Background - Objectives To identify risk factors for progression of knee joint osteoarthrosis (OA) in the first 5 years of disease. Methods Prospective 5-year study included 110 female-patients with primary knee OA (CCR criteria), in 52 of them disease duration did not exceed 5 years, (mean age – 59,11±8,95 years). All relevant patients9 data, including anthropometric parameters, case history, evaluation of pain intensity by VAS, knee joint status and therapeutic modalities used during the follow up period were recorded in individual patient9s file. Instrumental diagnostic methods used in each patient included plain radiography of knee joints (gonarthrosis stage was classified by Kellgren J.- Lawrence J. scale), dual energy X-ray absorptiometry (DEXA) of the lumbar spine, femoral neck and of subchondral bone of the hip and tibia, ultrasound (US) and MRI examination of knee joints. First OA stage was documented in 22 (42,3%) out of 52 patients, 2-nd - in 24 (46,2%) patients, 3d stage - in 6 (11,5%) patients. Results During 5 year follow up radiographic progression of knee OA was documented in 14 patients (Group with progression), while in 38 patients radiographic stage remained unchanged. Patients from both groups were similar in terms of age (58,29 ± 7,68 vs 56,05 ± 8,74 years), and disease duration (3,43 ± 1,34 vs 3,47 ± 1,33 years). Although, patients with OA progression had more intense knee pain when walking: 60,36 ± 18,33 vs 48,71 ± 17,81, p=0,043 (mm); higher BMI: 34,45 ± 4,60 vs 28,92 ± 4,92, p=0,001 (kg/m2); higher incidence of synovitis: 57,1% vs 18,4%, p=0,006 based on US findings, bone marrow edema in medial tibia aspect 64,3% vs 13,2%, p=0,001, based on MRI findings, and higher rate of serious medial condyle damage: 50,0% vs 7,8%, p=0,001 distinct from patients without OA progression. DEXA identified significantly higher absolute bone mineral density (BMD) values in the lumbar spine 0,91 ± 0,08 vs 0,82 ± 0,11, p=0,015 (g/cm2) and femoral neck 0,85 ± 0,09 vs 0,76 ± 0,08, p=0,007 (g/cm2), as well as higher BMD in the medial condyle of the tibia 0,95 (0,85–1,24) vs 0,75 (0,65–0,82), p=0,001 (g/cm2) as compared to patients without OA progression. Patients9 re-examination in 5 years revealed similar statistically significant differences between the groups. Multifactorial analysis identified the following major risk factors, responsible for gonarthrosis progression: synovitis, bone marrow edema, and high BMD values in the medial condyle of the tibia, while intake of chondroitin sulfate (ChS) and glucosamine (GA) combination for more than 6 months a year during 5 years was identified as risk reduction factor. Based on identified factors and their coefficients a predictive model was suggested (with area under the ROC curve equal to 0,93), allowing to prognosticate the future course of the disease in an individual patient with high accuracy, i.e. 85,7%, sensitivity and 84,2% specificity. Conclusions synovitis, bone marrow edema, and high subchondral BMD in the medial condyle of the tibia are the major risk factors responsible for progression of knee OA in patients with disease duration up to 5 years. While intake of ChS and GA had a positive impact on radiological OA progression. Disclosure of Interest None declared

