Mesenchymal Stem Cell Therapy for Bone Repair of Human Hip Osteonecrosis with Bilateral Match-Control Evaluation: Impact of Tissue Source, Cell Count, Disease Stage, and Volume Size on 908 Hips.

We investigated the impact of mesenchymal stem cell (MSC) therapy on treating bilateral human hip osteonecrosis, analyzing 908 cases. This study assesses factors such as tissue source and cell count, comparing core decompression with various cell therapies. This research emphasizes bone repair according to pre-treatment conditions and the specificities of cell therapy in osteonecrosis repair, indicating a potential for improved bone repair strategies in hips without femoral head collapse. This study utilized a single-center retrospective analysis to investigate the efficacy of cellular approaches in the bone repair of osteonecrosis. It examined the impact on bone repair of tissue source (autologous bone marrow concentrate, allogeneic expanded, autologous expanded), cell quantity (from none in core decompression alone to millions in cell therapy), and osteonecrosis stage and volume. Excluding hips with femoral head collapse, it focused on patients who had bilateral hip osteonecrosis, both pre-operative and post-operative MRIs, and a follow-up of over five years. The analysis divided these patients into seven groups based on match control treatment variations in bilateral hip osteonecrosis, primarily investigating the outcomes between core decompression, washing effect, and different tissue sources of MSCs. Younger patients (<30 years) demonstrated significantly better repair volumes, particularly in stage II lesions, than older counterparts. Additionally, bone repair volume increased with the number of implanted MSCs up to 1,000,000, beyond which no additional benefits were observed. No significant difference was observed in repair outcomes between different sources of MSCs (BMAC, allogenic, or expanded cells). The study also highlighted that a 'washing effect' was beneficial, particularly for larger-volume osteonecrosis when combined with core decompression. Partial bone repair was the more frequent event observed, while total bone repair of osteonecrosis was rare. The volume and stage of osteonecrosis, alongside the number of injected cells, significantly affected treatment outcomes. In summary, this study provides comprehensive insights into the effectiveness and variables influencing the use of mesenchymal stem cells in treating human hip osteonecrosis. It emphasizes the potential of cell therapy while acknowledging the complexity and variability of results based on factors such as age, cell count, and disease stage.

Detection of periprosthetic fractures around the femoral stem by resonance frequency analysis: An in vitro study.

Periprosthetic femoral bone fractures are frequent complications of Total Hip Arthroplasty (THA) and may occur during the insertion of uncemented Femoral Stems (FS), due to the nature of the press-fit fixation. Such fracture may lead to the surgical failure of the THA and require a revision surgery, which may have dramatic consequences. Therefore, an early detection of intra-operative fractures is important to avoid worsening the fracture and/or to enable a peroperative treatment. The aim of this in vitro study is to determine the sensitivity of a method based on resonance frequency analysis of the bone-stem-ancillary system for periprosthetic fractures detection. A periprosthetic fracture was artificially created close to the lesser-trochanter of 10 femoral bone mimicking phantoms. The bone-stem-ancillary resonance frequencies in the range (2-12) kHz were measured on an ancillary instrumented with piezoelectric sensors, which was fixed to the femoral stem. The measurements were repeated for different fracture lengths from 4 to 55 mm. The results show a decrease of the resonance frequencies due to the fracture occurrence and propagation. The frequency shift reached up to 170 Hz. The minimum fracture length that can be detected varies from 3.1±1.7 mm to 5.9±1.9 mm according to the mode and to the specimen. A significantly higher sensitivity (p = 0.011) was obtained for a resonance frequency around 10.6 kHz, corresponding to a mode vibrating in a plane perpendicular to the fracture. This study opens new paths toward the development of non-invasive vibration-based methods for intra-operative periprosthetic fractures detection.

Patient information pathway in orthopedic surgery: Roles of ERAS and pharmacists.

