eNAMPT Is Localised to Areas of Cartilage Damage in Patients with Hip Osteoarthritis and Promotes Cartilage Catabolism and Inflammation.

Obesity increases the risk of hip osteoarthritis (OA). Recent studies have shown that adipokine extracellular nicotinamide phosphoribosyltransferase (eNAMPT or visfatin) induces the production of IL-6 and matrix metalloproteases (MMPs) in chondrocytes, suggesting it may promote articular cartilage degradation. However, neither the functional effects of extracellular visfatin on human articular cartilage tissue, nor its expression in the joint of hip OA patients of varying BMI, have been reported. Hip OA joint tissues were collected from patients undergoing joint replacement surgery. Cartilage explants were stimulated with recombinant human visfatin. Pro-inflammatory cytokines and MMPs were measured by ELISA and Luminex. Localisation of visfatin expression in cartilage tissue was determined by immunohistochemistry. Cartilage matrix degradation was determined by quantifying proteoglycan release. Expression of visfatin was elevated in the synovial tissue of hip OA patients who were obese, and was co-localised with MMP-13 in areas of cartilage damage. Visfatin promoted the degradation of hip OA cartilage proteoglycan and induced the production of pro-inflammatory cytokines (IL-6, MCP-1, CCL20, and CCL4) and MMPs. The elevated expression of visfatin in the obese hip OA joint, and its functional effects on hip cartilage tissue, suggests it plays a central role in the loss of cartilage integrity in obese patients with hip OA.

Detecting Periprosthetic Joint Infection by Using Mass Spectrometry.

BACKGROUND: Novel methods for diagnosing periprosthetic joint infection (PJI) are currently being explored. Mass spectrometry (MS) is an approach that can detect whole-protein changes in synovial fluid and may represent a promising method. METHODS: Between March 2017 and July 2018, we successively collected synovial fluid samples from patients who were undergoing diagnostic hip or knee aspiration because PJI was suspected. A PJI diagnosis was based on the modified Musculoskeletal Infection Society (MSIS) criteria. Cluster analysis and receiver operating characteristic (ROC) curves were used to evaluate the results, which were quantitatively confirmed with parallel reaction monitoring in another patient group who underwent aspiration between August 2018 and January 2019. RESULTS: A total of 117 synovial samples, including 51 PJI and 66 non-PJI samples, were analyzed with liquid chromatography-tandem MS (LC-MS/MS). The cluster analysis sensitivity and specificity based on differentially expressed proteins were 0.961 (95% confidence interval [CI], 0.854 to 0.993) and 0.924 (95% CI, 0.825 to 0.972), respectively. Myeloid nuclear differentiation antigen (MNDA) and polymorphonuclear leukocyte serine protease 3 (PRTN3) were the 2 most important markers for detecting PJI. The areas under the curves (AUCs) of MNDA and PRTN3 were 0.969 (95% CI, 0.936 to 1.000) and 0.900 (95% CI, 0.844 to 0.956), respectively. When MNDA and PRTN3 were combined as variables of a predictive model to diagnose PJI, the AUC reached 0.975 (95% CI, 0.943 to 1.000). Our parallel reaction monitoring-based quantitative analysis of another 40 synovial samples confirmed this result. CONCLUSIONS: MS could be a powerful tool for diagnosing PJI using proteome information or 2 specific markers, MNDA and PRTN3. The parallel reaction monitoring strategy simplified the PJI detection process and provided quantitative results with similar conclusions. CLINICAL RELEVANCE: The clinical application of MS adds a new powerful tool for the diagnosis of PJI, and the parallel reaction monitoring strategy lays a foundation for the clinical application of MS. LEVEL OF EVIDENCE: Diagnostic Level II. See Instructions for Authors for a complete description of levels of evidence.

The Glycosaminoglycan Content of Hip Cartilage in Osteonecrosis of Femoral Head: Evaluation with Delayed Gadolinium-Enhanced Magnetic Resonance Imaging of Cartilage.

