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This is a prospective randomized double-blind controlled clinical trial with parallel arms and 1:1 allocation.
The main objective of the BIOMAT project is to demonstrate, through an RCT, whether the combined approach by knee osteotomy and MAT can provide clinical improvement over knee osteotomy alone for the treatment of patients with monocompartmental knee OA associated with meniscal insufficiency and lower extremity malalignment. Secondary objectives are to demonstrate whether the addition of MAT to knee osteotomy in patients with monocompartmental OA can improve biomechanical parameters and whether this treatment has protective effects on the joint environment and cartilage degeneration.
Patients with single-compartment arthritic pathology of the knee, axial deviation and meniscal deficit, for whom a surgical indication of corrective osteotomy is placed, will be recruited into the study.
Enrollment takes place during hospitalization and is by the physician. All patients will undergo a knee osteotomy to achieve proper alignment of the lower limb and an arthroscopic procedure to macroscopically verify the status of the cartilage and menisci, with associated minor procedures for surgical cleanup when necessary. After intraoperative confirmation of inclusion criteria (complete meniscal deficit and absence of severe articular cartilage impairment) all patients will undergo synovial biopsy and synovial fluid sampling, half of the patients will also undergo arthroscopic homologous meniscus transplantation.
Clinical, biomechanical and biological evaluations will be performed:
Clinical evaluation of the patient will be done through validated questionnaires before surgery and at 1-3-6-12 months. These will document subjective clinical improvement, functional measurements, and imaging using radiographs as per clinical practice and MRI.
Pitch Analysis will be used for biomechanical assessments, and will be performed before surgery and at 12-month follow-up after surgery for all patients enrolled in the two groups.
basal inflammation will be assessed on synovial tissue and synovial fluid samples collected after intraoperative confirmation of patient inclusion criteria (complete meniscal deficit and absence of severe articular cartilage impairment). Serum/plasma and urine samples will be collected before surgical treatment and at 1-3-6-12 months follow-up.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Knee Ostetomy combined with meniscal allograft transplantation | Experimental | The treatment group will perform osteotomy and meniscal allograft transplantation to restore the meniscal deficiency. |
|
| Knee Osteotomy | Active Comparator | The control group will consist of patients who will perform an isolated osteotomy. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Knee osteotomy associated with meniscal allograft transplantation | Procedure | Patients will undergo knee osteotomy associated with meniscal allograft transplantation, which will be implanted by arthroscopic technique with body fixation by all-inside and transosseous sutures to the posterior horn and if necessary to the anterior horn. |
| Measure | Description | Time Frame |
|---|---|---|
| IKDC-Subjective Score (Subjective International Knee Documentation Committee) | This is a subjective, knee-specific rating scale that is considered one of the most reliable assessment tools in the evaluation of knee pathology. The questionnaire examines 3 categories: symptoms, sports activity, and knee function | 12 months follow-up |
| Measure | Description | Time Frame |
|---|---|---|
| IKDC-Subjective Score (Subjective International Knee Documentation Committee) | This is a subjective, knee-specific rating scale that is considered one of the most reliable assessment tools in the evaluation of knee pathology. The questionnaire examines 3 categories: symptoms, sports activity, and knee function | baseline, 1 month, 3 months and 6months follow-up |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Role | Phone | Extension | |
|---|---|---|---|---|
| Alessandro Di Martino, MD | Contact | 6366567 | 051 | roberta.licciardi@ior.it |
| Roberta Licciardi, MSc | Contact | 6366567 | 051 | roberta.licciardi@ior.it |
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| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Istituto Ortopedico Rizzoli | Recruiting | Bologna | 40136 | Italy |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 34239195 | Background | Nicolini AP, Christiano ES, Abdalla RJ, Cohen M, de Carvalho RT. Return to Sports After High Tibial Osteotomy Using the Opening Wedge Technique. Rev Bras Ortop (Sao Paulo). 2021 Jun;56(3):313-319. doi: 10.1055/s-0040-1715514. Epub 2020 Sep 25. | |
| 31169641 | Background | McClure PK, Herzenberg JE. The Natural History of Lower Extremity Malalignment. J Pediatr Orthop. 2019 Jul;39(Issue 6, Supplement 1 Suppl 1):S14-S19. doi: 10.1097/BPO.0000000000001361. |
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We will be able to share a subset of aggregated data, wich will not allow for the identification of participants.