INTRODUCTION: Enhanced Rehabilitation After Surgery (ERAS) pathways significantly improve the care of patients in orthopedic surgery. However, patient knowledge and memorization of the information provided are currently poorly documented. HYPOTHESIS: The information provided by a postoperative pharmacist could have a positive impact on patient care, in particular by improving knowledge about their prosthesis. MATERIAL AND METHOD: This prospective feasibility study included a cohort of 80 patients operated on for a hip or knee prosthesis and who received postoperative pharmacist interviews (POPI). These POPIs informed the patient about the prosthesis, the complications, positions to avoid, as well as the postoperative follow-up. The objective was to measure the patient's knowledge before and after the POPI. Qualitative and quantitative analyses, by indication and patient pathway, were performed. RESULTS: The patient's knowledge before POPI was 70% correct. After POPI this rate rose to 91%. DISCUSSION: Patients' knowledge was weak and heterogeneous, especially regarding the implanted prosthesis. The POPI led to significant improvement and standardization of knowledge which should contribute to the prevention of iatrogenic harm (positions to avoid, infection prevention, compliance with analgesics and anticoagulants). CONCLUSION: A POPI with a pharmacist improves overall patient management during hip or knee arthroplasty. LEVEL OF EVIDENCE: III; non-randomized prospective feasibility study.

Long-Term Results of Anterior-Only Lumbar Interbody Fusions in Rheumatoid Arthritis Patients: Comparative Retrospective Cohort Study.

OBJECTIVE: Rheumatoid arthritis (RA) is a risk factor of lumbar spine surgical failure. The interest of anterior lumbar fusion in this context remains unknown. This retrospective study aimed to compare the outcome of anterior-only fusions between RA patients and non-RA (NRA) patients to treat lumbar spine degenerative disorders. METHODS: NRA and RA groups including anterior-only fusion were compared. Clinical data (Visual Analog Scale score axial back pain scale, the Oswestry Disability Index, and a questionnaire of satisfaction regarding the surgical result); radiologic data (bone fusion, sagittal balance analysis); and adverse events were assessed using repeated measure 1-way analysis of variance. RESULTS: The mean follow-up was 9.5 years (95% confidence interval [7.1-12.2]) for the RA group (n = 13) and 9.4 years (95% confidence interval [8.7-10.3]) for the NRA group (n = 36). Anterior fusion improved clinical outcome without any effect of RA (Visual Analog Scale score axial back pain scale; P < 0.001/Oswestry Disability Index; P = 0.01). The presence of RA influenced neither the satisfaction as the regards the surgical result nor spine balance nor bone fusion. Context of RA increased the surgical revision rate (10 patients [76.9%] for RA group vs. 3 patients [8.8%] for the NRA group; P = 0.001) because of the occurrence of an adjacent segment disease needing surgical revision (P = 0.028), especially the occurrence of intervertebral frontal dislocation (P = 0.02). CONCLUSIONS: As noticed for posterior-only fusion, the anterior lumbar approach in RA patients does not seem to avoid the occurrence of an adjacent segment disease.

Determinants of the primary stability of cementless acetabular cup implants: A 3D finite element study.

Primary stability of cementless implants is crucial for the surgical success and long-term stability. However, primary stability is difficult to quantify in vivo and the biomechanical phenomena occurring during the press-fit insertion of an acetabular cup (AC) implant are still poorly understood. The aim of this study is to investigate the influence of the cortical and trabecular bone Young's moduli Ec and Et, the interference fit IF and the sliding friction coefficient of the bone-implant interface µ on the primary stability of an AC implant. For each parameter combination, the insertion of the AC implant into the hip cavity and consequent pull-out are simulated with a 3D finite element model of a human hemi-pelvis. The primary stability is assessed by determining the polar gap and the maximum pull-out force. The polar gap increases along with all considered parameters. The pull-out force shows a continuous increase with Ec and Et and a non-linear variation as a function of µ and IF is obtained. For µ > 0.6 and IF > 1.4 mm the primary stability decreases, and a combination of smaller µ and IF lead to a better fixation. Based on the patient's bone stiffness, optimal combinations of µ and IF can be identified. The results are in good qualitative agreement with previous studies and provide a better understanding of the determinants of the AC implant primary stability. They suggest a guideline for the optimal choice of implant surface roughness and IF based on the patient's bone quality.

Ankle osteonecrosis in fifty-one children and adolescent's leukemia survivors: a prospective randomized study on percutaneous mesenchymal stem cells treatment.

