Perioperative glucocorticoids have been used as a successful non-opioid analgesic adjunct for various orthopaedic procedures. Here we describe an ongoing randomized control trial assessing the efficacy of a post-operative methylprednisolone taper course on immediate post-operative pain and function following surgical distal radius fixation. We hypothesize that a post-operative methylprednisolone taper course following distal radius fracture fixation will lead to improved patient pain and function. This study is a randomized control trial (NCT03661645) of a group of patients treated surgically for distal radius fractures. Patients were randomly assigned at the time of surgery to receive intraoperative dexamethasone only or intraoperative dexamethasone followed by a 6-day oral methylprednisolone (Medrol) taper course. All patients received the same standardized perioperative pain management protocol. A pain journal was used to record visual analog pain scores (VAS-pain), VAS-nausea, and number of opioid tablets consumed during the first 7 post-operative days (POD). Patients were seen at 2-weeks, 6-weeks, and 12-weeks post-operatively for clinical evaluation and collection of patient reported outcomes (Disabilities of the Arm, Shoulder and Hand Score [qDASH]). Differences in categorical variables were assessed with χ2 or Fischer's exact tests. T-tests or Mann-Whitney-U tests were used to compare continuous data. Forty-three patients were enrolled from October 2018 to October 2019. 20 patients have been assigned to the control group and 23 patients have been assigned to the treatment group. There were no differences in age (p=0.7259), Body Mass Index (p=0.361), race (p=0.5605), smoking status (p=0.0844), or pre-operative narcotic use (p=0.2276) between cohorts. 83.7% (n=36) of patients were female and the median age was 56.9 years. No differences were seen in pre-operative qDASH (p=0.2359) or pre-operative PRWE (p=0.2329) between groups. In the 7 days following surgery, patients in the control group took an average of 16.3 (±12.02) opioid tablets, while those in the treatment group took an average of 8.71 (±7.61) tablets (p=0.0270). We see that significant difference in Opioid consumption is formed at postoperative day two between the two groups with patients in the control group taking. Patient pain scores decreased uniformly in both groups to post-operative day 7. Patient pain was not statistically from POD0 to POD2 (p=0.0662 to 0.2923). However, from POD4 to POD7 patients receiving the methylprednisolone taper course reported decreased pain (p=0.0021 to 0.0497). There was no difference in qDASH score improvement at 6 or 12 weeks. Additionally, no differences were seen for wrist motion improvement at 6 or 12 weeks. A methylprednisolone taper course shows promise in reducing acute pain in the immediate post-operative period following distal radius fixation. Furthermore, although no statistically significant reductions in post-operative opioid utilization were noted, current trends may become statistically significant as the study continues. No improvements were seen in wrist motion or qDASH and continued enrollment of patients in this clinical trial will further elucidate the role of methylprednisolone for these outcomes

To study in resolution of triggering 12 months after injection with either a soluble methylprednisolone acetate or dexamethasone for idiopathic trigger finger. Twenty-eight patients were enrolled in a prospective randomized controlled trial comparing methylprednisolone acetate and dexamethasone injection for idiopathic trigger finger. Twenty-seven patients completed the 6-week follow-up (11 methylprednisolone acetate arm, 16 dexamethasone arm) and thirteen patients completed the 3-month follow-up (4 methylprednisolone acetate arm, 9 dexamethasone arm). Outcome measures included resolution of triggering, recurrence rate of trigger finger, satisfaction on a visual analog scale, tender, snapping, locking, the Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire and tip to palm distance (mm.) at 2, 6, 12 and 24 weeks follow-up. Eight patients were repeated a second injection (3 methylprednisolone acetate arm, 5 dexamethasone arm) at 6-week follow-up. To preserve autonomy, patients were permitted operative treatment any time. The analysis was according to intention to treat principles. Six weeks after injection. Absence of triggering was documented in 6 of 11 patients in the methylprednisolone cohort and in 6 of 16 patients in the dexamethasone cohort. The rate 3-month after injection were 2 of 4 patients in the methylprednisolone cohort and in 8 of 9 patients in the dexamethasone cohort. There were no significant difference between recurrence rate of trigger finger, satisfaction on a visual analog scale, tender, snapping, locking, the Disabilities of the Arm, Shoulder and Hand (DASH) scores and tip to palm distance (mm.) at 2, 6, 12 and 24 weeks follow-up. Although there were no differences 3months after injection, our data suggest that in the dexamethasone cohort was better in resolution of triggering than the methylprednisolone cohort at 12-week follow-up

