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Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_1 | Pages 126 - 126
2 Jan 2024
Schmidt S Klampfleuthner F Diederichs S
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The signaling molecule prostaglandin E2 (PGE2), synthesized by cyclooxygenase-2 (COX-2), is immunoregulatory and reported to be essential for skeletal stem cell function. Nonsteroidal anti-inflammatory drugs (NSAIDs) are widely used in osteoarthritis (OA) analgesia, but cohort studies suggested that long-term use may accelerate pathology. Interestingly, OA chondrocytes secrete high amounts of PGE2. Mesenchymal stromal cell (MSC) chondrogenesis is an in vitro OA model that phenocopies PGE2 secretion along with a hypertrophic OA-like cell morphology. Our aim was to investigate cause and effects of PGE2 secretion in MSC-based cartilage neogenesis and hypertrophy and identify molecular mechanisms responsible for adverse effects in OA analgesia. Human bone marrow-derived MSCs were cultured in chondrogenic medium with TGFβ (10ng/mL) and treated with PGE2 (1µM), celecoxib (COX-2 inhibitor; 0.5µM), AH23848/AH6809 (PGE2 receptor antagonists; 10µM), or DMSO as a control (n=3–4). Assessment criteria were proteoglycan deposition (histology), chondrocyte/hypertrophy marker expression (qPCR), and ALP activity. PGE2 secretion was measured (ELISA) after TGFβ withdrawal (from day 21, n=2) or WNT inhibition (2µM IWP-2 from day 14; n=3). Strong decrease in PGE2 secretion upon TGFβ deprivation or WNT inhibition identified both pathways as PGE2 drivers. Homogeneous proteoglycan deposition and COL2A1 expression analysis showed that MSC chondrogenesis was not compromised by any treatment. Importantly, hypertrophy markers (COL10A1, ALPL, SPP1, IBSP) were significantly reduced by PGE2 treatment, but increased by all inhibitors. Additionally, PGE2 significantly decreased ALP activity (2.9-fold), whereas the inhibitors caused a significant increase (1.3-fold, 1.7-fold, 1.8-fold). This identified PGE2 as an important inhibitor of chondrocyte hypertrophy. Although TGFβ and WNT are known pro-arthritic signaling pathways, they appear to induce a PGE2-mediated antihypertrophic effect that can counteract pathological cell changes in chondrocytes. Hampering this rescue mechanism via COX inhibition using NSAIDs thus risks acceleration of OA progression, indicating the need of OA analgesia adjustment


Orthopaedic Proceedings
Vol. 105-B, Issue SUPP_9 | Pages 67 - 67
17 Apr 2023
Sharp V Bury N Masieri F
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The development of a representative human, in vitro OA model could deepen understanding of disease mechanisms. Our research aimed to reprogram healthy and OA-derived synoviocytes to induced pluripotent stem cells (iPSCs), thereby generating a novel OA in vitro model. Comparison between the two models shall enable research into underlying processes with potential for clinical translation. A meta-analysis of OA synovial biomarkers was conducted, identifying up to thirteen relevant pathophysiology-related factors, including, amongst others, IL-13, IL-10, IL-6, PIICP, and HA, with PIICP demonstrating the largest effect (SMD 6.11 [3.50, 8.72], p <0.00001). With these findings in mind, human fibroblast-like synoviocytes (HFLS) from healthy and OA patients were transduced using Sendai viral reprogramming. Two clones for each of the resulting iPSC lines were expanded and preliminarily analysed in triplicate by ICC and RT-qPCR for pluripotency characteristics. Healthy HFLS-derived and OA-HFLS-derived iPSC (UoS-B and UoS-C lines, respectively) were generated, indicating successful reprogramming. Morphological observations demonstrated typical iPSC appearance, and ICC confirmed presence of pluripotency markers Tra-1-60, Oct3/4 and Nanog. Expression of Oct3/4, Nanog and Sox2 were confirmed by RT-qPCR with OA-iPSC lines expressing higher levels of all markers compared to non-OA iPSC. In particular, expression of Oct3/4 and Sox2 was 3.5 fold and 4.6 fold higher (p <0.001) in OA-iPSCs (UoS-C) vs. non-OA iPSCs (UoS-B), respectively. Sendai virus clearance was confirmed by passage 4. The successfully obtained OA and non-OA iPSCs can be differentiated towards mesenchymal lineages, including chondrocyte and bone progenitor cells, enabling phenotypic comparison and biomarker analysis as identified in meta-analysis. Cell bank dissemination of these cell lines could deepen further in vitro OA research, with potential impact for clinical translation via the identification of novel cellular and molecular targets