PURPOSE: Corticoid treatment associated with haematologic treatments can lead to ankle osteonecrosis in children's survivors of acute leukemia (ALL). Based on the efficiency of mesenchymal stem cells (MSCs) in hip osteonecrosis, we performed an evaluation of this treatment in 51 children and adolescents who had symptomatic ankle osteonecrosis after therapy for haematologic cancer. MATERIAL AND METHODS: The 51 patients had a total of 79 osteonecrosis sites on MRI, with 29 talus sites, 18 metaphyseal tibia sites, 12 epiphyseal tibia sites, eight calcaneus sites, six fibula sites, four navicular sites, and two cuboid sites. In this prospective randomized trial, 37 ankles were addressed for cell therapy, 37 others for core decompression alone, and 20 were considered as a control group without treatment. We analyzed the outcome of this treatment osteonecrosis, the number and characteristics of bone marrow mesenchymal cells (MSCs) that could be transplanted, and the risks of tumorigenesis in these patients with haematologic cancers. The patients were operated on over a period of ten years from 2000 to 2010 and were monitored through December 31, 2019. RESULTS: Despite a normal systemic blood cells count, MSCs in the iliac crest (counted as CFU-F) were in low number (1021 MSCs/mL; range 314-3015) and were of host origin after even allogeneic bone marrow transplantation. Better clinical outcomes (pain, foot and ankle deformity) and osteonecrosis repair on MRI with absence of collapse were obtained in ankles that received cell therapy as compared with those with core decompression alone or those without initial surgery. No tumour was found on MRI at the sites of injection and this study found no increased risk of recurrence or of new cancer in this population after an average follow-up of 15 years. CONCLUSIONS: These results suggest that autologous MSCs can improve the quality of life of leukemia survivors with ankle osteonecrosis.

Stress shielding at the bone-implant interface: Influence of surface roughness and of the bone-implant contact ratio.

Short and long-term stabilities of cementless implants are strongly determined by the interfacial load transfer between implants and bone tissue. Stress-shielding effects arise from shear stresses due to the difference of material properties between bone and the implant. It remains difficult to measure the stress field in periprosthetic bone tissue. This study proposes to investigate the dependence of the stress field in periprosthetic bone tissue on (i) the implant surface roughness, (ii) the material properties of bone and of the implant, (iii) the bone-implant contact ratio. To do so, a microscale two-dimensional finite element model of an osseointegrated bone-implant interface was developed where the surface roughness was modeled by a sinusoidal surface. The results show that the isostatic pressure is not affected by the presence of the bone-implant interface while shear stresses arise due to the combined effects of a geometrical singularity (for low surface roughness) and of shear stresses at the bone-implant interface (for high surface roughness). Stress-shielding effects are likely to be more important when the bone-implant contact ratio value is low, which corresponds to a case of relatively low implant stability. Shear stress reach a maximum value at a distance from the interface comprised between 0 and 0.1 time roughness wavelength λ and tend to 0 at a distance from the implant surface higher than λ, independently from bone-implant contact ratio and waviness ratio. A comparison with an analytical model allows validating the numerical results. Future work should use the present approach to model osseointegration phenomena.

Subchondral bone or intra-articular injection of bone marrow concentrate mesenchymal stem cells in bilateral knee osteoarthritis: what better postpone knee arthroplasty at fifteen years? A randomized study.

PURPOSE: There is an increasing number of reports on the treatment of knee osteoarthritis (OA) using mesenchymal stem cells (MSCs). However, it is not known what would better drive osteoarthritis stabilization to postpone total knee arthroplasty (TKA): targeting the synovial fluid by injection or targeting on the subchondral bone with MSCs implantation. METHODS: A prospective randomized controlled clinical trial was carried out between 2000 and 2005 in 120 knees of 60 patients with painful bilateral knee osteoarthritis with a similar osteoarthritis grade. During the same anaesthesia, a bone marrow concentrate of 40 mL containing an average 5727 MSCs/mL (range 2740 to 7540) was divided in two equal parts: after randomization, one part (20 mL) was delivered to the subchondral bone of femur and tibia of one knee (subchondral group) and the other part was injected in the joint for the contralateral knee (intra-articular group). MSCs were counted as CFU-F (colony fibroblastic unit forming). Clinical outcomes of the patient (Knee Society score) were obtained along with radiological imaging outcomes (including MRIs) at two year follow-up. Subsequent revision surgeries were identified until the most recent follow-up (average of 15 years, range 13 to 18 years). RESULTS: At two year follow-up, clinical and imaging (MRI) improvement was higher on the side that received cells in the subchondral bone. At the most recent follow-up (15 years), among the 60 knees treated with subchondral cell therapy, the yearly arthroplasty incidence was 1.3% per knee-year; for the 60 knees with intra-articular cell therapy, the yearly arthroplasty incidence was higher (p = 0.01) with an incidence of 4.6% per knee-year. For the side with subchondral cell therapy, 12 (20%) of 60 knees underwent TKA, while 42 (70%) of 60 knees underwent TKA on the side with intra-articular cell therapy. Among the 18 patients who had no subsequent surgery on both sides, all preferred the knee with subchondral cell therapy. CONCLUSIONS: Implantation of MSCs in the subchondral bone of an osteoarthritic knee is more effective to postpone TKA than injection of the same intra-articular dose in the contralateral knee with the same grade of osteoarthritis.

