Effect of Intraarticular Injection of Platelet-Rich Plasma on Knee Osteoarthritis: A Multicenter Retrospective Clinical Study

This study aimed to evaluate the effect of intraarticular injection with platelet-rich plasma on knee osteoarthritis. A total of 250 patients with stages I–III osteoarthritis from December 2018 to June 2020 were included in this study. All the patients had received autologous PRP injection (3 ml) into the affected knee joint every week for totally 3 injections. The VAS score and WOMAC index were used to evaluate knee function before and at 3 days, 1 month, and 3 months after injection. A total of 250 patients were enrolled in this study, including 130 patients in the PRP group and 120 patients in the control group. The content of platelets in PRP of patients in the PRP group was 958.0 ± 283.1 × 109/L. The VAS score and WOMAC index of patients in the PRP group before treatment were not significantly different from those in the control group. At 3 days, 1 month, and 3 months after PRP treatment, the VAS score and WOMAC index of the PRP group were significantly lower than those of the control group. PRP is effective in treatment of knee osteoarthritis. The pain symptoms can be alleviated at 3 days after injection.

Comparative effectiveness of intra-articular administration of different drugs of hyaluronic acid with various physico-chemical properties in knee osteoarthritis

Knee osteoarthritis (KOA) is a chronic disease that leads to a significant deterioration in the quality of life and disability. In the treatment of OA, hyaluronic acid (HA) drugs have an important place.Objective: to compare the effectiveness of ROA treatment with different HA drugs with different physicochemical properties and molecular weight.Patients and methods. A 12-week prospective randomized study of the comparative efficacy of a single intra-articular injection of three HA drugs – Armaviscon Forte (AF), Flexotron Cross (FCr) and Flexotron Ultra (FUL) was carried out. The study group consisted of 90 patients with knee osteoarthritis, aged from 43 to 50 years (the majority were women – 63.3%) with an initial severity of pain >40 mm according to the visual analogue scale (VAS). The result of therapy was assessed by the dynamics of pain (VAS), WOMAC index, and subjective assessment of the effect 3 months after intra-articular administration of HA.Results and discussion. Eight patients dropped out of the study: in the AF group – 3, FCr – 4, FUL – 1. After 90 days, the decrease in pain compared to baseline values in the AF group was 30%, in FCr – 46% and in FUL – 57% (p ≤0,05), and the dynamics of the WOMAC index – 27, 36, and 42%, respectively. After 90 days, 85.0, 93.4 and 96.5% of patients noted improvement and significant improvement in the AF, FCr and FUL groups, respectively. No serious adverse events were recorded.Conclusion. All investigated drugs demonstrated high analgesic potential, but the best clinical effect was observed with FUL.

Disease Modifying Treatment of Osteoarthritis with Triple Combination Anti-Microbial Therapy

