Spinopelvic interactions in total hip arthroplasty: 295 patients followed for a minimum follow-up of 10 years.

BACKGROUND: Concurrent spinal pathology is frequent in patients undergoing total hip arthroplasty (THA). In this study we examined whether spinopelvic interactions affect THA outcomes at a minimum follow-up of 10 years. PATIENTS AND METHODS: 295 patients with a mean age of 63.3 (range 56‒80) years receiving a THA between 2006 and 2009 were assessed. Of these, 195 had mild lumbar disc degeneration and 100 had advanced lumbar spondylosis. We analysed the changes in the Harris Hip Score (HHS) and the survival rate for postoperative low back pain (LBP) and dislocation. Changes in acetabular component position, sacro-femoral-pubic (SFP) and pelvic obliquity (PO) angles were assessed with radiological images. RESULTS: The mean HHS was lower in female patients (p = 0.009), patients >65 years of age (p < 0.001) and those with advanced lumbar spondylosis (p = 0.002). 52 (71.2%) of the patients reporting preoperative LBP experienced improvement after THA while 47 (21.1%) of those without preoperative LBP postoperatively reported new onset LBP. Female patients (p = 0.025; hazard ratio [HR]: 1.831; 95% CI, 1.081-3.101) and those with preoperative LBP (p = 0.007; HR 2.068; 95% CI, 1.221-3.504) were at a higher risk of developing postoperative LBP at 10 years. 4 out of 9 THA dislocations were late and had shown decreasing SFP angle values over time. Acetabular component inclination and anteversion angles increased over time, whereas the SFP angle was associated with sex and age and the PO angle with age and the severity of any preoperative lumbar degeneration. CONCLUSIONS: Concurrent spinal pathology influences THA outcomes at a minimum follow-up of 10 years. Sex, age, and associated lumbar degeneration can affect clinical and radiological changes over time. A decrease in SFP angle values over time was found in patients sustaining late dislocation.

Long-term results of total hip arthroplasty in severe congenital hip disease: A ten- to 20-year follow-up study.

INTRODUCTION: The impact of bone deformities, previous surgeries, and the surgical technique in total hip arthroplasty (THA) for congenital dislocation of the hip (CDH) at a long-term has not been clearly defined yet. In this single-centre observational study we sought to assess patients undergoing THA due to osteoarthritis secondary to severe CDH with low or high dislocation ten- to 20-years after surgery. To determine this purpose, we assessed: (1) THA-related complications and reoperations; (2) the clinical outcome, patients' satisfaction and radiological results; and (3) the possible risk factors for reoperation with particular attention to the surgical technique and the influence of prior surgeries. HYPOTHESIS: We hypothesized that an anatomical reconstruction of the hip would decrease the reoperations rates in patients undergoing THA with severe CDH. METHODS: Seventy-five patients (85 hips) operated between 1999 and 2012 at our large tertiary hospital were analyzed. Fifty-six hips were diagnosed as low dislocation (group 1) and 29 hips as high dislocation (group 2). The existence of prior surgeries was frequent: group 1, pelvic osteotomies 6 hips, femoral osteotomies 7, tectoplasty (shelf) 6, resection arthroplasty 1 and lowering of the greater trochanter 1; group 2 included pelvic osteotomies 10 hips, femoral osteotomies 10, and a femoral lengthening 2. The number of additional procedures during THA was: group 1 (19/56 [34%]), acetabular roof bone autograft 8 hips, acetabular medial wall autograft 2, hardware removal 6, extended femoral osteotomy 2, and a femoral shortening 1; group 2 (20/29 [69%]), acetabular bone autograft 12 hips, medial autograft 1, hardware removal 1, extended femoral osteotomy 2, and a femoral shortening 4 hips. The clinical and the radiological analysis were compared in both groups for a minimum follow-up of ten years. Cox regression models were used to detect risk factors for reoperation. RESULTS: Nine patients (13.8%) required reoperation for the following reasons: cup loosening (5 hips), periprosthetic femoral fracture (3) and stem loosening (1); seven had prior surgeries. The 12-year survival rate for reoperation for any reason was 96.3% (95% confidence interval [CI] 91.2-100) in group 1 and 75.7% (95% CI, 65.8-90.8) in group 2 (p=0.003). Patients with high dislocation (p=0.02, hazard ratio [HR]: 6.25, 95% CI, 1.26-30.9) and those with an acetabular component inclination placed out of the target zone between 35° and 50° (p=0.03, HR: 4.27, 95% CI, 1.13-16.1) had a higher risk of reoperation. DISCUSSION: An optimal placement of the acetabular component decreased the reoperation rates in patients undergoing THA for severe CDH. Hips with high dislocation and the existence of prior surgery can affect THA implantation. LEVEL OF EVIDENCE: III; retrospective; comparative.