OBJECTIVE: Hip cartilage quality is essential for the success of joint-preserving surgery for osteonecrosis. This study aimed to characterize cartilage changes in osteonecrosis of femoral head (ONFH) using delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC). DESIGN: Fifteen asymptomatic (control) and 60 ONFH subjects were included in this study. The ONFH subjects were stratified in accordance with the Association Research Circulation Osseous (ARCO) classification (n = 15 hips per ARCO stage). All participant hips were investigated using dGEMRIC and theT1Gd data were collected and analyzed. RESULTS: T1Gd value was significantly lower in the ONFH group (365.1 ± 90.5 ms; range 200-498 ms) compared with the control group (546.1 ± 26.0 ms; range 504-580 ms) (P < 0.001). The T1Gd values of ARCO stage I-IV ONFH were 460.2 ± 17.3 ms (439-498 ms), 408.9 ± 43.4 ms (337-472 ms), 359.9 ± 34.5 ms (303-412 ms), 231.5 ± 15.1 ms (200-253 ms), respectively. Decreased T1Gd value was found to correlate significantly with increased ONFH severity (P < 0.001). T1Gd value in collapse stage was significantly lower than that of noncollapse stage (295.7 ± 70.3 ms [range 200-412 ms] vs. 434.6 ± 41.7 ms [range 337-498 ms]; P < 0.001). CONCLUSIONS: dGEMRIC identified hip cartilage as abnormal in ONFH, even at early-stage, as represented by decreased T1Gd, and this was further aggravated by ONFH collapse.

Piezo2 expressed in proprioceptive neurons is essential for skeletal integrity.

In humans, mutations in the PIEZO2 gene, which encodes for a mechanosensitive ion channel, were found to result in skeletal abnormalities including scoliosis and hip dysplasia. Here, we show in mice that loss of Piezo2 expression in the proprioceptive system recapitulates several human skeletal abnormalities. While loss of Piezo2 in chondrogenic or osteogenic lineages does not lead to human-like skeletal abnormalities, its loss in proprioceptive neurons leads to spine malalignment and hip dysplasia. To validate the non-autonomous role of proprioception in hip joint morphogenesis, we studied this process in mice mutant for proprioceptive system regulators Runx3 or Egr3. Loss of Runx3 in the peripheral nervous system, but not in skeletal lineages, leads to similar joint abnormalities, as does Egr3 loss of function. These findings expand the range of known regulatory roles of the proprioception system on the skeleton and provide a central component of the underlying molecular mechanism, namely Piezo2.

Proximal femur fat fraction variation in healthy subjects using chemical shift-encoding based MRI.

The objective of this study was to describe the normal variation of bone marrow fat content in the proximal femur considering the influence of side, age, sex and body mass index using fat fraction MRI. From September 2012 to July 2016, the MRI of 131 patients (258 hips) considered to have a normal MRI appearance were retrospectively evaluated. Patient records were searched to allow calculation of the body mass index (BMI). Water-fat based chemical shift MRI was available for all patients included. Proton density fat fraction maps were calculated, and measurements were performed in the femoral epiphysis, intertrochanteric region, and greater trochanter. The influence of patient age, sex, hip side and BMI on fat fraction values was assessed. Fat fraction was significantly different in the different locations evaluated (P = 0.0001). Patient sex and age significantly influenced fat fraction values in all regions evaluated (P < 0.02) with the exception of the epiphysis for sex (p = 0.07). In all locations, PDFF values were higher in men compared to women (3.3%, 4.4% and 13.1% higher in the epiphysis, greater trochanter and intertrochanteric region respectively). The intertrochanteric region presented the lowest fat fraction values with the highest variation compared to the greater trochanter and the epiphysis. BMI only influenced fat fraction values in the intertrochanteric region of females over 42 years old (P = 0.014). The interobserver variability of the measurements performed was considered to be excellent (ICC = 0.968). In conclusion, patient sex, age, and measurement location significantly influenced fat fraction values indicating that specific standards of reference are needed depending on these factors.