Objectives To identify risk factors for progression of knee joint osteoarthrosis (OA). Methods Prospective 5-year study included 110 female-patients with primary knee OA (ACR criteria), mean age – 59,11±8,95 y., average disease duration – 12,2±10,4 y. All relevant patients9 data, including anthropometric parameters, case history, clinical examination findings, evaluation of pain intensity by VAS, knee joint status and therapeutic modalities used during the follow up period were recorded in individual patient9s file. Instrumental diagnostic methods used in each patient included plain radiography of knee joints (gonarthrosis stage was classified by Kellgren J.- Lawrence J. scale), dual energy X-ray absorptiometry (DEXA) of lumbar spine, femoral neck and of subchondral bone of the hip and tibia, ultrasound (US) and MRI examination of knee joints. Results After 5 year follow up radiographic progression was stated in 40 patients (Group 1), while in 70 patients Kellgren J.- Lawrence J. stage remained unchanged (Group 2). Patients from both groups were similar in terms of age and disease duration. Although, patients with OA progression had more intense knee pain when walking: 66,2±17,9 vs 55,1±18,24 (p=0,003) (mm); higher BMI: 33,2±6,05 vs 30,5±5,63 (p=0,021) (kg/m2); higher incidence of synovitis: 50,0% vs 18,6%, p=0,001, and bone marrow edema in medial tibia aspect: 72,5% vs 27,1%, p=0,001, higher rate of serious medial meniscus damage: 52,5% vs 24,3%, p=0,003 as compared to patients from Group 2 without OA progression. Patients9 re-examination in 5 years revealed similar statistically significant difference between the groups in all evaluated parameters. Discriminate analysis identified the following major risk factors, responsible for gonarthrosis progression: obesity, synovitis and bone marrow edema. Based on identified factors and their coefficients a predictive model was suggested (with area under the curve – AUC- equal to 0,87), allowing to prognosticate the future course of the disease in a particular patient with high precision, i.e. 75% sensitivity and 78% specificity. Conclusions Obesity, synovitis, bone marrow edema- are major risk factors responsible for progression of knee OA. Disclosure of Interest None declared

Dynamic electroneurostimulation (DENS) is a type of percutaneous electroneurostimulation with a differentiation approach to choosing exposure areas and to optimizing electrocutaneous therapeutic action on the reflexogenic areas and acupuncture points for analgesia and for the treatment of functional disorders.Objective: to study the clinical efficiency and safety of therapy using a DiaDENS-PC apparatus in the treatment of knee osteoarthritis (OA).Subjects and methods. A multicenter randomized double-blind placebo-controlled study was conducted in 132 knee OA patients with pain value above 40 mm on visual analogue scale (VAS) and Lequesne’s index of 4–12. In a study group (n = 66), DENS was carried outwith a DiaDENS-PC apparatus using a trailing electrode applicator to the knee target in a Therapy stimulation mode at a frequency 77 Hz, a power of 15 units. In the placebo group, the similar procedure was performed with a switched-on placebo apparatus that did not differ in appearance from the working apparatus; but produced no electrical pulses. The treatment cycle consisted of 10 sessions lasting 30 min. Changes in Lequesne’s algofunctional index were primary end point. The results of the Get-Up to Go test (in seconds) and changes pain on VAS and WOMAC were used as secondary end points.Results and discussion. Both groups showed a statistically significant reduction of painand improvement of Get-Up and to Go test results by the end of the treatment course (p < 0.0001). Therewas a statistically significant difference in pain in the compared groups after a treatment session during the first (p = 0.037) and second (p = 0.010) visits. The analgesic effect of therapy was observed to persist in the DENS group 2 weeks (p = 0.006) and 1 month (p = 0.070) after treatment termination. After 10 sessions, there was a statistically significant difference between the groups in the Get-Up and Go test (p = 0.033) and Lequesne’s index (p = 0.022). Both groups exhibited a significant decrease in the total WOMAC scores. In the DENS group, positive changes in all subscales were statistically significant starting from the second visit whereas in the control group, the total WOMAC scores improvedonly at the expense of the pain subscale.

