Orthopaedic implant failure: aseptic implant loosening--the contribution and future challenges of mouse models in translational research.

Aseptic loosening as a result of wear debris is considered to be the main cause of long-term implant failure in orthopaedic surgery and improved biomaterials for bearing surfaces decreases significantly the release of micrometric wear particles. Increasingly, in-depth knowledge of osteoimmunology highlights the role of nanoparticles and ions released from some of these new bearing couples, opening up a new era in the comprehension of aseptic loosening. Mouse models have been essential in the progress made in the early comprehension of pathophysiology and in testing new therapeutic agents for particle-induced osteolysis. However, despite this encouraging progress, there is still no valid clinical alternative to revision surgery. The present review provides an update of the most commonly used bearing couples, the current concepts regarding particle-cell interactions and the approaches used to study the biology of periprosthetic osteolysis. It also discusses the contribution and future challenges of mouse models for successful translation of the preclinical progress into clinical applications.

Does AMIC® provide improvements at least two years after surgery for knee osteochondral lesions? A multicentre retrospective study of 101 patients.

BACKGROUND: Osteochondral defects of the knee due to trauma or osteochondritis are associated with osteoarthritis in the medium term. Defects 2 to 8cm2 in size can be managed by autologous matrix-induced chondrogenesis (AMIC®), in which sub-chondral micro-fractures are created within the lesion and the defect is then covered by a matrix of type I and type III collagen to induce de novo cartilage formation. Although promising outcomes have been observed in small single-centre cohorts, the medium-term clinical and radiological effectiveness of AMIC® remains to be demonstrated in larger populations. The objective of this study was to evaluate outcomes of patients at least 2 years after AMIC® for knee osteochondral defects. HYPOTHESIS: AMIC® is associated with clinical and radiological improvements after at least 2 years. MATERIAL AND METHOD: This multicentre (16 centres), multisurgeon (18 senior orthopaedic surgeons), retrospective study included consecutive patients who underwent AMIC® with Chondro-Gide® membrane implantation between September 2011 and January 2020. The 36-item Short Form quality-of-life (SF-36) score, Knee Injury and Osteoarthritis Outcome Score (KOOS), and International Knee Documentation Committee (IKDC) score were determined before the procedure and during follow-up. The Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score was assessed by magnetic resonance imaging 2 years after the procedure. RESULTS: In total, 101 patients aged 12 to 60 years were included. Mean follow-up was 30 months. Mean defect size was 3.44cm2 (range, 2-8cm2). Significant improvements were documented in the SF-36 score, KOOS, and IKDC score. The mean MOCART score at 2 years was 75% (range, 20-100). DISCUSSION: The AMIC® procedure was associated with significant improvements at 2.5 years in patients treated for knee osteochondral defects measuring 2 to 8cm2. This method seems to provide similar outcomes to those of other available methods with the advantages of single-step surgery and elimination of osteochondral graft donor-site complications. LEVEL OF EVIDENCE: IV, retrospective observational cohort study.

Role of the OPG/RANK/RANKL triad in calcifications of the atheromatous plaques: comparison between carotid and femoral beds.

Recent works demonstrated the difference of calcification genesis between carotid and femoral plaques, femoral plaques being more calcified. It has been clearly demonstrated that the molecular triad osteoprotegerin (OPG)/Receptor Activator of NFkB (RANK)/RANK Ligand (RANKL) exerts its activities in the osteoimmunology and vascular system. The aim of this study was to determine their expression and their potential role in calcifications of the atheromatous plaques located in two different peripheral arterial beds, carotid and femoral. The expression of OPG, RANK and RANKL was analyzed by immunochemistry in 40 carotid and femoral samples. Blood OPG and RANKL were quantified using specific ELISA assays. OPG staining was more frequently observed in carotid than in femoral plaques, especially in lipid core. Its expression correlated with macrophage infiltration more abundantly observed in carotid specimens. Surprisingly, serum OPG concentration was significantly lower in carotid population compared to femoral population while RANK and RANKL were equally expressed in both arterial beds. Carotid plaques that are less rich in calcium than femoral specimens, express more frequently OPG, this expression being correlated with the abundance of macrophages in the lesions. These data strengthen the key role played by OPG in the differential calcification in carotid and femoral plaques.