Gene expression in hip soft tissues in incipient canine hip dysplasia and osteoarthritis.

Canine hip dysplasia and developmental dysplasia of the human hip share demographic, phenotypic, and clinical features including the predisposition to develop osteoarthritis in affected joints. To support the results of genetic mapping studies for CHD and its concomitant osteoarthritis with functional information, we performed RNA-seq on hip capsule and teres ligament of affected and unaffected dogs. RNA seq showed that expressed genes segregated according age, capsule or ligament, and hip phenotype. Expression of HHIP, DACT2, and WIF1 was significantly higher in capsule from control hips than dysplastic hips indicating a disruption of the hedgehog signaling pathway. Expression of SPON 1, a key component of the WNT pathway, was increased significantly in both dysplastic capsule and ligament while FBN2 and EMILIN3 were significantly increased in dysplastic capsule. Of genes associated with human hip osteoarthritis, expression of ACAN, IGF1, CILP2, COL11A1, COL8A1, and HAPLN was increased significantly in dysplastic capsule. The significant increase in expression of PLA2F, TNFRSF, TMEM, and IGFBP in dysplastic capsule indicated an injury response. Gene set enrichment analysis revealed that genes involved in extracellular matrix structure, epithelial to mesenchymal transition, myogenesis, growth factor signaling, cancer and immune pathways were enriched in dysplastic capsule. For teres ligament from dysplastic joints, genes in retinoic signaling pathways and those encoding extracellular matrix molecules, but not proteoglycans, were enriched. Hip tissues respond to abnormal mechanics early in dysplastic hip development and these pathways present targets for intervention in the early synovitis and capsulitis secondary to canine and human hip dysplasia. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:313-324, 2019.

Spread of injectate around hip articular sensory branches of the femoral nerve in cadavers.

BACKGROUND: Anatomical knowledge dictates that regional anaesthesia after total hip arthroplasty requires blockade of the hip articular branches of the femoral and obturator nerves. A direct femoral nerve block increases the risk of fall and impedes mobilisation. We propose a selective nerve block of the hip articular branches of the femoral nerve by an ultrasound-guided injection in the plane between the iliopsoas muscle and the iliofemoral ligament (the iliopsoas plane). The aim of this study was to assess whether dye injected in the iliopsoas plane spreads to all hip articular branches of the femoral nerve. METHODS: Fifteen cadaver sides were injected with 5 mL dye in the iliopsoas plane guided by ultrasound. Dissection was performed to verify the spread of injectate around the hip articular branches of the femoral nerve. RESULTS: In 10 dissections (67% [95% confidence interval: 38-88%]), the injectate was contained in the iliopsoas plane staining all hip articular branches of the femoral nerve without spread to motor branches. In four dissections (27% [8-55%]), the injection was unintentionally made within the iliopectineal bursa resulting in secondary spread. In one dissection (7% [0.2-32%]) adhesions partially obstructed the spread of dye. CONCLUSION: An injection of 5 mL in the iliopsoas plane spreads around all hip articular branches of the femoral nerve in 10 of 15 cadaver sides. If these findings translate to living humans, injection of local anaesthetic into the iliopsoas plane could generate a selective sensory nerve block of the articular branches of the femoral nerve without motor blockade.

A case report of basic calcium phosphate deposition disease mimicking septic arthritis.

We report a case of a 53-year-old man who presented with a diagnostic dilemma mimicking septic arthritis. It is important to consider the diagnosis of calcific peri-arthritis clinically and recognize the hallmarks on radiograph and magnetic resonance imaging as this disease process resolves completely with conservative management like in our patient, and does not require operative intervention.

