The study of clinical efficacy supplements ART LIFE Joint Flex osteoporosis

(12-month study)
VN Khodyrev, City Hospital 1, Pervouralsk, Sverdlovsk region
Treatment of osteoarthritis (OA) - a task very difficult in the absence of a unified approach to this problem. For a long time OA therapy was limited to treatment of secondary inflammatory reaction. To this end, we used a variety of non-steroidal anti-inflammatory drugs (NTTVP) and analgesics. So far in this country and abroad, the appointment of NSAIDs and paracetamol in OA is popular among physicians and patients.
In the last decades of the XX century some progress in studying the pathogenesis of OA, which led to the creation of a number of pathogenic agents (structure-modifying drugs). These primarily include those which are the main component of sulfated glycosaminoglycans (GAG): glikozaminsulfat and chondroitin sulfate. The action of these drugs is to suppress enzymes that cause destruction of cartilage, increased metabolic processes in subkoidralnoy bone and stimulation of chondrocytes full-GAG. As the structural components of the normal hyaline cartilage, these drugs are capable of with a systematic chronic administration to reduce the clinical symptoms of osteoarthritis of any location due to the suppression hondroliticheskih enzymes. The big advantage of preparations of sulfated GAG is a possibility of oral administration. However, prolonged systemic medication exhausting for the patient, especially in the psychological aspect.
Given the above, in our opinion, a very promising path may be long-term use of dietary supplements with a high content of GAG of natural origin. This contributes to the increasing demand of the population, despite the undeserved negativity to a biologically active additives of some representatives of official medicine. The latter is due, primarily, the lack of serious evidence-based studies of their clinical efficacy.
In this regard, special attention should be orthomolecular medicine Joint Flex Company ARTLIFE (Tomsk), the main component of which are sulfated GAGs (chondroitin sulfate and glikozaminsulfat).
The presented data shows that currently known doses of all components of the product does not exceed 50% of daily needs. All components are directly or indirectly influence the metabolism of cartilage and bone tissues. Thus, the results of many studies demonstrate the high performance glyukozaminsulfata and chondroitin sulfate in clinical trials.
Others, minor components of vegetable origin are designed to provide maximum absorption core in the gastrointestinal tract and reduce the secondary inflammation in OA. Known involvement of ascorbic acid in the synthesis of collagen and regulation of redox processes due to the presence in the molecule dienolnoy group (-COH = COH-) and bromeline in the microcirculation by reducing blood clotting. However, very little scientific data on the study of plant assets in connection with this, many do not know the dose and mechanism of action. Most publications on herbal remedies, are classified as popular and are an empirical question, and so far from the principles of evidence-based medicine. All this makes it difficult to explain the clinical efficacy of complex multicomponent biological products.
Nevertheless, the study of the application of biologically active compounds is very important and deserves the attention of researchers.
The aim of our study was to investigate the clinical effectiveness of prolonged use of GAG-containing complex orthomolecular medicine Joint Flex in osteoarthritis.
Materials and methods
To assess the clinical effectiveness of Joint Flex A randomized open controlled study, which included 63 patients with significant osteoarthritis in age from 40 to 75 years (mean age 52,49 ± 1,26 years). All patients were randomly selected were divided into two groups: primary (29 patients) and control (34 patients). Study of 24 patients completed in the first group and 34 in the second. Five patients refused treatment after 1-2 months of research on economic grounds. Inclusion criteria were the presence of osteoarthritis according to the diagnostic criteria (LI Benevolenskaya et al (1993), X-ray 1-II-III stages of OA on Kellgen-Lawrence, patients with marked pain syndrome - pain when walking 30 mm a visual analogue scale (VAS), functional index Lekena of 4 points or more, regular or frequent (3-4 short, up to 5 days duration of episodes per month) IPVP intermittent use during the last three months, the consent of the patient to participate in the study.
Criteria for exclusion from the study: administration of drugs with hondroprotektivnym action within 6 months prior to the study, patients with OA with radiographic stage IV of Kellgen-Lawrence, patients with pain syndrome of less than 30 mm on VAS for walking, functional index Lekena less than 4 points, patients with concomitant renal diseases with the violation of their function, patients with high laboratory parameters of activity that do not allow delete of primary inflammatory disease of the joints.