Orthopaedic Proceedings
Vol. 100-B, Issue SUPP_4 | Pages 81 - 81
1 Apr 2018
Ripmeester E Caron MMJ van Rhijn LW Welting TJM
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Osteoarthritis (OA) is the most common degenerative joint disease causing joint immobility and chronic pain. Treatment is mainly based on alleviating pain and reducing disease progression. During OA progression the chondrocyte undergoes a hypertrophic switch in which extracellular matrix (ECM) -degrading enzymes are released, actively degrading the ECM. However, cell biological based therapies to slow down or reverse this katabolic phenotype are still to be developed. Bone morphogenetic protein 7 (BMP-7) has been shown to have OA disease-modifying properties. BMP-7 suppresses the chondrocyte hypertrophic and katabolic phenotype and may be the first biological treatment to target the chondrocyte phenotype in OA. However, intra-articular use of BMP-7 is at risk in the proteolytic and hydrolytic joint-environment. Weekly intra-articular injections are necessary to maintain biological activity, a frequency unacceptable for clinical use. Additionally, production of GMP-grade BMP-7 is challenging and expensive. To enable its clinical use, we sought for BMP-7 mimicking peptides better compatible with the joint-environment while still biologically active and which potentially can be incorporated in a drug-delivery system. We hypothesized that human BMP-7 derived peptides are able to mimic the disease modifying properties of the full-length human BMP-7 protein on the OA chondrocyte phenotype. A BMP-7 peptide library was synthesized consisting of overlapping 20-mer peptides with 18 amino-acids overlap between sequential peptides. OA human articular chondrocytes (HACs) were isolated from OA cartilage from total knee arthroplasty (n=18 donors). HACs were exposed to BMP-7 (1 nM) or BMP-7 library peptides at different concentrations (1, 10, 100 or 1000 nM). Gene-expression levels of important chondrogenic-, hypertrophic-, cartilage degrading- and inflammatory mediators were determined by RT-qPCR. GAG and ALP activity were determined using a colorimetric assay and PGE levels were measured by EIA. During the BMP-7 peptide library screening human BMP-7 derived peptides were screened for their full-length human BMP-7 mimicking properties at different concentrations (1, 10, 100 or 1000nM) on a pool of human chondrocytes. Gene expression as well as GAG, ALP and PGE2 level analysis revealed two distinct peptide regions in the BMP-7 protein based on their pro-chondrogenic and anti-OA phenotype actions on human OA chondrocytes. The two most promising peptides were further analysed for their OA chondrocyte disease modifying properties in the presence of OA synovial fluid, showing similar OA phenotype suppressive activity. Conclusively, we successfully identified two peptide regions in the BMP-7 protein with in vitro OA suppressive actions. Further biochemical fine-tuning of the peptides, and in vivo evaluation, will potentially result in the first peptide-based experimental OA treatment, addressing the hypertrophic and katabolic chondrocyte phenotype in OA


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_17 | Pages 1 - 1
1 Nov 2016
Romeo A
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Glenohumeral osteoarthritis (OA) is a challenging clinical problem in young patients. Given the possibility of early glenoid component loosening in this population with total shoulder arthroplasty (TSA), and subsequent need for early revision, alternative treatment options are often recommended to provide pain relief and improved range of motion. While nonoperative modalities including nonsteroidal anti-inflammatory medications and physical therapy focusing on rotator cuff strengthening and scapular stabilization may provide some symptomatic relief, young patients with glenohumeral OA often need surgery for improved outcomes. Joint preserving techniques, such as arthroscopic debridement with removal of loose bodies and capsular release, with or without biceps tenotomy or tenodesis, remains a viable nonarthroplasty option in these patients. Clinical studies evaluating the outcomes of arthroscopic debridement for glenohumeral OA in young patients have had favorable outcomes. Evidence suggests that earlier stages of glenohumeral OA have more favorable outcomes with arthroscopic debridement procedures, with worse outcomes being observed in patients with complete joint space loss and bipolar chondral lesions. More advanced arthroscopic options include inferior osteophyte excision and axillary neurolysis or microfracture of chondral lesions, both of which have demonstrated favorable early clinical outcomes. Patients with some preserved joint space and small osteophytes can avoid arthroplasty and have improved functional outcomes after arthroscopic debridement for glenohumeral OA. Caution should be advised when indicating this procedure for patients with large osteophytes, grade IV bipolar lesions, biconcave glenoids, and complete loss of joint space