1st EFORT European Consensus "Medical & Scientific Research Requirements for the Clinical Introduction of Artificial Joint Arthroplasty Devices": Background, Delphi Methodology & Consensus process.

The objectives of the 1st EFORT European Consensus on 'Medical and Scientific Research Requirements for the Clinical Introduction of Artificial Joint Arthroplasty Devices' were foremost to focus on patient safety by establishing performance requirements for medical devices. The 1st EFORT European Consensus applied an a priori-defined, modified Delphi methodology to produce unbiased, high-quality recommendation statements, confirmed by consensus voting of a European expert panel. Intended key outcomes are practical guidelines justified by the current stage of knowledge and based on a broad European Expert Consensus, to maintain innovation and optimisation of orthopaedic devices within the boundaries of MDR 2017/745. Twenty-one main research areas of relevance were defined relying on input from the EFORT IPSI WG1 'Introduction of Innovation' recommendations and a related survey. A modified Delphi approach with a preparatory literature review and work in small groups were used to prepare answers to the research questions in the form of 32 draft Consensus statements. A Consensus Conference in a hybrid format, on-site in the Carl Gustav Carus University of Dresden was organised to further refine the draft statements and define consensus within the complete group of participants by final voting, intended to further quantify expert opinion knowledge. The modified Delphi approach provides practical guidelines for hands-on orientation for orthopaedic surgeons, research institutes and laboratories, orthopaedic device manufacturers, patient representatives, Notified Bodies, National Institutes and authorities. For the first time, initiated by the EFORT IPSI (WG1 'Introduction of Innovation'), knowledge of all related stakeholders was combined in the 1st EFORT European Consensus to develop guidelines and result in a comprehensive set of recommendations.

New polyethylenes in total hip arthroplasty : a 20- to 22-year follow-up study.

AIMS: A significant reduction in wear at five and ten years was previously reported when comparing Durasul highly cross-linked polyethylene with nitrogen-sterilized Sulene polyethylene in total hip arthroplasty (THA). We investigated whether the improvement observed at the earlier follow-up continued, resulting in decreased osteolysis and revision surgery rates over the second decade. METHODS: Between January 1999 and December 2001, 90 patients underwent surgery using the same acetabular and femoral components with a 28 mm metallic femoral head and either a Durasul or Sulene liner. A total of 66 hips of this prospective randomized study were available for a minimum follow-up of 20 years. The linear femoral head penetration rate was measured at six weeks, one year, and annually thereafter, using the Dorr method on digitized radiographs with a software package. RESULTS: In the Durasul group, no patients underwent revision due to loosening or showed radiological evidence of osteolysis. In the Sulene group, four patients (four hips) were revised due to femoral component loosening. The 20-year cumulative failure incidence in the presence of the competing event of death for revision surgery was 4.5% (95% confidence interval (CI) 0.8 to 13.6) in the Durasul group, and 8.9% (95% CI 2.8 to 19.5) in the Sulene group. The mean wear one year after surgery was 0.09 mm (SD 0.007) in the Durasul group and 0.24 (SD 0.015) in the Sulene group (p < 0.001). From one to 20 years after surgery, the mean total penetration was 0.32 mm (SD 0.045) in the Durasul group and 1.07 mm (SD 0.13) in the Sulene group (p < 0.001). Mean femoral head penetration at 20 years was approximately 70.0% less in the Durasul group than the Sulene group. CONCLUSION: The significant reduction in femoral head penetration obtained with the Durasul compared with Sulene in uncemented THA resulted in lower osteolysis and revision rates after 20 years.Cite this article: Bone Joint J 2022;104-B(9):1032-1038.