A new convenient dosage form of aceclofenac (sashet bags) has recently been launched on the Russian market. The powder in a single sashet bag weighs 3 g, which corresponds to 100 mg of the active ingredient per tablet. A prospective study (including evaluation of the effectiveness and safety of the sashet form of aceclofenac in real-life clinical practice) was carried out in 40 outpatients with osteoarthrosis (OA) of the knee and hip joints during 2 weeks. A clear pain relief by 25% vs the beginning of therapy was observed; joint stiffness decreased by 34%; joint function improved by 17%; and the total WOMAC score decreased by 18% by the end of the therapy (262.7±127.7 vs 198.5±111.6; 88.5±42.21vs 57.7±32.6; 789.9±307.2 vs 650.6±242.6 and 1087.7±369.3 vs 886.4±326.0, p<0.05, respectively, in all cases). The results of our surveillance study in real-life clinical practice have shown that sashet aceclofenac rapidly relieves pain and reduces joint stiffness, thus improving the functional condition of joints. Adverse effects related to the gastrointestinal tract were observed in only one (2.5%) patient when using sashet aceclofenac. The drug in this dosage form can be recommended as an effective and safe agent, especially for patients who typically receive non-steroidal anti-inflammatory drugs in liquid forms.

Osteoarthritis (OA) is one of the most common diseases, pain and joint dysfunction being its main symptoms. Although OA is a progressive disease causing disability, rapid progression is observed only in some patients. According to the data obtained by different authors, the progressive course of gonarthrosis is typical of 34–55% patients, which is likely to be attributed to variability of the risk factors of disease progression that every single patient has. As the reasons behind OA progression have been studied more thoroughly, the notion of the disease pathogenesis has recently changed. While articular cartilage lesion was considered to be the main reason and the joint space narrowing and concomitant changes in the subchondral bone (SCB) were regarded as a secondary process SCB is now believed to play the initiating role in disease evolution. It was found that acceleration of metabolic processes in SCB in OA patients causes incomplete mineralization of bone and reduces its biomechanical properties. These data initiated the search for new approaches to therapy for OA. A large number of medications that are potentially able to inhibit disease progression are being actively studied. Special attention is paid to the agents affecting the processes of bone tissue remodeling. In addition to bisphosphonates and calcitonin (whose effectiveness in treating OA has been studied over the past decades), much attention has recently been paid to strontium derivatives, in particular, to strontium ranelate (SR). It has been proved that SR stimulates preosteoblast replication, osteoblast differentiation, type 1 collagen synthesis, and mineralization of bone matrix. Meanwhile, SR inhibits osteoclast differentiation and activity, resulting in the reduction of SCB resorption, which is a potentially significant effect in OA therapy. In addition to its effect on SCB, SR can influence the bone tissue. It wasfound during the studies that SR reliably enhances the formation of bone matrix (namely, synthesis of high molecular weight proteoglycans) both in the normal articular cartilage and in patients with OA. The symptomatic effect of SR has been demonstrated in clinical trials. A reliable deceleration of joint space narrowing in patients who received SR therapy (compared to those who received placebo) has also been proved.

Нестероидные противовоспалительные препараты(НПВП) являются наиболее востребованными в клиниче-ской практике. Они обладают выраженными обезболиваю-щими, жаропонижающими и противовоспалительнымисвойствами, поэтому в фармакотерапии ревматических за-болеваний (РЗ) им придается первостепенное значение. На-считывается более 100 нозологий РЗ, они отличаются по па-тогенезу и клинической картине, но имеют одно общее про-явление – болевой синдром. Самое распространенное забо-левание этой группы – остеоартроз (ОА). По данным одногоиз недавних эпидемиологических исследований [1], в Рос-сии ОА с преимущественным поражением коленных и/илитазобедренных суставов страдает 13% населения. РазвитиеОА приводит к ухудшению качества жизни пациентов, огра-ничивает их физические возможности и социальное функ-ционирование из-за постоянного болевого синдрома. ОА яв-ляется причиной инвалидности и вследствие этого предста-вляет собой важную социально-экономическую проблему.Все болевые синдромы по патогенезу разделяют на триосновные группы: ноцицептивные, нейропатические и дис-функциональные. Для всех РЗ и, в частности для ОА, наибо-лее характерна ноцицептивная боль, которая возникает прираздражении (активации) периферических болевых рецеп-торов – ноцицепторов. Ноцицептивные болевые синдромы

The paper discusses the new mechanisms of osteoarthritis (OA) pathogenesis. Particular emphasis is placed on the role of subchondral bone remodeling, inflammatory mediators, bone morphogenetic proteins, etc. These data may be of great importance for elaborating new approaches to OA treatment.