Background: The study author, while still a medical student, observed microscopic evidence of chronic inflammation in joint tissue of patients suffering with osteoarthritis and hypothesized that osteoarthritis was caused by an infectious process. After graduating from medical school and entering into private practice, the study author had several patients who informed him that when they were on tetracycline therapy, for reasons other than arthritis, their arthritis symptoms diminished to some extent. After reporting improvement of arthritic symptoms with tetracycline, one of these patients subsequently received metronidazole and while taking both tetracycline and metronidazole reported that his arthritic symptoms improved to an even greater extent, as his joint pain further diminished but did not resolve. Subsequent treatment of osteoarthritis in other patients included the combination of tetracycline, metronidazole, other antibiotics and some natural products but only when L-lysine was added to the tetracycline and metronidazole combination therapy did the author observe yet further improvement in arthritic pain. Since L-lysine was reported to inhibit the growth of herpes simplex virus, the author and another colleague concluded that acyclovir might be a beneficial addition to the tetracycline, metronidazole, L-lysine combination. This four-component combination treatment resulted in total resolution or a marked diminution of osteoarthritis joint pain, joint tenderness and joint stiffness in most patients treated. It was further determined that L-lysine could be eliminated; that acyclovir could be replaced with valicyclovir; and that tetracycline could be replaced with minocycline or doxycycline. Preliminary studies of patients diagnosed with osteoarthritis and treated with tetracycline alone or the combination of tetracycline and metronidazole demonstrated improvement in their osteoarthritic symptoms. However the triple combination of doxycycline (broad spectrum antibiotic), metronidazole (antiprotozoal and antibacterial imidazole) and acyclovir (antiviral purine nucleoside) administered orally twice daily for eight weeks showed marked success in a group of patients suffering with osteoarthritis by substantially eliminating their joint pain, joint tenderness and joint stiffness while overcoming their fatigue and increasing their energy level. The data in this report substantiate that this triple combination is a disease modifying therapy that eliminates or markedly diminishes the symptomatology of osteoarthritis and further supports the hypothesis that osteoarthritis is an infectious disease. Objective: To evaluate the effect of the triple combination therapy of doxycycline, metronidazole, and acyclovir on the joint pain, joint stiffness and functionality in patients suffering with osteoarthritis. Design: Non-blinded study of treatment of patients suffering with osteoarthritis Setting: Primary care internal medicine practice in Alameda County, California. Sample: Six adult individuals suffering with osteoarthritis. Patients: Six patients, ages 53 through 82 years. Patient 1 was treated for 28 days and Patients 2 through 6 were treated for 56 days. Method: After obtaining informed consent, six patients suffering with osteoarthritis were prescribed a 56 day course of treatment with the triple combination of doxycycline, metronidazole, and acyclovir for treatment of their osteoarthritis. Utilizing the WOMAC index for assessment of the effectiveness of treatment of osteoarthritis, pre-treatment pain, stiffness and functional limitation, were compared to post-treatment pain, stiffness and functional limitations. Results: Three patients demonstrated total resolution of pain and stiffness and greater than 95% improvement in functional limitations. One of the remaining three patients demonstrated a 70% improvement in pain, total resolution of stiffness, and an 85% improvement in functional limitations; another one of the three remaining patients demonstrated an 86% improvement in pain, total resolution of stiffness, and a 79% improvement in functional limitations; while the last of the three remaining patients demonstrated at least an 85% improvement in pain, 67% improvement in stiffness, and a 63% improvement in functional limitations. Limitations: No randomization. No placebo. No control group. Small sample size. Conclusion: The results of treatment of these patients suffering the osteoarthritis support the hypothesis that osteoarthritis is an infectious disease. These results further suggest that osteoarthritis is, at a minimum, modifiable with the triple combination therapy of doxycycline, metronidazole, and acyclovir and is even curative of with this breakthrough treatment in many cases. The medical treatment reported in this article represents the first truly Disease Modifying medication therapy developed for osteoarthritis. Keywords: WOMAC index

Effect of Ginseng Extracts on the Improvement of Osteopathic and Arthritis Symptoms in Women with Osteopenia: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Ginsenosides are active compounds that are beneficial to bone metabolism and have anti-osteoporosis properties. However, very few clinical investigations have investigated the effect of ginseng extract (GE) on bone metabolism. This study aims to determine the effect of GE on improving bone metabolism and arthritis symptoms in postmenopausal women with osteopenia. A 12-week randomized, double-blind, placebo-controlled clinical trial was conducted. A total of 90 subjects were randomly divided into a placebo group, GE 1 g group, and GE 3 g group for 12 weeks based on the random 1:1:1 assignment to these three groups. The primary outcome is represented by bone metabolism indices consisting of serum osteocalcin (OC), urine deoxypyridinoline (DPD), and DPD/OC measurements. Secondary outcomes were serum CTX, NTX, Ca, P, BsALP, P1NP, OC/CTX ratio, and WOMAC index. The GE 3 g group had a significantly increased serum OC concentration. Similarly, the GE 3 g group showed a significant decrease in the DPD/OC ratio, representing bone resorption and bone formation. Moreover, among all the groups, the GE 3 g group demonstrated appreciable improvements in the WOMAC index scores. In women with osteopenia, intake of 3 g of GE per day over 12 weeks notably improved the knee arthritis symptoms with improvements in the OC concentration and ratios of bone formation indices like DPD/OC.

