Influence of treatment with a hydrolyzed collagen formulation on the movements of the human knee with early-stage gonarthrosis

The integrated automation system (IAS) for proton radiography and ion radiobiological experiments on the fast extraction beamline of the TWAC-ITEP accelerator-accumulator facility has been developed and successfully used. The subsystems that are parts of the IAS perform the following functions: acquisition, storage, and processing of experimental data; control of the magnetic lenses of the charged-particle beam transport line; beam diagnostics; and radiation safety and monitoring. The subsystems are composed of hardware-software modules, each dealing with a particular measuring or actuating device and a program for readout, storing, and processing of experimental data corresponding to this device. The modules communicate via a TCP/IP socket in a configuration dependent on the requirements of a particular experiment. Data are transmitted from one module to the other in the real time mode within the closed ring network, which allows consecutive processing of incoming experimental data. The status of the system elements, incoming experimental data, and results of their rapid analysis are displayed in the real time mode on the web server. Owing to the flexible structure of the integrated automation system, it is possible to promptly create new configurations for acquisition and processing of experimental data.

Serum hyaluronan levels are associated with disability for activity of daily living in patients with knee osteoarthritis regardless of the radiographic severity of the disease

The prevalence of knee osteoarthritis has increased significantly over recent decades. Osteoarthritis causes pain, swelling, stiffness, loss of function, and decreased quality of life (QoL). Although evidence suggests that increased BMI contributes to both the development and severity of knee OA, research examining the relationship between BMI, OA stage, and the degree of knee pain remains limited, highlighting the need for further investigation. This study aims to determine the relationship between BMI, the stage of knee osteoarthritis, and the degree of pain in patients with knee OA. This research is an analytical observational study with a cross-sectional design, utilizing secondary data (patient medical records). We conducted sample selection using purposive sampling. Data analysis: descriptive analysis, Chi-Square test, and logistic regression. A total of 101 respondents participated in the study, with the majority had a normal BMI (52.5%), had mild-to-moderate knee OA (56.4%), and reported mild pain (52.5%). There was a significant relationship between BMI and the stage of knee osteoarthritis with the degree of pain (p-value <0.05), with odds ratios (OR) for BMI and OA stage at 3.93 and 3.96, respectively. This indicates that higher BMI and more advanced OA stage are associated with a greater degree of knee pain in patients. Weight loss is an effective strategy to reduce mechanical stress on joints and decrease inflammatory mediators, thereby lowering chronic inflammation and alleviating pain. Further research on effective management strategies for knee OA is essential to help reduce the disease burden and improve the QoL of knee OA patients.

A comparison of obesity related adipokine concentrations in knee and shoulder osteoarthritis patients

IntroductionEvidence has demonstrated greater benefit of intra-articular hyaluronic acid (IA-HA) within earlier stages of knee osteoarthritis (OA) rather than waiting for patients to have progressed to later stages of disease progression. High molecular weight (HMW) HA has also been shown to be more effective than low molecular weight (LMW) HA products in mild to moderate knee OA, providing an important distinction to make within the class of IA-HA therapies. The purpose of this study is to evaluate the cost-effectiveness of treating patients with knee OA with HMW HA compared to LMW and conservative treatment, while taking into account disease stage.MethodsDecision analytic models were created for early/moderate, as well as late stage knee OA. Models for late stage knee OA were created by assuming a range of response rates to IA-HA treatments from 10% to 50%. These models included conservative treatment using physical therapy/exercise, braces/orthosis, and medications such as non-steroidal anti-inflammatory drugs (NSAIDs) and analgesics. The models compared the cost per quality adjusted life year (QALY) gained for these treatments to the use of either LMW or HMW HA. Incremental cost-effectiveness ratios (ICERs) were calculated for each treatment in relation to HMW HA.ResultsWhen evaluating treatment in early to moderate knee OA, HMW HA was dominant over LMW HA and physical therapy/exercise, as it was less expensive and provided greater benefit. HMW HA was cost-effective versus braces/orthosis and NSAID/analgesic medications based on a willingness to pay threshold of $50,000. In the model of 50% response rate to IA-HA for late stage OA, HMW HA remained cost-effective in comparison to physical therapy/exercise and braces/orthosis at a willingness to pay threshold of $50,000; but not NSAID/analgesic medications. In the worst-case scenario of a 10% responder rate to IA-HA, HMW HA was no longer cost-effective in any circumstance.ConclusionIA-HA, particularly HMW formulations, demonstrate cost-effectiveness when compared to conservative treatment options and LMW HA in patients with early/mid stage knee OA. The cost-effectiveness of HMW HA in patients with later stage knee OA was not as apparent, particularly because of the uncertainty in the proportion of patients with late stage OA who have a meaningful improvement after receiving IA-HA. This cost-effectiveness finding supports the use of IA-HA in patients with early and moderate knee OA, as the benefits of IA-HA are apparent within the patient population with mild to moderate knee OA. The findings of this study suggest that there is a potential cost savings benefit as a result of utilizing HMW HA in earlier stages of knee OA as opposed to later stages.FundingFerring Pharmaceuticals Inc.Electronic Supplementary MaterialThe online version of this article (10.1007/s12325-019-01142-x) contains supplementary material, which is available to authorized users.