Introduction: Objective of our study is to present the effect of methylprednisolone sodium succinate (Solu-Medrol) on post-traumatic edema and on skin quality after a malleolar fracture. Material and Methods: 35 patients with an ankle fracture presented in our clinic from October 2001 till April 2002, 14 of whom had a surgical treatment by the day of their admission. The rest of them (a total of 21) were admitted in our clinic and were classified into 3 groups of 7 patients each. In two first groups was administered methylprednisolone in I.V. infusion during the first post-traumatic 8 hrs. Most specifically: In the first group was administered methylprednisolone I.V. in a dosage form of 500 mg every 12 hrs, for a day. In the second group was administered methylprednisolone I.V. in a dosage form of 250 mg every 8 hrs, also for a day, while in the third group there was no methylprednisolone administration. The perimeter of the ankle in lateral malleolus area was measured in both injured and healthy leg, the day of patient’s admission and the day after. The healthy leg was used as a control and skin condition was estimated clinically. Results: In group 3 there was a great increase in injured limb perimeter (of about 4–5 cm) the 2nd day and we found Chassaignac blisters of a good size (about 3–4 cm) in two patients. The first two groups presented a similar result, that means a moderate increase in injured limb perimeter without blister formation or skin necrosis. Discussion: In time intravenous administration of methylprednisolone minimized the post-traumatic edema in malleolar fractures and improved the quality of the skin which is usually an important problem in injuries of that type and prolong the hospitalization of these patients. Dosage of 250 mg x 3 for a day is equally effective compared to bigger doses and we suggest it because of the reduced danger for corticosteroids side effects

Introduction: In the pathogenesis of steroid-associated femoral head necrosis only intra- and extravascular factors have been discussed. This study investigated the effect of long term glucocorticoid treatment on contraction of intraosseous femoral head arteries in a porcine model. Materials and Methods: From 24 immature female Danish Landrace pigs from 12 litters, 12 animals received 100 mg methylprednisolone daily for 3 months. Their 12 sister pigs served as controls and received no steroids. Resistance arteries (diameter approximately 250 μm) were isolated from the femoral head epiphyseal cancellous bone and mounted as ring preparations on a small vessel myograph for measurement of isometric force development. Results: Increasing doses of endothelin-1 evoked significantly stronger vasoconstriction after 3 months of methylprednisolone treatment. The vasocontractory response to increasing doses of noradrenaline was not altered by the previous methylprednisolone treatment. After submaximal precontraction by noradrenaline, vasorelaxation by bradykinin was not altered by methylprednisolone treatment. Discussion: The vasocontractory response of isolated intraosseous femoral head epiphyseal arteries to endothelin-1 after long term glucocorticoid treatment in the pig was enhanced. Enhanced contraction of FH lateral epiphyseal arteries can diminish femoral head blood flow as vessel diameter decreases. This may be a relevant cofactor in the early pathogenesis of steroid-associated femoral head necrosis

