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Abstract Background Osteoporosis has been recognized as a significant health issue in Thailand. Pharmacological interventions are important way to prevent fracture. However, one of the main challenges in selecting a medication is high cost, particularly for brand-name drugs. Data on generic bisphosphonate use in Thai are still lacking. Therefore, our study aimed to assess the efficacy and safety of generic risedronate in postmenopausal Thai women with osteoporosis. Methods This prospective study was conducted at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, from December 2022 to January 2024. Serum C-terminal cross-linking telopeptide of type I collagen (CTX) and procollagen type I N-propeptide (P1NP) were measured at baseline. All participants subsequently received 35 milligrams of oral risedronate once weekly for 52 weeks. Serum CTX and P1NP were remeasured at different time points. BMD was reevaluated at 52 weeks after risedronate treatment initiation. Results A total of 80 participants were included. The mean age was 65.2 ± 6.6 years. The mean body mass index (BMI) was 23.45 ± 3.49 kg/m2. The median (IQR) serum CTX level at 12 weeks was significantly lower than that at baseline (0.28 (0.16–0.46) ng/mL versus 0.44 (0.26–0.64) ng/mL, respectively; p value

Abstract In osteoarthritis (OA), extracellular matrix (ECM) digestion by cartilage-degrading enzymes drives cartilage destruction and generates ECM fragments, such as proteoglycan aggrecan (PG) peptides. PG peptides have been shown to induce immunological functions of chondrocytes. However, the role of PG peptides in stimulating catabolic mediators from chondrocytes has not been investigated. Therefore, we aim to determine the effects and its mechanism by which PG peptides induce chondrocytes to produce catabolic mediators in OA. Human chondrocytes were stimulated with IFNγ and various PG peptides either (i) with or (ii) without TLR2 blockade or (iii) with Lactobacillus species-conditioned medium (LCM), a genus of bacteria with anti-inflammatory properties. Transcriptomic analysis, cartilage-degrading enzyme production and TLR2-intracellular signaling activation were investigated. Chondrocytes treated with PG peptides p16-31 and p263-280 increased expression levels of genes associated with chondrocyte hypertrophy, cartilage degradation and proteolytic enzyme production. TLR2 downstream signaling proteins (STAT3, IkBα and MAPK9) were significantly phosphorylated in p263-280 peptide-stimulated chondrocytes. MMP-1 and ADAMTS-4 were significantly reduced in p263-280 peptides-treated condition with TLR2 blockade or LCM treatment. Phosphorylation levels of IkBa, ERK1/2 and MAPK9 were significantly decreased with TLR2 blockade, but only phosphorylation levels of MAPK9 was significantly decreased with LCM treatment. Our study showed that PG peptide stimulation via TLR2 induced cartilage-degrading enzyme production via activation of MAPK, NFκB and STAT3 pathways.

ObjectivesIn knee osteoarthritis (OA), macrophages are the most predominant immune cells that infiltrate synovial tissues and infrapatellar fat pads (IPFPs). Both M1 and M2 macrophages have been described, but their role in OA has not been fully investigated. Therefore, we investigated macrophage subpopulations in IPFPs and synovial tissues of knee OA patients and their correlation with disease severity, examined their transcriptomics, and tested for factors that influenced their polarization.MethodsSynovial tissues and IPFPs were obtained from knee OA patients undergoing total knee arthroplasty. Macrophages isolated from these joint tissues were characterized via flow cytometry. Transcriptomic profiling of each macrophage subpopulations was performed using NanoString technology. Peripheral blood monocyte-derived macrophages (MDMs) were treated with synovial fluid and synovial tissue- and IPFP-conditioned media. Synovial fluid-treated MDMs were treated with platelet-rich plasma (PRP) and its effects on macrophage polarization were observed.ResultsOur findings show that CD11c+CD206+ macrophages were predominant in IPFPs and synovial tissues compared to other macrophage subpopulations (CD11c+CD206-, CD11c-CD206+, and CD11c-CD206- macrophages) of knee OA patients. The abundance of macrophages in IPFPs reflected those in synovial tissues but did not correlate with disease severity as determined from Mankin scoring of cartilage destruction. Our transcriptomics data demonstrated highly expressed genes that were related to OA pathogenesis in CD11c+CD206+ macrophages than CD11c+CD206-, CD11c-CD206+, and CD11c-CD206- macrophages. In addition, MDMs treated with synovial fluid, synovial tissue-conditioned media, or IPFP-conditioned media resulted in different polarization profiles of MDMs. IPFP-conditioned media induced increases in CD86+CD206+ MDMs, whereas synovial tissue-conditioned media induced increases in CD86+CD206- MDMs. Synovial fluid treatment (at 1:8 dilution) induced a very subtle polarization in each macrophage subpopulation. PRP was able to shift macrophage subpopulations and partially reverse the profiles of synovial fluid-treated MDMs.ConclusionOur study provides an insight on the phenotypes and genotypes of macrophages found in IPFPs and synovial tissues of knee OA patients. We also show that the microenvironment plays a role in driving macrophages to polarize differently and shifting macrophage profiles can be reversed by PRP.

Introduction Genicular nerve blocks (GNBs) are an emerging technique that have been used as a part of multimodal analgesia for total knee arthroplasty. The efficacy of intraoperative landmark-based GNBs, a recently introduced technique, has been established. We hypothesized that it would provide non-inferior postoperative analgesia compared with periarticular infiltration (PAI) when combined with continuous adductor canal block. Methods This study randomized 140 patients undergoing total knee arthroplasty to receive either intraoperative landmark-based GNB (GNB group) or PAI (PAI group), with 139 completing the study. The primary outcomes were the pain scores at rest and during movement at 12 hours postoperatively on an 11-point Numerical Rating Scale; the non-inferiority margin was 1. Pain scores at additional time points, intravenous morphine consumption, time to first rescue analgesia, functional performance and muscle strength tests, and sleep disturbance were also assessed. Results At 12 hours postoperatively, the PAI and GNB groups had median resting pain scores of 0 (0-2) and 0 (0-2), respectively. The median difference was 0 (95% CI -0.4 to 0.4, p=1), with the 95% CI upper limit below the prespecified non-inferiority margin. The median pain score during movement was 1.5 (0-2.3) and 2 (1-3.1) in the PAI and GNB groups, respectively. The median difference was 0.9 (95% CI 0.3 to 1.6, p=0.004), failing to demonstrate non-inferiority. The GNB group had higher intravenous morphine consumption at 12 hours postoperatively and a shorter time to first rescue analgesia. Conclusions GNB compared with PAI provides non-inferior resting pain relief. Non-inferiority was not established for pain during movement. Trial registration number TCTR20220406001 (www.thaiclinicaltrials.org). [ABSTRACT FROM AUTHOR]