mobic and Osteoarthritis--Knee

To observe the effect of warm acupuncture combined with meloxicam and comprehensive nursing on pain improvement and joint function in patients with knee osteoarthritis.. Eighty-one patients with KOA were randomly divided into control group (CG), traditional Chinese medicine group (TCMG), and combined group (JG). The CG was treated with meloxicam. The TCMG received warm acupuncture treatment. The JG was treated with meloxicam combined with warm acupuncture. Three groups were given comprehensive nursing intervention, and the course of treatment was 4 weeks. Knee function was assessed by knee pain, activity, stability, walking ability, and ability to walk up and down stairs. Improvement time of clinical symptoms of patients was assessed from knee pain, swelling, and movement limitation. Pain mediators (prostaglandin E2 (PGE2), substance P (SP), dopamine (DA), 5-hydroxytryptamine (5-HT)) were detected by enzyme-linked immunosorbent assay (ELISA). Oxidative stress indicators (superoxide dismutase (SOD) and malondialdehyde (MDA)) of the enrolled patients were detected by water-soluble tetrazolium-1 (WST-1) and the thiobarbituric acid (TBA) method. The clinical efficacy was assessed by the visual analog scale (VAS) score.. After treatment, the pain scores of the three groups decreased, and the scores of mobility, stability, walking ability, and the ability to walk up and down stairs increased. Compared with the CG and the TCMG, the JG had a greater range of changes in pain, mobility, stability, walking ability, and ability to walk up and down stairs after treatment. After 7 d, 14 d, and 28 d treatment, PGE2, SP, DA, 5-HT, and MDA in the three groups were decreased compared with before treatment, and the decrease in the JG was more obvious than that in the CG and the TCMG. SOD levels in the three groups were increased, and the increase in the JG was more obvious than that in the CG and the TCMG. The total effective rate of the JG (96.30%) was significantly different from that of the CG (77.78%) and the TCMG (81.48%). The improvement time of knee pain, swelling, and movement limitation in the JG was shorter than that in the CG and the TCMG, and the difference in the improvement time of movement limitation in the TCMG was statistically significant.. Warm acupuncture combined with meloxicam and comprehensive nursing can effectively improve knee swelling and pain in patients with KOA, and the mechanism may be related to reducing the content of inflammatory mediators.

Topics: Acupuncture Therapy; Dinoprostone; Humans; Knee Joint; Meloxicam; Osteoarthritis, Knee; Pain; Serotonin; Superoxide Dismutase; Treatment Outcome

Meloxicam is commonly administrated to control postoperative pain in orthopedic surgery, while its efficacy in total knee arthroplasty (TKA) is not clear. Therefore, this study aimed to explore the postoperative analgesic effect and tolerance of meloxicam in knee osteoarthritis (OA) patients undergoing TKA.Totally, 128 knee OA patients scheduled for TKA were enrolled in this randomized, controlled, double-blind study, then randomized into meloxicam group (N = 65) and control group (N = 63) as 1:1 ratio. Patients took meloxicam or placebo from 4 hours (h) to 72 h after TKA. Patients were followed up at 6 h, 12 h, day (D)1, D2, D3, D7, month (M)1, and M3.Pain visual analog scale score at rest was decreased in meloxicam group at 12 h, D1 and D3 compared to control group; pain visual analog scale score at flexion was reduced in meloxicam group at 6 h, 12 h, D1, D2, and D3 compared to control group. Additional and total consumption of patient-controlled analgesia were both attenuated in meloxicam group compared to control group. Furthermore, patient satisfaction score was higher on D1, D2, D3 in meloxicam group compared to control group. However, no difference of hospital for special surgery knee score score at M1 or M3 was found between the 2 groups. Moreover, the occurrence of adverse events was similar between the 2 groups.Meloxicam displays good effect on controlling postoperative pain and improving patient satisfaction, while does not affect long-term knee function recovery or safety profile in knee OA patients undergoing TKA.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthroplasty, Replacement, Knee; Chi-Square Distribution; Double-Blind Method; Female; Humans; Male; Meloxicam; Middle Aged; Osteoarthritis, Knee; Pain Management; Pain Measurement; Recovery of Function