The use of intra-articular corticosteroid injections for their anti-inflammatory effects is widespread amongst clinicians. Despite their use in both rheumatoid arthritis and osteoarthritis, the effect of these agents on articular chondrocytes is not fully established. Previous reports suggest a detrimental effect on cartilage explants resulting from inhibition of matrix synthesis. 1. However it has also been suggested that the beneficial effects in vivo may be due to prevention of inflamed synovium causing cartilage degradation. 2. Our aim was to assess the effect of a commercially available preparation of methylprednisolone (MP), at clinical doses, on articular chondrocytes cultured in vitro. Bovine articular chondrocytes were isolated by sequential digestion with pronase and collagenase and seeded in 2% alginate at 1x10. 7. cells/ml. The constructs were cultured for up to 15 days in standard culture medium (DMEM + 20% Fetal calf serum) containing varying concentrations of MP, including doses equivalent to those found in vivo. The medium was replaced every 3 days and representative constructs were removed from culture, digested and assayed for DNA and glycosaminoglycans. Further constructs were fixed in 4% paraformaldehyde for standard histology and immunolocalisation of collagen types I, II and chondroitin-6-sulphate. Chondrocytes cultured in MP containing medium showed a significant abnormality in cell morphology compared to controls at the day 15 time point. Histologically there was evidence of cell necrosis, reduced amounts of extracellular matrix and loss of collagen type II staining. The effects were dose dependant, with significant damage occurring even at clinical doses. Biochemical analysis revealed a reduction in DNA content and an inhibition of glycosaminoglycan and collagen type II synthesis. In contrast, in the controls, there was cell proliferation with a cell doubling time of 14 days, collagen type II containing extracellular matrix synthesis occurred and the chondrocytes maintained their phenotype throughout the culture period. Methylprednisolone has a significant detrimental effect on cultured articular chondrocytes in vitro. There was significant cell necrosis associated with inhibition of extracellular matrix synthesis. Based on these results, intra-articular corticosteroid injections should be used with extreme caution

Introduction: The aim of this study was to investigate if steroids enhance the vasoconstrictive effect of endothe-lin-1 (ET-1) on femoral arteries. Materials and Methods: Ten female Wistar rats 59 to 88 days of age and 238 to 310 g of body weight, were used. Forty femoral artery segments were harvested. These arterial segments were mounted as ring preparations on a small vessel myograph. Two vessels from each animal were randomized to incubation with methylprednisolone 5 μg/ml [1] while the other 2 vessels were incubated with placebo. The arteries were stimulated cumulatively with endothelin-1. Isometric wall tension was quantified by the EC50; the vasoconstrictor concentration resulting in half maximal contraction. Results: Thirty-eight arteries could be harvested in total; 20 were randomized to steroid treatment while 18 served as controls. The endothelin-1 dose-response curve displayed a stronger contraction for the steroid group in relation to the controls with increasing doses of ET-1. The EC50 of 4.4*10. −8. M ± 1.8*10. −8. M for the steroid vessels was lower compared to 5.9*10. −8. M ± 3.4*10. −8. M for the controls (mean ±SD; n.s.). Discussion: Endothelin-1 is a potent vasoconstrictor. This study showed that incubation with methylprednisolone enhanced ET-1 mediated contraction of femoral arteries which can diminish blood flow within the vascular bed supplying the femoral head. This may be a relevant cofactor in the early pathogenesis of steroid-associated femoral head necrosis

A powered, randomised control trial was instigated to evaluate the advantages of subacromial injection of Methylprednisolone over conservative treatment in the management of partial rotator cuff injuries of the shoulder. Consecutive patients with possible partial rotator cuff tears were reviewed at 1 week. Inclusion criteria for a diagnosis of partial rotator cuff tear included; traumatic mechanism, greater tuberosity tenderness, painful arc, and complete resolution of disability post-Bupivicaine block. Exclusion criteria included; age < 16 years, chronic shoulder disease, acromioclavicular tenderness, and abnormal shoulder radiograph. Patients were randomly allocated to receive either 1 immediate subacromial injection of 40mg Methylprednisolone (group S) or no injection (group N). Initial outcomes measured were; visual analogue pain score (0–10) and active abduction (nearest 5°), repeated at 3, 6, and 12 weeks. All patients were instructed in analgesia usage and given identical shoulder exercises. Of 279 patients reviewed over 3 years, 90 met the inclusion criteria (6/90 patients were lost to follow-up). 50 patients were randomised to group S, 40 to group N. Mean pain score improvement at 12 weeks was comparable (S=4.95, N=4.44) (p> 0.1, CI=0.16–0.86). In patients aged > 40 years group S had significantly higher mean improvement in abduction at completion (64.28°) compared to group N (34.63°) (p< 0.02, CI 1.29–58.01). Conversely in patients aged < 40 years group S had lower mean improvements in abduction (40.55°) compared to group N (77.73°), though this was not statistically significant (p=0.1, CI 2.06–72.29). Methylprednisolone injection is more efficacious than conservative treatment alone in some patients. This benefit appears age-dependent and consequently such treatment should be reserved for patients aged > 40 years