High rate of ceramic sandwich liner fracture.

BACKGROUND: Ceramic bearing surfaces for THA were introduced to reduce the risk of wear. However, owing to liner fracture in some of the early series and presumption that the fractures were the result of the modulus mismatch of the implant and the bone, a ceramic sandwich liner with lower structural rigidity was introduced. Fractures of these devices also were reported subsequently, although the incidence is unclear and it is unknown whether there are any risk factors associated with the fractures. QUESTIONS/PURPOSES: We therefore determined the incidence of these fractures. METHODS: We retrospectively reviewed 298 active patients in whom we implanted 353 ceramic-polyethylene sandwich liner acetabular components between November 1999 and February 2008. The mean age of the patients was 53.6 years (range, 17-84 years). The minimum followup was 6 months (mean, 41 months; range, 6-106 months). All patients were assessed clinically and radiographically. RESULTS: Seven of the 353 (2%) ceramic sandwich liners fractured at a mean of 4.3 years (range, 1.3-7.6 years) after surgery without trauma. Neither patient-related factors nor radiographic position of the implants were risk factors for fracture. CONCLUSIONS: Owing to the high rate of fractures of the sandwich ceramic polyethylene liners in our patients, we have discontinued use of this device. LEVEL OF EVIDENCE: Level IV, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.

Improving diagnostic criteria for Propionibacterium acnes osteomyelitis: a retrospective analysis.

The identification of Propionibacterium acnes in cultures of bone and joint samples is always difficult to interpret because of the ubiquity of this microorganism. The aim of this study was to propose a diagnostic strategy to distinguish infections from contaminations. This was a retrospective analysis of all patient charts of those patients with >or=1 deep samples culture-positive for P. acnes. Every criterion was tested for sensitivity, specificity, and positive likelihood ratio, and then the diagnostic probability of combinations of criteria was calculated. Among 65 patients, 52 (80%) were considered truly infected with P. acnes, a diagnosis based on a multidisciplinary process. The most valuable diagnostic criteria were: >or=2 positive deep samples, peri-operative findings (necrosis, hardware loosening, etc.), and >or=2 surgical procedures. However, no single criterion was sufficient to ascertain the diagnosis. The following combinations of criteria had a diagnostic probability of >90%: >or=2 positive cultures + 1 criterion among: peri-operative findings, local signs of infection, >or=2 previous operations, orthopaedic devices; 1 positive culture + 3 criteria among: peri-operative findings, local signs of infection, >or=2 previous surgical operations, orthopaedic devices, inflammatory syndrome. The diagnosis of P. acnes osteomyelitis was greatly improved by combining different criteria, allowing differentiation between infection and contamination.

rhBMP-2 (Recombinant Human Bone Morphogenetic Protein-2) in real world spine surgery. A phase IV, National, multicentre, retrospective study collecting data from patient medical files in French spinal centres.

