lipoproteins. In addition to LPL-mediated fatty acid uptake, adipocytes are able to synthesize fatty acids from non-lipid precursor, a process called de novo lipogenesis (DNL). As the physiological relevance of fatty acid uptake versus DNL for brown and white adipocyte function remains unclear, we studied the role of adipocyte LPL using adipocyte-specific LPL knockout animals (aLKO). ALKO mice displayed a profound increase in DNL-fatty acids, especially palmitoleate and myristoleate in brown adipose tissue (BAT) and white adipose tissue (WAT) depots while essential dietary fatty acids were markedly decreased. Consequently, we found increased expression in adipose tissues of genes encoding DNL enzymes (Fasn, Scd1, and Elovl6) as well as the lipogenic transcription factor carbohydrate response element binding protein-ß. In a high-fat diet (HFD) study aLKO mice were characterized by reduced adiposity and improved plasma insulin and adipokines. However, neither glucose tolerance nor inflammatory markers were ameliorated in aLKO mice compared to controls. No signs of increased BAT activation or WAT browning were detected in aLKO mice either on HFD or after 1 week of ß3-adrenergic stimulation using CL316,243. We conclude that despite a profound increase in DNL-derived fatty acids, proposed to be metabolically favorable, aLKO mice are not protected from metabolic disease per se. In addition, induction of DNL alone is not sufficient to promote browning of WAT. This article is part of a Special Issue entitled Brown and White Fat: From Signaling to Disease.

Vitamin E-enriched medium cross-linked polyethylene in total knee arthroplasty (VIKEP): clinical outcome, oxidation profile, and wear analysis in comparison to standard polyethylene-study protocol for a randomized controlled trial.

BACKGROUND: The gliding surface of total knee endoprostheses is exposed to high loads due to patient weight and activity. These implant components are typically manufactured from ultra-high molecular weight polyethylene (UHMWPE). Crosslinking of UHMWPE by ionizing radiation results in higher wear resistance but induces the formation of free radicals which impair mechanical properties after contact with oxygen. Medium-crosslinked UHMWPE enriched with vitamin E (MXE) provides a balance between the parameters for a sustainable gliding surface, i.e., mechanical strength, wear resistance, particle size, and oxidation stability. Therefore, a gliding surface for knee endoprostheses made up from this material was developed, certified, and launched. The aim of this study is to compare this new gliding surface to the established predecessor in a non-inferiority design. METHODS: This multicenter, binational randomized controlled trial will enroll patients with knee osteoarthritis eligible for knee arthroplasty with the index device. Patients will be treated with a knee endoprosthesis with either MXE or a standard gliding surface. Patients will be blinded regarding their treatment. After implantation of the devices, patients will be followed up for 10 years. Besides clinical and patient-related outcomes, radiological data will be collected. In case of revision, the gliding surface will be analyzed biomechanically and regarding the oxidative profile. DISCUSSION: The comparison between MXE and the standard gliding surface in this study will provide clinical data to confirm preceding biomechanical results in vivo. It is assumed that material-related differences will be identified, i.e., that the new material will be less sensitive to wear and creep. This may become obvious in biomechanical analyses of retrieved implants from revised patients and in radiologic analyses. TRIAL REGISTRATION: ClinicalTrials.gov, NCT04618016. Registered 27 October 2020, https://clinicaltrials.gov/study/NCT04618016?term=vikep&checkSpell=false&rank=1 . All items from the World Health Organization Trial Registration Data Set can be found in Additional file 1.

Mid-term improvement of cognitive performance after total hip arthroplasty in patients with osteoarthritis of the hip : a prospective cohort study.

AIMS: The aim of this study was to determine whether total hip arthroplasty (THA) for chronic hip pain due to unilateral primary osteoarthritis (OA) has a beneficial effect on cognitive performance. METHODS: A prospective cohort study was conducted with 101 patients with end-stage hip OA scheduled for THA (mean age 67.4 years (SD 9.5), 51.5% female (n = 52)). Patients were assessed at baseline as well as after three and months. Primary outcome was cognitive performance measured by d2 Test of Attention at six months, Trail Making Test (TMT), FAS-test, Rivermead Behavioural Memory Test (RBMT; story recall subtest), and Rey-Osterrieth Complex Figure Test (ROCF). The improvement of cognitive performance was analyzed using repeated measures analysis of variance. RESULTS: At six months, there was significant improvement in attention, working speed and concentration (d2-test; p < 0.001), visual construction and visual memory (ROCF; p < 0.001), semantic memory (FAS-test; p = 0.009), verbal episodic memory (RBMT; immediate recall p = 0.023, delayed recall p = 0.026), as well as pain (p < 0.001) with small to large effect sizes. Attention, concentration, and visual as well as verbal episodic memory improved significantly with medium effect sizes over η2 partial = 0.06. In these cognitive domains the within-group difference exceeded the minimum clinically important difference. CONCLUSION: THA is associated with clinically relevant postoperative improvement in the cognitive functions of attention, concentration, and memory. These data support the concept of a broad interaction of arthroplasty with central nervous system function. Cite this article: Bone Joint J 2022;104-B(3):331-340.