Osteoarthritis of the trapezometacarpal joint is a common form of arthritis. At present, there is a significant void between conservative and operative managements. Viscosupplementation is occasionally considered as an in-between therapy. We aimed to compare the therapeutic benefit of a single intra-articular injection of Sodium Hyaluronate (SH; Ostenil®mini) to a single intra-articular injection of Methylprednisolone Acetate (MA; Depomedrone) in the management of rhizarthrosis (TMOA; Trapezometacarpal Osteoarthritis). A retrospective review was performed over a 12 month period. We reviewed 25 patients who had received a single injection of viscosupplementation (SH) performed with fluoroscopic guidance and had been followed up at 12 weeks. These patients were compared with 21 patients who had received a single steroid injection (MA) and had been followed up at 12 weeks. Of the SH group, 52% (n = 13) reported some benefit from the injection. The MA group reported an 86% (n=18) benefit from the injection. We found that a single injection of viscosupplementation (SH) is effective in relieving pain and improving function in about half of patients with rhizarthrosis (TMOA). The efficacy of a single steroid injection (MA), however, was superior with a far greater proportion of patients reporting analgesic and functional benefits

Objective: The purpose of this study was to assess whether the use of high dose methylprednisolone (MPS) given to trauma patients with acute spinal cord injury improves neurological and long term functional outcomes. Summary of Background Data: The National Acute Spinal Cord Injury Studies (NASCIS II and III) recommend the early administration of high dose MPS in the context of acute spinal cord injury. However, controversy exists surrounding its long term benefits. Methods: A retrospective data analysis was performed using the Helicopter Emergency Medical Service (HEMS) trauma registry, medical records, and rehabilitation notes of 263 trauma patients with acute spinal injury admitted over a 6-year period. All survivors over 16 years of age with documented spinal cord injuries were selected. Frankel grade, Injury Severity Score (ISS), and Functional Independence Measure (FIM) scores (minimum FIM of 18 implies total dependence, and a maximum of 126 implies no disability) as indicators of neurological and functional morbidity were recorded at initial presentation, hospital discharge, and intervals up to 12 months post injury. Details of the age, gender, mechanism of injury, nature of injury and associated injuries were also recorded. Results: There were 139 patients (107 males and 32 women) with documented acute spinal cord injuries, of which 74 patients had neurological deficits (Frankel A–D) at presentation. 49 patients were given high dose MPS within 8 hours of injury according to a standard protocol. The remaining 25 patients with documented neurological injury did not meet criteria or failed to receive the agent within the recommended time. The mean ISS scores were shown to be comparable in both groups. 59% (29/49) of patients who were given MPS showed an improvement of one or greater Frankel grade at the time of discharge whereas 52% (13/25) of patients who did not receive MPS showed a similar improvement in Frankel grades. We had long term functional outcome data (FIM scores) on 48% (67/139) of the total number of patients. At the time of discharge, the mean FIM scores for the MPS treated group and non MPS treated group were 68 and 90, respectively. Whereas at 12 months, there was no significant difference in the mean FIM scores between the two groups (both of which were > 100). Conclusions: The Frankel grade assesses the degree of neurological impairment while FIM scores are a basic measure of the severity of disability regardless of the underlying impairment. In our study, patients given high dose MPS in the context of acute spinal cord injury showed some early improvement in Frankel grades. However, we have shown, there is no short term or long term benefit in terms of functional outcome by using MPS in trauma patients with acute spinal cord injury

Study Design: A retrospective cross sectional cohort study of degeneration of the lumbar spine, using pre- and post-discography MRI scans of 28 patients, as compared to two consecutive MRI scans of an age and sex matched control group of 32 patients.