This study aimed to compare the efficacy and safety of pre-operative and post-operative meloxicam administration regarding post-operative pain control and knee joint function recovery in knee osteoarthritis (KOA) patients who underwent total knee arthroplasty (TKA).. Totally, 196 KOA patients who underwent TKA were consecutively enrolled and randomly assigned into pre-operative (N = 98) and post-operative administration group (N = 98) as 1:1 ratio. Pre-operative administration group received meloxicam 15 mg at 24 h pre-operation and 7.5 mg at 4 h, 24 h, 48 h, and 72 h post-operation, respectively. Post-operative administration group received meloxicam 15 mg at 4 h post-operation and 7.5 mg at 24 h, 48 h, and 72 h post-operation, respectively. Pain visual analog scale (VAS) at rest and at flexion, patient's global assessment (PGA), patient-controlled analgesia (PCA) consumption, hospital for special surgery (HSS), knee score, and adverse events were assessed.. Pre-operative meloxicam administration attenuated pain VAS score at rest at 6 h, 12 h, and 24 h; and pain VAS score at flexion at 6 h, 12 h, 24 h, and 48 h; as well as PGA score at 6 h, 12 h, 48 h post-TKA compared with post-operative meloxicam administration. Additional and total consumption of PCA were both decreased in pre-operative meloxicam administration group than post-operative meloxicam administration group, while HSS knee score at 3 months post-TKA was similar between pre-operative and post-operative meloxicam administration groups. Regarding safety, the incidence of adverse events was of no difference between the two groups.. Pre-operative administration of meloxicam might assist the post-operative pain management and care in KOA patients who underwent TKA.

Topics: Aged; Analgesics; Arthroplasty, Replacement, Knee; Female; Humans; Male; Meloxicam; Osteoarthritis, Knee; Pain, Postoperative; Postoperative Period; Preoperative Care; Recovery of Function

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly prescribed for knee osteoarthritis. However, they are associated with uncertain long-term clinical benefit and significant toxic effects.. To evaluate whether discontinuing NSAIDs and engaging in a telephone-based cognitive behavioral therapy (CBT) program is noninferior to continuing NSAIDs for patients with knee osteoarthritis.. The Stopping NSAIDs for Arthritis Pain multicenter randomized withdrawal trial was conducted for 364 patients taking NSAIDs for knee osteoarthritis pain on most days of the week for at least 3 months between September 1, 2013, and September 30, 2018. Analysis was performed on an intent-to-treat basis.. Participants discontinued their current NSAID and took 15 mg per day of meloxicam daily during a 2-week run-in period. Those who remained eligible were randomized in a 1:1 ratio to receive meloxicam or placebo for 4 weeks (blinded phase 1). Participants receiving meloxicam then continued this medication for 10 weeks, while those receiving placebo participated in a 10-week CBT program (unblinded phase 2).. The primary outcome measure was the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain score at 4 weeks with the noninferiority margin set at 1. Secondary outcomes included the area under the curve of the pain score after 4 weeks as well as the WOMAC pain score, area under the curve of the pain score, WOMAC disability score, and global impression of change after treatment at 14 weeks.. A total of 180 participants (161 men; mean [SD] age, 58. 2 [11.8] years) were randomized to receive placebo followed by CBT, and a total of 184 participants (154 men; mean [SD] age, 58.5 [10.0] years) were randomized to receive meloxicam. After adjustment for baseline pain and study site, the estimated mean difference in WOMAC pain score between the placebo and meloxicam groups after 4 weeks was 1.4 (95% CI, 0.8-2.0; noninferiority test P = .92). At week 14, the adjusted mean difference in WOMAC pain score between the placebo (followed by CBT) and meloxicam groups was 0.8 (95% CI, 0.2-1.4; noninferiority P = .28). There was no statistically significant difference in the global impression of change (mean difference in scores, -0.2; 95% CI, -0.4 to 0.1; P = .15) or lower extremity disability (mean difference in scores, 0.9; 95% CI, -1.4 to 3.2; P = .45) between the 2 groups after 14 weeks.. Among patients with knee osteoarthritis, placebo and CBT (after placebo) are inferior to meloxicam. However, the WOMAC pain score differences between the 2 groups were small, and there were no statistically significant differences in participants' global impression of change or function after 14 weeks.. ClinicalTrials.gov Identifier: NCT01799213.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Cognitive Behavioral Therapy; Double-Blind Method; Female; Humans; Male; Meloxicam; Middle Aged; Osteoarthritis, Knee; Pain Measurement; Telemedicine; Treatment Outcome

Objective To evaluate the efficacy and safety of adalimumab (ADA) versus hyaluronic acid (HA) by intra-articular injection for moderate to severe knee osteoarthritis. Methods Fifty-six consecutive patients with moderate to severe knee osteoarthritis were randomly allocated to either the ADA group or HA group. On day 0, patients in the ADA group received 10 mg of ADA by intra-articular injection, while those in the HA group received 25 mg of HA. All patients received celecoxib at 200 mg/day for 4 weeks. The pain visual analog scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Patient Global Assessment (PGA), and Physician Global Assessment (PhGA) scores were assessed. Results At baseline, the pain VAS, WOMAC, PGA, and PhGA scores were similar between the two groups. The decrease in the pain VAS score, WOMAC pain score, WOMAC physical function score, and WOMAC total score from baseline to week 4 were greater in the ADA than HA group. A greater decrease in the PGA and PhGA scores from baseline to week 4 was noted in the ADA than HA group. No difference in adverse events was observed between the two groups. Conclusion ADA by intra-articular injection was effective and tolerated for moderate to severe knee osteoarthritis.