Patients in both groups at study entry had a different co-morbidities, many of which require a permanent or ad hoc anti-recidivism therapy. The combination of multiple comorbidities in the study group had 10 (41,7%) patients in the control group - 14 (41,2%). Significant differences in comorbidity in patients and control group was not. The main objectives of the research was to study the following issues:
1.Opportunity long-term use of GAG-containing complex orthomolecular Joint Flex, its portability and compatibility with drug treatment of opportunistic diseases. 
2.Influence of "low doses" GAG of natural origin on the level of intensity of pain by VAS at rest, when walking and when descending the stairs. 
3.Analiz dynamics of motor activity of patients with OA of the functional index Lekena depending on the dose.
JOINT FLEX study group received 2 tablets 2 times a day with meals for 6 months, then 2 tablets at breakfast time in a permanent form of maintenance therapy. All patients in both groups continued to take previously designated NGTVP, as well as drugs on the associated diseases. Clinical examination was performed before the study began, and then every 3 months for 1 year. In the study, in addition to general clinical, laboratory and radiological (before the study) survey, used to date generally accepted criteria for evaluating the effectiveness of treatments for OA.
Functional status of the joints were analyzed by the main criterion - total index Lekena, including parameters characterizing the pain, the maximum distance traversed and the daily motor activity of the patient. Intensity of pain assessed by VAS at rest, walking and walking up the stairs (down). Analyzed the dynamics of change regimen of NSAIDs (permanent, the number of episodes of admission to a month), as well as a comparative description of the subjective assessment of treatment effectiveness of doctor-patient (better, unchanged, worse).
Tolerability and safety were studied in the dynamic monitoring of general condition and the following laboratory parameters: blood count, coagulation, transaminase (AST, ALT), bilirubin, creatinine blood C-reactive protein, a general analysis of urine levels of potassium and sodium levels. Patients in both groups strictly adhere to general guidelines on secondary prevention of OA (driving mode, walking with support, if necessary, exercise therapy discharge type, maintaining the stability of weights, etc.).
Statistical processing of the data was performed by a computer program Biostat.
Results and discussion
Initially, a comparative analysis of the intensity of pain at rest, walking and walking up the stairs (down) revealed no statistical differences among patients and control group, although the intensity of pain while walking and while walking up the stairs was somewhat higher in the experimental group decrease in the intensity of pain alone was observed after 3 months of Joint Flex. Rate of decline in the main group of patients was more pronounced and constant throughout the study, but statistically significant (p <0.05) compared with the control group, he became only after 9 months of treatment.
Rate of decline did not decrease even after reducing the dose to 2 pills a day, ranging from 7 months of the study. After nine months of treatment in patients with the main group level of pain intensity at rest is significantly (p <0.05) lower than the initial value. The first case of complete disappearance of pain at rest among the study group appeared after 3 months of treatment, and after 12 months like we have seen in four patients (16,7%), whereas in the control group, complete disappearance of pain was not.
A similar pattern was observed in a comparative analysis of the intensity of pain on VAS while walking. Rate of reduction in pain intensity was constant, smoother and more pronounced in the intervention group than in controls. Statistical differences compared to control became significant (p <0.001) only at the end of the study. Complete disappearance of pain during walking was observed in two patients (8.3%) of the main group and the comparison group complete disappearance of pain was not a single patient.
One of the main conditions for improving the quality of life of patients with OA is the ability to fully communicate with the outside world, associated with the release of the home and return back. Since 91.7% of patients with the main group and 85.3% in the control had an apartment on the second and higher floors, it becomes apparent urgency of the problem of walking on stairs for our patients.
According to Professor MG Astanenko, especially the expression of pain in OA patients experience while running up the stairs. In this regard, we analyzed the intensity of pain during the descent on the stairs as a separate line. Thus, when analyzing the pain intensity on VAS during the descent on the stairs noticeably smoother, from survey to survey, declines in the intervention group, significant (p <0,05) after nine months of treatment compared with the control group and with baseline data. Level of pain when walking up the stairs in the experimental group decreased and reached reliable indicators, but remained relatively high (more than 45 mm), which corresponds to the category marked arthritic changes.
In the comparison group pain level has not undergone significant changes, although there was a tendency to decrease, probably due to careful medical check-up and implementation of patient's general recommendations for secondary prevention of OA.
Complete disappearance of pain during the descent on the stairs was observed in two (8.3%) patients of the group.