Objective: To determine whether injection of steroid into a lumbar intervertebral disc causes degeneration, as assessed by magnetic resonance imaging (MRI).

Methods: Twenty-eight patients with chronic discogenic low back pain were selected. Each had been investigated with an MRI, discography (with intradiscal injection of methylprednisolone), and a post-discography MRI scan. A randomly selected control group of thirty-two age and sex matched patients, having been examined on two occasions with MRI, was established. Two interpreters blinded to the patient groups assessed the degree of lumbar disc degeneration on the MRI scans on two separate occasions, using the Pfirrmann grading system.

Results: Kappa values proved interpretation consistency as compared with the published Pfirrmann paper. Variables of age and sex in the two groups showed no true variation in whether the discs improved, stayed the same or degenerated. The difference in the proportions for those with and without the injection gave a test statistic of 11.92 (p-value=0.002), indicating a discrepancy in the degeneration between those discs with and without an injection.

Conclusion: Previous studies on intradiscal steroid injections have shown variable results. Animal studies have shown that steroid administered intradiscally causes degeneration and primary calcification in discs. Two prospective double blind clinical trials using intradiscal steroids identified no significant benefit or improvement in the clinical outcome. This study indicates that intradiscal steroid injections cause MRI visible disc degeneration. In association with the results of the clinical trials, this study questions the indications for the use of intradiscal steroids in the management of discogenic low back pain.

Juvenile bone cysts in children and adolescents are often discovered incidentally or in connection with a pathologic fracture. Although the diagnostic procedure in this type of lesion affecting the skeleton has become uniform, the treatment varies according to the principles established at different clinics. The aim of our study was to compare two Methods: applied in the treatment of juvenile bone cysts, i.e. the established method of a series of Methylprednisolone injections and a new mini-invasive method using a Tricalcium phosphate. In both groups of patients, we performed an evaluation of the number of required surgeries, general anaesthesias and subsequent hospitalizations (including the length of hospitalization), the treatment results and the interval between surgery and complete cyst healing using Neer’s evaluation criteria. The group of patients treated with Methylprednisolone consisted of 24 patients and the group of patients treated with Tricalcium phosphate comprised 20 patients. The outcome of the statistical analysis proves that in patients treated with Tricalcium phosphate significantly better results were obtained compared to patients where Methylprednisolone was applied. A subsequent surgery (additional application) was necessary only in two Tricalcium phosphate patients (10%) compared to nineteen Methylprednisolone patients (79%). The average length of hospitalization was 4 days in Tricalcium phosphate patients and 3.5 days in Methylprednisolone patients. Excellent and good results according to the Neer classification were documented in eighteen Tricalcium phosphate patients (19%) and in twelve Methylprednisolone patients (50%). The treatment of juvenile bone cysts with a biocompatible resorbable synthetic filler Tricalcium phosphate helps reduce the number of surgeries necessary for complete cyst healing and produces better results in terms of Neer’s evaluation criteria of bone cyst treatment results compared to the application of Methylprednisolone into the cyst. This work was supported by the Internal Grant Agency of the Ministry of Health of the Czech Republic (NS9860-3/2008)

Purpose: Intra-articular (IA) injections of corticosteroids and hyaluronic acid (HA) products are used to treat patients with knee osteoarthritis pain that has not responded to more conservative treatment. Corticosteroids are a standard of care despite only suggestive clinical evidence of 12 or more weeks of pain relief. Method: A double-blinded, randomized, active controlled, multicenter non-inferiority trial with 442 subjects provided a pragmatic comparison of HA to methylprednisolone. Both groups received one intrar-ticular injection, and underwent pain and function evaluations over 26 weeks. The primary endpoint for study success was WOMAC pain responder rate at 12 weeks. The outcome of two prior trials influenced the patient selection criteria and provided a saline cohort for propensity score analyses comparing HA and methylprednisolone to saline. Results: The responder rate of HA was non-inferior to methylprednisolone at 12 weeks. Reductions in WOMAC pain, stiffness and physical function scores at all time points, and improvements in time to ‘get-up-and-go’ and walk 10 meters occurred in both treatment groups. The trends favored the HA responder rates at the later time points while the methylprednisolone rate decreased significantly by 26 weeks. Propensity score analyses confirmed that the responder rates of meth-ylprednisolone and HA were statistically significantly superior to a saline control at 12 weeks. Conclusion: The responder rate from a single injection of HA was non-inferior to methylprednisolone at 12 weeks, and the trend favored HA at later time points. The responder rates of HA and methylprednisolone were statistically significantly greater than that of saline at 12 weeks