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| ID | Term |
|---|---|
| D017760 | Bone Malalignment |
| D020370 | Osteoarthritis, Knee |
| ID | Term |
|---|---|
| D001847 | Bone Diseases |
| D009140 | Musculoskeletal Diseases |
| D010003 | Osteoarthritis |
| D001168 | Arthritis |
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Parallel Assignment
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Clinical evaluations will be carried out by medical personnel not involved in treatment to ensure double-blinding
|
| Knee osteotomy | Procedure | Knee osteotomy |
|
| WOMAC (Western Ontario and McMaster Universities Osteoarthritis Index) score | It's a standardized and widely used questionnaire to assess the condition of patients with knee OA and includes assessment of pain, stiffness and physical function of the joints. It can be administered to the patient. It measures 5 items for pain (range 0-20), two for stiffness (range 0-8), and 17 for functional limitation (range 0-68) that mainly relate to activities of daily living (e.g., getting up from a sitting position, bending over, going up and down stairs etc.); the score is then normalized on a 0-100 scale. Higher values indicated a worse outcome. | baseline, 1 month, 3 months, 6 months and 12 months follow-up |
| KOOS Score ( Knee Injury and Osteoarthritis Outcome score) | The full questionnaire consists of five subscales and they cover: pain (9 items), symptoms (7 items of which two relate to stiffness), functions and activities of daily living (17 items) physical function, sports activities and leisure (5 items) and quality of life in relation to the knee (4 items). All items in the relevant subscales have the same response mode, use a 5-point Likert scale, and each question is assigned a score from 0 to 4, where 0 indicates "no difficulty" and 4 "a severe difficulty). Score range 0-100 for each subscale | baseline, 1 month, 3 months, 6 and 12 months follow-up |
| VAS-dolore (Visual Analogue Scale) | Visual analog scale consisting of a straight line segment (10 cm length), the ends of which correspond to "no pain" and "the strongest pain imaginable." | baseline, 1 month, 3 months, 6 and 12 months follow-up |
| EQ-VAS | Visual analog scale consisting of a straight line segment (10 cm length), the ends of which correspond to "no pain" and "the strongest pain imaginable." | baseline, 1 month, 3 months, 6 and 12 months follow-up |
| Tegner Activity Level Scale | It is a questionnaire to find out the patient's level of physical activity. | baseline, 1 month, 3 months, 6 and 12 months follow-up |
| Final treatment opinion | The patient should indicate satisfaction and relative degree with treatment at the end of the clinical trial (24 months follow-up). All patients will be able to indicate their health condition by choosing from this answers; "Full recovery", "much better", "somewhat better", "no change", "a little worse", "much worse". | 6 and 12 months follow-up |
| WORMS (Whole-Organ Magnetic Resonance Imaging Score) | It's a semiquantitative, multifunctional scoring method for knee assessment applicable to conventional MRI techniques. | baseline, 12 months follow-up |
| Kellgren-Lawrence score | The Kellgren Lawrence scale classifies knee OA into 4 grades of subsequent greater severity, the parameters used being reduced joint space and the presence of osteophytes | baseline, 1 month, 6 months, 12 months follow-up. |
| Biomechanical analysis | Collection of three-dimensional spatial motion data using a 9-camera stereophotogrammetric system combined with wireless 16-channel electromyograph and two force platforms for monitoring foot-ground reaction force. The acquired data will be used to estimate joint rotations and moments, spatiotemporal data, electromyography, and dynamometric data. | baseline, 12 months follow-up |
| Biological assessments | Synovial tissue and fluid samples will be collected after intraoperative confirmation of patient inclusion criteria (complete meniscal deficit and absence of severe articular cartilage impairment). Synovial tissue will be fixed, included and analyzed by immunohistochemistry methods for synovitis analysis using a standardized synovitis analysis score (IMSYC). Synovial fluid will be divided into aliquots and stored at -80°C. Inflammatory factors will be analyzed by enzyme immunoassays. Serum/plasma and urine samples will be collected from all patients included in the study at the indicated time points. | Baseline (pre-operative), 24 hours, 1 month, 3 months, 6 months, 12 months |