Total hip arthroplasty for sickle cell osteonecrosis: guidelines for perioperative management.

The prognosis of sickle cell disease (SCD) has greatly improved in recent years, resulting in an increased number of patients reporting musculoskeletal complications such as osteonecrosis of the femoral head. Total hip arthroplasty (THA) can be utilized to alleviate the pain associated with this disease.Although it is well known that hip arthroplasty for avascular necrosis (AVN) in SCD may represent a challenge for the surgeon, complications are frequent, and no guidelines exist to prevent these complications. Because patients with SCD will frequently undergo THA, we thought it necessary to fulfil the need for guidance recommendations based on experience, evidence and agreement from the literature.For all these reasons this review proposes guidelines that provide clinicians with a document regarding management of patients with SCD in the period of time leading up to primary THA. The recommendations provide guidance that has been informed by the clinical expertise and experience of the authors and available literature.Although this is not a systematic review since some papers may have been published in languages other than English, our study population consisted of 5,868 patients, including 2,126 patients with SCD operated on for THA by the senior author in the same hospital during 40 years and 3,742 patients reported in the literature. Cite this article: EFORT Open Rev 2020;5:641-651. DOI: 10.1302/2058-5241.5.190073.

Does augmented core decompression decrease the rate of collapse and improve survival of femoral head avascular necrosis? Case-control study comparing 184 augmented core decompressions to 79 standard core decompressions with a minimum 2 years' follow-up.

INTRODUCTION: Avascular necrosis of the femoral head often progresses to femoral head collapse if not treated. Conservative treatment yields highly variable results and is not standardised, mainly because it is typically evaluated in small patient populations. This led us to conduct a large retrospective comparative study with the goals of 1) analysing survival and functional outcomes, 2) looking for differences in survival between core decompression techniques (standard versus augmented), and 3) studying the risk factors for femoral head collapse and revision by arthroplasty. HYPOTHESIS: Core decompression limits the number of patients who suffer femoral head collapse requiring arthroplasty at 2 years' follow-up. METHODS: This multicentre, comparative, retrospective study analysed 330 patient records (1975-2016) where at least 2 years' follow-up was available. Sixty-two patients were excluded from the analysis: 5 had a stage III with collapse, 5 were lost to follow-up, 2 died within 24 months of the procedure and 50 had incomplete data. The study included 263 patients with a mean age of 42 years (15.7-70). In the Ficat classification, there were 51 cases of stage I necrosis, 186 cases of stage II and 22 cases of stage II with crescent sign (transition stage). The Kerboull angle on radiographs was between 5° and 20° in 40 patients, between 20° and 40° in 107 patients, between 40° and 60° in 52 patients and more than 60° in 29 patients. A standard core decompression was done in 79 patients and an augmented one in 184 patients. The more severe AVN cases (stage II) were more likely to be treated by augmented CD (160/184 patients, 87%) than by standard CD (48/79 patients, 61%) (p<0.001). RESULTS: In the 263 patients, the overall survival (no arthroplasty at 2 years) was 73% (196/263). At 2 years, the survival rate (without arthroplasty) was 71% (56/79) in the standard CD group versus 76% (140/184) in the augmented CD group. This difference was significant when adjusted for Ficat stage and Kerboull angle [HR=0.457, 95% CI (0.247-0.844) (p=0.012)]. When the survival data was adjusted to the Ficat stage, augmented CD was better than standard CD with 10-year survival of 58.1% vs. 57.9% (p=0.0082). More than 30% necrosis volume increased the risk of failure [HR=3.291 95%CI (1.494-7.248) (p=0.0031)]. Also, a Kerboull angle above 60° increased the risk of failure [HR=3.148 95%CI (1.346-7.5) (p=0.0083)]. CONCLUSION: After 2 years, CD for non-collapsed femoral head AVN prevents collapse and revision to arthroplasty in 73% of cases (196/268). Augmented CD improves the 2-year survival and the long-term survival after adjusting for preoperative characteristics (Kerboullangle and Ficat stage). The risk of collapse and need for arthroplasty is greater in patients with 30% necrosis volume on MRI and Kerboull angle above 60°. LEVEL OF EVIDENCE: III; retrospective case-control study.