Brain gray matter decrease in chronic pain is the consequence and not the cause of pain.

Recently, local morphologic alterations of the brain in areas ascribable to the transmission of pain were reported in patients suffering from chronic pain. Although some authors discussed these findings as damage or loss of brain gray matter, one of the key questions is whether these structural alterations in the cerebral pain-transmitting network precede or succeed the chronicity of pain. We investigated 32 patients with chronic pain due to primary hip osteoarthritis and found a characteristic gray matter decrease in patients compared with controls in the anterior cingulate cortex (ACC), right insular cortex and operculum, dorsolateral prefrontal cortex (DLPFC), amygdala, and brainstem. We then investigated a subgroup of these patients (n = 10) 6 weeks and 4 months after total hip replacement surgery, monitoring whole brain structure. After surgery, all 10 patients were completely pain free and we observed a gray matter increase in the DLPFC, ACC, amygdala, and brainstem. As gray matter decrease is at least partly reversible when pain is successfully treated, we suggest that the gray matter abnormalities found in chronic pain do not reflect brain damage but rather are a reversible consequence of chronic nociceptive transmission, which normalizes when the pain is adequately treated.

Total Hip Arthroplasty in Multiple Sclerosis. / Hüftendoprothetik bei multipler Sklerose.

Systemic neurological disease represents a risk factor for complications after total hip arthroplasty (THA), especially for dislocation, infections, gait disorders and fall-related periprosthetic fractures. There is little specific literature on total hip arthroplasty in patients with multiple sclerosis. However, increased revision rates have been reported, which are in part due to dislocations. Implants with increased dislocation safety, e.g. tripolar acetabular systems, can represent a reasonable alternative. Due to gait disorders and a higher prevalence of osteoporosis, specific osteological evaluation and treatment should be considered to prevent periprosthetic fractures. This short review summarizes the current literature on total hip arthroplasty in patients with multiple sclerosis.

Osteocyte necrosis triggers osteoclast-mediated bone loss through macrophage-inducible C-type lectin.

Although the control of bone-resorbing osteoclasts through osteocyte-derived RANKL is well defined, little is known about the regulation of osteoclasts by osteocyte death. Indeed, several skeletal diseases, such as bone fracture, osteonecrosis, and inflammation are characterized by excessive osteocyte death. Herein we show that osteoclasts sense damage-associated molecular patterns (DAMPs) released by necrotic osteocytes via macrophage-inducible C-type lectin (Mincle), which induced their differentiation and triggered bone loss. Osteoclasts showed robust Mincle expression upon exposure to necrotic osteocytes in vitro and in vivo. RNA sequencing and metabolic analyses demonstrated that Mincle activation triggers osteoclastogenesis via ITAM-based calcium signaling pathways, skewing osteoclast metabolism toward oxidative phosphorylation. Deletion of Mincle in vivo effectively blocked the activation of osteoclasts after induction of osteocyte death, improved fracture repair, and attenuated inflammation-mediated bone loss. Furthermore, in patients with osteonecrosis, Mincle was highly expressed at skeletal sites of osteocyte death and correlated with strong osteoclastic activity. Taken together, these data point to what we believe is a novel DAMP-mediated process that allows osteoclast activation and bone loss in the context of osteocyte death.

General synovitis score and immunologic synovitis score reflect clinical disease activity in patients with advanced stage rheumatoid arthritis.