Orthopaedic Proceedings
Vol. 84-B, Issue SUPP_III | Pages 351 - 352
1 Nov 2002
Dorn U Neumann D
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DDH with or without previous treatment is the most frequent source of early hip OA in adolescents. Others are hip joint deformation following Legg-Calve-Perthes disease, slipped capital epiphysis or trauma. Secondary OA after rheumatoid arthritis, bacterial infection or as result of an hemophilic hip joint are relatively infrequent. The choice of treatment depends on the type of the deformity and the severity of osteoarthritic changes. Osteotomies are favorably performed in adolescents. Arthrodesis is rarely accepted in this age group. In selected individuals THR is the matter of choice. Pain, limping gait, restricted joint motion and sometimes clicking phemomena are the usual complains. Pain is usually aggravated by running and other sports activities. Residual dysplasia of the hip with a spherical femoral head is best treated by a triple periacetabular osteotomy. The Bernese ostetomy of Ganz (. 3. ) and the triple osteotomy of Tönnis (. 9. ) are popular procedures. They mobilise an acetabular fragment, then reorient and stabilise the fragment in an optimal position. Internal fixation with screws provides stability and allows early mobilisation with partial weight bearing. Chiari’s osteotomy is a supracetabular rotatory displacement osteotomy. Femoral head and joint capsule are medialised and covered by the osteomised iliac bone. The joint capsule in the weight bearing zone is transformed into fibrous cartilage by time. Congruent remodelling of the acetabular roof and fibrous tissue transformation into cartilage are biased by inproper height and orientation of the osteotomy (. 5. ). There is still an indication in severe DDH with subluxation of the femoral head and those with a severely deformed femoral head. In pathomorphologies with aspherical femoral heads femoral osteotomies, usually valgus osteotomies, are required additionally in order to optimize the joint congruency. A dysplastic hip in a high dislocation and moderate to severe OA are contraindications. Radiographic work up includes pelvic ap view and faux profil view. Assessment of the anterior and posterior acetabular rim indicate orientation of the acetabulum in terms of anteversion / retroversion. Orientation of the subchondral sclerosis over the femoral head is an indicator of femoral head coverage as CE-angle and AC-angle. 20°–30° abduction view in neutral rotation mimikes the postoperative acetabulum / femoral head relation. From CT-scans acetabular orientation ( ante-version / retroversion ), degenerative bone cysts, posteroinferior joint space and femoral head deformities and femoral neck osteophytes are depicted. Labrum pathology is dedectable by MRT and MRT-arthrography. After treatment of DDH deformation of the femoral head and neck due to ischaemic necrosis develop in an incidence up to 20 %, depending on the method. Premature closure of the epiphyseal plate can also follow trauma, septic arthritis and Legg-Calve-Perthes disease. Most often an combination of acetabular dysplasia and coxa magna with short femoral neck and a high-standing greater trochanter are typical deformities. Specchiulli’s classification (. 8. ) is very helpful for deformations after avascular necrosis in DDH. Limping gait due to femoral shortening and insufficient strength of the abductor muscels are the major complains of adolescents. Symptoms exacerbate during walking of longer distances and restrict sports activities. Valgus osteotomy, Y-osteotomy, transfer of the greater trochanter alone or in combination with valgus osteotomy are appropiate methods to restore a better function and improve alignment of the mechanical axis to the knee joint. Femoral neck lengthening osteotomies (. 1. ,. 4. ) with distal-lateral transfer of the greater trochanter are advocated by several authors. Restoration of almost normal anatomy muscle function of the hip joint are realistic aims of these methods. If the abductor muscel deficit is dominant and only a minor leg length discrepancy is in slight deformities, e.g. some Specchiulli’s type B2, we do not always need such complex procedures. Isolated transfer of the greater trochanter also improves the lever arm of the abductor muscles and therefore joint function, but does not influence leg length discrepancy. Disappearance of the Tren-delenburg-type gait is the most visible improvement of this procedure (. 7. ). Total hip replacement (=THR) is rarely indicated in adolescents, but sometimes necessary for restoration of a almost normal quality of life. Especially in severe symptomatic OA after septic arthritis or trauma in some individuals remain only two options : arthrodesis or arthroplasty. Arthrodesis is a permanent solution for many years or even life time. Gait function is compromised remarkable (. 6. ) and specific compensatory mechanisms are adopted when walking. Excessive motion in the lumbar spine and ipsilateral knee provokes back and knee pain as well as osteoarthritic changes on the long run. THR in young patients includes the risk of several revisions over life time , due to wear problems particularly in physically active individuals. A deficient acetabular bone stock as usual in severe acetabular dysplasia or poor bone quality after trauma or septic arthritis may compromize primary stability and secondary osteointegration. Nevertheless functional results and outcome (. 2. ) in terms of life quality are superior compared with various non-substituting procedures


Orthopaedic Proceedings
Vol. 96-B, Issue SUPP_11 | Pages 100 - 100
1 Jul 2014
Smith M Schiavinato A Little C
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Introduction. Osteoarthritis (OA) involves pathological change in all joint tissues, including cartilage degradation and synovitis. Synovial inflammation is significantly associated with pain severity and incidence in knee OA. It is becoming evident that synovitis also plays an active role in the initiation and progression of cartilage erosion in OA, through direct secretion of catabolic enzymes as well as factors that stimulate chondrocyte catabolic activity. Therapeutic agents that target both synovitis and cartilage pathology are likely to be maximally beneficial in treating pain and slowing cartilage breakdown in OA. We have previously shown that an amide-derivative of HA (HYMOVIS™) was superior to native HA of the same MW in improving gait, and reducing synovial hyperplasia in a sheep OA model. In the present study the mechanisms whereby the chemically modified HA may be beneficial were examined using chondrocytes and synovial fibroblasts from knees of OA patients. Patients & Methods. Chondrocytes (HAC, n=6) and synovial fibroblasts (HSF, n=6) were isolated from OA patients at the time of knee replacement. HYMOVIS™ (0, 0.5, 1.0 or 1.5mg/mL) was added to simultaneously or 1 hour before interleukin-1β (IL1, 2ng/mL). Cultures were terminated 30 minutes later for Bioplex. ®. quantitation of p-JNK, p-NFκB and p-p38; or 24 hours later for RNA isolation and analysis of gene expression by real time RT-PCR, and measurement of MMP13 activity in the media. Only statistically significant results are reported. Results. In HAC in the absence of IL1, HYMOVIS™ decreased MMP13, ADAMTS5, PTGS2 and IL6 and increased COL2A1 mRNA (2–10fold). In HSF in absence of IL1, HYMOVIS™ decreased TIMP1, TIMP3, CD44, IL6 and increased PTGS2 (2–3fold). In HAC and HSF, IL1 increased expression of MMP1, MMP13, PTGS2, IL6 (>100fold), ADAMTS4 (∼10 fold), all phosphoproteins (3–10fold), and APMA-activated MMP13 activity in media. IL1 increased expression of ADAMTS5 (∼10fold) only in HSF. As expected, IL1 reduced expression of the key matrix proteins in HAC (2–3 fold decrease in COL2A1 and ACAN) and HSF (2 fold decrease in COL1A1). When added simultaneously with IL1, HYMOVIS™ decreased expression of MMP13, ADAMTS5, PTGS2, IL6 expression, and normalised matrix protein expression in both HAC and HAS. Pre-incubation with HYMOVIS™ for 1 hour inhibited IL1-stimulated p-JNK, p-NFκB and p-p38 in both cell types (excluding p-JNK in HSF). In HAC, HYMOVIS™ pre-incubation was superior to simultaneous addition in reducing expression of MMP1, MMP13, ADAMTS4, PTGS2, and IL6 expression. There was a less dramatic effect of HYMOVIS™ pre-incubation on gene expression in HSF compared with HAC. The inhibitory effects of HYMOVIS™ on IL1 stimulated gene expression in HAC and HSF was partially ameliorated by pre-incubation with a CD-44 blocking antibody. Discussion/Conclusions. The present studies have demonstrated several potential key mechanisms whereby the intra-articular injection of a hexadecylamide-derivative of HA (HYMOVIS™) may have both symptom and disease-modifying effects in OA. The previously described increased joint retention of the hexadecylamide-derivative, might act in a similar manner to the pre-incubation studies in our cell culture studies, to reduce the initiation of degradative events with recurrent/cyclic inflammatory episodes that typify OA