Ex vivo estimation of cementless femoral stem stability using an instrumented hammer.

BACKGROUND: The success of cementless hip arthroplasty depends on the primary stability of the femoral stem. It remains difficult to assess the optimal number of impacts to guarantee the femoral stem stability while avoiding bone fracture. The aim of this study is to validate a method using a hammer instrumented with a force sensor to monitor the insertion of femoral stem in bovine femoral samples. METHODS: Different cementless femoral stem were impacted into five bovine femur samples, leading to 99 configurations. Three methods were used to quantify the insertion endpoint: the impact hammer, video motion tracking and the surgeon proprioception. For each configuration, the number of impacts performed by the surgeon until he felt a correct insertion was noted Nsurg. The insertion depth E was measured through video motion tracking, and the impact number Nvid corresponding to the end of the insertion was estimated. Two indicators, noted I and D, were determined from the analysis of the time variation of the force, and the impact number Nd corresponding to a threshold reached in D variation was estimated. FINDINGS: The pullout force of the femoral stem was significantly correlated with I (R2 = 0.81). The values of Nsurg, Nvid and Nd were similar for all configurations. INTERPRETATION: The results validate the use of the impact hammer to assess the primary stability of the femoral stem and the moment when the surgeon should stop the impaction procedure for an optimal insertion, which could lead to the development of a decision support system.

Early efficacy evaluation of mesenchymal stromal cells (MSC) combined to biomaterials to treat long bone non-unions.

BACKGROUND AND STUDY AIM: Advanced therapy medicinal products (ATMP) frequently lack of clinical data on efficacy to substantiate a future clinical use. This study aims to evaluate the efficacy to heal long bone delayed unions and non-unions, as secondary objective of the EudraCT 2011-005441-13 clinical trial, through clinical and radiological bone consolidation at 3, 6 and 12 months of follow-up, with subgroup analysis of affected bone, gender, tobacco use, and time since the original fracture. PATIENTS AND METHODS: Twenty-eight patients were recruited and surgically treated with autologous bone marrow derived mesenchymal stromal cells expanded under Good Manufacturing Practices, combined to bioceramics in the surgical room before implantation. Mean age was 39 ± 13 years, 57% were males, and mean Body Mass Index 27 ± 7. Thirteen (46%) were active smokers. There were 11 femoral, 4 humeral, and 13 tibial non-unions. Initial fracture occurred at a mean ± SD of 27.9 ± 31.2 months before recruitment. Efficacy results were expressed by clinical consolidation (no or mild pain if values under 30 in VAS scale), and by radiological consolidation with a REBORNE score over 11/16 points (value of or above 0.6875). Means were statistically compared and mixed models for repeated measurements estimated the mean and confidence intervals (95%) of the REBORNE Bone Healing scale. Clinical and radiological consolidation were analyzed in the subgroups with Spearman correlation tests (adjusted by Bonferroni). RESULTS: Clinical consolidation was earlier confirmed, while radiological consolidation at 3 months was 25.0% (7/28 cases), at 6 months 67.8% (19/28 cases), and at 12 months, 92.8% (26/28 cases including the drop-out extrapolation of two failures). Bone biopsies confirmed bone formation surrounding the bioceramic granules. All locations showed similar consolidation, although this was delayed in tibial non-unions. No significant gender difference was found in 12-month consolidation (95% confidence). Higher consolidation scale values were seen in non-smoking patients at 6 (p = 0.012, t-test) and 12 months (p = 0.011, t-test). Longer time elapsed after the initial fracture did not preclude the occurrence of consolidation. CONCLUSION: Bone consolidation was efficaciously obtained with the studied expanded hBM-MSCs combined to biomaterials, by clinical and radiological evaluation, and confirmed by bone biopsies, with lower consolidation scores in smokers.