Topics: Adalimumab; Aged; Antirheumatic Agents; Celecoxib; Diclofenac; Female; Humans; Hyaluronic Acid; Ibuprofen; Injections, Intra-Articular; Male; Meloxicam; Middle Aged; Osteoarthritis, Knee; Pain; Pain Measurement; Patient Safety; Pilot Projects; Severity of Illness Index; Thiazines; Thiazoles; Treatment Outcome

Knee osteoarthritis (OA) is the most common cause of knee pain in older adults. Despite the limited data supporting their use, non-steroidal anti-inflammatory drugs (NSAID) are among the most commonly prescribed medications for knee OA. The use of NSAIDs for knee pain warrants careful examination because of toxicity associated with this class of medications.. We describe the design of a placebo-controlled, noninferiority, randomized withdrawal trial to examine discontinuation of an NSAID in patients with painful knee OA. Participants will be veterans enrolled in the VA Healthcare System with knee OA pain despite NSAID use and/or relatively higher risk of NSAID toxicity. After a two-week run-in period where eligible subjects will replace their current NSAID with the study NSAID (meloxicam), those remaining eligible (target N=544) will be randomized to receive four weeks of either placebo or continued meloxicam. The primary outcome is knee pain (Western Ontario and McMaster Universities Osteoarthritis Index pain subscale, range 0-20) at four weeks post-randomization. The primary hypothesis is that placebo will be noninferior to (that is, not much worse than) meloxicam within a noninferiority margin of 1. Secondary outcomes include lower extremity disability, global impression of change, adherence to study medication and use of co-therapies.. This study is the first clinical trial to date examining the effects of withdrawing an NSAID for OA knee pain. If successful, this trial will provide evidence against the continued use of NSAIDs in patients with OA knee pain.. ClinicalTrials.gov: NCT01799213. Registered February 22, 2013.

Topics: Acetaminophen; Adult; Age Factors; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Disability Evaluation; Double-Blind Method; Equivalence Trials as Topic; Female; Humans; Male; Meloxicam; Middle Aged; Osteoarthritis, Knee; Pain Measurement; Patient Education as Topic; Research Design; Severity of Illness Index; Sex Factors; Social Support; Young Adult

Resveratrol shows remarkable anti-inflammatory activities in experimental models. This study aims to evaluate the effect of resveratrol, as an adjuvant with meloxicam (Mlx), on the pain and functional activity during a 90-day period and monitor the adverse effects on kidney and liver functions, lipid profile, and hematological markers.. This study was a double-blind, placebo-controlled, randomized multi-center study that involved 110 patients with knee osteoarthritis (OA) and was performed at Sulaimani City, Iraq, from December 2016 to September 2017. To assess the effects of Mlx with or without resveratrol, pain severity and functional disability were evaluated at baseline and after 90 days using the Western Ontario and McMaster Universities Osteoarthritis Index. Fasting blood was collected to evaluate the lipid profile markers, hematological picture, and liver and kidney functions, in addition to vitamin D level.. Resveratrol significantly improves pain, functions, and associated symptoms compared with placebo. The clinical and biochemical markers indicated that 500 mg/day of resveratrol, as an adjuvant with Mlx, is safe and well tolerated by the knee OA patients.. Resveratrol, as an "add-on" medication with Mlx, was superior in terms of safety and efficacy to Mlx alone for the treatment of pain and improvement of physical function in patients with knee OA.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthralgia; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Kidney Function Tests; Liver Function Tests; Male; Meloxicam; Middle Aged; Osteoarthritis, Knee; Pain Measurement; Pilot Projects; Resveratrol; Treatment Outcome