BACKGROUND: This is a Phase IV, national, multicentre, retrospective study to observe the real-world use of rhBMP-2 in France. HYPOTHESIS: There was no statistical hypothesis, the statistical analyses were descriptive in nature. PATIENTS AND METHODS: Data was collected from patient medical files in 10 French spinal centres. Primary objectives were to understand which patients were treated with rhBMP-2, commercialised in Europe as InductOs™ and how rhBMP-2 was used during spinal fusion surgery in France between 2011 and 2012. RESULTS: Four hundred patients (634 levels) treated with rhBMP-2 were included in the analysis. The most frequent primary diagnostic indication for rhBMP-2 use was degenerative disc disease (DDD; 129/400; 32.3% of patients) followed by spondylolisthesis (119/400; 29.8%), deformity (59/400; 14.8%) and pseudoarthrosis (29/400; 7.3%). The most frequently treated level was L4-L5 (33.8% of levels in 53.5% of patients); followed by L5-S1 (29.8%, 47.3%), L3-L4 (16.7%, 26.5%), and L2-L3 (7.3%, 11.5%), all other levels (less than 5% of patients). No interbody fusion device was used in 42.7% of levels. Wetted matrix of rhBMP-2 was placed in the interbody space in 58.4% of levels (370/634). The most common procedure for rhBMP-2 treatment was posterior lumbar fusion (PLF) (221/634; 34.9% of levels), followed by anterior lumbar interbody fusion (ALIF) (188/634; 29.7%), posterior lumbar interbody fusion (PLIF) (111/634; 17.5%), lateral lumbar interbody fusion (LLIF) (106/634; 16.7%), transforaminal lumbar interbody fusion (TLIF) (4/634; 0.6%) and 'other' (4/634; 0.6%). Thirty-one adverse events of Interest (AEI) were recorded in 27 patients. One AEI was considered related to rhBMP-2. Unplanned secondary spine interventions at index level treated with rhBMP-2 were required in 4 patients. DISCUSSION: In years 2011 and 2012 when the surgeries captured in this retrospective study were done, rhBMP-2 was indicated for single level (L4-S1) anterior lumbar spine fusion as a substitute for autogenous bone graft in adults with DDD. The most common procedure for the treatment with rhBMP-2 was PLF (off-label use), followed by ALIF (on-label use). The safety findings confirm a predictable and manageable safety profile. LEVEL OF EVIDENCE: IV.

Epidural analgesia after scoliosis surgery: electrophysiologic and clinical assessment of the effects of bupivacaine 0.125% plus morphine versus ropivacaine 0.2% plus morphine.

STUDY OBJECTIVE: To study the electrophysiologic and clinical effects of epidural morphine combined with either bupivacaine 0.125% or ropivacaine 0.2%. DESIGN: Comparative, randomized, double-blind study. SETTINGS: Intensive care unit and hospital ward of a university hospital. PATIENTS: 18 adult ASA physical status I and II patients with degenerative or idiopathic scoliosis, undergoing posterior spinal fusion with instrumentation. INTERVENTIONS: Patients received epidural administration of 10-mL bolus of either bupivacaine or ropivacaine followed by a 6-mL/h infusion for 48 hours of unlabeled local anesthetic. In all patients, epidural morphine 5 mg was added daily. MEASUREMENTS: Assessment was focused mainly on somatosensory cortical evoked potentials, soleus H-reflex, and F waves. These electrophysiologic data were recorded before and after epidural medications. Second, respiratory rate, Paco(2), visual analog score (VAS), and side effects such as postoperative nausea and vomiting (PONV), gastrointestinal (GI) transit delay, and urinary retention were noted. MAIN RESULTS: Bupivacaine 0.125% + morphine was given to 9 patients, and ropivacaine 0.2% + morphine was given to 9 other patients. H-reflex, F waves, and somatosensory cortical evoked potential recording remained unchanged across the time of assessment. Respiratory rate and Paco(2) values were normal. VASs were indifferently low at rest, but they were lower with bupivacaine than with ropivacaine on mobilization. The frequency of PONV was indifferently high. No altered GI transit or urinary retention was noted. CONCLUSION: After epidural administration during the study conditions, bupivacaine 0.125% and ropivacaine 0.2% combined with morphine allow for neurologic examination.

Osteointegration of femoral stem prostheses with a bilayered calcium phosphate coating.