Objective: to study the impact of pain intensity on the progression of knee osteoarthrosis (OA). Subjects and methods. One hundred and ten patients with knee OA were examined at a 5-year interval. All the patients underwent a questionnaire survey and knee joint pain assessment using a visual analog scale (VAS) and standard radiography. Results. After 5-year follow-up, radiographic OA progression was seen in 40 patients (Group 2); its stage remained the same in 70 patients (Group 1). In both groups, the patients were matched for age (59.2+9.5 and 59.0+8.1 years) and disease duration (11.1+10.6 and 13.7+9.9 years). During the first examination, pain on walking was more severe in Group 1 than in Group 2: 57.8+16.6 and 48.7+13.3 mm by VAS (р=0.002), as well as severe joint pain was predominant in these patients: 22.5 and 11.4%, respectively. Over the 5-year period, there was an increase in pain intensity. At the end of the follow-up, the patients with progressive OA rated their knee joint pain as severe in 35% of cases whereas in this index the non-progression group was only 12.9 (p = 0.012). Conclusion. In the OA progression group, pain intensity was initially statistically higher than that in the non-progression group. During 5-year follow-up, Group 1 showed an increase in knee joint pain intensity on walking, which can be considered as one of the predictors of gonarthrosis progression.

Aim. To evaluate the efficacy and tolerance of ibandronic acid (bonviva) in patients with osteoporosis (OP) concurrent with osteoarthrosis (OA) in the knee joints (KJ).Subjects and methods. Twenty female outpatients aged 56 to 77 years with postmonopausal OP and primary KJ OA were examined. All the patients took bonviva in a dose of 150 mg monthly during a year.Results. During the treatment, the patients showed a significant reduction in the values of all components of the Western Ontario and McMasters Universities Osteoarthritis Index (WOMAC) (pain intensity from 51.7 +/- 11.6 to 34.6 +/- 20.7 mm, stiffness from 96.0 +/- 55.6 to 78.5 +/- 46.6 mm, and functional failure from 783.6 +/- 333.2 to 657.8 +/- 360.9 mm according to a visual analogue scale), the Oswestry disability index, as well as in the concentration of markers for bone resorption and cartilage degradation. The need for nonsteroidal anti-inflammatory drugs was stated to decrease.Conclusion. Bonviva therapy results in a significant reduction in pain, KJ stiffness, and locomotor functional failure in patients with gonoarthrosis.

Background Osteoarthritis (OA) is one of the most common joint pathologies, which is a result of cartilage or subchondral bone damage. Objectives to determine the risk factors of structural progression of knee OA at an early stage (less than 5 years). Methods a 5-year prospective study included 110 (women with primary knee OA according to the ACR criteria), 52 of whom had disease duration of 5 years (ages 46 to 78 years). All the patients were evaluated Womac Index, radiographs of the knee joints in the anteroposterior projection (Kellgren-Lawrence) and BMD of the lumbar spine, proximal femur, tibial and femoral subchondral bone (DXA, QDR-450W Hologic). Out of 52 patients, 22 (42,3%) had disease stage 1, 24 (46,2%) - stage 2, 6 (11,5%) - stage 3. Results After 5 years of observations OA stage increase was determined in 14 cases (group 1), 38 patients remained at the same stage (group 2). Patients in both groups wereof about the same age (years) 62,71±7,87 and 60,32±8,61. Compared to group 2, patients from group 1 had more intense pain in knee joints (mm VAS) 65,14±20,19 vs 52,32±20,12 (p=0,047), a higher BMI (kg/m2) 35,74±5,83 vs 30,64±4,64 (p=0,002), higher BMD (g/cm2) in the lumbar spine 0,96±0,13 vs 0,87±0,12 (p=0,023), proximal femur 0,83±0,96 vs 0,74±0,78 (p=0,001) and in the tibial and femoral subchondral bone 0,8 [0,5-0,9] vs 0,6 [0,4-0,7] (p=0,023). Conclusions High levels of intensive pain, BMI and BMD of the lumbar spine, proximal femur, tibial and femoral subchondral bone can be considered as risk factors of knee OA early progression. Disclosure of Interest None Declared