To determine the current practice and to review the literature regarding administration of high dose Methylprednisolone for acute spinal cord injury (SCI). Administration of high dose Methylprednisolone for Acute Spinal Cord Injury has been widely practised following the publication of the three National Acute Spinal Cord Injury Studies (NASCIS). NASCIS recommends a bolus intravenous dose of 30mg/kg of Methylprednisolone in 15 minutes, followed by a 45 min pause and then followed by a maintenance dose of 5.4 mg / kg / hr for 23 hours. This regime has been recommended by the Advanced Trauma Life Support. The Cochrane reviews also extol the three NASCIS randomised controlled trials. The mechanism of neuroprotection by Methylprednisolone is based on its inhibition of lipid peroxidation. Three hundred questionnaires were sent to Consultants practising Spinal surgery, Neurosurgery and Accident & Emergency to determine the popular thought regarding the use of Methylprednisolone for Acute SCI. A thorough review of current medical literature was also performed. The literature search showed contradictory evidence regarding the use of high dose Methylprednisolone. The current popular thought, the diversity of responses between the three groups, the results of the 3 NASCIS trials and a recent review of literature is presented

Summary Statement. The incidence of osteonecrosis was significantly lower in the anti-vasospasm agent group (32%) than that in the control group (75%). Vasospasm is one of the important factors involved in the pathogenesis of steroid-induced osteonecrosis. Introduction. A number of studies have suggested that ischemia is the principal pathomechanism of osteonecrosis, however, the detailed mechanism responsible for ischemia remains unclear. It has recently been reported that the Rho/Rho-kinase mediated pathway (Rho-kinase pathway) is considered to be involved in the possible pathogenesis of various cardiovascular disorders as well as cerebral vasospasm. We examined the effects of fasudil (Rho-kinase inhibitor), an anti-vasospasm agent, on the development of steroid-induced osteonecrosis in rabbits. Materials & Methods. One group of rabbits received 15 mg/kg of fasudil intravenously, which were then injected once intramuscularly with 20 mg/kg of methylprednisolone (n = 33, MF group), and one received methylprednisolone alone as a control (n = 28, M group). Eight rabbits from each group were sacrificed 24 hour after the methylprednisolone injection to analyze them by immunohistochemical staining, a Western blotting analysis. Two weeks after the steroid injection, the femora and humeri were examined histopathologically for the incidence of osteonecrosis. Results. The incidence of osteonecrosis was significantly lower in the MF group (32%) than that in the M group (75%) (P < 0.01). Immunohistochemically, endothelin. A. -receptor (ET. A. Rc) expressions levels were decreased in the smooth muscle of the bone marrow in the MF group in comparison to that in the M group. In the M group, the average relative phospho-myosin light chain (p-MLC) expression level in the bone marrow tissue was significantly higher than that observed in the MF group (P < 0.01). In the MF group, the average relative total-eNOS expression level as well as the average relative phospho-eNOS (p-eNOS) expression level was almost 1.5 times higher than that observed in the M group (P < 0.05). The eNOS expressions levels in both serum and bone marrow in the MF group were significantly higher than those in the M group (P < 0.05). Discussion/Conclusion. The potential mechanisms resulting in vasospasm include the increased release of vasoconstrictors or increased sensitivity to these vasoconstrictors. ET-1 has been demonstrated to cause vascular smooth muscle cell constriction via ET. A. Rc stimulation. The expression of ET. A. Rc in rabbits treated with methylprednisolone plus fasudil (MF group) decreased in comparison with that in rabbits treated with the methylprednisolone alone (M group). In this study, both the eNOS and p-eNOS expressions levels in the M group were decreased in comparison to those observed in the MF group. A previous study suggested that high-dose steroid administration causes the overproduction of reactive oxygen species, and thereby perturbs nitric oxide (NO) availability in the vascular endothelium, leading to vascular endothelial dysfunction in patients receiving high-dose steroid therapy. Considering the pathogenesis of the development of osteonecrosis, we speculate that endothelial dysfunction may thus be a preliminary condition leading to the vasospasm. In conclusion, this study indicates that vasospasm is one of the important factors involved in the pathogenesis of steroid-induced osteonecrosis and that the anti-vasospasm agents seem to decrease the incidence of steroid-induced osteonecrosis