To compare the clinical efficacy on knee osteoarthritis (KOA) at the early and middle stage between electroacupuncture (EA) and meloxicam.. Ninety patients of KOA at the early and middle stage were randomized into an EA group and a meloxicam group, 45 cases in each one. In the EA group, EA was applied to Dubi (ST 35), Neixiyan (EX-LE 4), Liangqiu (ST 34), Heding (EX-LE 2), Xuehai (SP 10), Yan- glingquan (GB 34) and Zusanli (ST 36); the needles were retained for 20 min and EA was applied once every two days. In the meloxicam group, the meloxicam tablets were prescribed for oral administration, 7. 5 mg, once a day. The treatment lasted for 6 weeks in the two groups. The Western Ontario and McMaster University Osteoarthritis Index (WOMAC) score, rectus femoris muscle tension, the 8-foot walking test and 5-time sit-to-stand test were adopted to observe and compare the effects in the two groups.. After treatment, every item score in WOMAC was reduced after treatment (all P < 0.05), but the difference was not significant between the two groups (all P > 0.05). In the EA group, the rectus femoris tension after treatment was reduced as compared with that before treatment (P < 0.05) and the reducing result was much more apparent as compared with that in the meloxicam group (P < 0.05). For the 8-foot walking test and 5-time sit-to-stand test, the time was shortened after treatment in the two groups (all P < 0.05) and the result in the EA group was much more obvious than that in the meloxicam group (both P < 0.05).. Both EA and meloxicam are effective in the treatment of KOA at the early and middle stage. EA improves rectus femoris tension and recovers the internal mechanics balance and the efficacy is better than that of meloxicam.

Topics: Acupuncture Points; Adult; Aged; Electroacupuncture; Female; Humans; Male; Meloxicam; Middle Aged; Osteoarthritis, Knee; Thiazines; Thiazoles; Treatment Outcome

Nonsteroidal anti-inflammatory drugs (NSAIDs) such as meloxicam are commonly used to treat osteoarthritis (OA) but are associated with potentially serious dose-related adverse events (AEs). SoluMatrix meloxicam has been developed with the goal of enabling effective treatment at low doses. This phase 3 study evaluated the efficacy and safety of low-dose SoluMatrix meloxicam capsules 5 mg and 10 mg administered once daily for 12 weeks in patients with OA-related pain.. This randomized, double-blind study enrolled patients ≥40 years of age with confirmed hip or knee OA (Kellgren-Lawrence grade II-III) who were chronic users of NSAIDs and/or acetaminophen for OA pain and had Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain subscale mean scores ≥40 mm. Eligible patients experienced an OA pain flare (defined as a ≥15 mm increase in the WOMAC pain subscale score) following discontinuation of NSAIDs/acetaminophen. Patients were randomized to receive once-daily SoluMatrix meloxicam 5 mg or 10 mg, or placebo for 12 weeks. ClinicalTrials.gov identifier: NCT01787188.. The primary outcome measure was the mean change from baseline in WOMAC pain subscale score at week 12.. Low-dose SoluMatrix meloxicam 5 mg (-36.52 [2.49]; P = 0.0005) and 10 mg (-34.41 [2.68]; P = 0.0059) once-daily treatment significantly reduced the mean (standard error) WOMAC pain subscale score from baseline at week 12 compared with placebo (-25.68 [2.64]). Patients treated with SoluMatrix meloxicam 5 mg or 10 mg reported significantly greater improvements in total WOMAC score and in WOMAC stiffness and function subscale scores at 12 weeks compared with placebo. The most common AEs in the combined low-dose SoluMatrix meloxicam group were headache, diarrhea, nausea, osteoarthritis, and urinary tract infection.. Low-dose SoluMatrix meloxicam may have a potential role as a new therapeutic option for the management of OA-related pain.

Topics: Acetaminophen; Adult; Aged; Aged, 80 and over; Anti-Inflammatory Agents, Non-Steroidal; Double-Blind Method; Female; Humans; Male; Meloxicam; Middle Aged; Osteoarthritis, Hip; Osteoarthritis, Knee; Pain; Pain Measurement; Thiazines; Thiazoles; Treatment Outcome

Osteoarthritic pain is largely considered to be inflammatory pain. Sensory nerve fibers innervating the knee have been shown to be significantly damaged in rat models of knee osteoarthritis (OA) in which the subchondral bone junction is destroyed, and this induces neuropathic pain (NP). Pregabalin was developed as a pain killer for NP; however, there are no reports on pregabalin use in OA patients. The purpose of this study was to investigate the efficacy of pregabalin for pain in OA patients.. Eighty-nine knee OA patients were evaluated in this randomized prospective study. Patients were divided into meloxicam, pregabalin, and meloxicam+pregabalin groups. Pain scores were evaluated before and 4 weeks after drug application using a visual analogue scale (VAS), and Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Pain scales among groups were compared using a Kruskal-Wallis test.. Before drug application, there was no significant difference in VAS and WOMAC scores among the three groups (p>0.05). Significant pain relief was seen in the meloxicam+pregabalin group in VAS at 1, 2, and 4 weeks, and WOMAC score at 4 weeks, compared with the other groups (p<0.05). No significant pain relief was seen in the meloxicam only group in VAS during 4 weeks and WOMAC score at 4 weeks compared with the pregabalin only group (p>0.05).. Meloxicam+pregabalin was effective for pain in OA patients. This finding suggests that OA pain is a combination of inflammatory and NP.