Our purpose was to evaluate the osteointegration of bilayered calcium phosphate (CaP)-coated femoral hip stems in a canine model. A first layer of hydroxyapatite (HA) 20 microm thick and a superficial layer of Biphasic Calcium Phosphate (BCP) 30 microm thick were plasma-sprayed on to the proximal region of sandblasted Ti6Al4V prostheses. Bilayered CaP-coated and non-coated canine femoral stems were implanted bilaterally under general anesthesia in 6 adult female Beagle dogs. After 6 and 12 months, a significant degradation of the bilayered coating occurred with a remainder of 33.1+/-12.4 and 23.6+/-9.2 microm in thickness, respectively. Lamellar bone apposition was observed on bilayered coated implants while fibrous tissue encapsulation was observed on non-coated femoral stems. The bone-implant contacts (BIC) were 91+/-3% and 81+/-8% for coated and 7+/-8% and 8+/-12% for non-coated implants, at 6 and 12 months, respectively. Our study supports the concept of a direct relationship between the biodegradation of CaP coating and the enhanced osteointegration of titanium prostheses. A bilayered CaP coating might therefore enhance bone apposition in the early stages because of the superior bioactivity of the BCP layer while the more stable HA layer might sustain bone bonding over long periods.

Pro-osteoclastic in vitro effect of Polyethylene-like nanoparticles: Involvement in the pathogenesis of implant aseptic loosening.

Polyethylene micro-sized wear particles released from orthopedic implants promote inflammation and osteolysis; however, less is known about the bioactivity of polyethylene nanosized wear particles released from the last generation of polymer-bearing surfaces. We aim to assess the internalization of fluorescent polyethylene-like nanoparticles by both human macrophages and osteoclasts and also, to determine their effects in osteoclastogenesis in vitro. Human macrophages and osteoclasts were incubated with several ratios of fluorescent polyethylene-like nanoparticles between 1 and 72 h, and 4 h, 2, 4, 6, and 9 days, respectively. The internalization of nanoparticles was quantified by flow cytometry and followed by both confocal and video time-lapse microscopy. Osteoclast differentiation and activity was semiquantified by tartrate-resistant acid phosphatase (TRAP) staining, TRAP mRNA relative expression, and pit resorption assay, respectively. Macrophages, osteoclast precursors and mature osteoclasts internalized nanoparticles in a dose- and time-dependent manner and maintained their resorptive activity. In addition, nanoparticles significantly increased the osteoclastogenesis as shown by upregulation of the TRAP expressing cell number. We conclude that polyethylene-like nanosized wear particles promote osteoclast differentiation without alteration of bone resorptive activity of mature osteoclasts and they could be considered as important actors in periprosthetic osteolysis of the last new generation of polymer-bearing surfaces. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2649-2657, 2016.

Development of an experimental model of pre-thrombosis in rats based on Wessler's principle using a calibrated venous stasis.

We have developed a model of a pre-thrombotic state in rats based on venous stasis induced by partial ligature of the inferior vena cava. The degree of stenosis was calibrated by using variations in upstream venous pressure. Different degrees of stasis were tested in order to obtain a pre-thrombotic state. Increasing doses of thromboplastin were infused. The thrombogenic potential of this model was evaluated by measuring thrombus weight and by the increase in levels of thrombin-antithrombin complexes. A pre-thrombotic state was induced by 2 h of exposure to a 40% stasis obtained by increasing by 40% the upstream venous pressure (mean thrombus weight, 0.2 +/- 0.6 mg). In these conditions of stasis, low doses of thromboplastin induced venous thrombosis (mean weight, 23 +/- 20 mg; P < 0.05). The increase in thrombus size was correlated to the rise in thrombin-antithrombin levels (r = 0.53, P < 0.001). In conclusion, we have developed the first animal model in which venous stasis can be calibrated by varying the degree of stenosis of the inferior vena cava. This model could be used to study the kinetics of biological markers of hypercoagulability, to study the pathogeny of thrombosis or to evaluate the therapeutic efficacy of new drugs in pre-clinical trials.

Antibiotic-loaded bone cement in orthopedic surgery.

Acrylic cement is used to secure implants to bone. When mixed with antibiotics or anticancer agents, acrylic cement slowly releases these agents while retaining its mechanical properties, thus providing specific in situ treatment.

Hamstring insertion site healing after anterior cruciate ligament reconstruction in patients with symptomatic hardware or repeat rupture: a histologic study in 12 patients.