Orthopaedic Proceedings
Vol. 91-B, Issue SUPP_I | Pages 172 - 172
1 Mar 2009
König D Güngör Ü Aydinli M Koebke J
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Introduction: The Donjoy OA Orthesis has been developed to treat unicompartimental osteoarthrosis of the knee joint. The idea is to reduce the load in the affected joint compartment. Sofar only clinical evaluations and gait analysis have been published. The aim of this study is to use intraarticular pressure sensors in an anatomical model to work out the existing intraarticular pressures. Method: 5 fresh non fixated anatomical knee models were used. The models were prepared leaving the 2/3 of the femur as well as the tibia and fibula. We used a right and left-sided version of the Donjoy OA Orthesis. A defined pressure was applied via the pressure application screw. The dorsal capsule of the knee joint was opened and the meniscus were mobilised in a way that the pressure foils (Fuji typ super low) could be placed between the undersurface of the meniscus and the tibia plateau in each joint compartment. The measurements were recorded in four different joint positions (0°, 30°, 60° flexion and 0° with removed meniscus). Each anatomical model was well fixed in a universal testing machine” (Instron, System ID: 5565 H1703). The used axial pressure in all set ups used was 1500N. We used 4 four different test series:. no pressure, no orthesis. no pressure, with orthesis. with pressure, no orthesis. with pressure, with orthesis. After removing the pressure foils the actual pressure could be estimated by the diameter of the coloured foil. Using the programm Mortphomet it was possible to calculate these pressure areas and give procentual figures. Results: The Antivarus Orthesis could reduce the intraarticular joint pressure between 55–70%. Without pressure:. Knee → 64,37 %. Knee → 55,30 %. Knee → 54,43 %. Knee → 58,75 %. Knee → 44,80 %. Mean value 55%. With pressure:. Knee → 74,59 %. Knee → 74,00 %. Knee → 67,91 %. Knee → 86,34 %. Knee → 49,69 %. mean value 70%. The Antivalgus Orthesis could reduce the intraarticular joint pressure between 46–74%. Without pressure:. Knee → 79,78 %. Knee → 76,22 %. Knee → 75,20 %. Knee → 62,55 %. Knee → 76,49 %. Mean value 74%. With pressure:. Knee → 42,68 %. Knee → 46,24 %. Knee → 64,61 %. Knee → 40,08 %. Knee → 37,20 %. Mean value 46%. Conclusion: This anatomical investigation has proved for the first time via intraarticular pressure measurements that it is possible to considerable reduce the intraarticular pressure using the Donjoy antivarus and antivalgus Orthesis


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXII | Pages 5 - 5
1 May 2012
Saltzman C
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Fusion remains the standard of care and is associated with a high satisfaction rate. But.… fusion generally requires 6 weeks of restricted weight bearing or immobilization. Potential problems include 1) nonunion, 2) malunion, 3) sesamoid pain (from DJD), 4) late onset IP1 DJD. Complete joint replacement has been performed with a number of different designs since the early 1970's. The metal and poly designed implants are associated with a high failure rate, presumably from high shear loads, eccentric axial loads, poor fixation and bone stock problems. Resurfacing of both sides of the joint with a one piece silicone based crosslinked rubber {“silastic”} in rheumatoid patients appears to function better with use of metal grommets to reduce generation of particle debris and foreign body reaction. These silastic implants are still used by surgeons in select low-demand rheumatoid patients. Salvage after failure of any of these total joint replacements can be challenging because of loss of bone stock. 3 other methods are used to resurface the joint in severe OA: 1) resurfacing the proximal phalangeal side only, 2) resurfacing the metatarsal head only and 3) resurfacing the joint with and interposition arthroplasty. 1) advantage of the proximal phalangeal side resurfacing is simplicity of geometry; the disadvantage is disruption of the FHB attachment and the relative scarcity of severe cartilage damage at that side of the joint. 2) Advantage of the metatarsal head side for resurfacing is that is the typical location of the arthritic change; the disadvantage is potential interference with the sesamoid complex and bulkiness of fixation could lead to a more difficult salvage. 3) The advantage of interposition arthroplasty is the maintenance of bone stock; disadvantages include inconsistent local tissue and somewhat less predictable outcomes. In this talk I will focus primarily on the technique and results of a proximal phalangeal resurfacing approach for OA of the MTP1 joint