The purpose of this study was to investigate the relationship between clinical disease activity in patients with advanced stage rheumatoid arthritis (RA) on treatment with Disease Modifying Antirheumatic Drugs (DMARDs) and histopathological scores of synovial inflammation. To this end, synovial biopsies of 62 RA patients who underwent surgery for either synovectomy or total joint arthroplasty were assessed by a general synovitis score (GSS) and an immunologic synovitis score (IMSYC). The clinical disease activity index (CDAI) was significantly correlated with both the GSS and the IMSYC (r = 0.65, p = <0.001, r = 0.68, p = <0.001). Compared to patients with moderate and high disease activity, there was a significantly lower expression of T cell (CD3), B cell (CD20) and neutrophil (CD15) markers in synovial tissue of patients with low activity, but similar expression of the macrophage marker CD68. Subgroup analyses revealed no differences between small and large joints, seropositive and seronegative RA and patients with or without prednisolone treatment. However, we found a significantly stronger correlation of CDAI with IMSYC in patients undergoing arthroplasty (r = 0.82) than in patients undergoing synovectomy (r = 0.55). In addition, there was a stronger correlation of CDAI with GSS in patients treated with methotrexate (r = 0.86) than in patients with TNFα blockade (r = 0.55). In summary, the present study demonstrates that the histopathological scores GSS and IMSYC in general reflect clinical disease activity in patients with advanced stage rheumatoid arthritis, but that there is some heterogeneity between subgroups of patients within the cohort. In the future, molecular characterization of synovial inflammatory cell populations, including plasma cell infiltrates, will help to further defined clinically important subtypes of RA and treatment response.

Uptake of postprandial lipoproteins into bone in vivo: impact on osteoblast function.

Dietary lipids and lipophilic vitamins are transported by postprandial lipoproteins and are required for bone metabolism. Despite that, it remains unknown whether bone cells are involved in the uptake of circulating postprandial lipoproteins in vivo. The current study was performed to investigate a putative participation of bone in the systemic postprandial lipoprotein metabolism in mice, to identify potentially involved cell type populations and to analyze whether lipoprotein uptake affects bone function in vivo. As a model for the postprandial state, chylomicron remnants (CR) were injected intravenously into mice. Next to the liver and compared to other organs, bone appeared to be the second most important organ for the clearance of radiolabeled CR particles from the circulation in vivo. In addition, uptake of radiolabeled CR by primary murine osteoblasts and hepatocytes was quantified to be in a similar range in vitro. A complementary approach with fluorescently labeled CR and immunohistochemical staining for apoE proved that intact CR particles were taken up into bone and liver. Electron microscopy localization studies of bone sections revealed CR uptake into sinusoidal endothelial cells, macrophages and osteoblasts. The relative amount of radiolabeled CR uptake into femoral cortical bone, representing predominantly osteoblasts, and bone marrow, representing predominantly non-osteoblast cells, was within the same range. Most importantly, the injection of vitamin K1-enriched CR resulted in an increase of the degree of osteocalcin carboxylation in vivo while total osteocalcin concentrations remained unaffected, giving functional proof that osteoblasts process CR in vivo. In conclusion, here we demonstrate that bone is involved in the postprandial lipoprotein metabolism in mice. Osteoblasts participate in CR clearance from the circulation, which has a direct impact on the secretory function of osteoblasts.

Labral calcification in end-stage osteoarthritis of the hip correlates with pain and clinical function.

The acetabular labrum of the hip (ALH) is recognized as a clinically important structure, but knowledge about the pathophysiology of this fibrocartilage is scarce. In this prospective study we determined the prevalence of ALH calcification in patients with end-stage osteoarthritis (OA) and analyzed the relationship of cartilage calcification (CC) with hip pain and clinical function. Cohort of 80 patients (70.2 ± 7.6years) with primary OA scheduled for total hip replacement. Harris Hip Score (HHS) was recorded preoperatively. Total ALH and femoral head (FH) were sampled intraoperatively. CC of the ALH and FH was analyzed by high-resolution digital contact radiography. Histological degeneration of the ALH (Krenn-Score) and FH (OARSI-Score) was determined. Multivariate linear regression model and partial correlation analyses were performed. The prevalence of cartilage calcification both in the ALH and FH was 100%, while the amount of CC in the ALH was 1.55 times higher than in the FH (p < 0.001). There was a significant inverse regression between the amount of calcification of both the ALH and the FH and preoperative HHS (ßALH = -2.1, p = 0.04), (ßFH = -2.9, p = 0.005), but pain was influenced only by ALH calcification (ßALH = -2.7, p = 0.008). Age-adjusted, there was a significant correlation between cartilage calcification and histological degeneration (ALH:rs = 0.53, p < 0.001/FH: rs = 0.30, p = 0.007). Fibrocartilage and articular cartilage calcification are inseparable pathological findings in end-stage osteoarthritis of the hip. Fibrocartilage calcification is associated with poor and painful hip function. CLINICAL SIGNIFICANCE: ALH fibrocartilage appears to be particularly prone to calcification, which may explain higher pain levels in individuals with a high degree of ALH calcification independent of age and histological degeneration. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:1248-1255, 2018.