The role of three phase bone scintigraphy in arthroplasty of hip and knee joints of clean-up workers of Chornobyl accident. / ROL' TRYFAZOVOÏ OSTEOSTsYNTYGRAFIÏ PRY ENDOPROTEZUVANNI KUL'ShOVYKh I KOLINNYKh SUGLOBIV UChASNYKIV LIKVIDATsIÏ NASLIDKIV AVARIÏ NA ChORNOBYL'S'KIY̆ ATOMNIY̆ ELEKTROSTANTsIÏ.

OBJECTIVE: The objective of the work to determine the diagnostic role of the three phase bone scintigraphy (3 F BS) in the early prediction of paraendoprosthetic complications of the hip and knee joints of the participants in clean up workers of Chornobyl accident. MATERIAL AND METHODS: The 3 F BS method were investigated the radionuclide kinetic parameters of the inclusion and distribution of radiopharmaceuticals (RF) in damaged joints in the 75 male clean up workers. RESULTS: It was established that calculating the quantitative indices of kinetics of the drug at various stages of the 3 F BS allowed to determine statistically significant differences in metabolic changes in focal lesions in articular structures. Thus, the differential diagnostic capabilities of the radionuclide method of examination of patients with arthroplasty of the hip and knee joints are elevated. CONCLUSIONS: The kinetics of osteotropic RF in the foci of fixing the damaged hip and knee joints in the infectious and inflammatory processes is characterized by the predominance of retention and specific accumulation of the drug in the early static phase and the delayed static phase of the 3 F BS compared with the centers of fixation of RF in deforming osteoarthroses, which correlates with the differences in destructive reparative processes in them.

Analysis of bearing wear, whole blood and synovial fluid metal ion concentrations and histopathological findings in patients with failed ASR hip resurfacings.

BACKGROUND: Adverse Reaction to Metal Debris (ARMD) is still a major reason for revision surgeries in patients with metal-on-metal (MoM) hip replacements. ARMD consists of a wide range of alterations in periprosthetic tissues, most important of which are metallosis, inflammation, pseudotumors and necrosis. Studies investigating histopathological findings and their association to implant wear or indirect measures of wear have yielded inconsistent results. Therefore, we aimed to investigate bearing surface wear volume, whole blood and synovial fluid metal ion concentrations, histopathological findings in periprosthetic tissues and their associations. METHODS: Seventy-eight patients with 85 hips revised for ARMD were included in the study. Prior to revision surgery, all patients had whole blood chromium and cobalt ion levels assessed. In revision surgery, a synovial fluid sample was taken and analyzed for chromium and cobalt. Periprosthetic tissue samples were taken and analyzed for histopathological findings. Explanted implants were analyzed for bearing wear volume of both acetabular cup and femoral head components. RESULTS: Volumetric wear of the failed components was highly variable. The total wear volume of the head and cup had a strong correlation with whole blood chromium and cobalt ion concentrations (Cr: ρ = 0.80, p < 0.001 and Co: ρ = 0.84, p < 0.001) and a bit weaker correlation with fluid chromium and cobalt ion concentrations (Cr: ρ = 0.50, p < 0.01 and Co: ρ = 0.41, p = 0.027). Most tissues displayed only low-to-moderate amounts of macrophages and lymphocytes. Total wear volume correlated with macrophage sheet thickness (ρ = 0.25, p = 0.020) and necrosis (ρ = 0.35, p < 0.01). Whole blood chromium and cobalt ion concentrations had similar correlations. Lymphocyte cuff thickness did not correlate with either total wear volume or whole blood metal ion concentrations, but correlated with the grade of necrosis. CONCLUSIONS: Bearing wear volume correlated with blood metal ion levels and the degree of necrosis and macrophage infiltration in periprosthetic tissues suggesting a dose-response relationship. Whole blood metal ion levels are a useful tool for clinician to estimate bearing wear and subsequent tissue response.

Noninvasive Assessment of Skeletal Microstructure and Estimated Bone Strength in Hypoparathyroidism.