PURPOSE: Our goal was to characterize the type of biologic anchor of hamstring tendons to the femoral tunnel in cases of transfixion fixation for the anterior cruciate ligament (ACL) reconstruction. The histologic bone-hamstring tendon anchorage is not yet clearly understood despite many experimental and some clinical studies. It constitutes the weak point of the ACL reconstruction. The type of fixation, either distant from the joint such as transfixion fixation or at the tunnel entrance such as aperture fixation will determine a specific tendon-bone healing process. TYPE OF STUDY: Histological study. METHODS: We performed ACL reconstruction with 4 strands of semitendinosus and gracilis tendons fastened by a transfixion fixation. Femoral fixation was secured by transfixion (Transfix; Arthrex, Naples, CA) and tibia fixation by a biodegradable interference screw and 2 staples. Between 3 and 20 months after surgery, we performed 12 hamstring tendon biopsies (in 9 men and 3 women; mean age, 29 years). Biopsies were performed 2 cm from the femoral outlet in 10 patients undergoing hardware removal or by coring the femoral tunnel in 2 cases of repeat rupture. In 8 cases, the femoral device was removed for persistent lateral pain, in 2 cases for instability of the hardware, and in 2 cases a repeat rupture of the graft occurred. The samples were taken by coring a tunnel 5 mm in diameter, with a tubular harvester, along the femoral Transfix axis. Each fragment was stained with H&E, Solochrome cyanine, or Masson-trichrome, and microscopical examination was performed, including polarized light. RESULTS: At 3 months (in 1 case), a fibrovascular interface was seen between the tendon and uncalcified osteoid with very few collagen fibers. At 5 and 6 months (in 2 cases), some Sharpey-like fibers and less immature woven bone was seen. Maturity of the secondary insertion was seen after at least 10 months in 5 cases. In 2 cases, no contact was seen at the biopsy site despite good clinical stability. The 2 remaining cases underwent repeat rupture at the midsubstance of the graft at 12 and 17 months after surgery. In the first case, the tendon-bone fixation was limited at the outlet of the femoral tunnel with no fixation inside the tunnel. In the second case, the fixation was continuous with Sharpey fibers along the tunnel. CONCLUSIONS: According to our histologic results in patients, the time to obtain a mature indirect anchorage at the top of the tunnel was 10 to 12 months, which is much longer than in reported animal models (6 to 24 weeks). To our knowledge, this is the first clinical study reporting the histologic type of femoral ligament insertion 2 cm from the outlet of the tunnel with hamstring autograft for ACL reconstruction.

Treatment of an aneurysmal bone cyst of the lumbar spine in children and teenagers, about five cases.

The aneurysmal bone cyst is a rare tumor. Its treatment is complex when localized to the lumbar spine, with neurological, mechanical, and tumoral complications. The aim of this study is to describe these tumors, their treatment, and their long-term evolution, as well as to define an appropriate therapeutic strategy. Four of the five cysts had anterior and posterior extension. Three patients had neurological symptoms at diagnosis and two of them presented with pathological fracture. Surgical treatment was performed by intralesional resection. Long-term progress was always favorable, without recurrence or functional limitation. Two patients had a stable, mild spine deformity.

Contribution of centralization phenomenon to the diagnosis, prognosis, and treatment of diskogenic low back pain.

The centralization phenomenon is the migration of low back and/or radiating pain to the spinal midline in response to specific positions or movements, for instance during a McKenzie mechanical assessment. However, differences in the definition of the centralization phenomenon occur across studies, most notably regarding the smallest required change in pain location and the time to centralization. Standardized criteria would be useful. Available data fail to establish that centralization is sufficiently specific of diskogenic pain as to obviate the need for investigations, particularly in patients considered for surgical treatment (e.g., fusion or implant). Although centralization correlates strongly with a positive diskography, the value of this last finding as a sign of diskogenic pain or an indicator that surgery is needed remains highly controversial. Nevertheless, centralization may indicate a high likelihood of diskogenic pain and may provide therapeutic guidance. Because centralization is associated with better outcomes after nonsurgical treatment, even in patients with nerve root pain, its presence may constitute an argument against surgical treatment. Finally, the McKenzie assessment may induce pain relief, albeit to a modest extent and for no longer than 3 months.