Influence of positioning of L4-5 disc prostheses on functional outcomes and sagittal balance: 2-year follow-up of a cohort of 38 patients.

OBJECTIVE: The main objective of this study was to evaluate the influence of L4-5 total disc replacement (TDR) positioning on functional outcome at the 2-year follow-up. The secondary objective was to assess its influence on sagittal balance. METHODS: Prospective data were compiled for 38 single-level L4-5 ProDisc-O TDRs. Anteroposterior placement (APP) was the distance between the center of the implant and the center of the L5 endplate divided by the total length of the L5 endplate. This ratio was expressed as a percentage (APP 0%-49%, anterior off-centering; 50%, perfect centering; and 51%-100%, posterior off-centering). The patients were divided into 3 groups depending on the APP and using quartile values: group 1, anterior placement (APP 0%-46%); group 2, central placement (APP 46.1%-52%, the 2 central quartiles); and group 3, posterior placement (APP 52.1%-100%). The sagittal balance parameters assessed were overall lordosis, segmental lordosis, and pelvic incidence. Adequate lordosis was defined for each patient according to their pelvic incidence. The Oswestry Disability Index and visual analog scale (VAS) scores for back and leg pain were assessed. RESULTS: The average APP was 48% (range 40%-64%). There were 10 patients in group 1, 18 in group 2, and 10 in group 3. There was a significant difference in functional outcomes among the 3 groups. APP influenced the VAS back (p = 0.04) and VAS leg (p = 0.05) scores. Group 1 consistently showed the highest performance scores. No significant association between APP and the sagittal balance parameters was found. Patients who had preoperative sagittal imbalance or those who significantly modified their balance after the surgery had the poorest outcomes. CONCLUSIONS: Disc prostheses at L4-5 seem to provide better functional outcome when they are positioned anteriorly to the center of the vertebral body.

A cadaveric validation of a method based on impact analysis to monitor the femoral stem insertion.

The success of cementless hip arthroplasty depends on the primary stability of the femoral stem (FS). It remains difficult to assess the optimal impaction energy to guarantee the FS stability while avoiding bone fracture. The aim of this study is to compare the results of a method based on the use of an instrumented hammer to determine the insertion endpoint of cementless FS in a cadaveric model with two other methods using i) the surgeon proprioception and ii) video motion tracking. Different FS were impacted in nine human cadaveric femurs. For each configuration, the number of impacts realized when the surgeon felt that the FS was correctly inserted was noted Nsurg. For each impact, the insertion depth E was measured and an indicator D was determined based on the time-variation of the force. The impact number Nvid (respectively Nd), corresponding to the end of the migration phase, was estimated analyzing the evolution of E (respectively D). The respective difference between Nsurg, Nvid and Nd was similar and lower than 3 for more than 85% of the configurations. The results allow a validation of the use of an impact hammer to assess the moment when the surgeon should stop the impaction, paving the way towards the development of a decision support system to assist the surgeon.

Contribution of adipocyte precursors in the phenotypic specificity of intra-articular adipose tissues in knee osteoarthritis patients.

BACKGROUND: Intra-articular adipose tissues (IAATs) are involved in osteoarthritis (OA) pathophysiology. We hypothesize that mesenchymal cells residing in IAATs may account for the specific inflammatory and metabolic patterns in OA patients. METHODS: Adipocyte precursors (preadipocytes and dedifferentiated fat cells (DFATc)) from IAATs (infrapatellar and suprapatellar fat pads) and autologous subcutaneous adipose tissues (SCATs) were isolated from knee OA patients. The ability of these precursors to differentiate into adipocytes was assessed by oil red O staining after 14 days of culture in adipogenic medium. The gene expression of adipocyte-related transcription factors (C/EBP-α and PPAR-γ) and development-related factors (EN1 and SFRP2) were analyzed. The inflammatory pattern was assessed by RT-qPCR and ELISA (interleukin 6 (IL-6), IL-8, Cox2, and prostaglandin E2 (PGE2)) after a 24-h stimulation by IL-1ß (1 ng/mL) and by conditioned medium from OA synovium. RESULTS: IAAT preadipocytes displayed a significantly higher ability to differentiate into adipocytes and expressed significantly more C/EBP-α mRNA than SCAT preadipocytes. IAAT preadipocytes expressed significantly less EN-1 and SFRP2 mRNA than SCAT preadipocytes. Unstimulated IAAT preadipocytes displayed a less inflammatory pattern (IL-6, IL-8, and Cox2/PGE2) than SCAT preadipocytes. In contrast, the response of IAAT preadipocytes to an inflammatory stimulus (IL-1ß and conditioned media of OA synovium) was exacerbated compared to that of SCAT preadipocytes. Similar results were obtained with DFATc. CONCLUSION: IAAT adipocyte precursors from OA patients have a specific phenotype, which may account for the unique phenotype of OA IAATs. The exacerbated response of IAAT preadipocytes to inflammatory stimulation may contribute to OA pathophysiology.