Background There are data demonstrated association between BMD and the risk of manifestation OA. Some researchers revealed association between high BMD score in hip and lumbar region and high risk of knee OA. Objectives To study of association between axis BMD and the age of the manifestation, clinical and instrumental features of OA. Methods 158 consecutive females aged 45 years and over with primary knee OA diagnosed according to the ACR criteria were included in the study. Bilateral knee radiographs was performed using posteroanterior position, DXA of lumbar spine and femoral neck was acquired on QDR-450w (Hologic). MRI and US of knee were performed. 74 patients with normal or increased spine BMD and 42 patients with osteoporosis (OP) were analyzed. Results OP had 30,8% patients, osteopenia - 14,7%, and normal or increased spine BMD had 54,4% patients. The duration of OA was comparable in all three groups. The manifestation of OA in the group with OP was in a older age (54,2±11,9 yr.) as compared with the group with osteopenia (47,5±10,4 yr.) and the group with normal BMD ((47±8,4 yr.) (P12=0,046, P13=0,005). The share of the person with early knee pain manifestation (before 45 yr.) among women with high or normal BMD was as twice more than among women with OP (67,6% vs 30% accordingly). At the age of over 45 yr. knee pain was in 32,4% in group with high or normal BMD and in 70% in group with OP. The odds ratio was 4,8 in group with early OA manifestation and high or normal lumbar BMD score. The OA stage was less among persons with combination of OA and OP. X-ray examination demonstrated more wide joint space and smaller osteophyte size in this persons. The results of the logistic regression analyses are presented in table. Parameters B S.E. Sign. BMD spine (g/sm2) –53,4 7,5 0,000 BMD Femoral neck (g/sm2) –60,3 8,8 0,000 Menopauseage(yrs) 1,2 0,2 0,000 R: medial joint space narrow (mm) 4,7 0,8 0,000 R: subchondral sclerosis –11,7 2,5 0,000 MRI: damage of medical tibia cartilage (points) –6,6 1,3 0,000 MRI: size of cysts in medial department of tibia (points) –4,1 1,8 0,034 MRI: damage of medial menisci (points) –2,9 0,8 0,002 US: cartilage thickness in medial department (mm) 9,3 2,6 0,002 US: cartilage thickness in lateral department (mm) 11,1 3,6 0,005 US: cartilageoutline –4,1 1,5 0,011 US: cartilage homogeneity –8,02 2,9 0,01 Constant –38,1 12,1 0,004 Overall percentage in logistic regression model = 93,0%. Conclusions Persons with high and normal lumbar BMD score have more early OA manifestation. Disclosure of Interest None Declared

Objective: To study whether the course of the disease can be predicted in patients with osteoarthrosis (OA), by monitoring mTOR (Mammalian Target Of Rapamycin) gene expression in their blood. Material and methods. The investigation was conducted on the peripheral blood samples from 33 outpatients (58.4±7.4 years) with OA; 10 patients (56.5±8.9 years) before endoprosthetic knee joint replacement, и 27 healthy individuals (55.6+8.3 years) who formed a control group. Total RNA was isolated from the blood and used to estimate the gene expression of mTOR, autophagy-related protein 1 (ATG1), the cyclin-dependent kinase inhibitor p21, caspase 3, and tumor necrosis factor-а (TNF-а) by real-time polymerase chain reaction. Results. Analysis of gene expression in the outpatients with OA identified two subgroups: in one subgroup (n = 13) mTOR expression was considerably much less than that in the control group; the expression of ATG1 and p21 did not differ greatly from the control and that of caspase 3 and TNF-α was significantly higher. The other outpatients (n = 20) and all the examined patients needing endoprosthetic replacement were ascertained to have a higher gene expression of mTOR, ATG1, p21, caspase 3, and TNF-α than in the control group. Before endoprosthetic replacement, severe joint destruction in patients with OA was associated with enhanced gene expression of mTOR, ATG1, p21, and caspase 3. Conclusion. In early-stage disease, increased mTOR gene expression may serve as a prognostic marker of the severity of the disease and articular cartilage destruction.

