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.

[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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Calcification of the acetabular labrum of the hip: prevalence in the general population and relation to hip articular cartilage and fibrocartilage degeneration.

BACKGROUND: Meniscal calcification is considered to play a relevant role in the pathogenesis of osteoarthritis of the knee. Little is known about the biology of acetabular labral disease and its importance in hip pathology. Here, we analyze for the first time the calcification of the acetabular labrum of the hip (ALH) and its relation to hip cartilage degeneration. METHODS: In this cross-sectional post-mortem study of an unselected sample of the general population, 170 ALH specimens and 170 femoral heads from 85 donors (38 female, 47 male; mean age 62.1 years) were analyzed by high-resolution digital contact radiography (DCR) and histological degeneration grade. The medial menisci (MM) from the same 85 donors served as an intra-individual reference for cartilage calcification (CC). Scanning electron microscopy (SEM), energy dispersive analysis (ED) and Raman spectroscopy were performed for characterization of ALH CC. RESULTS: The prevalence of CC in the ALH was 100% and that in the articular cartilage of the hip (ACH) was 96.5%. Quantitative analysis revealed that the amount of ALH CC was higher than that in the ACH (factor 3.0, p < 0.001) and in the MM (factor 1.3, p < 0.001). There was significant correlation between the amount of CC in the fibrocartilage of the left and right ALH (r = 0.70, p < 0.001). Independent of age, the amount of ALH CC correlated with histological degeneration of the ALH (Krenn score) (r = 0.55; p < 0.001) and the ACH (Osteoarthritis Research Society International (OARSI), r = 0.69; p < 0.001). Calcification of the ALH was characterized as calcium pyrophosphate dihydrate deposition. CONCLUSION: The finding that ALH fibrocartilage is a strongly calcifying tissue is unexpected and novel. The fact that ALH calcification correlates with cartilage degeneration independent of age is suggestive of an important role of ALH calcification in osteoarthritis of the hip and renders it a potential target for the prevention and treatment of hip joint degeneration.

Lrp1 in osteoblasts controls osteoclast activity and protects against osteoporosis by limiting PDGF-RANKL signaling.

Skeletal health relies on architectural integrity and sufficient bone mass, which are maintained through a tightly regulated equilibrium of bone resorption by osteoclasts and bone formation by osteoblasts. Genetic studies have linked the gene coding for low-density lipoprotein receptor-related protein1 (Lrp1) to bone traits but whether these associations are based on a causal molecular relationship is unknown. Here, we show that Lrp1 in osteoblasts is a novel regulator of osteoclast activity and bone mass. Mice lacking Lrp1 specifically in the osteoblast lineage displayed normal osteoblast function but severe osteoporosis due to highly increased osteoclast numbers and bone resorption. Osteoblast Lrp1 limited receptor activator of NF-κB ligand (RANKL) expression in vivo and in vitro through attenuation of platelet-derived growth factor (PDGF-BB) signaling. In co-culture, Lrp1-deficient osteoblasts stimulated osteoclastogenesis in a PDGFRß-dependent manner and in vivo treatment with the PDGFR tyrosine kinase inhibitor imatinib mesylate limited RANKL production and led to complete remission of the osteoporotic phenotype. These results identify osteoblast Lrp1 as a key regulator of osteoblast-to-osteoclast communication and bone mass through a PDGF-RANKL signaling axis in osteoblasts and open perspectives to further explore the potential of PDGF signaling inhibitors in counteracting bone loss as well as to evaluate the importance of functional LRP1 gene variants in the control of bone mass in humans.

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.

Differential effects of Calca-derived peptides in male mice with diet-induced obesity.

Key metabolic hormones, such as insulin, leptin, and adiponectin, have been studied extensively in obesity, however the pathophysiologic relevance of the calcitonin family of peptides remains unclear. This family includes calcitonin (CT), its precursor procalcitonin (PCT), and alpha calcitonin-gene related peptide (αCGRP), which are all encoded by the gene Calca. Here, we studied the role of Calca-derived peptides in diet-induced obesity (DIO) by challenging Calcr-/- (encoding the calcitonin receptor, CTR), Calca-/-, and αCGRP-/- mice and their respective littermates with high-fat diet (HFD) feeding for 16 weeks. HFD-induced pathologies were assessed by glucose tolerance, plasma cytokine and lipid markers, expression studies and histology. We found that DIO in mice lacking the CTR resulted in impaired glucose tolerance, features of enhanced nonalcoholic steatohepatitis (NASH) and adipose tissue inflammation compared to wildtype littermates. Furthermore, CTR-deficient mice were characterized by dyslipidemia and elevated HDL levels. In contrast, mice lacking Calca were protected from DIO, NASH and adipose tissue inflammation, and displayed improved glucose tolerance. Mice exclusively lacking αCGRP displayed a significantly less improved DIO phenotype compared to Calca-deficient mice. In summary, we demonstrate that the CT/CTR axis is involved in regulating plasma cholesterol levels while Calca, presumably through PCT, seems to have a detrimental effect in the context of metabolic disease. Our study provides the first comparative analyses of the roles of Calca-derived peptides and the CTR in metabolic disease.