The mechanism of pain in OA remains unclear. Nevertheless, the currently existing hypotheses of pain can be divided into two groups. The first combines the mechanisms associated with damage to the cartilage of the joint plate, the second
- Mechanisms, due to a secondary inflammatory reaction of the others (except cartilage) of the elements of the joint and periarticular tissues. If the mechanisms of pain, the second group rather fruitfully studied, the study of causes related to cartilage injury, meets with great difficulties.
In this connection it should be noted that most researchers tend to think of the primary lesion of cartilage in primary OA, although there is speculation about the primary lesion subhondrolnoy bone. It is known that the hyaline cartilage of the joints has no vascularization and innervation, it is related to the implementation of its main functions - the depreciation based on the ability to take its original shape after deformation. Lack of innervation makes it impossible for the appearance of pain in damaged cartilage plate of synovial joints. The pain occurs only with the involvement in the pathological process of the synovial membrane, periarticular tissues and underlying bone, with abundant blood supply and many nerve receptors. Thus, damage to the cartilage plates of synovial joints with primary OA ahead, sometimes for several years, the appearance of pain. It can be assumed that the restoration of hyaline cartilage, especially at 1-2 stages of the pathological process goes in reverse order, repeating the pathogenesis. This brings in the clinical trials of drugs with potential activity hondroprotektivnoy long-term, long-term nature. Short-term studies of these drugs may be little information or only reflect their anti-inflammatory action.
Marked reduction of pain in OA, resulting in short-term studies of clinical efficacy glikozaminsulfata and chondroitin sulfate with the use of full therapeutic dose, showed primarily anti-inflammatory drugs. In this regard, a comparison of our results with the results of these studies is highly conditional. Nevertheless, we obtained a smooth, steady decline in the intensity of all kinds of pain, despite the use of small doses, are fully consistent with the results of these studies. This is probably due to the high bioavailability and accumulation of chondroitin sulfate in the synovial fluid, their inclusion in the metabolism of the constituent elements of the joint. And, above all, the influence on the cellular component of inflammation, the stimulation of proteoglycan synthesis of full and hyaluronic acid on ingibitsigo proteolytic enzymes.
Significant role in the anti-inflammatory effect Joint Flex are vegetable and mineral components of the drug. The positive impact of hydroxyapatite of calcium metabolism in bone tissue, in particular, it increases the level of ionized calcium in blood plasma, regardless of breeding, the more so because, according to Professor EL Nasonova, osteoarthritis refers to calcium-deficient diseases in humans. Known stimulatory effect of vitamin C in the cells that synthesize collagen, and extract bosvelii (Boswellia serrata) for suppression of inflammation in synovial joints. Immunostimulating and anti-inflammatory effect of bark extract Cat's Claw (herb Uncaria tomentosa) is successfully combined with anticoagulant and anti-inflammatory properties bromeline, which undoubtedly affects the clinical effect of the drug as a whole. It remains unclear mechanism of action of grape seed extract and tropical plant yucca (Yucca sghidigera), belonging to the family agavovyh. However, according to observers, the first stabilizes the cell membrane and has antioxidant properties, while the second stimulates the production of cortisone by the adrenal cortex. It should be noted that all the vegetable ingredients Joint Flex require detailed study.
Nevertheless, our results suggest a direct effect on the synergy of all components of the drug.
Comparative analysis of physical activity of patients and control group on the total index Lekena showed gradual, sustained improvement in motor (functional) activity significantly (p <0,001) at the end of the study period. This confirms not only anti-inflammatory effect of the drug, but also suggests the presence hondroprotektivnoy activity. Index Lekena continued decline even after the transition to supportive therapy, ranging from 7 months of observation. We interpreted this as a manifestation of the phenomenon of "low doses".
All cases of complete disappearance of pain (16.7%) in study group patients belonged to stage I of OA.
Apparently, the assumption that reverse the development of arthritic process in patients with early stage disease has a right to exist. However, we believe that this is feasible if the following conditions: early onset of a balanced diet with an additional introduction to the diet of GAG in the form of biologically active compounds and implement recommendations for physical activity, age-appropriate patient. Unfortunately, to date the age norms of physical activity taking into account the individual's fitness there. Relapses of synovitis of the knee among the study group during the observation period were recorded in 4 patients (16,7%), while in the control group, 9 patients (26,5%), of whom three (33.3%) twice. This determined the mode of reception of NSAIDs. Thus, in the main group receive mode NSAIDs have undergone significant changes, both in qualitative and quantitative terms.