Topics: Aged; Aged, 80 and over; Drug Therapy, Combination; Female; gamma-Aminobutyric Acid; Humans; Male; Meloxicam; Middle Aged; Osteoarthritis, Knee; Pain Measurement; Pregabalin; Thiazines; Thiazoles

To evaluate the clinical efficacy of treating knee osteoarthritis (KOA, Bi syndrome of knee) by massage combined Chinese materia medica (CMM) footbath fumigation and washing, and to observe the changes of the Lysholm knee score (LKSS).. Totally 61 patients with grade I to III KOA were randomly assigned to two groups, the treatment group and the control group. Patients in the treatment group were treated with massage combined CMM footbath fumigation and washing, while those in the control group were treated with oral administration of meloxicam. They were treated for 20 days (times). The LKSS was assessed before treatment, 10 days of treatment, by the end of the treatment, and 1 month after treatment.. (1) The therapeutic efficacy in the treatment group was superior to that in the control group (P < 0.05). Thirteen cases were clinically controlled, with 11 markedly effective, 6 effective, and 1 ineffective in the treatment group, while 5 cases were clinically controlled, with 11 markedly effective, 10 effective, and 4 ineffective in the control group. (2) The LKSS: The post-treatment LKSS was higher than that before treatment in the two groups. The LKSS at 10 days (times) of treatment was lower in the treatment group than in the control group, but with no statistical difference (P > 0.05). The LKSS by the end of the treatment was higher in the treatment group than in the control group (P < 0.05). (3) The case number of patients in need of receiving the treatment again within 1-month follow-up and the difference between the LKSS at follow-ups and that by the end of the treatment were lower in the treatment group than in the control group (P < 0.01).. Massage combined CMM footbath fumigation and washing had better clinical efficacy on patients suffering from KOA.

Topics: Balneology; Drugs, Chinese Herbal; Female; Humans; Male; Massage; Meloxicam; Middle Aged; Osteoarthritis, Knee; Thiazines; Thiazoles; Treatment Outcome

The efficacy, tolerance and ease of administration of a nutraceutical, carprofen or meloxicam were evaluated in a prospective, double-blind study on 71 dogs with osteoarthritis. The client-owned dogs were randomly assigned to one of the three treatments or to a placebo control group. The influence of osteoarthritis on the dogs' gait was described by comparing the ground reaction forces of the arthritic dogs and 10 normal dogs. Before the treatments began, and 30 and 60 days later, measurements were made of haematological and biochemical variables and of the ground reaction forces of the arthritic limb, and subjective assessments were made by the owners and by the orthopaedic surgeons. Changes in the ground reaction forces were specific to the arthritic joint, and were significantly improved by carprofen and meloxicam but not by the nutraceutical; the values returned to normal only with meloxicam. The orthopaedic surgeons assessed that there had been an improvement with carprofen and meloxicam, but the owners considered that there had been an improvement only with meloxicam. The blood and faecal analyses did not reveal any changes. The treatments were well tolerated, except for a case of hepatopathy in a dog treated with carprofen.

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Ascorbic Acid; Carbazoles; Chondroitin Sulfates; Chronic Disease; Dog Diseases; Dogs; Double-Blind Method; Gait; Glucosamine; Lameness, Animal; Manganese Compounds; Meloxicam; Osteoarthritis; Osteoarthritis, Hip; Osteoarthritis, Knee; Prospective Studies; Severity of Illness Index; Stifle; Thiazines; Thiazoles; Treatment Outcome

Our objective was to evaluate the efficacy, the gastroduodenal safety, and the effects on arachidonic acid products of meloxicam, a new acidic enolic non-steroidal anti-inflammatory drug which preferentially inhibits cyclo-oxygenase-2 over cyclo-oxygenase-1, versus piroxicam in patients with osteoarthritis of the knee. Meloxicam 7.5 mg or piroxicam 20 mg daily was administered for 4 weeks in this double-blind parallel-groups randomised study. The efficacy for pain relief of the two tested medications was assessed by means of visual analogue scale and other clinical parameters. Pre- and post-treatment endoscopies were performed, and the findings were scored and recorded. The gastric fluid was aspirated at each time and prostaglandin E2, thromboxane B2 and leukotriene B4 were determined by ELISA. There was no significant difference between the groups regarding the primary efficacy. Changes in endoscopic findings by means of Lanza score showed statistically significant differences between the two treatment groups in favour of meloxicam at all sites--gastric, duodenal and total. Within-group comparisons showed a statistically significant difference (worsening) in gastric and total score with piroxicam, but no significant difference with meloxicam. The frequency of clinically relevant cases (total score >2) also showed a statistically significant worsening in the piroxicam group. The better GI tolerability of meloxicam was also suggested by fewer adverse GI events and no withdrawals due to adverse events compared with piroxicam. The pre-/post-study gastric juice concentration of PGE2, TXB2, and LTB4 in the meloxicam group was 135.2 +/- 85.8/71.2 +/- 32.2, 116.3 +/- 81.7/99.4 +/- 107.5 and 388 +/- 321/223 +/- 98 pg/ml respectively. The pre-/post-study gastric juice concentration of PGE2, TXB2 and LTB4 in the piroxicam group was 105.7 +/- 43.1/68.2 +/- 34.9, 94.0 +/- 50.9/105.9 +/- 121.1 and 625 +/- 1574/828 +/- 1464 pg/ml, respectively. Both meloxicam and piroxicam significantly inhibited gastric PGE2 levels after 4 weeks' treatment; however, there was no difference between these two groups. Neither of these medications had an effect on TXB2. Only meloxicam inhibited LTB4 concentration significantly, and the between-groups difference was significant. Meloxicam 7.5 mg once daily had better gastrointestinal tolerability and an efficacy comparable to that of piroxicam 20 mg over 4 weeks in patients with osteoarthritis of the knee.