Knee osteoarthritis (KOA) is the most prevalent type of OA and a leading cause of disability in the United States. Falls are a major public health concern in older adults. Our aim was to examine how the severity of radiographic KOA affects recurrent falls in a cohort of middle-aged and older individuals enrolled in the Osteoarthritis Initiative. About 3 972 participants, mean age of 63 years, 58% female were included. Participants were divided into 5 mutually exclusive groups based on their worst Kellgren-Lawrence grade of radiographic KOA from annual x-rays from baseline to 36 months. Generalized estimating equations for repeated logistic regression were used to model the association between KOA severity and the likelihood of recurrent falls (≥2 falls/year) over 5 years of follow-up (>36 to 96 months). Older adults (≥age 65) with KOA were at higher odds of recurrent falls in comparison to individuals without KOA in multivariate models (possible OA odds ratio [OR] = 2.22, 95% CI = 1.09-4.52; mild OA OR = 2.48, 95% CI = 1.34-4.62; unilateral moderate-severe OA OR = 2.84, 95% CI = 1.47-5.50; bilateral moderate-severe OA OR = 2.52, 95% CI = 1.13-5.62). Middle-aged adults (aged 45-64) with KOA did not have increased odds of recurrent falls in comparison to those without KOA except for possible KOA (OR = 1.86, 95% CI = 1.01-2.78; KOA severity × Age interaction = 0.025). Older adults with radiographic evidence of KOA have an increased likelihood of experiencing recurrent falls in comparison to those without KOA independent of established risk factors. Our results suggest that fall prevention efforts should include older adults with all stages of KOA.