Results of a prospective 6-year observational study of the efficacy and safety of a bioactive concentrate of small marine fish in senile patients with knee osteoarthritis and multimorbidity

Objective: to evaluate the efficacy and safety of Alflutop therapy in elderly patients (75–90 years old) with knee osteoarthritis (OA) and multimorbidity based on the results of a prospective 6-year follow-up.Patients and methods. The study included 38 elderly women with knee OA (according to ACR criteria, 1986) stage II–III by Kellgren–Lawrence grading system, with pain ≥40 mm by visual analogue scale (VAS), who needed to take non-steroidal anti-inflammatory drugs (NSAIDs). Alflutop was administered as 1 ml intramuscular injections 20 consecutive days with a 6-month interval (12 courses). The effectiveness of therapy was assessed by VAS, WOMAC index and EQ-5D questionnaire. The safety of therapy was monitored throughout the observation period. The duration of the study was 6 years.Results and discussion. The full course of treatment with Alflutop was completed by 29 (76.3%) patients. Nine (23.7%) patients discontinued the study due to their inability to visit the treatment center (for reasons unrelated to the study).In elderly patients with knee OA, high level of multimorbidity was revealed, 5 comorbidities on average.There was a significant decrease in pain according to VAS (≥20%): by visit (V) 1 – in 76.3%, by V2 – in 71.0%, by V3 – in 68.4%, by V4 – in 63.1% and by V5 – in 55.2% of patients. By the 21st day of Alflutop therapy, a statistically significant decrease in the total WOMAC index (p<0.001) and an improvement in the quality of life according to the EQ-5D questionnaire (p=0.016) were found. These indicators remained relatively stable throughout the follow-up. By the 12th month, a decrease of the need of NSAIDs was registered (p=0.005).X-ray progression of OA stage ≥1 according to Kellgren–Lawrence on Alflutop therapy after 36 months of observation was recorded in 10.5% of patients, after 72 months – in 50.0%. No serious adverse events were registered during entire observation period.Conclusion. The results of a 6-year prospective study demonstrate the high efficacy of Alflutop in elderly patients with knee OA. The obtained data confirm the safety of long-term treatment with this drug in elderly patients with high multimorbidity, which makes it the first-line drug in the complex therapy of OA.

Local use of Muscomed in the treatment of patients with knee osteoarthritis

The article presents the literature data and the results of our own investigation on the efficacy and safety of Muscomed cream in the treatment of patients with osteoarthritis of the knee joint. The study included 20 women (mean age 62 years). The study design included clinical and radiological examination of patients and survey using the Western Ontario and McMaster Universities Arthritis Index (WOMAC) and the visual analogue scale at the beginning of treatment, on days 7 and 14 of using Muscomed cream. Muscomed cream was applied topically as a component of physiotherapeutic procedures as a part of a comprehensive conservative treatment. Two weeks after completing the course of treatment, there was a significant decrease in the intensity of pain syndrome and a decrease in the total WOMAC index in patients who used Muscomed cream locally. There was also a more pronounced decrease in the need for non-steroidal anti-inflammatory drugs in patients of the main group. The safety and efficacy of the Muscomed cream in the treatment of osteoarthritis of the knee joints were demonstrated, which resulted in a decrease in the severity of pain syndrome and an improvement in the functional activity and quality of life of such patients.

AB0599 EFFICACY AND SAFETY OF COMBINATION THERAPY WITH NSAIDS AND ANTICONVULSANT, COMPARED WITH NSAID MONOTHERAPY FOR CHRONIC PAIN IN PATIENTS WITH OSTEOARTHRITIS OF THE KNEE JOINTS