Topics: Adult; Aged; Arachidonic Acid; Cyclooxygenase Inhibitors; Digestive System; Dinoprostone; Double-Blind Method; Endoscopy, Digestive System; Female; Gastric Juice; Humans; Leukotriene B4; Male; Meloxicam; Middle Aged; Osteoarthritis, Knee; Pain; Pain Measurement; Piroxicam; Safety; Thiazines; Thiazoles; Thromboxane B2

Meloxicam (MLX) is prescribed for the management of pain and inflammation allied with osteoarthritis (OA). However, MLX causes intestinal damage in long term administration. Hence, meloxicam loaded emulgel (MLX-emulgel) was optimized, formulated and examined under stringent parameters in monosodium-iodoacetate (MIA) induced knee OA in Wistar rats.. Nanoemulsion of MLX was fabricated by ultrasonication and microfluidization method with a droplet size of 66.81 ± 5.31-nm and zeta potential of -24.6 ± 0.72-mV. Further, MLX nanoemulsion was optimized with centrifugation, heating-cooling cycles and transmittance parameters in addition to scale-up feasibility with microfluidizer. Post optimization, MLX-nanoemulsion was tailored as emulgel with Carbopol Ultrez 10 NF and assessed for pH, rheology, textural properties, assay and stability features. The in-vitro release study revealed the Korsmeyer-Peppas release kinetics and ex-vivo skin permeation was improved by 6.71-folds. The skin distribution of MLX-emulgel evinced the transfollicular mode of permeation. In-vivo study indicated the protective action of MLX-emulegl expressed in terms of inflammatory cyctokines level, X-ray analysis of knee joints of rats, histopathology and OARSI (Osteoarthritis Research Society International) scoring. MLX-emulgel treated group displayed lower (P < 0.001) level of COX-2 intensity as compared to positive control group. However, it was comparable (P > 0.05) to the normal control group, MLX oral dispersion, i.v. solution and etoricoxib gel groups. MLX-emulgel showcased an alternative to the long term usage of analgesics for relieving the symptoms of knee OA.. MLX-emulgel may be a potential candidate for translating in to a clinically viable dosage form in the management of knee OA.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Meloxicam; Osteoarthritis, Knee; Rats; Rats, Wistar; Skin

Background Osteoarthritis (OA) is a chronic disease in the joints. One of the proinflammatory cytokines that is thought to have a major role in the inflammatory process, the emergence of pain, and cartilage damage in OA is tumor necrosis factor α (TNF-α). Meloxicam is a nonsteroidal anti-inflammatory drug class of drugs that is relatively selective in inhibiting the activity of cyclooxygenase 2 (COX-2) formation. This study is conducted to prove the change in TNF-α level in the use of meloxicam with model in animals suffering from OA. Methods The OA rat model was induced with sodium monoiodoacetate intra-articularly. Rats were divided into 5 groups: negative control group, positive control group, and treatment groups with various doses of meloxicam. Hyperalgesia effect was evaluated using a warm plate test, and TNF-α level was determined using enzyme-linked immunosorbent assay. Results The treatment groups that received meloxicam at a dose of 1.0, 3.0, or 10.0 mg/kg body weight (BW) did not show significant differences in rat knee joint diameter (p = 0.99), but showed a significant difference in sensitivity to heat stimulation (p = 0.02) compared to the control group. Osteoarthritis rats experienced a significant reduction in TNF-α level after being given meloxicam at a dose of 10 mg/kg BW compared with the control group. This shows that the 10 mg/kg BW of meloxicam is a potential dose in reducing the TNF-α level in OA rat models. Conclusions Based on these data, it can be concluded that the inhibition of pain and the development of OA by meloxicam in animal models may be assigned to a decreased level of TNF-α.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Disease Models, Animal; Dose-Response Relationship, Drug; Hyperalgesia; Iodoacetic Acid; Male; Meloxicam; Osteoarthritis, Knee; Rats; Tumor Necrosis Factor-alpha