Factores de riesgo de luxación en una serie de 2732 prótesis totales de cadera / Risk Factors for Dislocation in a Series of 2732 Total Hip Replacements

Introducción: La luxación de la prótesis total de cadera puede afectar los resultados del implante, la calidad de vida del paciente, y el costo del proceso. Su etiología es multifactorial. Objetivos: Identificar posibles factores de riesgo relacionados con la aparición de luxación en prótesis total de cadera en una serie de casos. Métodos: En una serie de 2732 prótesis total de cadera, en la que hubo 92 luxaciones (3,4 por ciento), se compararon factores relacionados con el paciente, el implante, y la técnica quirúrgica uilizada en el Hospital La Paz-IDIPaz de Madrid entre los años 2000 y 2016. Se utilizó el análisis de regresión para la significación de dichos factores. Resultados: De las 92 luxaciones, 62 fueron tratadas de manera conservadora (67,4 por ciento) y 30 pacientes precisaron de cirugía de revisión (32,6 por ciento). El estudio multivariado mostró significación estadística en los siguientes factores de riesgo: estado de la columna lumbar (p < 0,001), y una pobre reconstrucción del centro de rotación de la cadera (p= 0,035), y cúpulas posicionadas fuera de las ventanas de Lewinnek (p < 0,001) y del mecanismo abductor (p < 0,001) en relación con la técnica quirúrgica. No hubo factores significativos en relación con el tipo de implante, diámetro de la cabeza femoral o par de fricción. Conclusiones: La patología lumbar aumenta el riesgo de luxación en la prótesis total de cadera. Una adecuada reconstrucción de la cadera, que incluya la posición de la cúpula y el centro de rotación de la cadera, así como del mecanismo abductor ayudaría a mejorar la tasa de inestabilidad(AU)

Introduction: The dislocation of the total hip replacement can affect the results of the implant, the quality of life of the patient, and the cost of the process. Its etiology is multifactorial. Objectives: To identify possible risk factors related to the appearance of dislocation in total hip replacement in a series of cases. Methods: In a series of 2732 total hip prostheses, in which there were 92 dislocations (3.4percent), factors related to the patient, the implant, and the surgical technique used at La Paz-IDIPaz Hospital in Madrid were compared, from 2000 to 2016. Regression analysis was used for the significance of these factors. Results: Out of 92 dislocations, 62 were treated conservatively (67.4 percent) and 30 patients required revision surgery (32.6 pecent). The multivariate study showed statistical significance in the following risk factors: state of the lumbar spine (p <0.001), and poor reconstruction of the center of rotation of the hip (p = 0.035), and domes positioned outside Lewinnek windows (p <0.001) and the abductor mechanism (p <0.001) in relation to the surgical technique. There were no significant factors in relation to the type of implant, diameter of the femoral head or friction torque. Conclusions: Lumbar pathology increases the risk of dislocation in total hip replacement. Proper hip reconstruction, including the position of the dome and the center of rotation of the hip, as well as the abductor mechanism, would help to improve the rate of instability(AU)

Osteoblast function in patients with idiopathic osteonecrosis of the femoral head : implications for a possible novel therapy.

AIMS: To investigate whether idiopathic osteonecrosis of the femoral head (ONFH) is related to impaired osteoblast activities. METHODS: We cultured osteoblasts isolated from trabecular bone explants taken from the femoral head and the intertrochanteric region of patients with idiopathic ONFH, or from the intertrochanteric region of patients with osteoarthritis (OA), and compared their viability, mineralization capacity, and secretion of paracrine factors. RESULTS: Osteoblasts from the intertrochanteric region of patients with ONFH showed lower alkaline phosphatase (ALP) activity and mineralization capacity than osteoblasts from the same skeletal site in age-matched patients with OA, as well as lower messenger RNA (mRNA) levels of genes encoding osteocalcin and bone sialoprotein and higher osteopontin expression. In addition, osteoblasts from patients with ONFH secreted lower osteoprotegerin (OPG) levels than those from patients with OA, resulting in a higher receptor activator of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) ligand (RANKL)-to-OPG ratio. In patients with ONFH, osteoblasts from the femoral head showed reduced viability and mineralized nodule formation compared with osteoblasts from the intertrochanteric region. Notably, the secretion of the pro-resorptive factors interleukin-6 and prostaglandin E2 as well as the RANKL-to-OPG ratio were markedly higher in osteoblast cultures from the femoral head than in those from the intertrochanteric region. CONCLUSION: Idiopathic ONFH is associated with a reduced mineralization capacity of osteoblasts and increased secretion of pro-resorptive factors. Cite this article: Bone Joint Res 2021;10(9):619-628.