The vertebral interbody grafting site's low concentration in osteogenic progenitors can greatly benefit from addition of iliac crest bone marrow.

The ability of bone substitutes to promote bone fusion is contingent upon the presence of osteoinductive factors in the bone environment at the fusion site. Osteoblast progenitor cells are among these environmental osteoinductive factors, and one of the most abundant and available sources of osteoblastic cells is the bone marrow. As far as biological conditions are concerned, the vertebral interbody space appears as a favorable site for fusion, as it is surrounded by spongy bone, theoretically rich in osteogenic cells. This site may, however, not be as rich in osteogenic precursor cells especially at the time of grafting, because decortication of the vertebral end plates during the grafting process may modify cell content of the surrounding spongy bone. We tested this hypothesis by comparing the abundance of human osteogenic precursor cells in bone marrow derived from the iliac crest, the vertebral body, and the decorticated intervertebral body space. The number of potential osteoblast progenitors in each site was estimated by counting the alkaline phosphatase-expressing colony-forming units (CFU-AP). The results, however, demonstrate that the vertebral interbody space is actually poorer in osteoprogenitor cells than the iliac crest (P<0.001) and vertebral body (P<0.01), especially at the time of graft implantation. In light of our results, we advocate addition of iliac crest bone marrow aspirate to increase the success rate of vertebral interbody fusion.

Surgical treatment of idiopathic scoliosis in adults: an age-related analysis of outcome.

STUDY DESIGN: A retrospective outcome study was conducted. OBJECTIVE: To analyze the clinical and radiographic outcome of surgical treatment for idiopathic scoliosis in patients treated at the age of 20 years or older. SUMMARY OF BACKGROUND DATA: Idiopathic scoliosis continues to pose problems in many patients after adolescence. Surgical treatment of idiopathic scoliosis in adults still is a challenging subject, but no outcome analysis in terms of different age groups had been performed. METHODS: In this study, 58 adult patients with idiopathic scoliosis who underwent surgery using Cotrel-Dubousset instrumentation were followed up for 2 to 7 years, and the results were studied clinically and radiographically. RESULTS: The prevalence of pain that requires specific treatment decreased from 16% to 5%, and the pain improvement was reliably obtained in the older patients. Radiographically, the mean rate of Cobb angle correction was 53% for both the thoracic and lumbar curves, whereas it decreased age dependently, especially in relation to the thoracic curve. The sagittal plane correction generally was satisfactory in patients younger than 50 years, but appropriate lumbar lordosis was difficult to maintain after the age of 50 years. Frontal and sagittal balance often was difficult to achieve in patients older than 50 years. CONCLUSIONS: This study clarified specific characteristics and problems in the surgical treatment of adult idiopathic scoliosis according to different age groups. Although pain was the most important indication for surgery in patients older than 40 years, it was improved reliably by surgery in most of these patients. On the other hand, the radiographic results tended to be less satisfactory in the older patients in an age-dependent manner. These results provide useful information concerning the indications and strategies of adult scoliosis surgery.

Paradoxical air embolism from patent foramen ovale in scoliosis surgery.

STUDY DESIGN: A case was reported in which paradoxical air embolism arose from the patent foramen ovale in scoliosis surgery. OBJECTIVES: To present a case of suspected paradoxical air embolism after scoliosis surgery. SUMMARY OF BACKGROUND DATA: Embolic accident during scoliosis surgery may be caused by air, thrombus, or fat. There is growing attention on patent foramen ovale involved in paradoxical embolism. The devastating consequences are caused by multiple artery occlusions. METHODS: Details of a recent documented neurologic complication (paraplegia, weakness of right arm, and blurry vision) after scoliosis surgery have been analyzed in medical publications. RESULTS: The surgical procedure was not imputed. The causative role of epidural catheter for analgesia was considered, but it is likely that a paradoxical embolism occurred in this case, based on the multifocal (cerebral and spinal) neurologic dysfunction, the evidence of cerebral ischemia (on computed tomography), and the presence of a patent foramen ovale (on postoperative transesophageal echocardiography). Although no intraoperative embolism detection was available, air embolism was highly suspected because there was no absolute argument to exclude cruor or fatty embolism. CONCLUSIONS: It is critical to detect a patent foramen ovale before surgery and cerebral embolization intraoperatively. This might permit ascertainment of the etiologic diagnosis in case of a complication in surgery for scoliosis.