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXXVIII | Pages 97 - 97
1 Sep 2012
Dervin G Thurston PR
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Purpose. Patients with anterior cruciate ligament (ACL) deficiency and symptomatic medial compartment osteoarthritis (OA) present a challenge in management. These are often younger than typical primary OA patients and aspire to remain athletically active beyond simple ADLs. Combined ACL reconstruction and valgus tibial osteotomy (ACLHTO) is a well documented surgical option for patients deemed wither too young or too active for total knee arthroplasty. Unicompartmental knee arthroplasty (UKA) is an established surgical treatment for symptomatic medial osteoarthritis of the knee refractory to conservative management. A commonly cited contraindications is symptomatic ACL deficiency because of previous reports detailing premature failure through loosening of the tibial component. Improved results and endoscopic ACL reconstructive procedures have led to an enticing concept of combining ACL reconstruction with medial unicompartmental knee arthroplasty (ACLUKR) for those ACL-deficient medial osteoarthritic (OA) knees. We sought to compare the outcomes in 2 cohorts of patients who underwent either ACLHTO or ACLUKR for this clinical problem. Method. Patients presenting with symptomatic bone on bone medial compartment OA and concomitant ACL deficiency (clinical or asymptomatic) were evaluated for surgery after exhausting non operative management. Patients who were under 40 or had plans to return to high impact loading sports and/or who had more moderate OA were offered combined ACL – medial opening wedge tibia osteotomy as a surgical procedure of choice. Patients were considered for combined ACL Oxford replacement if they were primarily seeking pain relief and were not engaged or aspiring to return to high impact or pivoting sports. All cases but one were concurrent ACL with either HTO or UKR with autogenous hamstring grafts used in all but 2 cases. Results. Thirty of 34 consecutive cases were available for follow-up for a rate of 88%. The median ages for 14 cases of ACLUKR was 51 (range 43 60) whereas 16 patients with ACLHTO had median age 43.4 (range 32 −59). Median FU was 4.65 yrs with minimum 2 year follow up (range 2–8.3). Three of the cases were revision ACL cases all from previous Gore-Tex reconstructions. All but the first patient had concomitant ACL and Oxford unicompartmental knee replacement at 1 surgical sitting and are the subject of this report. The first patient had an autogenous patella bone tendon bone graft performed 6 months prior to the UKA. There were similar change scores for patients in both groups. For ACLUKR, WOMAC pain improvements from 48.1 10.2 SD preoperatively to 79.0 17 SD postop. For ACLHTO, WOMAC improvements from 55.1 13.2 SD preoperatively to 85.0 17 SD postop. To date there have been no cases of infection or bearing dislocation in the ACLUKR group. One patient in the ACLHTO group was revised to TKR for ongoing pain and postoperative flexion contracture. Patient activities ranged from ambulation to vigorous hiking, tennis, and downhill skiing in the UKR group whereas a few in the ACLHTO group were also running mid distances. Overall satisfaction was similar in both groups. Conclusion. ACL reconstruction can safely be combined with medial UKR. The procedure has been used in younger patients with a view toward bone preservation while anticipating need for future revision. Both cohorts showed similar improvements and can be considered. The choice should be geared toward patient athletic demand. While short term results are encouraging though longer term data are necessary to thoroughly evaluate the role of this procedure in patients with medial compartment osteoarthritis and ACL deficiency


Orthopaedic Proceedings
Vol. 98-B, Issue SUPP_3 | Pages 8 - 8
1 Jan 2016
Madadi F
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There are several case reports or small series of stress tibial fracture around the OA knees in literature. Our study goes on 10 tibial stress fracture in 9 patients. All of the fractures have been distal to proximal tibial methaphysis. 8 of them have been in mid shaft or proximal of mid tibia, only 2 had fractures in distal half of tibia 8 were manage by braces for at least 8 months post TKA. Left side of the Bilateral one was fixed by simple IM nail and in 10 months was changed by TKA. Another very interesting case after failure of plate fixation without revision of knee was fixed by custom – made extended nail that attached to tibial tray. Conclusion: for all patients who are candidate to underwent T K A procedure, an update 3 – joints view is mandatory. Beside of patho anatomy and preoperative planning 3-joints view helps us to assure about peri arthicular stress (pathologic) fractures


Orthopaedic Proceedings
Vol. 99-B, Issue SUPP_6 | Pages 44 - 44
1 Mar 2017
Tanimura E Niki Y Katoh S Matsumoto H
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Background. The indication of unicompartmental knee arthroplasty (UKA) for end-stage osteoarthritis (OA) remains controversial. This study aimed to investigate patient reported outcomes (PROs) of UKA in patients with severe varus deformity of the knee and compare the results with those of total knee arthroplasty (TKA) at mid-term follow up. Methods. A total of 96 TKAs of 69 patients and 61 UKAs of 50 patients were included. All patients presented with severe knee OA with hip-knee-ankle angle (HKA) ranged from −25 degree to −10 degree, preoperatively. Mean HKAs in TKA group and UKA group were −14.95º and −13.38º, respectively. PROs were assessed using Knee Society Score (KSS 2011), PainDETECT score (PD), and Pain Catastrophizing Scale (PCS) at a mean follow up of 58.65 months for TKA and 58.05 months for UKA. Kaplan-Meier survival analysis was performed to assess implant survival. Complication rate was also assessed. All data were compared between TKA group and UKA group. Results. Mean postoperative knee flexion angle was 124.38 º for TKA group and 133.69 º for UKA group, indicating that knee flexion angle of UKA was significantly greater than that of TKA (p=0.000). There were no statistically differences in KSS and their items, PD, and PCS. Regarding mid-term survivorship, TKA (96.0%) was less than UKA (96.8%), but there was no statistically significance. Major complications of the knee occurred in 4cases (4.0%) for TKA and 7 cases (11.1%) for UKA but there was also no statistically significance. Complications of UKA included 3 cases of OA progression in the lateral compartment. Discussion. Although greater flexion angle was observed in UKA group, there was no significant differences in PROs between the two groups. The survival rate are practically considered worse in TKA and the complication rate are practically considered worse in UKA, but there are no statistically significance. Further assessment should be needed after increasing the number of subjects and follow-up period