Impaction bone grafting in hip re-revision surgery.

AIMS: Bone stock restoration of acetabular bone defects using impaction bone grafting (IBG) in total hip arthroplasty may facilitate future re-revision in the event of failure of the reconstruction. We hypothesized that the acetabular bone defect during re-revision surgery after IBG was smaller than during the previous revision surgery. The clinical and radiological results of re-revisions with repeated use of IBG were also analyzed. METHODS: In a series of 382 acetabular revisions using IBG and a cemented component, 45 hips (45 patients) that had failed due to aseptic loosening were re-revised between 1992 and 2016. Acetabular bone defects graded according to Paprosky during the first and the re-revision surgery were compared. Clinical and radiological findings were analyzed over time. Survival analysis was performed using a competing risk analysis. RESULTS: Intraoperative bone defect during the initial revision included 19 Paprosky type IIIA and 29 Paprosky type IIIB hips; at re-revision, seven hips were Paprosky type II, 27 type IIIA and 11 were type IIIB (p = 0.020). The mean preoperative Harris Hip Score was 45.4 (SD 6.4), becoming 80.7 (SD 12.7) at the final follow-up. In all, 12 hips showed radiological migration of the acetabular component, and three required further revision surgery. The nine-year cumulative failure incidence (nine patients at risk) of the acetabular component for further revision surgery was 9.6% (95% confidence interval (CI) 2.9 to 21.0) for any cause, and 7.5% (95% CI 1.9 to 18.5) for aseptic loosening. Hips with a greater hip height had a higher risk for radiological migration (odds ratio 1.09, 95% CI 1.02 to 1.17; p = 0.008). CONCLUSION: Bone stock restoration can be obtained using IBG in revision hip surgery. This technique is also useful in re-revision surgery; however, a better surgical technique including a closer distance to hip rotation centre could decrease the risk of radiological migration of the acetabular component. A longer follow-up is required to assess potential fixation deterioration. Cite this article: Bone Joint J 2021;103-B(3):492-499.

Wear of hip prostheses increases serum IGFBP-1 levels in patients with aseptic loosening.

The biological mechanisms involved in aseptic loosening include inflammation-associated and bone resorption-associated processes. Coordinated cellular actions result in biochemical imbalances with devastating consequences for the joint. Given that this condition is not known for showing systemic signs, we investigated whether circulating levels of inflammation-related proteins are altered in patients with aseptic loosening. Our study included 37 patients who underwent revision surgery due to hip osteolysis and aseptic loosening and 31 patients who underwent primary total hip arthroplasty. Using antibody arrays, we evaluated the serum levels of 320 proteins in four patients from each group. The results showed differences in insulin-like growth factor-binding protein 1 (IGFBP-1) concentrations, which we then quantified using enzyme-linked immunosorbent assay tests in all study patients. The results confirmed that serum IGFBP-1 concentrations were higher in the revision surgery patients than in the hip arthroplasty patients. In vitro studies showed that exposure of human osteoblasts to titanium particles induced an IGFBP-1 release that further increased when exposure to particles was performed in media conditioned by human M1 macrophages. These findings suggest that elevated serum IGFBP-1 levels in patients with aseptic loosening can arise from increased local IGFBP-1 production in the inflammatory environment of the periprosthetic bed.

Do trabecular metal cups achieve better results when compared to hemispherical porous titanium cups in acetabular revision surgery?