In hypoparathyroidism, areal bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) is above average, and skeletal indices by bone biopsy are abnormal. We used high-resolution peripheral quantitative computed tomography (HRpQCT) and finite element analyses (FEA) to further investigate skeletal microstructure and estimated bone strength. We studied 60 hypoparathyroid subjects on conventional therapy using DXA, HRpQCT, and FEA of the distal radius and tibia compared with normative controls from the Canadian Multicentre Osteoporosis Study. In hypoparathyroid women and men, areal BMD was above average at the lumbar spine and hip sites by DXA; radial BMD was also above average in hypoparathyroid women. Using HRpQCT, cortical volumetric BMD was increased in the hypoparathyroid cohort compared with controls at both the radius and tibia. Cortical porosity was reduced at both sites in pre- and postmenopausal women and at the tibia in young men with a downward trend at the radius in men. At the tibia, trabecular number was increased in premenopausal women and men and trabecular thickness was lower in women. Ultimate stress and failure load at both sites for the hypoparathyroid subjects were similar to controls. Using a linear regression model, at both radius and tibia, each increment in age decreased ultimate stress and failure load, whereas each increment in duration of hypoparathyroidism increased these same indices. These results provide additional evidence for the critical role of parathyroid hormone in regulating skeletal microstructure. Longer disease duration may mitigate the adverse effects of age on estimated bone strength in hypoparathyroidism.

The Content of the 14 Metals in Cancellous and Cortical Bone of the Hip Joint Affected by Osteoarthritis.

The aim of the study was to determine the content of particular elements Ca, Mg, P, Na, K, Zn, Cu, Fe, Mo, Cr, Ni, Ba, Sr, and Pb in the proximal femur bone tissue (cancellous and cortical bone) of 96 patients undergoing total hip replacement for osteoarthritis using ICP-AES and FAAS analytical techniques. The interdependencies among these elements and their correlations depended on factors including age, gender, place of residence, tobacco consumption, alcohol consumption, exposure to environmental pollution, physical activity, and type of degenerative change which were examined by statistical and chemometric methods. The factors that exerted the greatest influence on the elements in the femoral head and neck were tobacco smoking (higher Cr and Ni content in smokers), alcohol consumption (higher concentrations of Ni, Cu in people who consume alcohol), and gender (higher Cu, Zn, and Ni concentrations in men). The factors influencing Pb accumulation in bone tissue were tobacco, alcohol, gender, and age. In primary and secondary osteoarthritis of the hip, the content and interactions of elements are different (mainly those of Fe and Pb). There were no significant differences in the concentrations of elements in the femoral head and neck that could be attributed to residence or physical activity.

Does periacetabular osteotomy have depth-related effects on the articular cartilage of the hip?

