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1.
Relationship between the Gut Microbiome and Osteoarthritis Pain: Review of the Literature.
Sánchez Romero, EA, Meléndez Oliva, E, Alonso Pérez, JL, Martín Pérez, S, Turroni, S, Marchese, L, Villafañe, JH
Nutrients. 2021;(3)
Abstract
BACKGROUND Osteoarthritis (OA) is the most common form of chronic pain in Europe (34%), representing a great economic and social cost to society. There are studies that suggest an intestine-brain-articulation axis and hint at the existence of low-grade intestinal inflammation in OA, which would be related to an alteration of the microbiota and to the impairment of the epithelial barrier, with leakage of the microbial components. PURPOSE The purpose of this study was to review the association between gut microbiome and pain in the OA population through a review of the literature. METHODS A literature search was conducted to identify all available studies on the association between the gut microbiome and pain in the OA population, with no publication date limit until September 2020 and no language limit, in the MEDLINE, CINAHL, Web of Science and Cochrane Central Register of Controlled Trials databases. RESULTS Only three of 2084 studies detected and analyzed by performing the proposed searches in the detailed databases, were finally selected for this review, of which one was with and two were without intervention. These studies only weakly support a relationship between the gut microbiome and OA, specifically a correlation between certain taxa or microbial products and the inflammatory landscape and severity of OA symptoms, including knee pain. Conclusions: Despite encouraging results, this review highlights the paucity of high-quality studies addressing the potential role of the gut microbiome in OA-related pain, along with the disparity of the techniques used so far, making it impossible to draw firm conclusions on the topic.
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Rheumatoid Arthritis Pathogenesis, Prediction, and Prevention: An Emerging Paradigm Shift.
Deane, KD, Holers, VM
Arthritis & rheumatology (Hoboken, N.J.). 2021;(2):181-193
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Abstract
Rheumatoid arthritis (RA) is currently diagnosed and treated when an individual presents with signs and symptoms of inflammatory arthritis (IA) as well as other features, such as autoantibodies and/or imaging findings, that provide sufficient confidence that the individual has RA-like IA (e.g., meeting established classification criteria) that warrants therapeutic intervention. However, it is now known that there is a stage of seropositive RA during which circulating biomarkers and other factors (e.g., joint symptoms) can be used to predict if and when an individual who does not currently have IA may develop future clinically apparent IA and classifiable RA. Indeed, the discovery of the "pre-RA" stage of seropositive disease has led to the development of several clinical trials in which individuals are studied to identify ways to delay or prevent the onset of clinically apparent IA/RA. This review focuses on several issues pertinent to understanding the prevention of RA. These include discussion of the pathogenesis of pre-RA development, prediction of the likelihood and timing of future classifiable RA, and a review of completed and ongoing clinical trials in RA prevention. Furthermore, this review discusses challenges and opportunities to be addressed to effect a paradigm shift in RA, where in the near future, proactive risk assessment focused on prevention of RA will become a public health strategy in much the same manner as cardiovascular disease is managed today.
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Effect of Turmacin supplementation on joint discomfort and functional outcome among healthy participants - A randomized placebo-controlled trial.
Raj, JP, Venkatachalam, S, Racha, P, Bhaskaran, S, Amaravati, RS
Complementary therapies in medicine. 2020;:102522
Abstract
OBJECTIVE Curcuma longa has been widely used in Ayurveda for its medicinal properties and Turmacin was developed from C. longa as a standardized extract containing turmerosaccharides. In this clinical trial, the effect of Turmacin on knee joint discomfort in healthy adults subjected to strenuous physical activity was evaluated. DESIGN Double-blind, triple-arm, parallel-group, randomized placebo-controlled trial. SETTING Healthy participants from an urban tertiary care teaching hospital. INTERVENTION Healthy participants were randomized in 1:1:1 ratio to receive either Turmacin 0.5 g/1 g or placebo once daily for 84 days. The participants were subjected to 10-minute strenuous exercise. OUTCOME MEASURES Time to initial pain, final pain score on a visual analogue scale, range of movement (ROM) of knee and the force of contractions of muscles around the knee joint. RESULTS A total of n = 90 participants were recruited. The mean final pain scores were significantly lower in the Turmacin 1 g and Turmacin 0.5 g when compared with the placebo from day-7 and day-5 onwards respectively. The survival analysis consistently showed a decreased hazard for early onset of pain in both the Turmacin groups. On day-84, the difference in mean ROM between Turmacin 0.5 g and placebo was 4.79 degrees (p = 0.008) and that for Turmacin 1 g and placebo was 2.34 degrees (p = 0.306). The difference in muscle force for isokinetic contractions of the quadriceps at angular velocities of 120 and 180 was significant between Turmacin 0.5 g and placebo (p = 0.002 and p = 0.005 respectively) while that for Turmacin 1 g & Turmacin 0.5 g (p = 0.206 and p = 0.414 respectively) and Turmacin 1 g & Placebo (p = 0.046 and p = 0.037) were not significant. However, in the within group analysis participants in Turmacin 1 g group had better preserved muscle functions than Turmacin 0.5 g group at angular velocities of 120 and 180 when compared with placebo. CONCLUSION Turmacin (0.5 g and 1 g) was efficacious when compared to placebo in increasing the pain threshold and knee ROM in healthy participants with minor adverse events.