BACKGROUND: Trabecular metal (TM) cups were introduced in order to achieve better ingrowth and stability of the cup in acetabular revision surgery. As their use has evolved over time, we have queried whether TM cups would improve results in terms of the rate of aseptic loosening when compared to historical uncemented porous titanium cups used in revision surgery for acetabular bone loss in Hospital La Paz (Madrid, Spain). METHODS: We retrospectively reviewed 197 acetabular revisions performed between 1991 and 2015. Titanium cups were used in 81 cases and TM cups in 116. The mean follow-up was 8.1 years (range 1-15); 12.0 ± 7.8 for titanium group and 5.4 ± 3.1 for TM group. The most common reason for revision was aseptic loosening. A Kaplan-Meier analysis was used to determine the survival of the cup, with radiological failure and re-revision due to aseptic loosening as the endpoints. Cox multivariate regression analyses were performed to assess different risk factors for failure. RESULTS: 1 TM cup and 1 titanium cup were re-revised due to aseptic loosening (p = 0.61). Radiological cup loosening was observed in 4 TM cups and 2 titanium cups (p = 1.0). At 6 years, the probability of not having radiological cup loosening was 97.4% (95% CI, 93.9-100) for the titanium cups and 95.1% for the TM cups (95% CI, 90.1-99.9) (p = 0.59). Another 5 cups were re-revised due to dislocation. Hips with a greater Paprosky defect showed a higher risk of loosening (p < 0.05, hazard risk (HR) 3.04; 95% CI, 0.97-9.54). CONCLUSIONS: This study shows there was no significant difference in re-revision due to aseptic loosening or radiological loosening between titanium and TM cups in revision surgery for acetabular bone loss. Both types of cups demonstrate excellent results with a low failure rate and minimal complications.

The fate of sagittal alignment in tapered uncemented femoral components in total hip arthroplasty: 889 hips followed for a minimum of 10 years.

PURPOSE: Aseptic loosening is rare after primary total hip arthroplasty (THA) with mostly uncemented tapered stems; however, different factors can modify the results. We question whether 3 different current femoral components and/or the surgical technique affect the clinical and radiological outcome after a minimum follow-up of 10 years. METHODS: 889 uncemented tapered stems implanted from 1999 to 2007 were evaluated for a minimum follow-up of 10 years. Group 1 (273 hips) shared a conical shape and a porous-coated surface, group 2 (286 hips) a conical splined shape and group 3 (330 hips) a rectangular grit-blasted stem. Groups 1 and 2 were implanted through a posterolateral approach and group 3 using an anterolateral approach. Clinical outcomes and anteroposterior and sagittal radiographic analyses were compared. RESULTS: No thigh pain was reported in unrevised patients. Mean Harris Hip score was lower for patients in group 3 for pain and function at all intervals. 14-year implant survival for aseptic loosening was 98.2% (95% confidence interval [CI] 96.2-100) in group 3. No revision for aseptic loosening was found with the other designs. A stem position outside neutral limits in the sagittal alignment (p = 0.001, hazard ratio: 6.17, 95% CI, 2.05-18.61) was associated with aseptic loosening in group 3. CONCLUSIONS: Most current uncemented straight tapered femoral components can provide adequate bone fixation in primary THA after 10 years. Conical stems inserted through a posterolateral approach are more reliable than rectangular ones inserted through an anterolateral approach.

Ceramic-on-ceramic cementless total hip arthroplasty in patients aged 40 years or under: Do preoperative conditions affect long-term results?

INTRODUCTION: Underlying diseases, bone deformities and polyethylene wear affect outcome in young patients undergoing total hip arthroplasty (THA). These issues are not widely confirmed for ceramic - on-ceramic THA, particularly regarding cup fixation. Therefore, we did a retrospective long-term investigation on a large population of cementless ceramic-on-ceramic THA in patients aged 40 years or younger aiming to analyze: 1) the complication rate; 2) clinical results; and 3) survival for cup loosening with regard to their preoperative conditions. HYPOTHESIS: Cup loosening could be related to preoperative diagnosis in young patients with a cementless ceramic-on-ceramic THA. PATIENTS AND METHODS: Two hundred and seven hips in 171 patients (97 men and 74 women) underwent a cementless ceramic-on-ceramic THA at a mean age of 31.6±6.8 years. The most frequent diagnoses were avascular necrosis (AVN) of the femoral head (74 hips), pediatric hip diseases (35 hips), severe congenital hip dysplasia (CHD) (31 hips), juvenile rheumatoid arthritis (30 hips) and mild CHD (26 hips). The prosthesis included a press-fit metal backed cup with a hydroxyapatite coating and a macrotexture surface on either the equatorial region (93 cups) or the entire surface of the shell (114 cups). Ceramics were made of pure alumina and had a femoral head size of 28 (60 hips) or 32mm (147 hips). In all cases same the straight cementless tapered stem was inserted. RESULTS: There were three early dislocations, one requiring cup revision No hip was revised due to infection, ceramic fracture, or femoral component loosening. Eight cups were revised for aseptic loosening (3,8%). The mean preoperative Harris Hip score was 52.8±6.2 and 93.4±6.9 at the end of follow-up. It was better in AVN (95.7±2.3) and worst in severe CHD (88.8±11.8) (p=0.001). If the end-point was cup aseptic loosening, the survival rate at 17 years was 95.1% (95% CI: 91.3-98.9), 100% for AVN and post-traumatic arthritis, and 86.8% (95% CI: 74.9-98.7) for severe CHD. CONCLUSIONS: Despite diagnoses frequently causing technical difficulties at the surgery, outcome of cementless ceramic-on-ceramic THA in patients under the age of 40 years is satisfactory over ten years of follow up. Cup aseptic loosening was the main cause of failure and appears more related to the initial hip diseases than the age of the patient. LEVEL OF EVIDENCE: III; retrospective comparative study.