BACKGROUND: Osteoarthritis may result from abnormal mechanics leading to biochemically mediated degradation of cartilage. In a dysplastic hip, the periacetabular osteotomy (PAO) is designed to normalize the mechanics and our initial analysis suggests that it may also alter the cartilage biochemical composition. Articular cartilage structure and biology vary with the depth from the articular surface including the concentration of glycosaminoglycans (GAG), which are the charge macromolecules that are rapidly turned over and are lost in early osteoarthritis. Delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) enables noninvasive measurement of cartilage GAG content. The dGEMRIC index represents an indirect measure of GAG concentration with lower values indicating less GAG content. GAG content can normally vary with mechanical loading; however, progressive loss of GAG is associated with osteoarthritis. By looking at the changes in amounts of GAG in response to a PAO at different depths of cartilage, we may gain further insights into the types of biologic events that are occurring in the joint after a PAO. QUESTIONS/PURPOSES: We (1) measured the GAG content in the superficial and deep zones for the entire joint before and after PAO; and (2) investigated if the changes in the superficial and deep zone GAG content after PAO varied with different locations within the joint. METHODS: This prospective study included 37 hips in 37 patients (mean age 26 ± 9 years) who were treated with periacetabular osteotomy for symptomatic acetabular dysplasia and had preoperative and 1-year follow up dGEMRIC scans. Twenty-eight of the 37 also had 2-year scans. Patients were eligible if they had symptomatic acetabular dysplasia with lateral center-edge angle < 20° and no or minimal osteoarthritis. The change in dGEMRIC after surgery was assessed in the superficial and deep cartilage zones at five acetabular radial planes. RESULTS: The mean ± SD dGEMRIC index in the superficial zone fell from 480 ± 137 msec preoperatively to 409 ± 119 msec at Year 1 (95% confidence interval [CI], -87 to -54; p < 0.001) and recovered to 451 ± 115 msec at Year 2 (95% CI, 34-65; p < 0.001), suggesting that there is a transient event that causes the biologically sensitive superficial layer to lose GAG. In the deep acetabular cartilage zone, dGEMRIC index fell from 527 ± 148 msec preoperatively to 468 ± 143 msec at Year 1 (95% CI, -66 to -30; p < 0.001) and recovered to 494 ± 125 msec at Year 2 (95% CI, 5-32; p = 0.008). When each acetabular radial plane was looked at separately, the change from before surgery to 1 year after was confined to zones around the superior part of the joint. The only significant change from 1 to 2 years was an increase in the superficial layer of the superior zone (1 year 374 ± 123 msec, 2 year 453 ± 117 msec, p < 0.006). CONCLUSIONS: This study suggests that PAO may alter the GAG content of the articular cartilage with a greater effect on the superficial zone compared with the deeper acetabular cartilage zone, especially at the superior aspect of the joint. Some surgeons have observed that surgery itself can be a stressor that can accelerate joint degeneration. Perhaps the decrease in dGEMRIC index seen in the superficial layer may be a catabolic response to postsurgical inflammation given that some recovery was seen at 2 years. The decrease in dGEMRIC index in the deep layer seen mainly near the superior part of the joint is persistent and may represent a response of articular cartilage to normalization of increased mechanical load seen in this region after osteotomy, which may be a normal response to alteration in loading. CLINICAL RELEVANCE: This study looks at the biochemical changes in the articular cartilage before and after a PAO for dysplastic hips using MRI in a similar manner to using histological methods to study alterations in articular cartilage with mechanical loading. Although PAO alters alignment and orientation of the acetabulum, its effects on cartilage biology are not clear. dGEMRIC provides a noninvasive method of assessing these effects.

Patterns of 18F-FDG PET images in patients with uncomplicated total hip arthroplasty.

OBJECTIVE: This retrospective study was carried out to determine the typical patterns of (18)F-FDG uptake in uncomplicated total hip arthroplasty (THA). SUBJECTS AND METHODS: (18)F-FDG-PET images of 62 asymptomatic THA patients who had undergone whole body scanning were evaluated for this retrospective study. The uptake was assessed qualitatively as positive or negative in the head/neck and the stem of the prosthesis. There were 76 hip prosthesis scans (34 left side and 42 right) and the average time following surgery was 75 months (range from 40 days to 372 months). Furthermore, the time course after surgery was subdivided into 3 time interval groups: Group I less than 2 years, Group II between 2 to 5 years, Group III more than 5 years. The regions of assessment were: head region including acetabulum and femoral head, femoral neck, trochanter, and femoral shaft. RESULTS: In patients who demonstrated increased peri-prosthetic (18)F-FDG uptake (59 of the 76 hip scans), the activity was confined to the femoral neck and proximal femoral shaft with the majority in the neck regions alone: 68% (40 of 59). Majority of the uptake was noted in the femoral neck, proximal shaft and trochanteric regions. CONCLUSION: Uptake of (18)F-FDG in the asymptomatic patients with THA is commonly visualized and appears to be confined to the proximal segment of the prosthesis with minimal or no activity in its femoral segment.