Combined spinal cord monitoring using neurogenic mixed evoked potentials and collision techniques.

STUDY DESIGN: Neurogenic mixed evoked potentials are used routinely to monitor the spinal cord during spine surgery. This study investigates the differential sensory-motor contribution by using collision techniques. OBJECTIVE: To demonstrate that neurogenic mixed evoked potentials do contain a motor component. SUMMARY OF BACKGROUND DATA: Spinal cord monitoring is now routinely used during spine deformity surgery. Neurogenic mixed evoked potentials (i.e., potentials recorded from lower limb nerves after spinal cord stimulation) represent a reliable and sensitive technique. However, their specificity (sensory and motor spinal pathways) remains debated. METHODS: Neurogenic mixed evoked potentials and collisions were performed in 24 consecutive patients during scoliosis surgery. Neurogenic mixed evoked potentials were elicited by a high thoracic spinal test stimulation and recorded from the tibial nerve at the ankle. A peripheral conditioning stimulation was delivered at the popliteal fossa 15 ms before spinal stimulation, inducing an ascending volley. The antidromic ascending motor component stops at the anterior horn cell level, whereas the orthodromic sensory component reaches the dorsal columns. The 15-ms interstimulus interval between peripheral conditioning and spinal test stimulation makes the collision with descending volleys occur in the spinal cord. The descending sensory volley is blocked, whereas the descending motor volley is unaffected. RESULTS: Reproducible evoked potentials were recorded from the tibial nerve in all the patients studied when the conditioning stimulation was performed. These conditioned neurogenic mixed evoked potentials consist of a small and polyphasic wave whose amplitude represents approximately 26% that of the wave of unconditioned neurogenic mixed evoked potentials. It is likely that they correspond to motor spinal pathway activation. CONCLUSION: Both standard and conditioned neurogenic mixed evoked potentials are proposed to provide combined sensory and motor spinal pathway monitoring.

Receptor activator of nuclear factor kappaB ligand (RANKL)/osteoprotegerin (OPG) ratio is increased in severe osteolysis.

Pathological osteolyses are considered a consequence of a disturbance in the mechanisms that govern the bone remodeling, mainly the communication between osteoclasts and osteoblasts. Osteoprotegerin (OPG) and receptor activator of NF-kappaB ligand (RANKL) are newly discovered molecules that play a key role in these communications. RANKL is essential for osteoclast differentiation via its receptor RANK located on the osteoclast membrane. OPG is a soluble decoy receptor that inhibits osteoclast differentiation through its binding to RANKL. The aim of this study is the analysis of the RANKL/OPG balance by complementary methods (semiquantitative reverse transcription-polymerase chain reaction, immunohistochemistry, and enzyme-linked immunosorbent assay) in human osteolysis associated to various bone etiologies (n = 60), tumoral (primitive, secondary) or not, compared to healthy tissues (n = 16). Results demonstrated that RANKL/OPG ratio was significantly increased in patients suffering from severe osteolysis compared to the control group and that this imbalance is involved in bone resorption mechanisms. In this study, OPG expression appears to reflect a protective mechanism of the skeleton to compensate increased bone resorption by inhibiting osteoclast formation and bone resorbing activity. Moreover, as revealed by immunohistochemistry, RANKL and OPG were colocalized in all of the tissues analyzed. To define the veracity of RANKL/OPG index in assessing and managing patients with severe osteolysis, an extended population of patients suffering from severe osteolysis must be now monitored.