Introduction. Although osteonecrosis of the femoral head has been observed in young adult patients with autoimmune diseases such as SLE and MCTD that are treated by corticosteroids, the pathogenesis of the osteonecrosis remains unclear. We established a rat model with osteonecrosis of the femoral head by injecting lipopolysaccharide (LPS) and corticosteroid, and assessed consequences of the histopathological alteration of the femoral head, the systemic immune response, and the lipid synthesis. Methods. Male Wistar rats were given 2 mg/kg LPS intravenously on days 0 and 1 and intramuscularly 20 mg/kg methylprednisolone on days 2, 3, and 4. The animals were sacrificed 1, 2, 3, or 4 weeks after the last injection of the methylprednisolone. Histopathological and biochemical analyses were performed every week. The bone samples were then processed for routine hematoxylin and eosin staining to assess the general architecture and injury of the tissue. The triglyceride and the total cholesterol concentrations in the PRP were measured. The levels of various cytokines (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, GM-CSF, IFN-γ, TNF-α) in blood samples were measured. Results. The body weight of the rats over time decreased for 2 weeks but had recovered by week 4. The plasma triglyceride concentrations had decreased significantly by weeks 2 and 3. The total plasma cholesterol concentrations had increased significantly by week 1 but then decreased significantly by week 4. The plasma concentrations of IL-1?α, IL-2, IL-4, IL-6, IL-10, GM-CSF, IFN-γ and TNF-α had increased significantly by week 1. These cytokines can all be induced by toll-like receptor 4 (TLR4) signaling. We defined osteonecrosis as the diffuse presence of empty lacunae or pyknotic nuclei of osteocytes in the bone trabeculae, accompanied by surrounding bone marrow cell necrosis. Osteonecrosis of the femoral head was observed only in the epiphysis of the femoral head in sacrificed specimen every week. Histological analysis revealed osteocytic death surrounded by necrotic bone marrow with or without repaired tissue. Conclusion. We established a new rat model of corticosteroid-induced femoral head osteonecrosis. The necrosis that is generated in this model is similar to that seen in patients treated with corticosteroid. In particular, the necrotic lesion was exclusively observed in the proximal epiphysis. LPS is known to activate the immune system via the TLR4 signaling pathway. It has been recognized that the unique immunogenic effects of LPS promote autoimmune disease . LPS and methylprednisolone induced osteonecrosis of the femoral head in rats and this was associated with a disruption of the innate immune system and lipid synthesis. These findings suggest that the TLR4 signaling pathway plays an important role in the pathogenesis for osteonecrosis of the femoral head