Elemene, the essential oil of Curcuma wenyujin, inhibits osteogenic differentiation in ankylosing spondylitis.

OBJECTIVE: To explore the effects of Elemene, the essential oil of Curcuma wenyujin, on Bone morphogenetic protein/drosophila mothers against decapentaplegic proteins (BMP/SMADs) signal pathway in ankylosing spondylitis (AS) fibroblasts. METHODS: Hip joint capsules were obtained from AS patients (n=10) receiving total hip replacement. Healthy hip joint capsules from patients with hip fracture (n=10) receiving surgery were included as a control. Primary fibroblast cell lines were established from these tissue samples. Fibroblasts were incubated with Elemene for 48 hours. The protein expression was detected by Western blot. The mRNA expression was detected by real-time fluorescent quantitative polymerase chain reaction (PCR). RESULTS: The results showed that the expression of proteins including SMAD1, pSMAD1, SMAD4 and Runt-related transcription factor 2 (RUNX2), and mRNA of RUNX2, which were over-expressed in AS fibroblasts were decreased in the AS fibroblasts cultured in medium with Elemene. CONCLUSIONS: Ele could have a hand in anti-osteogenic differentiation of AS fibroblasts by inhibiting the BMP/SMADs signal pathway and subsequently blocking expression of ossification marker genes RUNX2 that initiate the osteogenic differentiation.

Legg-Calvé-Perthes disease produces chronic hip synovitis and elevation of interleukin-6 in the synovial fluid.

Legg-Calvé-Perthes disease (LCPD) is a childhood hip disorder of ischemic osteonecrosis of the femoral head. Hip joint synovitis is a common feature of LCPD, but the nature and pathophysiology of the synovitis remain unknown. The purpose of this study was to determine the chronicity of the synovitis and the inflammatory cytokines present in the synovial fluid at an active stage of LCPD. Serial MRI was performed on 28 patients. T2-weighted and gadolinium-enhanced MR images were used to assess synovial effusion and synovial enhancement (hyperemia) over time. A multiple-cytokine assay was used to determine the levels of 27 inflammatory cytokines and related factors present in the synovial fluid from 13 patients. MRI analysis showed fold increases of 5.0 ± 3.3 and 3.1 ± 2.1 in the synovial fluid volume in the affected hip compared to the unaffected hip at the initial and the last follow-up MRI, respectively. The mean duration between the initial and the last MRI was 17.7 ± 8.3 months. The volume of enhanced synovium on the contrast MRI was increased 16.5 ± 8.5 fold and 6.3 ± 5.6 fold in the affected hip compared to the unaffected hip at the initial MRI and the last follow-up MRI, respectively. In the synovial fluid of the affected hips, IL-6 protein levels were significantly increased (LCPD: 509 ± 519 pg/mL, non-LCPD: 19 ± 22 pg/mL; p = 0.0005) on the multi-cytokine assay. Interestingly, IL-1ß and TNF-α levels were not elevated. In the active stage of LCPD, chronic hip synovitis and significant elevation of IL-6 are produced in the synovial fluid. Further studies are warranted to investigate the role of IL-6 on the pathophysiology of synovitis in LCPD and how it affects bone healing.

What is the utility of biomarkers for assessing the pathophysiology of hip osteoarthritis? A systematic review.