Orthopaedic Proceedings
Vol. 93-B, Issue SUPP_IV | Pages 430 - 431
1 Nov 2011
Tada M Inui K Yoshida H Takei S Fukuoka S Matsui Y Yoshida K
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Good mid-term results of Oxford UKA (OxUNI) for anteromedial osteoarthritis (OA) were reported. The designers of prosthesis reported a 98% 10-year survival rate for a combined series of phase I and II, and these findings were supported by published results from other series, with 10-year survival ranging from 91% to 98%. In order to obtain good results, the designers of this prosthesis mentioned the importance of adhering to strict indication for OxUNI, especially only for OA cases with intact anterior cruciate ligament (ACL). OxUNI combined with ACL reconstruction (ACLR) is a viable treatment option for only young active patients, in whom the ACL has been primarily ruptured. On the other hand, it was not clear whether the result of OxUNI combined with ACLR for OA with secondary ruptured ACL was good. In this study we compare the short-term results of OxUNI combined with ACLR for OA with secondary ruptured ACL with that for usual OA with intact ACL. 382 OxUNI were performed at two hospitals by one surgeon between January 2002 and August 2005. Among those, 367 cases, followed over two years postoperatively (272 patients, women: 283, men: 84) were assessed. Follow up ratio was 96.1%. The mean patient age at the time of surgery was 72.0 (47~93) years. The mean follow-up period was 39.3 (24~67) months. Thirty three knees of OA were treated with OxUNI combined with ACLR, by using synthetic graft. Clinical results were assessed by the Oxford Knee Score (OKS) and active range of motion (ROM). Patients are asked a series of 12 questions, and their response scores range from 0 (worse) to 4 (best) for each, yielding an overall score range of 0–48. All living patients were contacted, and the status of the implant was established at the time of last follow from hospital records. We evaluate the survival rate for OxUNI with or without ACLR, using the endpoint of revision for any reason. The pre-and postoperative clinical scores were compared using the paired Student’s t-test. Survivor-ship curves were constructed using the Kaplan-Meier method, and survivorship between groups was compared using logrank and Wilcoxon methods. All analyses were performed using 95% confidence intervals and a P value of < 0.05 was considered significant. The mean OKS at final follow-up was 42.1 (preoperative; 21.7), and the mean active ROM was 125.2° (preoperative; 113.4°). OKS and active ROM were significantly improved. There were no significant differences in OKS and active ROM between OxUNI with ACLR and OxUNI with intact ACL. Fourteen knees among 367 knees were revised; nine for loosening of tibial component, four for dislocation of bearing and one for progression of lateral OA. Overall 5-year survival rate was 95.6%. When survival rate was assessed separately with or without ACLR, that of OxUNI with intact ACL was 96.7% and that of OxUNI with ACLR was 83.8%. There was significant worse survival rate between the two groups (P=0.0071). The 5-year survival rate for OxUNI with intact ACL was 96.7%, which was equivalent to those of original series from Oxford. However, 5-year survival rate for Oxford UKA with ACLR was 83.8% in our series. Four knees in nine of loosening of tibial component were replaced by OxUNI combined with ACLR. Therefore, even if ACL was reconstructed, the results of OxUNI for OA with secondary ruptured ACL was proved to be pessimistic. There was significantly worse survival rate for OxUNI with ACLR, compared with OxUNI with intact ACL. So we conclude that combined ACL reconstruction and OxUNI for anteromedial OA with secondary ruptured ACL is not recommended, which must be treated with TKA


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XLI | Pages 127 - 127
1 Sep 2012
Fearon A Scarvell J Cook J Neeman T Smith P
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Greater trochanteric pain syndrome (GTPS) is common, yet the impact on function and quality of life has not been measured. The aim of this study was to quantify the impact on function and quality of life, comparing the results to people with severe hip osteoarthritis and an asymptomatic control group. Forty two people with GTPS – including 11 not actively seeking treatment and 11 seeking surgical treatment, 20 with severe hip osteoarthritis (OA), and 23 age and sex matched asymptomatic participants (ASC) where recruited from public and private hospitals, and the community. Upon confirming meeting inclusion and exclusion criteria participants were interviewed. Exclusion criteria included lumbar nerve root signs; inflammatory, neoplastic and metabolic disorders. Measured used were the Harris hip score (HHS); the Oswestry disability index (ODI); the Australian quality of life instrument (AQoL); the Functional co-morbidity index (FCI); and fulltime work assessments. No difference was found between the GTPS and the OA group on the HHS, ODI, AQoL or the FCI measures. Both symptomatic groups were significantly more disabled than the ASC group on the HHS and ODI (p<0.001). The GTPS and OA groups had lower AQoL than the ASC group (p<0.001); and higher FCI results than the ASC group (GTPS vs ASC, p=0.005; OA vs ASC, p=0.019). GTPS participants were least likely to be in full time work; full time work participation probability (95% C.I.): GTPS Prob=0.288 (0.160 to 0.463), OA Prob= 0.518 (0.273 to 0.753); ASC group of Prob=0.676 (0.439 to 0.847). People with GTPS have similar levels of pain, disability and quality of life, but are less likely to be in full time employment than people with severe hip OA which puts them at risk of economic hardship. Research on conservative and surgical treatments should measure pain, disability and work participation