Background:In 20-44% of patients with osteoarthritis of the knee joints neuroplastic changes occur due to central sensitization (1,2), which is the rationale for complex therapy, including centrally acting drugs, for more effective pain control.Objectives:To evaluate the efficacy and safety of combination therapy with NSAID and anticonvulsant in comparison with NSAID monotherapy in patients with osteoarthritis of the knee joints and signs of central sensitization or nocyplastic painMethods:The study included 60 women with osteoarthritis of the knee joints (OAK) with signs of nocyplastic pain. Nocyplastic pain were revealed by neuropathic scales (DN4 questionnaire > 4 points), subject to the absence of patients lesions of the somatosensory nervous system. All patients were randomized into two age- and sex-matched groups: group I (n=30) received combination therapy with aceclofenac and pregabalin, group II (n=30) - monotherapy with aceclofenac. The observation period was 42 days and included three visits. All patients underwent a clinical and neurological examination, we assessed the overall WOMAC index, pain intensity at rest with the visual analogue scale (VAS), nocyplastic pain (DN4 and Pain DETECT questionnaires), anxiety and depression (HADS questionnaire) and the quality of life (EQ-5D questionnaire).Results:The intensity of pain at rest according to VAS in patients of group I significantly decreased after 14 days (visit 2) and even further after 42 days (visit 3) (64.0 [50.0; 72.0] vs 49.0 [33.0; 55.0] vs 33.5 [22.0; 49.0] p = 0.006). In group II the intensity of pain at rest also decreased after 14 days (visit 2) (63.0 [41.0; 72.0] vs 48.0 [35.0; 58.0] p <0.001), however, did not change significantly from visit 2 to 3 (48.0 [35.0; 58.0] vs 44.0 [35.0; 60.0]) (p = 0.57).The dynamics of neuropathic pain indicators according to the DN4 and Pain DETECT questionnaires was as follows: group I (visit 1-3) DN4 (6.0 [5.0; 7.0] vs 3.0[1.0; 4.0], p=0.001) and Pain DETECT (17.0 [16.0;20.0] vs 8.0 [5.0; 14.0], p=0.001). Group II DN4 (6.0[5.0;6.0] vs 5,0 [3,0; 6,0],p=0,05), Pain DETECT (17,0 [15,0; 19,0] vs 16.0 [14,0; 19,0],p=0,53).The overall WOMAC index decreased significantly in both groups.Significant positive dynamics in terms of the level of anxiety (9.0 [7.0;14.0] vs 7.0 [4.0;10.0], p=0.001), depression (8.0 [5.0;10.0] vs 6.5 [4.0;9.0], p= 0.03) and quality of life (0.52 [-0.02;0.52] vs 0.52 [0.52;0.59], p=0.01) was observed compared to baseline in group I but not in group II. Before the start of therapy, the groups were comparable in the studied parameters, however, after 42 days, anxiety (7.0 [4.0;10.0]vs 9.0 [7.0;12.0], p=0.02) and depression levels (6.5 [4.0;9.0] vs 8.0 [6.0;9.0], p=0.05) were statistically different. Moreover, the median anxiety and depression levels still exceeded 7 points in group II, indicating the presence of anxiety and depression.Conclusion:Combination therapy of chronic pain with signs of nocyplastic pain with pregabalin and aceclofenac in patients with knee osteoarthritis has been shown to be effective in terms of pain intensity, the presence of neuropathic descriptors and the severity of anxiety compared with aceclofenac alone.References:[1]Hochman JR, French MR, Bermingham SL, Hawker GA. The nerve of osteoarthritis pain. Arthritis Care Res (Hoboken). 2010;62:1019–23.[2]Hochman JR, Gagliese L, Davis AM, Hawker GA. Neuropathic pain symptoms in a community knee OA cohort. Osteoarthr Cartil. 2011;19:647–54.Disclosure of Interests:None declared.

Treatment Efficacy with a Novel Hyaluronic Acid-Based Hydrogel for Osteoarthritis of the Knee

Background: Prior trials investigating the treatment of symptomatic osteoarthritis (OA) with hyaluronic-acid-derived products injections have provided optimistic results. The study was directed to assess the effectiveness of an innovative hyaluronic-acid-based hydrogel (Hymovis®) in the treatment of symptomatic knee OA. Methods: A prospective, single-center, clinical trial was performed. Thirty-five patients with degenerative knee OA were included. Inclusion criteria were: age between 45–80, radiographic Kellgren grade II or III osteoarthritis, minimum 35 mm score on the Visual Analogue Scale (VAS), pain for at least 6 months and agreement to participate in the study. Patients received two injections at a one-week interval. The evaluator assessed the patients using the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and VAS. Evaluation was performed before, at 2 and 6 months after the injections. Results: A significant improvement on the WOMAC Index pain subscale was observed at 6 months after the injection. At two months, pain subscale score decreased from 10.34 to 9.34. At six months, a significant decrement in pain parameters compared to baseline was observed (from 10.34 to 7.72; p = 0.0004). Median points on VAS significantly ameliorated after 6 months (from 74.2 to 57.3 cm; p < 0.0001). Regarding physical function, a statistically significant difference compared to baseline was observed at the end of the study (from 29.74 to 25.18; p = 0.0025). WOMAC Index stiffness component did not differ from baseline at any time during follow-up. Conclusions: Pain relief installed with a delayed on-set but had a prolonged duration. The novel hyaluronic acid-based hydrogel (Hymovis®) had effective results, particularly after six months post-injections and offers a therapeutic advancement in the treatment of moderate to severe osteoarthritis.