| 32953923 | Background | Smoak JB, Matthews JR, Vinod AV, Kluczynski MA, Bisson LJ. An Up-to-Date Review of the Meniscus Literature: A Systematic Summary of Systematic Reviews and Meta-analyses. Orthop J Sports Med. 2020 Sep 9;8(9):2325967120950306. doi: 10.1177/2325967120950306. eCollection 2020 Sep. |
| 31079771 | Background | Liu JN, Agarwalla A, Gomoll AH. High Tibial Osteotomy and Medial Meniscus Transplant. Clin Sports Med. 2019 Jul;38(3):401-416. doi: 10.1016/j.csm.2019.02.006. |
| 32011458 | Background | Wang K, Sun H, Zhang K, Li S, Wu G, Zhou J, Sun X. Better outcomes are associated with cementless fixation in primary total knee arthroplasty in young patients: A systematic review and meta-analysis of randomized controlled trials. Medicine (Baltimore). 2020 Jan;99(3):e18750. doi: 10.1097/MD.0000000000018750. |
| 15224164 | Background | Sheng P, Lehto M, Kataja M, Halonen P, Moilanen T, Pajamaki J. Patient outcome following revision total knee arthroplasty: a meta-analysis. Int Orthop. 2004 Apr;28(2):78-81. doi: 10.1007/s00264-003-0526-x. Epub 2003 Nov 20. |
| 27387307 | Background | Huizinga MR, Gorter J, Demmer A, Bierma-Zeinstra SMA, Brouwer RW. Progression of medial compartmental osteoarthritis 2-8 years after lateral closing-wedge high tibial osteotomy. Knee Surg Sports Traumatol Arthrosc. 2017 Dec;25(12):3679-3686. doi: 10.1007/s00167-016-4232-9. Epub 2016 Jul 7. |
| 27655985 | Background | Ekhtiari S, Haldane CE, de Sa D, Simunovic N, Musahl V, Ayeni OR. Return to Work and Sport Following High Tibial Osteotomy: A Systematic Review. J Bone Joint Surg Am. 2016 Sep 21;98(18):1568-77. doi: 10.2106/JBJS.16.00036. |
| 34242204 | Background | Murray R, Winkler PW, Shaikh HS, Musahl V. High Tibial Osteotomy for Varus Deformity of the Knee. J Am Acad Orthop Surg Glob Res Rev. 2021 Jul 9;5(7):e21.00141. doi: 10.5435/JAAOSGlobal-D-21-00141. |
| 32055878 | Background | Berruto M, Maione A, Tradati D, Ferrua P, Uboldi FM, Usellini E. Closing-wedge high tibial osteotomy, a reliable procedure for osteoarthritic varus knee. Knee Surg Sports Traumatol Arthrosc. 2020 Dec;28(12):3955-3961. doi: 10.1007/s00167-020-05890-0. Epub 2020 Feb 13. |
| 29792399 | Background | De Bruycker M, Verdonk PCM, Verdonk RC. Meniscal allograft transplantation: a meta-analysis. SICOT J. 2017;3:33. doi: 10.1051/sicotj/2017016. Epub 2017 Apr 21. |
| 26860105 | Background | Zaffagnini S, Grassi A, Marcheggiani Muccioli GM, Benzi A, Serra M, Rotini M, Bragonzoni L, Marcacci M. Survivorship and clinical outcomes of 147 consecutive isolated or combined arthroscopic bone plug free meniscal allograft transplantation. Knee Surg Sports Traumatol Arthrosc. 2016 May;24(5):1432-9. doi: 10.1007/s00167-016-4035-z. Epub 2016 Feb 9. |
| 31395185 | Background | Zaffagnini S, Grassi A, Macchiarola L, Stefanelli F, Coco V, Marcacci M, Andriolo L, Filardo G. Meniscal Allograft Transplantation Is an Effective Treatment in Patients Older Than 50 Years but Yields Inferior Results Compared With Younger Patients: A Case-Control Study. Arthroscopy. 2019 Aug;35(8):2448-2458. doi: 10.1016/j.arthro.2019.03.048. |
| 31240420 | Background | Zaffagnini S, Di Paolo S, Stefanelli F, Dal Fabbro G, Macchiarola L, Lucidi GA, Grassi A. The biomechanical role of meniscal allograft transplantation and preliminary in-vivo kinematic evaluation. J Exp Orthop. 2019 Jun 25;6(1):27. doi: 10.1186/s40634-019-0196-2. |
| 23370980 | Background | Marcacci M, Zaffagnini S, Kon E, Marcheggiani Muccioli GM, Di Martino A, Di Matteo B, Bonanzinga T, Iacono F, Filardo G. Unicompartmental osteoarthritis: an integrated biomechanical and biological approach as alternative to metal resurfacing. Knee Surg Sports Traumatol Arthrosc. 2013 Nov;21(11):2509-17. doi: 10.1007/s00167-013-2388-0. Epub 2013 Jan 31. |
| 39672576 | Derived | Zanasi L, Boffa A, De Marziani L, Lisignoli G, Belvedere C, Miceli M, Zaffagnini S, Filardo G, Di Martino A. Knee osteotomy combined with meniscal allograft transplantation versus knee osteotomy alone in patients with unicompartmental knee osteoarthritis: a prospective double-blind randomised controlled trial protocol. BMJ Open. 2024 Dec 12;14(12):e087552. doi: 10.1136/bmjopen-2024-087552. |
| D007592 |
| Joint Diseases |
| D012216 | Rheumatic Diseases |