Objective: to study the pattern of impaired regulatory mechanisms of the mammalian target of rapamycin (TOR) signaling pathway, by monitoring gene expression in the blood of patients with osteoarthrosis (OA) at different stages of the disease. Subjects and methods. The study covered 33 outpatients with OA, 14 patients with this condition prior to knee joint endoprosthesis, and 27 healthy individuals (controls) (mean age 58.0+7.4, 56.5+8.9, and 55.0+8.3 years, respectively). Total RNA was isolated from their blood and used to determine the level of gene expression by a real-time polymerase chain reaction for AMP-activated protein kinase (AMPK), hypoxia-inducible factor-1α (HIF1α), the rate-limiting proteins of the hexosamine signaling pathway — glutamine-fructose-6-phosphate amidotransferase and acetylglucosaminyltransferase, as well as the glucose transporter GLUT1 and steps 6 and 7 glycolytic pathway components — glucose-6-phosphate dehydrogenase and phosphoglycerate kinase-1, respectively; the lipogenesis-related genes — fatty acid synthase (FAS) and the activity of the pentose phosphate pathway — glucose-6-phosphate dehydrogenase in the blood of patients with OA at different stages of the disease. Results. Analysis of gene expressions showed that in the OA patients with a low expression of the mTOR gene (a LOW subgroup), the expression of AGT and GLUT1 genes proved to be significantly lower and that of the AMPK gene was higher than in the healthy individuals. In the OA patients with a high expression of the mTOR gene (a HIGH subgroup), the expression of all the genes under study was much higher, except for the FAS gene; moreover, the greatest expression excess as compared to the controls was observed for the AMPK and HIFlα genes. In the patients with endstage disease (an ES subgroup), the expression of all the study genes, including the FAS gene, turned out to be higher than in the healthy individuals. Conclusion. The development of OA is accompanied by a considerable decrease in the efficiency of energy metabolism. At the same time, in the patients with a low mTOR gene expression, energy deficiency may be due to decreased cellular metabolite transport. It may be caused by the deficiency of the end electron acceptor oxygen in the patients with a high mTOR gene expression and the pathological redistribution of energy substrate in favor of lipogenesis cannot be ruled out in those with end-stage disease.

Aim. To study risk factors of knee joint osteoarthrosis (KJO) progression within 5 years since the disease onset. Material and methods. We examined 158 females with primary KJO (by ACR criteria). Each patient's record contained demographic and disease history information, pain score in the knee joints by visual analog scale and joint status.. All the patients have undergone standard rhoentgenography of the knee joints in two projections and two-energy x-ray densitometry of the lumbar spine, the neck of the femur (NF), subchondral condyles of the femur and of the tibia. Results. We found factors promoting rapid progression of gonarthrosis within the first 5 years of the disease: high body mass index and mineral bone density (MBD) in subchondral parts of the tibia, low MBD in NF and bone marrow edema in the tibia. Conclusion. We revealed factors contributing to rapid progression of gonarthrosis in initial disease. MBD of the axial skeleton and subchondral MBD among them. Using established variables it is possible to distinguish a cohort of patients with initial signs of OA who need earlier treatment. This is of practical importance and can improve the disease prognosis.