Treatment of osteoarthritis of large and small joints using an injectable complex action chondroprotector

В многоцентровом исследовании «КОЛИБРИ» оценивали эффективность и переносимость инъекционного средства замедленного действия для терапии остеоартроза крупных и мелких суставов. Исследуемую группу составили 49 больных (87,8% женщин, 12,2% мужчин, медиана возраста – 63,4 [52,3; 75,2] года, длительность болезни – 5,86 [3,07; 11,4] года, индекс массы тела – 30,06 [23,1; 41,4] кг/м2): 14,6% – с поражением мелких суставов кистей (1-я группа), 62,5% – с поражением крупных суставов, получавшие препарат внутримышечно (2-я группа), и 22,9% – с поражением крупных суставов, получавшие препарат внутрисуставно (в/с) и внутримышечно (в/м) (3-я группа). В течение года проведено 2 курса инъекций с интервалом 6 мес и последующим наблюдением в течение 3 мес. Результаты лечения оценивали в динамике по визуально-аналоговой шкале (ВАШ) боли, индексам AUSCAN и WOMAC, удовлетворенности пациента и врача по 5-балльной шкале и потребности в нестероидных противовоспалительных препаратах (НПВП). После первого курса лечения отмечено статистически значимое уменьшение боли по шкале ВАШ на 45,4-57,7%, индекса AUSCAN– на 49,3%, индекса WOMACво 2-й группе – на 44,9%, в 3-й группе – на 53,2%. Около 1/3 больных отказались от приема НПВП. К началу второго курса указанные показатели возросли, но не до исходного уровня. После второго курса терапии отмечено дальнейшее улучшение показателей боли по ВАШ – на 20,2-30,8%, индекса AUSCAN – на 28,4%, индекса WOMAC во 2-й группе – на 20,5%, в 3-й группе – на 22,9%. Через 3 месяца наблюдения отмечено уменьшение по сравнению с исходными показателями боли по ВАШ на 60,8-64,8%, индекса AUSCAN – на 34,3%, WOMAC во 2-й группе – на 51,3%, в 3-й группе – на 35,4%. Наиболее выражена была динамика скованности в суставах. 50% пациентов отказались от приема НПВП. Нежелательные реакции (дерматит в месте инъекции и синовит после внутрисуставного введения препарата) выявлены у 2 больных. The aim of the study was to assess the efficacy and tolerability of slow-acting injectable agent for the treatment of osteoarthritis in the treatment of osteoarthritis of large and small joints. The study group consisted of 49 patients (87,8% women, 12,2% men, whose median age – 63,4 [52,3; 75,2] years, the duration of the disease – 5,86 [3,07; 11.4] years, body mass index – 30,06 [23,1; 41,4] kg/m2): 14,6% – with damage to small joints of the hands (group 1), 62,5% with damage to large joints, who received the drug only intramuscularly (group 2) and 22,9% with lesions of large joints, who received the drug intra-articularly and intramuscularly (group 3). During the year, 2 courses of injections were carried out with an interval of 6 months. 3 months follow-up period was held. The results of treatment were assessed by the dynamics of the VAS of pain, AUSCAN and WOMAC indices, patient and doctor satisfaction on a 5-point scale, and the need for non-steroidal anti-inflammatory drugs (NSAIDs). After 1 course of treatment, there was a statistically significant decrease in pain according to VAS in all groups by 45,4-57,7%, in the AUSCAN index – by 49,3%, in the WOMAC index in group 2 – by 44,9%, in group 3 – by 53,2%. About 1/3 of patients refused to take NSAIDs. By the beginning of the 2nd course, these indicators increased, but not to the initial level. After the 2nd course of therapy, further improvement was noted pain according to VAS – by 20,2-30,8%, AUSCAN index – by 28,4%, WOMAC index in group 2 – by 20,5%, in group 3 – by 22 ,9%. After 3 months of follow-up there was a decrease in comparison with the initial indicators: pain according to VAS – by 60,8-64,8%, AUSCAN index – by 34,3%, WOMAC in group 2 – by 51,3%, in group 3 – by 35,4%. The dynamics of joint stiffness was most pronounced. Half of the patients stopped taking NSAIDs. Adverse reactions (dermatitis at the injection site and synovitis after i/a administration of the drug) were detected in 2 patients.