Pelvic motion the key to understanding spine-hip interaction.

Pelvic motion acting as a hinge between the spine and hips is essential to maintain proper balance during bipedalism. Pelvic rotation is recruited as a compensation mechanism when spinal malalignment occurs.This pelvic rotation can affect functional acetabular orientation, and consequently functional cup positioning if a total hip arthroplasty (THA) is needed. Pelvic retroversion, frequently associated with degenerative spinal changes, implies an increase of acetabular version.Patients with flexible lumbar spines (spine users) protect the hip joint. Patients with stiff, degenerated or fused lumbar spines (hip users) demand higher hip mobility, placing the THA at risk.Pelvises in retroversion place the THA at risk for anterior dislocation when standing. In contrast, pelvises in anteversion or with low pelvic incidence (PI) can place THA at risk for posterior dislocation when sitting.Try to set the cup in an anatomic position. However, bear in mind that low PI pelvises may need more acetabular ante-inclination, and high PI pelvises more acetabular retroversion.If surgery is needed, start first by addressing the hip, except in patients with compensation (high pelvic retroversion), who may need spine surgery first to place the pelvis, and consequently the acetabulum, in a proper position. Cite this article: EFORT Open Rev 2020;5:522-533. DOI: 10.1302/2058-5241.5.200032.

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 inflammatory conditions provided by macrophages on osteogenic ability of mesenchymal stem cells.

BACKGROUND: The mechanisms by which macrophage phenotype contributes to mesenchymal stem cells (MSC)-mediated bone repair remain unclear. In this work, we investigated the influence of factors released by human macrophages polarized to a pro-inflammatory or an anti-inflammatory phenotype on the ability of human MSC to attach, migrate, and differentiate toward the osteoblastic lineage. We focused on the role of TNF-α and IL-10, key pro-inflammatory and anti-inflammatory cytokines, respectively, in regulating MSC functions. METHODS: MSC were treated with media conditioned by pro-inflammatory or anti-inflammatory macrophages to study their influence in cell attachment, migration, and osteogenic differentiation. The involvement of TNF-α and IL-10 in the regulation of MSC functions was investigated using neutralizing antibodies and recombinant cytokines. RESULTS: Treatment of MSC with media conditioned by pro-inflammatory or anti-inflammatory macrophages promoted cell elongation and enhanced MSC ability to attach and migrate. These effects were more noticeable when MSC were treated with media from pro-inflammatory macrophages. Interestingly, MSC osteogenic activity was enhanced by factors released by anti-inflammatory macrophages, but not by pro-inflammatory macrophages. Significant IL-10 levels originated from anti-inflammatory macrophages enhanced MSC osteogenesis by increasing ALP activity and mineralization in MSC layers cultured under osteogenic conditions. Moreover, macrophage-derived IL-10 regulated the expression of the osteogenic markers RUNX2, COL1A1, and ALPL. Notably, low TNF-α levels secreted by anti-inflammatory macrophages increased ALP activity in differentiating MSC whereas high TNF-α levels produced by pro-inflammatory macrophages had no effects on osteogenesis. Experiments in which MSC were treated with cytokines revealed that IL-10 was more effective in promoting matrix maturation and mineralization than TNF-α. CONCLUSIONS: Factors secreted by pro-inflammatory macrophages substantially increased MSC attachment and migration whereas those released by anti-inflammatory macrophages enhanced MSC osteogenic activity as well as cell migration. IL-10 was identified as an important cytokine secreted by anti-inflammatory macrophages that potentiates MSC osteogenesis. Our findings provide novel insights into how environments provided by macrophages regulate MSC osteogenesis, which may be helpful to develop strategies to enhance bone regeneration.