We aimed to examine whether the current users of specific NSAIDs have an increased risk of venous thromboembolism (VTE) among knee OA patients.. We conducted a population-based case-control study using The Health Improvement Network, a database of patient records from general practices in the UK. For every VTE case, we identified five controls matched on age, sex and calendar year of study enrolment. We used conditional logistic regression to assess the association between current use of specific NSAIDs and risk of VTE relative to remote NSAID users.. Among knee OA patients with at least one NSAID prescription, we identified 4020 incident cases of VTE and 20 059 matched controls. Adjusted odd ratios (ORs) relative to the remote users were 1.38 (95% CI: 1.32, 1.44) for recent users and 1.43 (95% CI: 1.36, 1.49) for current users. Among the current NSAID users, the risk of VTE was increased with diclofenac [OR 1.63 (95% CI: 1.53, 1.74)], ibuprofen [OR = 1.49 (95% CI: 1.38, 1.62)], meloxicam [OR = 1.29 (95% CI: 1.11, 1.50)] and coxibs [celecoxib, OR = 1.30 (95% CI: 1.11, 1.51); rofecoxib, OR = 1.44 (95% CI: 1.18, 1.76)]; naproxen did not increase VTE risk [OR = 1.00 (95% CI: 0.89, 1.12)].. Compared with the remote users of NSAIDs, the risk of VTE increased for current users of diclofenac, ibuprofen, meloxicam, and coxibs, but not for naproxen, in the knee OA population. Clinicians should consider the risk profile for specific NSAIDs when recommending their use.

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Case-Control Studies; Cyclooxygenase 2 Inhibitors; Diclofenac; Female; Humans; Ibuprofen; Lactones; Logistic Models; Male; Meloxicam; Middle Aged; Naproxen; Odds Ratio; Osteoarthritis, Knee; Risk Factors; Sulfones; Thiazines; Thiazoles; Treatment Outcome; United Kingdom; Venous Thromboembolism

Topics: Aged; Anti-Inflammatory Agents, Non-Steroidal; Antihypertensive Agents; Drug Interactions; Humans; Hypertension; Lisinopril; Male; Meloxicam; Middle Aged; Osteoarthritis, Knee; Pain Management; Renal Insufficiency; Thiazines; Thiazoles

Develop a sensitive, functional biomarker of persistent joint pain in a large animal model of experimental osteoarthritis. Evaluate Impulse Ratio as a measure of weight distribution among supporting limbs throughout the early natural history of osteoarthritis and with local anaesthesia and analgesia.. The distribution of weight bearing in the trot of 11 skeletally-mature dogs was analyzed before and after unilateral surgical intervention (cranial cruciate transection or distal femoral focal impact). The short-term effects of two analgesic treatments (intra-articular lidocaine and intra-dermal meloxicam) were then evaluated as an index of pain relief based on the redistribution of weight-bearing impulse between normal and injured limbs.. Impulse Ratio was able to resolve weight redistribution between limbs in both long-term (weekly for over 400 days) and short-term (15 min intervals) joint evaluations. Joint pain relief from lidocaine administration could be reliably tracked over its brief acting time course. Meloxicam administration resulted in ambiguous results, where average weight bearing in the injured limb did not increase, but the variability of limb use changed transiently and reversibly.. Joint function and the role of persistent joint pain in the development of osteoarthritis can be investigated effectively and efficiently in a large animal model through the use of Impulse Ratio. Impulse Ratio can be a functionally relevant and sensitive biomarker of locomotion-related joint pain.

Topics: Anesthetics, Local; Animals; Anterior Cruciate Ligament Injuries; Anti-Inflammatory Agents, Non-Steroidal; Arthralgia; Arthritis, Experimental; Biomarkers; Disease Models, Animal; Dogs; Female; Femoral Fractures; Gait; Injections, Intra-Articular; Injections, Intradermal; Lidocaine; Male; Meloxicam; Osteoarthritis, Knee; Pilot Projects; Thiazines; Thiazoles; Weight-Bearing

