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Significant Changes in Serum MicroRNAs after High Tibial Osteotomy in Medial Compartmental Knee Osteoarthritis: Potential Prognostic Biomarkers.

ABSTRACT: High tibial osteotomy (HTO) is an effective alternative for medial compartmental knee osteoarthritis (OA). Circulating microRNAs (miRNAs) are known to serve as OA-related biomarkers. The present study investigated the differential expression of serum miRNAs before and after HTO to identify potential miRNAs as prognostic biomarkers. miRNA-polymerase chain reaction (PCR) arrays were used to screen for miRNAs in the serum at preoperative and 6-month postoperative time points from six patients, and the differentially expressed miRNAs identified in the profiling stage were validated using real-time PCR at post-operative months 6 and 18 in 27 other HTO-treated patients. Among 84 miRNAs involved in the inflammatory process, three (miR-19b-3p, miR-29c-3p, and miR-424-5p) showed differential expression patterns in the profiling stage (p = 0.011, 0.015, and 0.021, respectively). Levels of these three and four other miRNAs (miR-140-3p, miR-454-3p, miR-let-7e-5p, and miR-885-5p) known to be related to OA progression were evaluated in the serum of 27 patients. Only four miRNAs (miR-19b-3p, miR-140-3p, miR-454-3p, and miR-let-7e-5p) were significantly upregulated at postoperative month 6 (p = 0.003, 0.005, 0.004, and 0.004, respectively), and only miR-140-3p was significantly upregulated up to 18 months after operation (p = 0.003). Together, this study reveals the significantly upregulated serum miRNAs after HTO as potential prognostic biomarkers; however, further studies are warranted to elucidate their clinical implications.

SUBMITTER: Kwak YH

PROVIDER: S-EPMC7914593 | biostudies-literature | 2021 Feb

REPOSITORIES: biostudies-literature

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Significant Changes in Serum MicroRNAs after High Tibial Osteotomy in Medial Compartmental Knee Osteoarthritis: Potential Prognostic Biomarkers.

Kwak Yoon Hae YH Kwak Dae-Kyung DK Moon Hyun-Soo HS Kim Nan Young NY Yee Jae-Sung JS Yoo Je-Hyun JH

Diagnostics (Basel, Switzerland) 20210207 2

High tibial osteotomy (HTO) is an effective alternative for medial compartmental knee osteoarthritis (OA). Circulating microRNAs (miRNAs) are known to serve as OA-related biomarkers. The present study investigated the differential expression of serum miRNAs before and after HTO to identify potential miRNAs as prognostic biomarkers. miRNA-polymerase chain reaction (PCR) arrays were used to screen for miRNAs in the serum at preoperative and 6-month postoperative time points from six patients, and ...[more]

PMID: 33562261

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Project description:High tibial osteotomy (HTO) is a well-established treatment for medial compartmental knee osteoarthritis. Several microRNAs (miRNAs) are involved in osteoarthritis progression and are useful as osteoarthritis-related biomarkers. In this prospective study, we investigated differentially expressed microRNAs in the synovial fluid (SF) before and after HTO in patients with medial compartmental knee osteoarthritis to identify microRNAs that can be used as prognostic biomarkers. We used miRNA-PCR arrays to screen for miRNAs in SF samples obtained preoperatively and 6 months postoperatively from 6 patients with medial compartmental knee osteoarthritis who were treated with medial open wedge HTO. Differentially expressed miRNAs identified in the profiling stage were validated by real-time quantitative PCR in 22 other patients who had also been treated with HTO. All patients radiographically corresponded to Kellgren-Lawrence grade II or III with medial compartmental osteoarthritis. These patients were clinically assessed using a visual analogue scale and Western Ontario McMaster Universities scores. Mechanical axis changes were measured on standing anteroposterior radiographs of the lower limbs assessed preoperatively and at 6 months postoperatively. Among 84 miRNAs known to be involved in the inflammatory process, 14 were expressed in all SF specimens and 3 (miR-30a-5p, miR-29a-3p, and miR-30c-5p) were differentially expressed in the profiling stage. These 3 miRNAs, as well as 4 other miRNAs (miR-378a-5p, miR-140-3p, miR-23a-3p, miR-27b-3p), are related to osteoarthritis progression. These results were validated in the SF from 22 patients. Clinical and radiological outcomes improved after HTO in all patients, and only 2 miRNAs (miR-30c-5p and miR-23a-3p) were significantly differentially expressed between preoperative and postoperative 6-month SF samples (p = 0.006 and 0.007, respectively). Of these two miRNAs, miR-30c-5p correlated with postoperative pain relief. This study provides potential prognostic miRNAs after HTO and further investigations should be considered to determine clinical implications of these miRNAs.