Validation of a long bone fracture non-union healing score after treatment with mesenchymal stromal cells combined to biomaterials.

The available scores to clinically evaluate fracture consolidation encounter difficulties to interpret progression towards consolidation in long-bone non-union, particularly when incorporating biomaterials in the surgical treatment. The aims of this study were to validate the REBORNE bone healing scale in tibia, humerus and femur non-unions treated by a combination of mesenchymal stromal cells (MSCs) and biomaterials, through the interclass correlation (ICC) among raters, and to define reliability and concordance in anteroposterior and lateral radiographs, compared to computed tomography (CT). METHODS: Twenty-six cases from the EudraCT 2011-005441-13 clinical trial underwent bone healing evaluation, if at least 3 out of 4 cortical views clearly identified. Three senior orthopaedic surgeons evaluated radiographs and CTs at 3 and 6 months FU. All cases included preoperative imaging and radiographs at 12 months. The 4-stage scale score was obtained from each cortical view in orthogonal radiographs or CTs. A score of 0.6875 (11/16) was set as a threshold for bone healing. Statistically, ICC evaluated agreement among raters. Cronbach's alpha coefficient tested reliability. Lin's concordance correlation coefficients (CCC) were estimated between mean CT scores and mean radiographic scores. Bland and Altman graphs provided the limits of agreement between both imaging techniques. Sensitivity and specificity were assessed in radiographs (against CT), and the Area Under the Receiver Operating Characteristics (ROC) Curve was estimated. The probability to predict bone consolidation with REBORNE scores obtained from radiographs was modelled. RESULTS: An ICC of 0.88 and 0.91 (CT and radiographs) confirmed agreement in the REBORNE score for non-union bone healing, with an inter-rater reliability of 0.92 and 0.95. Scores through the radiographic evaluation were found equivalent to the CTs at 6 months FU. A CCC of 0.79 was detected against CT. The radiographic scores in the REBORNE bone healing scale correctly classified bone consolidation in 77%, with an accuracy of 83% based on ROC curves. CONCLUSIONS: The REBORNE score measured with CT or radiographic images was reliable among raters at a follow-up time above 6 months for long bone non-union fractures. The REBORNE scale measured with radiographs proved valid to assess consolidation against CT measurements.

Radiological subsidence and acetabular erosion after tapered uncemented hemiarthroplasty in femoral neck fractures a 10- to 13- year follow-up study.

BACKGROUND: Contemporary uncemented hemiarthroplasties are being used after displaced femoral neck fractures, however, their functional and radiological results remain controversial. The aim of this study was to evaluate the clinical and radiological results of a tapered uncemented stem combined with a uni- or bipolar hemiarthroplasty after a minimum follow-up of ten years. PATIENTS AND METHODS: 135 patients underwent uncemented hip hemiarthroplasty after a displaced femoral neck fracture between 2004 and 2007. Their mean age was 81.5 years old (range, 70 to 90). 38 patients were evaluated with a minimum follow-up of ten years. We analysed the complications and the postoperative clinical result according to the Merle D´Aubigné and Postel scale. Radiological femoral type according to Dorr et al., femoral canal filling and the appearance of stem loosening, subsidence and acetabular erosion according to Baker et al., were also assessed. RESULTS: There were two early periprosthetic femoral fractures. The mean clinical score was 15.8 (range, 9 to 17). Six hips were converted to a total hip arthroplasty due to acetabular erosion, and three stems were revised due to an infection, a late periprosthetic fracture and one aseptic loosening. The survival rate for any cause was 85.4% (Confidence interval (CI) 76 - 92.4%). The survival rate for revision surgery on the acetabular side at 10 years was 92.6% (CI 85 - 100%) and on the femoral side was 97.6% (CI 94.4 - 100%). 14 hips showed non-progressive radiological subsidence and 9 acetabular erosion. Stem subsidence was related to a femoral canal filling < 80% (p = 0.035) and acetabular erosion to a cylindrical femur (p = 0.024). CONCLUSION: Bone fixation can be obtained with a contemporary uncemented stem in hemiarthroplasty for patients over 70 years old with a femoral neck fracture. Acetabular erosion was frequent after ten years, however, the rate of revision surgery was low.