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_II | Pages 303 - 303
1 May 2006
Wertz S Franchimont N Malaise M Gangji V Van Cauwenberge H Hauzeur J
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Introduction: Abnormalities of mesenchymal stem cells and osteoblastic cells (Obs) might play a role in producing bone collapse due to insufficient repair of the necrotic area in osteonecrosis of the femoral head (ON). Osteoblast and osteocyte apoptosis should be increased at the osteonecrotic site. Materials and Methods: We compared the TRAIL (TNF-related apoptosis-inducing ligand) cytotoxicity in primary Obs isolated from femoral heads from patients with ON or osteoarthritis (OA) and on two human osteosarcoma cell lines, MG-63 and SaOS. 2. . Results and Discussion: We showed that ON but also OA Obs were sensitive to TRAIL. We also observed TRAIL cytotoxicity on MG-63 but not SaOS. 2. cells. Moreover, we saw that TRAIL negatively regulated Akt and ERK survival pathways in MG-63 cells. We also investigated the IL-6 influences on apoptotic response of Obs to TRAIL. Even though decreased IL-6 and sIL-6R levels were observed at peripheral sites of the ON in regard to the levels produced in the iliac crest, IL-6 had no protective effects on TRAIL-induced apoptosis in ON Obs and only a weak protective effect in MG-63 cells. However, TRAIL stimulated IL-6 production in MG-63 cells and, cells and OA Obs, suggesting to a lesser extend, in SaOS. 2. other roles of TRAIL in the bone environment


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_II | Pages 97 - 97
1 Feb 2012
Hart A Dowd G
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Early stabilisation after an anterior cruciate ligament (ACL) rupture reduces future meniscal injury. We may therefore expect protection of articular cartilage from ACL reconstruction, but this has yet to be shown. Our aim wasto determine the effect of meniscal injury on the long term risk of osteoarthritis (OA) following ACL reconstruction using Single Photon Emission Computed Tomography (SPECT, a 3 dimensional radionuclide scan). We studied a prospective series of 31 patients (mean age at injury of 29 years) who had bone-patellar tendon-bone ACL reconstruction for unstable, ACL deficient knees. Mean follow-up was 10 years (range 9-13). Patients were separated into two groups according to the status of their menisci at the time of ACL reconstruction, those with intact menisci in group 1 (n=15) and those who required partial meniscectomy in group 2 (n=16). The contra-lateral normal knee was used as a control. All knees were clinically stable with high clinical scores (mean Lysholm score 93 and mean Tegner activity score 6). In group 1 (intact menisci) only one patient (7%) had clinical symptoms of OA and was the only patient with increased uptake on SPECT compatible with early OA. In group 2 (partial meniscectomy), two had clinical symptoms of osteoarthritis, and five patients (32%) had increased uptake on SPECT compatible with early OA. None of the control knees had early OA on SPECT. The prevalence of OA 10 years post ACL reconstruction, using the most sensitive investigation available, is very low in patients who had intact menisci (7%), but increases 5 fold (32%) if a meniscal tear was present. We recommend early ACL reconstruction to preserve the menisci to minimise the long term risk of OA


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XLI | Pages 56 - 56
1 Sep 2012
Waller C Hayes D
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Joint load reduction is effective for alleviating OA pain. Treatment options for joint unloading include braces and HTO, both of which may be impractical for patients. The purpose of the present study was to examine the biomechanical rationale of a practical, partial unloading implant (KineSpring® System, Moximed) for knee OA. Device durability was tested by cyclically loading bone-implant constructs through simulated use for at least 10 million cycles. Joint load reduction with the implant was quantified by measuring changes in medial and lateral knee compartment loads generated by cadaver knees in simulated gait. Safety of the device was tested by 3, 6, and 12 month follow-up of implants in an in vivo ovine model. Surgical technique and device safety and efficacy were assessed in human clinical studies. The unloader device survived over 15 million cycles of simulated use without failure. In the simulated gait cadaver model, the unloading device significantly reduced medial compartment (29 ± 13 lbs, p<0.05) and overall knee joint loads during the stance phase of gait testing but did not significantly increase lateral compartment loading. Chronic ovine implants demonstrated good tolerance of the implant with normal wound healing and secure device fixation. Clinical experience (n=49) demonstrated uneventful device implantation. Unlike HTO, the implantation technique for the unloader does not alter joint alignment. This surgical technique avoids removal of bone, ligament, and cartilage, thus preserving future primary arthroplasty, if required. Early-term clinical experience also demonstrates good outcomes for patients, the earliest of whom are beyond 2.6 years with the implant. This unloading device offers a practical and attractive treatment option for patients with medial knee OA: load reduction without load transfer, durability, preservation of downstream treatment options, safety, and early-term efficacy


Orthopaedic Proceedings
Vol. 87-B, Issue SUPP_III | Pages 275 - 275
1 Sep 2005
Huijsmans P Roberts C van Rooyen K du Toit D de Beer J
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Treatment of OA of the shoulder in young and active patients remains a problem. Present treatment options are debridement, microfracturing, arthrodesis or shoulder replacement. We report the preliminary results of soft-tissue interposition arthroplasty with an acellular allograft skin-derived collagen matrix (Graft Jacket®, Wright Medical). Between July and December 2003 five men and one woman with severe glenohumeral OA had a soft-tissue interposition arthroplasty of the shoulder. The mean age of the patients was 47 years (34 to 58). In four patients the procedure was done arthroscopically. The Graft Jacket® was sutured to the labrum with a minimum of five sutures. The mean postoperative follow-up was 6.2 months. Four patients experienced notable pain relief after the operation. Preoperatively the mean visual analogue pain score was 7.2 and postoperatively it was 2.6. One patient had no improvement and elected to wait before having further treatment. One patient needed a hemi-arthroplasty. The range of motion improved in only one patient. The mean Constant score improved 14 points, from 45 to 59. There were no complications peroperatively or postoperatively. While the long-term results are still unknown, soft-tissue interposition arthroplasty with the Graft Jacket® shows promising results