Background:Objectives:To evaluate the relationship of hyperuricemia (GU) with the course of knee osteoarthritis (OA) and the components of metabolic syndrome (MS).Methods:The prospective study included 107 women aged 40-75 y.o, with a reliable diagnosis of I-III Kellgren J. - Lawrence J. stage of knee OA (ACR), who signed an informed consent. The average age of patients was 59.1 ± 8.9 y.o. (from 38 to 74), the duration of the disease was 9 (4-12) years. The average values of the body mass index (BMI) corresponded to obesity (30.6 ± 5.7 kg / m2), waist circumference (WC) - 93.9 ± 12.1 cm. An individual card was filled out for each patient, including anthropometric parameters, anamnesis and clinical examination data, an assessment of knee joint pain according to VAS, and concomitant diseases. All patients underwent standard X-ray of the knee joints, DEXA scan of the lumbar spine and total hip, and laboratory examination.Results:Hyperuricemia was diagnosed in 26.2% of patients. Patients with GU had a higher BMI and WC (p<0.05). X-ray examination revealed significantly larger sizes of osteophytes (p = 0.02) and smaller sizes of the medial space of the knee joint (p = 0.02), while the patients of both groups were comparable in age and duration of OA (Table 1). Patients with GU had a statistically significantly higher bone mineral density (BMD) values were observed in L1-L4 and total hip (p<0.05). MS was almost 2 times more often diagnosed in patients with GU (83.3% vs. 49.2%, RR=1.71, 95%Cl 1.21-2.36, p=0.01). Higher levels of CRP, COMP, leptin, triglycerides (TG), creatinine, ALT and AST were determined in patients with GU (Table 1). Spearman rank ordered correlation coefficients between GU and BMI (r=0.22, p=0.03), WC (r=0.26, p=0.02), MS (r=0.29, p=0.01), and CHD (r=0.21, p=0.04). There were a correlation between GU and the stage of knee OA (X-ray) (r=0.34, p=0.02), the size of medial osteophytes in the femur (mm) (r=0.37, p=0.01) and the medial space of the knee joint (mm) (r=-0.27, p=0.01), BMD L1-L4 (r=0.37, p=0.03) and the total hip (r=0.37, p=0.04). There were also significant positive associations with the following laboratory parameters: CRP (r=0.27, p=0.007), COMP (r=0.25, p=0.05), leptin (r=0.29, p=0.03), creatinine (r=0.45, p<0.0001), TG (r=0.44, p=0.0001), ALT (r=0.32, p=0.002), AST (r=0.25, p=0.02).Table 1.Comparative characteristics of OA patients with and without GUParameterOA Patients with GU (n = 28)OA Patients without GU (n = 79)pAge, y.o.61 (53-68)60 (54-66)0.33Duration OA, years10 (6-14)7.5 (3-12)0.06WC, сm99.3 ± 12.892.2 ± 11.40.02BMI, kg/m233.5 ± 5.630 ± 5.60.04The size of the medial space of joint according to X-ray, mm2.3 (1.2-3.3)3.2 (2.0-4.3)0.02The size of the osteophytes of the femur, mm5.8 (3.7-6.3)2.9 (1.7-4.5)0.02BMI L1-L4, g/сm21.18 (1.12-1.24)1.0 (0.86-1.15)0.04BMI total hip, g/сm21.05 (1.0-1.13)0.9 (0.82-0.98)0.04CRP, mg/l2.8 (1.9-6.2)1.9 (1.2-3.6)0.007COMP, ng/ml31.9 (27.6-45)24.2 (18.9-38.7)0.05Leptin, ng/ml46.2 (36.5-72)30.5 (19.5-45.6)0.03TG, mmol/l1.97 (1.61-2.41)1.26 (0.87-1.63)0.002Creatinine, mmol/l79 (74.9-86)68 (62-74)0.0001ALT, mmol/l26.5 (17.2-32.9)17.9 (13.2-21.7)0.003АST, mmol/l22.5 (18.5-27.8)18.9 (16.8-21.9)0.02Conclusion:GU may be an aggravating predictor of not only MS-associated diseases such as obesity, dyslipidemia, but also OA. Thus, at high levels of uric acid, more advanced radiological stages of OA, high values of the BMD of the axial skeleton and increased values of CRP, COMP are noted. In this connection, therapeutic interventions of OA in patients with GU should also be aimed at reducing the concentration of uric acid, which may provide a slowdown in the progression of the disease. Further study of this issue is needed.Disclosure of Interests:None declared

Activity impairments in adult patients with Ehlers–Danlos hypermobility type; the importance of pain and psychological factor