Total hip arthroplasty after acetabular fracture: does initial treatment make any difference to the outcome? A 5- to 23-year follow-up with clinical and radiological analysis.

PURPOSE: To determine if initial treatment affects the outcome of total hip arthroplasty (THA) after acetabular fracture. METHODS: 49 patients (49 hips) initially treated non-operatively followed some months later by THA in conjunction with acetabular reconstruction (Group 1) and 29 patients (29 hips) who had undergone THA after a previous osteosynthesis (Group 2) were assessed. The mean follow-up was 11.7 (range 5-23) years. RESULTS: 3 acetabular components were revised for aseptic loosening in Group 1 and 2 in Group 2. The survival rate for cup loosening at 16 years was 90.6% (95% confidence interval [CI], 78.1-100) for Group 1 and 94.1% (95% CI, 86.5-100) for Group 2 (p = 0.76). There were 2 sciatic palsies in Group 2 after osteosynthesis. The mean preoperative clinical score and postoperative range of mobility were better in Group 1. There were more heterotopic ossifications in Group 2. CONCLUSION: Despite the good results found in both groups, THA after previous osteosynthesis for acetabular fractures had more complications than a primary THA in conjunction with acetabular reconstruction.

Complications in Total Joint Arthroplasties.

Total joint arthroplasties (TJA) are today considered highly successful operations [...].

Immunoregulatory potential of mesenchymal stem cells following activation by macrophage-derived soluble factors.

BACKGROUND: Immunoregulatory capacity of mesenchymal stem cells (MSC) is triggered by the inflammatory environment, which changes during tissue repair. Macrophages are essential in mediating the inflammatory response after injury and can adopt a range of functional phenotypes, exhibiting pro-inflammatory and anti-inflammatory activities. An accurate characterization of MSC activation by the inflammatory milieu is needed for improving the efficacy of regenerative therapies. In this work, we investigated the immunomodulatory functions of MSC primed with factors secreted from macrophages polarized toward a pro-inflammatory or an anti-inflammatory phenotype. We focused on the role of TNF-α and IL-10, prototypic pro-inflammatory and anti-inflammatory cytokines, respectively, as priming factors for MSC. METHODS: Secretion of immunoregulatory mediators from human MSC primed with media conditioned by human macrophages polarized toward a pro-inflammatory or an anti-inflammatory phenotype was determined. Immunomodulatory potential of primed MSC on polarized macrophages was studied using indirect co-cultures. Involvement of TNF-α and IL-10 in priming MSC and of PGE2 in MSC-mediated immunomodulation was investigated employing neutralizing antibodies. Collagen hydrogels were used to study MSC and macrophages interactions in a more physiological environment. RESULTS: Priming MSC with media conditioned by pro-inflammatory or anti-inflammatory macrophages enhanced their immunomodulatory potential through increased PGE2 secretion. We identified the pro-inflammatory cytokine TNF-α as a priming factor for MSC. Notably, the anti-inflammatory IL-10, mainly produced by pro-resolving macrophages, potentiated the priming effect of TNF-α. Collagen hydrogels acted as instructive microenvironments for MSC and macrophages functions and their crosstalk. Culturing macrophages on hydrogels stimulated anti-inflammatory versus pro-inflammatory cytokine secretion. Encapsulation of MSC within hydrogels increased PGE2 secretion and potentiated immunomodulation on macrophages, attenuating macrophage pro-inflammatory state and sustaining anti-inflammatory activation. Priming with inflammatory factors conferred to MSC loaded in hydrogels greater immunomodulatory potential, promoting anti-inflammatory activity of macrophages. CONCLUSIONS: Factors secreted by pro-inflammatory and anti-inflammatory macrophages activated the immunomodulatory potential of MSC. This was partially attributed to the priming effect of TNF-α and IL-10. Immunoregulatory functions of primed MSC were enhanced after encapsulation in hydrogels. These findings may provide insight into novel strategies to enhance MSC immunoregulatory potency.