Project description:BackgroundOsteoarthritis of knee is one of the important causes of knee pain in elderly patients and is a debilitating disease. It often leads to varus deformity of knee. Many treatment options are available for this progressive knee joint disorder. Proximal fibular osteotomy (PFO) is a novel yet simple procedure used to alleviate the symptoms of medial compartment knee osteoarthritis. The present study was undertaken to evaluate whether this procedure improves the symptoms, functions and limb alignment in patients with medial compartment knee osteoarthritis.MethodsFollowing approval by the Institutional Review Board, this prospective study included 42 cases (56 knees) with Kellgren-Lawrence grade II and III medial compartment knee osteoarthritis and underwent proximal fibular osteotomy. Clinical assessment was done by visual analogue scale (VAS) score and The Western Ontario and McMaster universities osteoarthritis Index (WOMAC) score pre-operatively and at 3, 6 and 12 months follow-up for pain and functional improvement. Radiological assessment was done by measuring femoro-tibial angles (FTA) pre-operatively and at 1 year follow-up.ResultsThe mean age was 58.30 years. There were 30 females and 12 males. The preoperative mean WOMAC score was 87.3, at 3 months follow-up it was 29.4 this was significantly better (p < 0.05) but the improvement was not significant at subsequent follow-up visits. Similarly the VAS scores also showed significant improvement at 3 months, but not at 6 and 12 months follow-up. There was no significant improvement in the femoro-tibial angle (FTA) at 1 year follow-up.ConclusionThe study highlights that both the VAS scores and WOMAC scores were significantly better at 3 months after surgery. However these did not show any significant improvement at 6 and 12 months. It does not change the alignment of knee at one year follow-up. The authors conclude that proximal fibular osteotomy provides only short-term relief in patients of medial compartment knee osteo-arthritis.

Project description:ObjectiveThe purpose of this study was to evaluate the usefulness of preoperative planning of the femurofibular angle (FFA) in medial open-wedge high tibial osteotomy (OWHTO) for mild medial knee osteoarthritis.MethodsThirty-two patients (32 knees) with mild medial knee OA were retrospectively reviewed. The patients underwent preoperative planning of the FFA for OWHTO. For preoperative planning, a full-length weight-bearing X-ray photograph of the lower limb was opened within Adobe Photoshop Software, and a targeted corrective mechanical axis line of the lower limb and its intersecting point at the lateral tibial plateau surface was drawn using rectangle selection and filling tools. A frame, which encircled the tibia and fibula, was created around the predicted osteotomy plane and then rotated until the ankle center was on the targeted mechanical axis line. Subsequently, a distal femoral condyle line and a proximal fibula axis line were drawn, and the angle between the two lines was measured and defined as the femurofibular angle (FFA). During biplane OWHTO, the preoperatively determined FFA was used to complete the correction of the mechanical axis. During follow-up, the postoperative mechanical weight-bearing line (WBL) of the lower limb, the mechanical femorotibial angle (mFTA), and the FFA were measured and compared with the preoperatively determined values.ResultsThe mechanical WBL shifted from a preoperative value of 25.36 ± 5.02% to a postoperative value of 56.19 ± 0.10% from the medial border along the mediolateral width of the tibial plateau, and it was 56.57 ± 0.08% at the final follow-up (P < 0.01). The preoperatively determined value was 56.25%, and no significant difference was found compared with postoperative week-one and final follow-up values (P > 0.05). The mFTA was corrected from a preoperative varus of 4.02 ± 0.63° to a postoperative week-one valgus of 2.37 ± 0.28°, and it had a valgus of 2.48 ± 0.39° at the final follow-up (P < 0.01). No significant difference in the valgus was found compared with the postoperative week-one, final follow-up and preoperatively determined valgus of 2.34 ± 0.26° (P > 0.05). The postoperative week-one and final follow-up FFAs were 90.34 ± 1.53° and 90.33 ± 1.52°, respectively, and no significant difference was found compared with the preoperatively determined value of 90.12 ± 1.72° and the intraoperative setting value of 90.25 ± 1.67° (P > 0.05). All corrected values were within the acceptable range of preoperative planning.ConclusionPreoperative planning of the FFA may be useful in OWHTO for patients with mild medial knee OA. Satisfactory correction of the postoperative targeted mechanical axis line of the lower limb can be obtained.