Orthopaedic Proceedings
Vol. 88-B, Issue SUPP_I | Pages 25 - 25
1 Mar 2006
Christ R Hagena F
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Introduction and aim: In a prospective comparative study we were interested in the question, wether the total ankle arthroplasty in the midterm FU, especially in patients with RA, is a successful and correctly indicated surgical procedure. We compared our clinical and radiological results with a cohort of patients with OA. Furthermore we analysed especially the rheuma patients for their known periarticular osteopenia and the cementless fixation as a possible contraindication for the ankle arthroplasty. Material and methods: With a mean FU of 4,4 years and a total number of 153 total ankle arthroplasties from 07/1997 to 12/2003 we assessed 92 patients with 94 S.T.A.R total ankle arthroplasties. Indication for this surgical procedure was the rheumatoid arthritis in 26 patients (27.7%) and an idiopathic osteoarthritis of the upper ankle joint in 29 cases (30.8%), furthermore a posttraumatic osteoarthritis in 39 patients (41.5%). Results: The functional increase in their range of motion (ROM) and the significant decrease of pain are the most important and impressing facts for the patients. The increase of ROM in all patients is 17.9 (RA: 18.7 /OA: 16.6). Significant pain relief is described by 92.4% of patients, here all the groups showed no significant differences. An increase in the clinical outcome measured by the Kofoeds Ankle Score is seen from < 70 pts. preoperatively (100% of patients) to > 75 pts. postoperatively (82.3% of patients). The most frequent complication especially in patients with RA is a delayed wound healing (19%), but the revision rate is higher in patients with traumatic and idiopathic osteoarthritis (17% OA /13% RA). A secondary arthrodesis has to be performed only in 2 OA cases. Conclusion: Rheumatoid arthritis in the LDE stage IV and V is the adequate indication for the S.T.A.R. prosthesis. The functional benefit and the clinical outcome is satisfying, the results for the rheumatoid arthritis patients are comparable to other indications. Periarticular osteopenia is not considered as a contraindication


Bone & Joint Research
Vol. 5, Issue 5 | Pages 169 - 174
1 May 2016
Wang Y Chu M Rong J Xing B Zhu L Zhao Y Zhuang X Jiang L

Objectives. Previous genome-wide association studies (GWAS) have reported significant association of the single nucleotide polymorphism (SNP) rs8044769 in the fat mass and obesity-associated gene (FTO) with osteoarthritis (OA) risk in European populations. However, these findings have not been confirmed in Chinese populations. Methods. We systematically genotyped rs8044769 and evaluated the association between the genetic variants and OA risk in a case-controlled study including 196 OA cases and 442 controls in a northern Chinese population. Genotyping was performed using the Sequenom MassARRAY iPLEX platform. Results. We found that the variant T allele of rs8044769 showed no significant association of OA risk (p = 0.791), or association with body mass index (BMI) (pmeta = 0.786) in an additive genetic model. However, we detected a significant interaction between rs8044769 genotypes and BMI on OA risk (p = 0.037), as well as a borderline interaction between rs8044769 genotypes and age on OA risk (p = 0.062). Conclusions. Our findings indicate that rs8044769 in the FTO gene may not modify individual susceptibility to OA or increased BMI in the Chinese population. Further studies are warranted to validate and extend our findings. Cite this article: Prof L. Jiang. No association of the single nucleotide polymorphism rs8044769 in the fat mass and obesity-associated gene with knee osteoarthritis risk and body mass index: A population-based study in China. Bone Joint Res 2016;5:169–174. DOI: 10.1302/2046-3758.55.2000589


Bone & Joint Research
Vol. 3, Issue 2 | Pages 32 - 37
1 Feb 2014
Singh A Goel SC Gupta KK Kumar M Arun GR Patil H Kumaraswamy V Jha S

Introduction. Osteoarthritis (OA) is a progressively debilitating disease that affects mostly cartilage, with associated changes in the bone. The increasing incidence of OA and an ageing population, coupled with insufficient therapeutic choices, has led to focus on the potential of stem cells as a novel strategy for cartilage repair. Methods. In this study, we used scaffold-free mesenchymal stem cells (MSCs) obtained from bone marrow in an experimental animal model of OA by direct intra-articular injection. MSCs were isolated from 2.8 kg white New Zealand rabbits. There were ten in the study group and ten in the control group. OA was induced by unilateral transection of the anterior cruciate ligament of the knee joint. At 12 weeks post-operatively, a single dose of 1 million cells suspended in 1 ml of medium was delivered to the injured knee by direct intra-articular injection. The control group received 1 ml of medium without cells. The knees were examined at 16 and 20 weeks following surgery. Repair was investigated radiologically, grossly and histologically using haematoxylin and eosin, Safranin-O and toluidine blue staining. Results. Radiological assessment confirmed development of OA changes after 12 weeks. Rabbits receiving MSCs showed a lower degree of cartilage degeneration, osteophyte formation, and subchondral sclerosis than the control group at 20 weeks post-operatively. The quality of cartilage was significantly better in the cell-treated group compared with the control group after 20 weeks. Conclusions. Bone marrow-derived MSCs could be promising cell sources for the treatment of OA. Neither stem cell culture nor scaffolds are absolutely necessary for a favourable outcome. Cite this article: Bone Joint Res 2014;3:32–7