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The effect of curcumin ointment on knee pain in older adults with osteoarthritis: a randomized placebo trial.
Jamali, N, Adib-Hajbaghery, M, Soleimani, A
BMC complementary medicine and therapies. 2020;(1):305
Abstract
BACKGROUND Some studies have shown the effect of oral administration of curcumin on knee pain. However, limited studies are available on the effect of topical curcumin. This study aimed to investigate the effect of curcumin ointment on knee pain in older adults with osteoarthritis. METHODS This double-blind randomized placebo trial was conducted on 72 older adults with knee pain associated with osteoarthritis. The subjects were randomly assigned into an intervention and a placebo group to apply either curcumin 5% ointment or Vaseline ointment twice daily for 6 weeks. Using a Visual Analog Scale, the severity of knee pain was measured at the beginning of the study, at the end of the fourth and sixth week. Data were analyzed using descriptive and inferential methods. RESULTS The mean baseline knee pain intensity was not significantly different between the two groups (P = 0.15). The mean pain intensity was significantly lower in the intervention group than in the placebo group at the third measurement (P = 0.02). The repeated-measures analysis showed that over time, the curcumin significantly decreased the mean pain intensity in the intervention group (P = 0.001). The mixed model showed an absolute difference of 1.133 (i.e. 11.33 mm) score which signifies a medium effect size and that the patient in the intervention group achieved the minimal clinically important difference. CONCLUSION Topical administration of curcumin 5% ointment can significantly reduce knee pain in older adults with knee osteoarthritis. Curcumin ointment can be used as an alternative treatment in older adults with knee pain associated with osteoarthritis. TRIAL REGISTRATION Retrospectively registered in the Iranian Registry of Clinical Trials (IRCT) (IRCT20100403003618N6, 2019-03-08), https://en.irct.ir/trial/37155.
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An infrapatellar nerve block reduces knee pain in patients with chronic anterior knee pain after tibial nailing: a randomized, placebo-controlled trial in 34 patients.
Leliveld, MS, Kamphuis, SJM, Verhofstad, MHJ
Acta orthopaedica. 2019;(4):377-382
Abstract
Background and purpose - Anterior knee pain is common after tibial nailing. Its origin is poorly understood. Injury of the infrapatellar nerve is a possible cause. In this randomized controlled trial we compared changes in knee pain after an infrapatellar nerve block with lidocaine or placebo in patients with persistent knee pain after tibial nailing. Patients and methods - Patients with chronic knee pain after tibial nailing were randomized to an infrapatellar nerve block with 5 ml 2% lidocaine or placebo (sodium chloride 0.9%), after which they performed 8 daily activities. Before and after these activities, pain was recorded using a numeric rating scale (NRS; 0-10). Primary endpoint was the change in pain during kneeling after the infrapatellar nerve block. Secondary outcomes were changes in pain after the nerve block during the other activities. Results - 34 patients (age 18-62 years) were equally randomized. A significant reduction of the NRS for kneeling pain with an infrapatellar nerve block with lidocaine was found compared with placebo (-4.5 [range -10 to -1] versus -1 [-9 to 2]; p = 0.002). There were no differences between the treatments for the NRS values for pain during other activities. Interpretation - Compared with placebo, an infrapatellar nerve block with lidocaine was more effective in reducing pain during kneeling in patients with chronic knee pain after tibial nailing. Our findings support the contention that kneeling pain after tibial nailing is a peripheral nerve-related problem.
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Rheumatologic manifestations in celiac disease: what should we remember?
Dima, A, Jurcut, C, Jinga, M
Romanian journal of internal medicine = Revue roumaine de medecine interne. 2019;(1):3-5
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Effect of a low-intensity, self-management lifestyle intervention on knee pain in community-based young to middle-aged rural women: a cluster randomised controlled trial.