Objective – to assess the effect of patient-specific parameters (age, body mass index (BMI), stage of the knee osteoarthritis (KOA), the osteotomy gap size, concomitant medial opening angle high tibial osteotomy (MOWHTO) arthroscopic plastic (AP) and open chondroplasty (OCHP) on the development of complications and the outcome of the operation.Materials and methods. The study included 76 patients who underwent MOWHTO. To study the influence of each of the parameters, comparison groups were created: 1) by age: patients younger and older than 60 years (45 versus 31); 2) by BMI: patients with BMI<30 kg/m2 versus patients with a BMI from 30 to 40 kg/m2 (35 versus 41); 3) by the osteotomy gap size: ≤10 mm and >10 mm (29 versus 47); 4) by stages of KOA: patients with stage I and II versus patients with stage III (43 versus 33); 5) patients with MOWHTO + AP of the knee or OCHP versus patients who underwent only MOWHTO (34 versus 42). To assess the result, we studied the change in pain intensity according to the visual analogue scale (VAS), as well as the state of the knee joint according to the Knee Society Score (KSS) scale before surgery and 1 year after MOWHTO.Results. The development of complications had a weak direct relationship with stage III of the KOA (r=–0.24) and moderate strength a direct relationship with the osteotomy gap size >10 mm (r=–0.42). Age, BMI, the presence of concomitant AP of the knee or OCHP did not affect the development of complications. However, the number of complications was statistically significantly higher among patients with stage III and osteotomy gap size >10 mm relative to patients with stage II of the KOA (p=0.03) and patients with deformity correction ≤10 mm (p=0.0002). Age over 60 years and BMI<30 kg/m2 had a direct weak relationship (r=0.27 and r=0.23) with the achievement of a satisfactory result. An excellent result had a direct weak relationship with a BMI<30 kg/m2 and stages I–II of the KOA (r=0.34 and r=0.31), as well as a direct moderate strength relationship with an osteotomy gap size ≤10 mm (r=0.46). At the age of patients over 60 years, a satisfactory result was significantly more frequent compared with patients of young and middle age (p=0.016). 71.1% of excellent results were obtained in patients with a BMI<30 kg/m2 (p=0.002), and there were significantly more good and satisfactory results in the group of patients with a BMI>30 kg/m2 (p=0.08 and p=0.04). At stage III, an excellent result was obtained 3 times less frequently than in patients with stages I and II of the KOA (p=0.004). In patients with gap size ≤10 mm, excellent results were 1.5 times greater than in patients with a gap size >10 mm (p=0.00006). There were no differences in the results in patients who underwent MOWHTO in isolation and in patients in whom MOWHTO was supplemented with AP of the knee or OCHP.Conclusions. The development of complications is associated with stage III of the KOA and the need for correction (the osteotomy gap size) >10 mm. The best result of MOWHTO can be obtained in patients under the age of 60 years, with a BMI <30 kg/m2 at stages I–II of the KOA and deformity correction within 10 mm. Concomitant AP of the knee or OCHP don’t affect the development of complications and the outcome of the operation.

Chronic injury to the rectus femoris muscle induces and exacerbates the progression of knee osteoarthritis (KOA). However, the lesion characteristics of the rectus femoris muscle in KOA at different stages have not been fully characterized. The aim of this study was to analyze the pattern of lesion characteristics of the rectus femoris muscle at different stages of KOA and to investigate the mechanism by which ultrasound-guided acupotomy operations can prevent and control KOA. Early, middle, and late-stage rabbit KOA models were constructed using the modified Videman method. Ultrasonography was used to record the elastic modulus and cross-sectional area of the rectus femoris muscle, and morphology was used to observe the ultramicroscopic changes in the rectus femoris muscle and assess the degree of fibrosis. Additionally, ultrasound-guided acupotomy operations were performed on the rabbit model of late-stage KOA, and alterations in the key molecular markers of rectus femoris fibrosis were determined using Western Blot and qPCR methods. As the disease progressed, the elastic modulus of the rectus femoris muscle in KOA rabbits gradually increased, the cross-sectional area gradually decreased, and the degree of fibrosis increased. In contrast, the degree of fibrosis in the rectus femoris muscle improved after ultrasound-guided acupotomy intervention. These findings highlight the gradual increase in the modulus of elasticity, the gradual decrease in cross-sectional area, and the increased fibrosis of the rectus femoris muscle in KOA rabbits as the disease progressed. Ultrasoundguided acupotomy operations have been shown to have a protective effect on KOA cartilage and to delay the progression of KOA by ameliorating pathological changes in the rectus femoris muscle. The mechanism may involve reducing chronic injury to the rectus femoris muscle and protecting joint homeostasis by attenuating the degree of rectus femoris fibrosis.

Inter-rater reliability for measurement of passive physiological movements in lower extremity joints is generally low: a systematic review.

This paper presents an experimental study of the flexion-extension movement of the human lower limb joints. Measurements were performed on a group of fourteen healthy subjects, experimental data being obtained for flexion-extension cycles during five different walking tests on horizontal and inclined treadmills. Experimental data were obtained using the Biometrics system, which is based on electrogonimeter sensors. Average cycles for each joint were obtained for all subjects in the experimental group and for all experimental tests. The flexion-extension angles at the lower limbs joints have a pronounced increase with the increase of the walking speed, but also with the increase of the treadmill inclination.