To study the effect of intra-articular injection of meloxicam (Mobic) on the development of osteoarthritis (OA) in rats and examine concomitant changes in nociceptive behavior and the expression of mitogen-activated protein kinases (MAPKs) in articular cartilage chondrocytes.. OA was induced in Wistar rats by right anterior cruciate ligament transection (ACLT); the left knee was not treated. The OA + meloxicam (1.0 mg) group was injected intra-articularly in the ACLT knee with 1.0 mg of meloxicam once a week for 5 consecutive weeks starting 5 weeks after ACLT. The OA + meloxicam (0.25 mg) group was treated similarly with 0.25 mg meloxicam. The sham group underwent arthrotomy only and received vehicle of 0.1 mL sterile 0.9% saline injections, whereas the naive rats in meloxicam-only groups were treated similarly with 1.0- and 0.25-mg meloxicam. Nociception was measured as secondary mechanical allodynia and hind paw weight-bearing distribution at before (pre-) and 5, 10, 15, and 20 weeks post-ACLT. Histopathology of the cartilage and synovia was examined 20 weeks after ACLT. Immunohistochemical analysis was performed to examine the effect of meloxicam on MAPKs (p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK)) expression in the articular cartilage chondrocytes.. OA rats receiving intra-articular meloxicam treatment showed significantly less cartilage degeneration and synovitis than saline-treated controls. Nociception were improved in the OA + meloxicam groups compared with the OA group. Moreover, meloxicam attenuated p38 and JNK but enhanced ERK expression in OA-affected cartilage.. Intra-articular injection of meloxicam (1) attenuates the development of OA, (2) concomitantly reduces nociception, and (3) modulates chondrocyte metabolism, possibly through inhibition of cellular p38 and JNK, but enhances ERK expression.

Topics: Animals; Anterior Cruciate Ligament Injuries; Arthritis, Experimental; Cartilage, Articular; Chondrocytes; Cyclooxygenase 2 Inhibitors; Extracellular Signal-Regulated MAP Kinases; Injections, Intra-Articular; JNK Mitogen-Activated Protein Kinases; Meloxicam; Mitogen-Activated Protein Kinases; Nociception; Osteoarthritis, Knee; p38 Mitogen-Activated Protein Kinases; Rats; Rats, Wistar; Synovial Membrane; Thiazines; Thiazoles

To determine whether treatment with an antiresorptive drug in combination with an antiinflammatory drug reduces periarticular bone and soft tissue adaptations associated with the progression of posttraumatic secondary osteoarthritis (OA).. We used in vivo microfocal computed tomography (micro-CT) to map bony adaptations and in vivo micro-magnetic resonance imaging (micro-MRI) to examine joint inflammation in a rat model of surgically induced OA secondary to knee triad injury. We examined the arthroprotective effects of the bisphosphonates alendronate and risedronate and the nonsteroidal antiinflammatory drug (NSAID) meloxicam.. Micro-CT revealed reduced levels of periarticular trabecular bone loss in animals with knee triad injury treated with the bisphosphonate drugs alendronate or risedronate, or the NSAID meloxicam, compared with untreated animals. Alendronate treatment reduced bony osteophyte development. While risedronate as a monotherapy did not positively impact osteophytogenesis, combination therapy with risedronate and meloxicam reduced osteophyte severity somewhat. Micro-MRI revealed an increased, diffuse water signal in the epiphyses of untreated rats with knee triad injury 8 weeks after surgery, suggestive of a bone marrow lesion-like stimulus. In contrast, meloxicam-treated rats showed a significant reduction in fluid signal compared with both bisphosphonate-treated groups 8 weeks after surgery. Histologic analysis qualitatively confirmed the chondroprotective effect of both bisphosphonate treatments, showing fewer degradative changes compared with untreated rats with knee triad injury.. Our findings indicate that select combinations of bisphosphonate and NSAID drug therapy in the early stages of secondary OA preserve trabecular bone mass and reduce the impact of osteophytic bony adaptations and bone marrow lesion-like stimulus. Bisphosphonate and NSAID therapy may be an effective disease-modifying drug regimen if administered early after the initial injury.

Topics: Alendronate; Animals; Anti-Inflammatory Agents, Non-Steroidal; Bone Density Conservation Agents; Disease Models, Animal; Drug Therapy, Combination; Epiphyses; Etidronic Acid; Female; Femur; Magnetic Resonance Imaging; Meloxicam; Osteoarthritis, Knee; Osteophyte; Rats; Rats, Sprague-Dawley; Risedronic Acid; Stifle; Thiazines; Thiazoles; Tibia; Tomography, X-Ray Computed; Water

Topics: Anti-Inflammatory Agents, Non-Steroidal; Clinical Trials as Topic; Cyclooxygenase Inhibitors; Diarrhea; Dose-Response Relationship, Drug; Drug Interactions; Humans; Meloxicam; Nausea; Osteoarthritis; Osteoarthritis, Hip; Osteoarthritis, Knee; Thiazines; Thiazoles