Dependence of the primary stability of cementless acetabular cup implants on the biomechanical environment.

Biomechanical phenomena occurring at the bone-implant interface during the press-fit insertion of acetabular cup implants are still poorly understood. This article presents a nonlinear geometrical two-dimensional axisymmetric finite element model aiming at describing the biomechanical behavior of the acetabular cup implant as a function of the bone Young's modulus Eb, the diametric interference fit (IF), and the friction coefficient µ. The numerical model was compared with experimental results obtained from an in vitro test, which allows to determine a reference configuration with the parameter set: µ* = 0.3, Eb*=0.2GPa, and IF* = 1 mm for which the maximal contact pressure tN = 10.7 MPa was found to be localized at the peri-equatorial rim of the acetabular cavity. Parametric studies were carried out, showing that an optimal value of the pull-out force can be defined as a function of µ, Eb, and IF. For the reference configuration, the optimal pull-out force is obtained for µ = 0.6 (respectively, Eb = 0.35 GPa and IF = 1.4 mm). For relatively low value of µ (µ < 0.2), the optimal value of IF linearly increases as a function of µ independently of Eb, while for µ > 0.2, the optimal value of IF has a nonlinear dependence on µ and decreases as a function of Eb. The results can be used to help surgeons determine the optimal value of IF in a patient specific manner.

Is the discopathy associated with Modic changes an infectious process? Results from a prospective monocenter study.

BACKGROUND: The local infectious origin and the putative role of Cutibacterium acnes (CA) of a particular subtype of discopathy (Modic 1) are still debated. PURPOSE: To establish the association of CA in intervertebral disc (IVD) and Modic 1 discopathy in patients with low back pain. METHODS: The prevalence of bacteria in IVD samples obtained by anterior approach in patient with chronic low back pain harboring Modic type 1, 2 or no Modic changes was compared to that measured in IVD samples obtained by posterior approach for sciatica. From 45 patients included in the study, 77 discs samples were obtained: 58 by anterior approach (32 Modic 1/2 changes, 26 without Modic change) and 19 by posterior approach. Conventional microbial cultures, universal 16S rRNA molecular detection and a CA specific PCR were performed. RESULTS: 12 /77 (15.6%) disc samples were culture positive. Among the 10 CA positive cultures, 5 out of 58 (8.6%) were identified from specimens obtained by anterior approach and 5/19 (26.3%) from posterior approach (p = 0.046). Moreover, the percentage of CA culture positive sample was statistically no different between the patient with or without Modic changes. The CA prevalence was lower through molecular, culture-free approaches: the universal 16S rRNA PCR was positive for 6 specimens, including one CA positive sample and the CA specific PCR was positive for one specimen obtained by posterior approach. CONCLUSIONS: In spine surgery the prevalence of CA in culture was significantly higher in IVD samples collected through a posterior approach compared to an anterior approach, suggesting a contamination process. This study did not support the CA related local infectious origin of Modic 1 discopathy.

Risk factors of instrumentation failure and pseudarthrosis after stand-alone L5-S1 anterior lumbar interbody fusion: a retrospective cohort study.