BACKGROUND: Innovations in biologics offer great promise in the treatment of patients with orthopaedic conditions and in advancing our ability to monitor underlying disease pathophysiology. Our understanding of the pathophysiology of hip osteoarthritis (OA) has improved significantly in the last decade. Femoroacetabular impingement (FAI) and hip dysplasia are increasingly recognized and treated as forms of prearthritic hip disease, yet the inability of radiographic and MR imaging to identify patients before the onset of irreversible articular cartilage injury limits their use for early diagnosis and treatment of patients with these conditions. Molecular biomarkers, as objectively measureable indicators of the pathophysiology of hip OA, have the potential to improve diagnosis, disease staging, and prognosis of hip OA and prearthritic hip disease. Although research into molecular biomarkers of hip OA has been conducted, investigations in prearthritic hip disease have only recently begun. QUESTIONS/PURPOSES: The purpose of our review was to assess the use of molecular biomarkers in the pathophysiology of hip OA, including (1) diagnosis; (2) disease staging; and (3) prognosis. We additionally aimed to summarize the available literature investigating the use of biomarkers in (4) prearthritic hip disease, including FAI and hip dysplasia. METHODS: We conducted a systematic review of molecular biomarkers associated with hip OA or prearthritic hip disease by searching four major electronic databases for keywords "hip", "osteoarthritis", "biomarker", and all synonyms. The search terms "femoroacetabular impingement" and "hip dysplasia" were also included. The biologic source of biomarkers was limited to serum, plasma, urine, and synovial fluid. The literature search yielded a total of 2740 results. Forty studies met all criteria and were included in our review. Studies were categorized regarding their relevance to (1) diagnosis; (2) disease staging; (3) prognosis; and/or (4) prearthritic hip disease. RESULTS: Biomarker studies were characterized as relevant to diagnosis (16 studies), disease staging (15 studies), prognosis (11 studies), and prearthritic hip disease (three studies). Sixteen different biomarkers demonstrated associations relevant to the diagnosis of hip OA, 16 biomarkers demonstrated similar associations for disease staging, and six for prognosis. Six biomarkers seemed to be the most promising, demonstrating associations with hip OA in multiple studies, including: urinary level of type II collagen telopeptide (n = 5 studies), serum cartilage oligomeric protein (n = 4 studies), and serum C-reactive protein (n = 4 studies). Only three studies investigated the role of biomarkers in prearthritic hip disease, including two in FAI and one in unspecified etiology of pain. There were no studies about biomarkers in hip dysplasia. CONCLUSIONS: Molecular biomarkers are increasingly investigated for their use in evaluating the pathophysiology of hip OA, but less so for prearthritic hip disease. Several biomarkers have demonstrated significant associations with hip OA across multiple studies. Further validation of these biomarkers is needed to assess their clinical use and potential application to prearthritic hip disease.

[APPLICATION OF PREPARATION OF COCARNIT FOR PATIENTS AFTER ENDOPROSTHESIS OF HIP AND KNEE JOINTS].

In the article the results of clinical researches of efficiency of preparation of Cocarnit are resulted for patients after endoprosthesis of large joints. It is routine that for patients, receiving preparation of Cocarnit after the operation period there was a decline in the amount of complaints of patients on the total somatical state. Preparation of Ccocarnit was positively estimated outside patients, meaningful by-reactions, serving reason of abolition of preparation, was not marked. At the reception preparation of Cocarnit greater part of investigational laboratory indexes (table of contents of glucose, ß-lipoproteines, total chondroitisulfates, TBC-productes (malonic dyaldehyde), activity of aspartataminotransferase, alkaline phosphatase and ß-glutamyltranspeptidase), the indexes of clinical blood test and leucocytar indexes during a supervision did not have reliable differences from such as the persons of the control group, that confirms good bearab leness of the indicated preparation. Application preparation of Cocarnit for patients in composition the chart of treatment of patients after endoprosthesis of large joints brought maintenance over of cholesterol to the decline, glycoproteins, TBC-products (malonic dyaldehyde), activity of alaninaminotransferase, that specifies on normalizing influence of the indicated preparation in relation to the basic types of exchange of matters.

[New phytotherapeutic composition for restoring bone and cartilage. Experimental study].

Presents a new import-substituting the composition of the powder mixture 60 medicinal plants and dead bees. In prednisolonbuy models of osteoporosis have shown dose-dependent regenerative effects bone and cartilage of the hip joints of mice. Unwanted side effects when taking composition was observed. It is assumed the possibility of effective application of the composition as a complementary treatment for osteoporosis.