Wang, Y, Lombard, C, Hussain, SM, Harrison, C, Kozica, S, Brady, SRE, Teede, H, Cicuttini, FM
Arthritis research & therapy. 2018;(1):74
Abstract
BACKGROUND Knee pain is common with obesity and weight gain being important risk factors. Previous clinical trials have focused on overweight or obese adults with knee pain and osteoarthritis and demonstrated modest effects of intense weight loss programs on reducing knee pain despite very significant weight loss. There has been no lifestyle intervention that targets community-based adults to test its effect on prevention of knee pain. We aimed to determine the effect of a simple low-intensity self-management lifestyle intervention (HeLP-her), proven in randomised controlled trials to improve lifestyle and prevent weight gain, on knee pain in community-based young to middle-aged rural women. METHODS A 1-year pragmatic, cluster randomised controlled trial was conducted in 649 community-based women (aged 18-50 years) to receive either the HeLP-her program (consisting of one group session, monthly SMS text messages, one phone coaching session, and a program manual) or one general women's health education session. Secondary analyses were performed in 390 women who had knee pain measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at baseline and 12-month follow-up. "Any knee pain" was defined as a WOMAC pain score ≥ 1. Knee pain worsening was defined as an increase in WOMAC pain score over 12 months. RESULTS Thirty-five percent of women had "any knee pain" at baseline. The risk of knee pain worsening did not differ between the intervention and control groups over 12 months. For women with any knee pain at baseline, those in the intervention arm had a lower risk of knee pain worsening compared with those in the control arm (OR 0.37, 95% CI 0.14-1.01, p = 0.05), with a stronger effect observed in women with body mass index ≥ 25 kg/m2 (OR 0.28, 95% CI 0.09-0.87, p = 0.03). CONCLUSIONS In community-based young to middle-aged women, a simple low-intensity lifestyle program reduced the risk of knee pain worsening in those with any knee pain at baseline, particularly in those overweight or obese. Pragmatic lifestyle programs such as HeLP-her may represent a feasible lifestyle intervention to reduce the burden of knee pain in the community. TRIAL REGISTRATION ACTRN12612000115831 , registered 24 January 2012.
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Joint involvement in Mexican patients with ulcerative colitis: a hospital-based retrospective study.
Yamamoto-Furusho, JK, Sarmiento-Aguilar, A
Clinical rheumatology. 2018;(3):677-682
Abstract
The most frequent extra-intestinal manifestation in ulcerative colitis (UC) around the world is joint involvement. There are no previous data in Latin America that is about this aspect of disease; hence, the aim of this study was to determine the frequency and factors associated to joint involvement in Mexican patients with UC. A total of 295 patients with histological diagnosis of UC were studied, divided into two groups: (1) 154 cases with at least one joint affection (arthralgia, peripheral, or axial arthropathy (sacroilitis (SI) or ankylosing spondylitis (AS))) and (2) 141 controls that had never presented any joint involvement during the clinical course of UC. Demographic, clinical, and laboratory variables were collected from the clinical records, at the time of presentation of the joint involvement for the cases and with the last information available for controls. A total of 52.2% of the patients had joint involvement, which was also the most frequent extra-intestinal manifestation (EIM). The frequency of peripheral arthralgia was 46.8% and of axial arthropathy was 5.4% (2.7% AS, 2.4% SI, and 0.3% both). The female gender (P = 0.01, OR = 3.061 95% CI: 1.311-7.15), elevated erythrocyte sedimentation rate (ESR) (P = 0.07, OR = 8.04 95% CI: 1.759-36.764), and moderate disease activity by Truelove and Witts criteria (P = 0.024, OR = 4.37 95% CI: 1.211-15.78) were factors associated at the time of presentation of the joint affection. Joint involvement is the most frequent EIM in Mexican patients with UC. The female gender, elevated ESR, and disease activity are factors associated with its presentation.
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Individuals With Patellofemoral Pain Have Less Hip Flexibility Than Controls Regardless of Treatment Outcome.
Hamstra-Wright, KL, Earl-Boehm, J, Bolgla, L, Emery, C, Ferber, R
Clinical journal of sport medicine : official journal of the Canadian Academy of Sport Medicine. 2017;(2):97-103
Abstract
OBJECTIVE To examine differences in hip flexibility before and after a 6-week muscle strengthening program between those with patellofemoral pain (PFP) and healthy controls. DESIGN Single-blind, multicentered, randomized controlled trial. SETTING Four clinical research laboratories. SUBJECTS Physically active individuals (199 PFP and 38 controls). INTERVENTIONS Patellofemoral pain and control subjects were randomized into either a hip-focused or a knee-focused muscle strengthening treatment program. MAIN OUTCOME MEASURES Pain-visual analog scale (centimeter), function-Anterior Knee Pain Scale (points), flexibility-passive goniometry (degrees): hip adduction (HADD), hip external rotation (HER), hip internal rotation (HIR), total hip rotation (HROT), hip extension (HEXT) were measured before and after the muscle strengthening treatment program. RESULTS Subjects with patellofemoral pain who successfully completed the treatment program (n = 153) had 65%, 25%, 18%, and 12% less HADD, HER, HROT, and HIR ranges of motion (ROMs), respectively, than controls (P < 0.05). Patellofemoral pain subjects who did not successfully complete the program (n = 41) had 134%, 31%, 22%, and 13% less HADD, HER, HROT, and HIR ROMs, respectively, than controls (P < 0.05). All subjects increased their HIR, HROT, and HEXT ROMs pretest to posttest (P < 0.05), but by less than 2 degree. CONCLUSIONS Individuals with PFP had less hip flexibility than controls regardless of treatment outcome or time. After the 6-week muscle strengthening program, and regardless of treatment success, PFP and control subjects experienced a small but clinically insignificant improvement in hip flexibility. CLINICAL RELEVANCE Hip ROM should be considered as a targeted area of focus in a rehabilitation program for physically active individuals with PFP.