OBJECTIVE: L5-S1 stand-alone anterior lumbar interbody fusion (ALIF) is a reliable technique to treat symptomatic degenerative disc disease but remains controversial for treatment of isthmic spondylolisthesis. In the present study the authors aimed to identify risk factors of instrumentation failure and pseudarthrosis after stand-alone L5-S1 ALIF and to evaluate whether instrumentation failure influenced the rate of fusion. METHODS: The study included 64 patients (22 [34.4%] male and 42 [65.6%] female, mean age 46.4 years [range 21-65 years]) undergoing stand-alone L5-S1 ALIF using radiolucent anterior cages with Vertebridge plating fixation in each vertebral endplate. Clinical and radiographic data were reviewed, including age, sex, pelvic parameters, segmental sagittal angle (SSA), C7/sacro-femoral distance (SFD) ratio, C7 sagittal tilt, lumbar lordosis (LL), segmental LL, percentage of L5 slippage, L5-S1 disc angle, and posterior disc height ratio. Univariate and multivariate analyses were used to identify risk factors of instrumentation failure and pseudarthrosis. RESULTS: At a mean follow-up of 15.9 months (range 6.6-27.4 months), fusion had occurred in 57 patients (89.1%). Instrumentation failure was found in 12 patients (18.8%) and pseudarthrosis in 7 patients (10.9%). The following parameters influenced the occurrence of instrumentation failure: presence of isthmic spondylolisthesis (p < 0.001), spondylolisthesis grade (p < 0.001), use of an iliac crest bone autograft (p = 0.04), cage height (p = 0.03), pelvic incidence (PI) (p < 0.001), sacral slope (SS) (p < 0.001), SSA (p = 0.003), and LL (p < 0.001). Instrumentation failure was statistically linked to the occurrence of L5-S1 pseudarthrosis (p < 0.001). On multivariate analysis, no risk factors were found. CONCLUSIONS: L5-S1 isthmic spondylolisthesis and high PI seem to be risk factors for instrumentation failure in case of stand-alone L5-S1 ALIF, findings that support the necessity of adding percutaneous posterior pedicle screw instrumentation in these cases.

Feasibility and safety of treating non-unions in tibia, femur and humerus with autologous, expanded, bone marrow-derived mesenchymal stromal cells associated with biphasic calcium phosphate biomaterials in a multicentric, non-comparative trial.

BACKGROUND: ORTHO-1 is a European, multicentric, first in human clinical trial to prove safety and feasibility after surgical implantation of commercially available biphasic calcium phosphate bioceramic granules associated during surgery with autologous mesenchymal stromal cells expanded from bone marrow (BM-hMSC) under good manufacturing practices, in patients with long bone pseudarthrosis. METHODS: Twenty-eight patients with femur, tibia or humerus diaphyseal or metaphyso-diaphyseal non-unions were recruited and surgically treated in France, Germany, Italy and Spain with 100 or 200 million BM-hMSC/mL associated with 5-10 cc of bioceramic granules. Patients were followed up during one year. The investigational advanced therapy medicinal product (ATMP) was expanded under the same protocol in all four countries, and approved by each National Competent Authority. FINDINGS: With safety as primary end-point, no severe adverse event was reported as related to the BM-hMSC. With feasibility as secondary end-point, the participating production centres manufactured the BM-hMSC as planned. The ATMP combined to the bioceramic was surgically delivered to the non-unions, and 26/28 treated patients were found radiologically healed at one year (3 out of 4 cortices with bone bridging). INTERPRETATION: Safety and feasibility were clinically proven for surgical implantation of expanded autologous BM-hMSC with bioceramic. FUNDING: EU-FP7-HEALTH-2009, REBORNE Project (GA: 241876).

[Hip osteoarthritis]. / Coxarthrose.

HIP OSTEOARTHRITIS. The hip is a common localization for osteoarthritis. Hip osteoarthritis can have a profound effect on daily life activities, such as walking and using the stairs. Hip osteoarthritis can be broadly categorized into two types: primary and secondary. In primary hip osteoarthritis, the disease is of idiopathic origin and it affects a relatively elderly population. Secondary hip osteoarthritis is a monoarticular condition and develops as a result of an underlying pathology modifying the articular surface.

COXARTHROSE. L'articulation de la hanche est fréquemment le siège d'arthrose. En tant que telle, l'arthrose peut avoir un retentissement important sur les activités de la vie quotidienne et entraîner une invalidité et une dépendance importantes à la marche et lors de la pratique des escaliers. La coxarthrose peut être globalement classée en deux types, primitive et secondaire. En cas d'arthrose primitive, la maladie est d'origine idiopathique (aucune cause connue) et touche généralement plusieurs articulations d'une population relativement âgée. L'arthrose secondaire est généralement une affection mono-articulaire et se développe à la suite d'une anomalie sous-jacente affectant la surface articulaire.