Background and aimKnee osteoarthritis (OA) is characterized by joint deformity and pain, both of which exert physical and psychological effects on affected individuals. The pain that often appears in the early stages is influenced by the production of inflammatory pain-related factors that respond to nociceptive stimulation from the periarticular tissues. These factors are expressed in small cells within the dorsal root ganglion (DRG) of the spinal cord. Furthermore, neuropathic pain involved in knee OA pain is influenced by neuropathic pain-related factors expressed in DRG small and medium cells, as well as inflammatory pain-related factors expressed in medium cells, which induce chronic pain. However, how these pain-related factors change during the progression of knee OA remains unclear. In addition, joint instability accelerates the progression of knee OA. Reduction of instability reduces mechanical stimulation and delays cartilage degeneration. However, the effect of pain suppression is unknown and requires further investigation. This study aimed to clarify some of the pathological changes in pain generation in the knee OA stage and verify the effect of joint instability suppression on pain reduction.Materials and methodsForty-seven adult Wistar rats were divided into OA, controlled abnormal joint movement (CAM), and sham groups, then tissues were collected at four and 12 weeks postoperatively. Knee OA was induced by anterior cruciate ligament transection. In CAM, a tibial suture controlled anterior displacement post-transection. Joint instability was assessed using soft radiography. Histological analysis of the knee joints, fluorescent immunohistochemistry of DRG for inflammatory and neuropathic pain-related factors, and assessments of pain behavior were performed. One-way analysis of variance (ANOVA) followed by Tukey’s multiple comparison test was used to evaluate joint instability and DRG-positive cells-related pain. The Kruskal-Wallis test with Steel-Dwass multiple comparisons was used for histological data. Pain behavior was evaluated using a mixed-design two-way ANOVA.ResultsKnee joint instability was greatest in the OA compared with the CAM and sham. Articular cartilage degeneration was significantly more severe in the OA and CAM than in the sham at both time points. Calcitonin gene-related peptide (CGRP) expression in the DRG was higher in the OA than in the sham at four weeks postoperatively. No significant differences were observed in substance P, isolectin B4, and P2X3 expressions across groups or time points. Pain-related factors were mostly expressed in the small DRG cells. The paw withdrawal thresholds for pain behavior decreased immediately postoperatively, improved by two weeks, and decreased significantly again at 12 weeks postoperatively; however, no significant differences between the groups were noted.ConclusionCGRP expression in early knee OA contributes to inflammatory pain, and reacquisition of joint stability suppresses inflammatory pain. In this study, neuropathic pain, including allodynia, was not observed in advanced knee OA.

To analyze knees in varying stages of osteoarthritis (OA) for the presence of coronal tibiofemoral (CTF) subluxation and to determine if CTF subluxation severity is related to knee OA worsening. We retrospectively evaluated CTF subluxation and limb alignment in 113 patients with different stages of knee OA who were being considered for an arthroplasty procedure. Knee OA was classified as "mild" or "severe" according to Kellgren-Lawrence scale. CTF subluxation was measured in the study groups and in 40 knees of healthy controls using software developed specifically on the basis of Iterative Closest Point mathematical algorithm. Mean CTF subluxation in "mild OA" and "severe OA" groups was 3.5% (±2) and 3.5 % (±5) of the tibial plateau, respectively. For both the mild and severe OA groups, CTF subluxation was significantly increased compared to the 1.4% (±1) CTF subluxation in the control group, (p < 0.0001) and (p = 0.012), respectively. However, there was no significant difference in CTF subluxation between the mild OA and severe OA groups (p = 0.75). Limb varus malalignment in mild OA and severe OA groups was 3.6° (±2.2) and 5.3° (±2.6), respectively. Both significantly increased comparing to the 1° (±0.7) control group alignment (p < 0.0001). Varus malalignment in the severe OA group was significantly increased comparing to the mild OA group (p = 0.0003). CTF subluxation is a radiographic finding related to knee OA which occurs mainly in the early stages of the osteoarthritic process and stagnates as OA progresses.

Knee joint functional range of movement prior to and following total knee arthroplasty measured using flexible electrogoniometry.