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.

Microcalcification of lumbar spine intervertebral discs and facet joints is associated with cartilage degeneration, but differs in prevalence and its relation to age.

Cartilage calcification (CC) is associated with degeneration in non-vertebral joints, but little is known about CC and lumbar vertebral joints. The goal of this study was to analyze the prevalence of CC in lumbar facet joints (FJ) and intervertebral discs (IVD) and its relation to cartilage degeneration and age in a non-selected cohort of the general population. The segment L4/5 of 85 consecutive donors (mean age 61.9 years) was analyzed by high-resolution imaging digital-contact radiography (DCR). Quantification was achieved by measuring CC in % of total cartilage area. Histological degeneration of FJs and IVDs was determined by OARSI and Boos scores. Prevalence of CC was 36.5% for FJ (95%CI (0.26, 0.48)) and 100% for IVD (95%CI (0.96, 1.00)). The amount of IVD CC (3.36% SD ± 7.14) was 16.3 times higher (p < 0.001) than that of the FJ (0.23% SD ± 0.53) and independent of each other (p = 0.07). The amount of FJ CC correlated significantly with FJ and IVD degeneration (FJ r = 0.44, p = 0.01, IVD r = 0.49, p = 0.006) while the amount of IVD CC correlated only with IVD degeneration (r = 0.54, p < 0.001). Age correlated with IVD CC (rs = 0.35, p < 0.001), but not FJ CC (rs = 0.04, p = 0.85). We conclude that IVD fibrocartilage is particularly prone to calcification. A causal relationship between lumbar CC and degeneration is possible, but the clear differences in IVD fibrocartilage CC and FJ synovial joint CC in regard to prevalence and in relation to age point to a differential role of CC in single compartments of the respective motion segment in lumbar spine degeneration. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2692-2699, 2017.

Symptomatic Os VesalianumA Case Report and Review of the Literature.

Os vesalianum is a rare accessory bone located proximal to the base of the fifth metatarsal in the peroneus brevis tendon. It is a radiographic diagnosis and mostly an asymptomatic incidental finding with a reported prevalence of 0.1% to 0.9%. Only 11 symptomatic cases have been described in the literature. Surgical therapy has been reported with good outcome in adults, whereas recurrence may follow excision during skeletal growth. We report a case of a 19-year-old girl with chronic weightbearing pain proximal to the base of the fifth metatarsal of her left foot. She first experienced exacerbated pain on increased loading when she started professional training as a shop assistant. Because several months of nonsurgical therapy failed, the decision was made to surgically excise the accessory bone from the peroneus brevis tendon via a longitudinal incision and a simple tendon-to-tendon reconstruction. Postoperative treatment consisted of using a walker to avoid weightbearing for 6 weeks, followed by a gradual return to full weightbearing as tolerated. At final follow-up, the patient was fully asymptomatic and was able to return to work. Citing this case, this article discusses differential diagnoses and treatment options for os vesalianum.

Thermogenic adipocytes promote HDL turnover and reverse cholesterol transport.

Brown and beige adipocytes combust nutrients for thermogenesis and through their metabolic activity decrease pro-atherogenic remnant lipoproteins in hyperlipidemic mice. However, whether the activation of thermogenic adipocytes affects the metabolism and anti-atherogenic properties of high-density lipoproteins (HDL) is unknown. Here, we report a reduction in atherosclerosis in response to pharmacological stimulation of thermogenesis linked to increased HDL levels in APOE*3-Leiden.CETP mice. Both cold-induced and pharmacological thermogenic activation enhances HDL remodelling, which is associated with specific lipidomic changes in mouse and human HDL. Furthermore, thermogenic stimulation promotes HDL-cholesterol clearance and increases macrophage-to-faeces reverse cholesterol transport in mice. Mechanistically, we show that intravascular lipolysis by adipocyte lipoprotein lipase and hepatic uptake of HDL by scavenger receptor B-I are the driving forces of HDL-cholesterol disposal in liver. Our findings corroborate the notion that high metabolic activity of thermogenic adipocytes confers atheroprotective properties via increased systemic cholesterol flux through the HDL compartment.