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Effects of dietary supplementation with a standardized aqueous extract of Terminalia chebula fruit (AyuFlex®) on joint mobility, comfort, and functional capacity in healthy overweight subjects: a randomized placebo-controlled clinical trial.
Lopez, HL, Habowski, SM, Sandrock, JE, Raub, B, Kedia, A, Bruno, EJ, Ziegenfuss, TN
BMC complementary and alternative medicine. 2017;(1):475
Abstract
BACKGROUND Joint and connective tissue integrity, comfort and function are paramount to optimal performance in exercise, recreational and occupational activities. The fruit of Terminalia chebula has been used extensively in various traditional health systems for different ailments, with additional preclinical and clinical data demonstrating antioxidant and anti-inflammatory potential. The aim of this study was to evaluate the effects of a standardized aqueous extract of Terminalia chebula fruit (AyuFlex®) dietary supplementation on joint mobility, comfort, and functional capacity in healthy overweight subjects. METHODS One-hundred and five (105) overweight, apparently healthy male and female subjects (35-70 years of age) were pre-screened and randomized to one of three groups for 84 days: placebo, AyuFlex1 (250 mg twice daily) or AyuFlex2 (500 mg twice daily) in a randomized, double-blind, placebo-controlled design. A two-week placebo lead-in period was used to improve data quality/validity. All subjects had no knee joint discomfort at rest, but experienced knee joint discomfort only with activity/exercise of at least 30 on 100 mm Visual Analog Scale (VAS). Primary outcome measures included symptoms of joint health and function as measured by modified-Knee Injury & Osteoarthritis Outcomes Score (mKOOS) global & modified-Western Ontario and McMaster Universities Arthritis Index (mWOMAC) subscales (discomfort, stiffness and function). Secondary outcomes included VAS questionnaires on overall/whole-body joint health, low back health, knee mobility, willingness and ability to exercise, 6-min walk test for distance and range of motion (ROM) of pain-free knee flexion/extension. Tertiary outcome measures included inflammatory (high sensitivity C-reactive protein (hsCRP), tumor necrosis factor (TNF)-α) and extracellular matrix (ECM)/Connective Tissue (COMP) biomarkers, and safety (vital signs and blood markers) & tolerability (Adverse Event (AE)/ side effect profiles). RESULTS Compared to placebo, at day 84 AyuFlex® treatment significantly: 1) improved mKOOS global scores in AyuFlex1 + AyuFlex2 (P = 0.023), and improved total and physical function subscale of mWOMAC relative to baseline, 2) improved VAS scores for Knee Discomfort with activity/exercise in AyuFlex1 + AyuFlex2 (P = 0.001) relative to baseline, 3) improved VAS scores for whole-body joint function in AyuFlex1 + AyuFlex2 (P < 0.029) relative to baseline, 4) improved VAS score for decreased knee joint soreness following leg extension challenge for AyuFlex1 (P = 0.022) and AyuFlex2 (P = 0.043) relative to baseline, 5) improved 6-min walk performance distance covered (P = 0.047) and VAS discomfort (P = 0.026) post-6 min walk in AyuFlex1 + AyuFlex2 relative to baseline, 6) and tended to decrease COMP levels in AyuFlex1 + AyuFLex2 (P = 0.104) relative to baseline. All biomarkers of safety remained within normative limits during the study. Low back health tended to improve in the AyuFlex1 and AyuFlex2 group, but failed to reach significance relative to placebo group. CONCLUSIONS AyuFlex® improved mKOOS global scores, knee joint discomfort with activity/exercise, 6-min walk test distance covered and discomfort post-6 min walk test, overall whole-body joint function, knee soreness following leg extension resistance exercise in a healthy, overweight population, without AE. Differences between 250 mg/BID and 500 mg/BID were non-significant for most of the outcome measures, validating the efficacy of the lower dose. TRIAL REGISTRATION ClinicalTrials.gov identifier NCT02589249 ; October 26, 2015.