Project description:BackgroundHigh tibial osteotomy (HTO) has been used for over 60 years in clinical practice and mainly comprises two major techniques: closed wedge high tibial osteotomy (CWHTO) and open wedge high tibial osteotomy (OWHTO). However, these have been gradually replaced by total knee arthroplasty (TKA), due to inconsistent clinical results and many complications. With the concept of knee-protection and ladder treatment of osteoarthritis, as an effective minimally invasive treatment for knee osteoarthritis, HTO has once again received attention.MethodsA systematic literature search was conducted in PubMed, Embase, ClinicalKey, CNKI, and the China Wanfang database. The search terms relating to osteoarthritis and high tibial osteotomy were used. Studies were considered eligible if the participants were adults with knee osteoarthritis (KOA) who had undergone HTO. A total of two reviewers participated in the selection of the studies. Reviewer 1 was assigned to screen titles and abstracts, and reviewer 2 to screen full-text data. Data extraction was completed by reviewer 2, and 30% were checked by the research team. Potential conflicts were resolved through discussion. The methodological quality was assessed using a risk of bias, based on the Cochrane handbook and Newcastle-Ottawa assessment scale. The outcome indicators are (1) posterior slope of tibial plateau, (2) the height of the patella, (3) fracture in the osteotomy plane, (4) survival rate, (5) special surgery knee score (HSS), and (6) the recurrence of varus deformity of the included studies were evaluated according to the guidelines of the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) working group (Atkins et al., BMJ 328:1490, 2004).ResultsAmong the 18 articles included, 10 were prospective cohort studies, five were randomized controlled trial (RCT) studies, one was prospective comparative study (PCS), one was retrospective comparative study (RCS), and one was retrospective cohort. The earliest publication year was 1999, and the most recent was 2018. A total of 6555 eligible cases were included, comprised of 3351 OWHTO patients and 3204 CWHTO patients. Five RCT were assessed using risk of bias, based on the Cochrane handbook. Eleven cohort studies and two case-control studies were assessed using the Newcastle-Ottawa assessment scale. These six outcome indicators for a total of twenty-four evidence individuals were evaluated separately, among which the GRADE classification of 1, 2, and 6 was medium quality, and 3, 4, and 5 were low quality. Based on our systematic review, regardless of whether the chosen procedure was OWHTO or CWHTO, both HSS scores increased significantly as compared with the preoperative scores. Compared with CWHTO, the height of the patella and tibial posterior slope angle increased following OWHTO. Additionally, OWHTO has a better long-term survival rate and lower fracture rate, supporting OWHTO as the first treatment choice.ConclusionsFor young patients with knee osteoarthritis (KOA), high tibial osteotomy (HTO) can be considered as a treatment option to replace total knee arthroplasty (TKA) to reduce the economic burden and promote the reasonable allocation of medical resources. This study shows that compared with CWHTO, OWHTO has certain advantages in long-term survival rate and lower fracture rate, but the level of evidence is lower. In the future, we will need larger sample sizes and longer follow-up randomized controlled trials to improve our research.

Dataset Information

Significant Changes in Serum MicroRNAs after High Tibial Osteotomy in Medial Compartmental Knee Osteoarthritis: Potential Prognostic Biomarkers.

Publications

Significant Changes in Serum MicroRNAs after High Tibial Osteotomy in Medial Compartmental Knee Osteoarthritis: Potential Prognostic Biomarkers.

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