Starting at 4 months of reception Joint Flex, episodes receiving NSAIDs were short-lived. There was a tendency for their curtailment, and to 12 months, this trend is clearly entrenched.
By the end of the study 41.7% patients of the group refused to receive NSAIDs, and 45.8% went on episodic (from several days to isolated cases) admission and only three patients (12.5%) retained mode and dose of NSAIDs at the initial level .
Whereas in the control group, 79.4% of patients have kept the old regime admission, 5.9% reduced the dose of medication and switched to intermittent use, and five patients (14.7%) increased the dose to the maximum, by resorting to a local hormone therapy for up to two once a year.
Thus, reducing the frequency of relapses of synovitis and changes in regimen and dose of NSAIDs confirms our view that anti-inflammatory effect Joint Flex.
Within 12 months of observation for patients taking Joint Flex, we did not record adverse or allergic reactions. Tolerability was good. This confirms the fourfold clinical and laboratory research on the above parameters, which are indicators of the dynamics were not beyond the normal range. Moreover, during the entire study period, we did not encounter negative attitudes of patients to the drug.
Children's Food Company Company ART LIFE Joint Flex is well combined with medication maintenance treatment of opportunistic diseases. Antirelapse and supportive therapy for their entire period of observation did not change significantly, the dose of drugs used have not changed.
Progression-associated diseases were detected.
The essential point in our study was to examine the views of a doctor and patient in assessing the clinical effectiveness of Joint Flex. Full convergence was observed in 91.7% of cases. In 83,3% of cases a doctor and 91.7% of patients noted clinical improvement, 12.5% and 4.2% respectively - no changes, only 1 (4.2%) case and noted the deterioration of the doctor and patient.
Thus, the steady decline in the intensity of pain at rest, when walking and when descending the stairs led to increased motor activity of patients with OA. This indirectly indicates hondroprotektivnom Action Joint Flex. To study the stability of the obtained data for longer, at least 2-3 years of research.
It is of interest to study the Supplements Joint Flex as the background of the drug in the treatment of OA funds with proven hondroprotektivnymi properties. Results of the study allowed to propose practical recommendations for the use Joint Flex.
1.Use GAG-containing supplements of natural origin Joint Flex firm ART LIFE in OA in a dose of 4 tablets per day significantly reduces the intensity of pain at rest, when walking and when descending the stairs after six months of regular use, with the subsequent transition to maintenance therapy on 2 tablets per day.
2.Nesmotrya to small doses of all components of the Joint Flex, clearly traced a smooth, steady expansion of the motor activity of patients with OA of the total value of the functional index Lekena, which indirectly indicates hondroprotektivnuyu activity of the drug.
3.Reduction dose Joint Flex has not led to a decrease in clinical effect achieved previously. 
4.Otchetlivy anti-inflammatory effect of the drug made a difference up to receive NSAIDs and their cumulative dose.
5.Perenosimost Joint Flex in a dose of 2-4 tablets per day is good, is safe for prolonged use and works well in conjunction with supportive therapy and preventive treatment of opportunistic diseases.
Practical recommendations for the use of complex orthomolecular medicine "JDC Flex
• Women's Food of natural origin Joint Flex is suitable for long-term treatment of primary and secondary prevention of osteoarthritis in combination with general preventive recommendations, particularly on physical activity.
• Application of Joint Flex effectively in a complex secondary prevention of pain associated with secondary synovitis of supporting joints with primary osteoarthritis. Initial dose - 4 tablets per day for at least six months with the transition to a permanent maintenance dose - 2 tablets per day after or during a meal in the morning. The latter is associated with activation of metabolic processes in tissues during daily physical activity.
• The duration of the drug should not be limited timeframes. If possible, Joint Flex can be taken for many years. The drug is safe for prolonged use.
• Joint Flex is compatible with non-steroidal anti-inflammatory drugs and drugs most frequently used for maintenance and preventive treatment of concomitant diseases (coronary heart disease, hypertension, diabetes, diseases of the gastrointestinal tract, thyroid disease).
• We believe that the Joint Flex should not be administered to persons with cancer because the drug belongs to the promoters of collagen metabolism, glycosaminoglycans and proteoglycans.