Introduction: Increased levels of IL-6 and IL-8 have been found in intervertebral disc (IVD) tissue from patients undergoing fusion for discogenic low back pain. The stimuli that induce these mediators in degenerate discs remain unknown. Impaired diffusion of nutrients and wastes to and from the nucleus pulposus (NP) is believed to be an important factor in the degenerative process. The oxygen tension and pH in the NP of degenerating discs are significantly decreased. Aims: The aims of this study were to (1) demonstrate the ability of porcine NP to respond to a proinflamma-tory stimulus (lipopolysaccharride) in vitro, (2) investigate the effects of pH, pO. 2. and glucose concentration on NP proinflammatory mediator secretion and (3) determine if methylprednisolone or indomethacin can block NP proinflammatory mediator secretion. Methods: IVDs were harvested from 6-month old pigs and dissected under sterile conditions in the laboratory. 200mg samples of NP were cultured under optimal conditions (control), in a 1% O. 2. environment, at pH6 and in culture medium without glucose for 72 hours. Blocking experiments were performed by culturing LPS-stimulated samples with either methylprednisolone or indomethacin for 24 hours. IL-6 and IL-8 levels were estimated by ELISA. Results: Time and dose-response curves were generated for each experiment (results not shown). Results for the optimum dose and at 72 hours incubation were note. Data = mean ± standard deviation. Statistical analysis was by students t test. A significant result between control and stimulated groups is indicated by: * p=0.024m, † p=0.0007 or ‡ p=0.012. Methylprednisolone (2mg/ml) caused a significant (p=0.044) 30-fold reduction in IL-6 production and a significant (p=0.00004) 500-fold reduction in IL-8 levels as compared with nucleus pulposus cultured with 5 μg/ml LPS alone for 24 hours. Addition of 500 μM indomethacin significantly (p=0.04) decreased IL-6 production by a factor of 120 and IL-8 levels by a factor of 50 (p=0.00004). Necrotic cell death, as measured by lactate dehydrogenase (LDH) concentration, was not significant in any of the experiments

Introduction. In early stage osteonecrosis of the femoral head (ONFH), core decompression (CD) is often performed; however, approximately 30% of CD cases progress to femoral head collapse. Bone healing can be augmented by preconditioning MSCs (pMSCs) with inflammatory cytokines. Another immunomodulatory approach is the timely resolution of inflammation using cytokines such as IL-4. We investigated the efficacy of pMSC and genetically modified MSCs that over-express IL-4 (IL4-MSCs) on steroid-associated ONFH in rabbits. Methods. Thirty-six male skeletally mature NZW rabbits received methylprednisolone acetate (20mg/kg) IM once 4 weeks before surgery. There were 6 groups:. CD alone – a 3 mm drill hole. + injection into the CD of:. hydrogel (HG) - 200 μl of hydrogel carrier. MSCs–1 million rabbit MSCs. pMSC - LPS (20 μg/ml) + TNFα (20 ng/ml) preconditioned MSCs. IL4-MSCs – rabbit IL-4 over-expressing MSCs. IL4-pMSCs – preconditioned IL-4 over-expressing MSCs. Eight weeks after surgery, femurs were harvested, and evaluated by microCT, biomechanical, and histological analyses. Results. Bone mineral density (BMD) and bone volume fraction (BVF) increased in the pMSC group compared to the CD and MSC groups . outside. of the CD area (p < 0.05, Fig.1). Similarly, the IL4-pMSC group was increased compared to the CD group (p < 0.05). The percentage of empty lacunae in the IL4-MSC group was significantly less than other groups . outside. the CD area (p < 0.05, Fig.2); however, IL4-MSC group had less trabecular bone formation . inside. the CD. The mechanical tests demonstrated no differences. Discussion. This rabbit steroid-associated ONFH model demonstrated that pMSC increased new bone formation after CD; IL4-MSCs that continuously secreted IL-4 decreased the number of empty lacunae . Immunomodulation of bone healing has the potential to improve bone healing after CD for early stage ONFH; these interventions must be applied in a temporally sensitive fashion. For any figures, tables, or references, please contact the authors directly

Introduction. Intra-articular (IA) injections of corticosteroids and hyaluronic acid (HA) products are used to treat patients with knee osteoarthritis pain that has not responded to more conservative treatment. Corticosteroids are a standard of care despite only suggestive clinical evidence of 12 or more weeks of pain relief. However the duration of pain relief with this treatment appears to be short and not a long term solution. Methods. A double-blinded, randomised, active controlled, multicentre non-inferiority trial with 442 subjects provided a pragmatic comparison of HA to methylprednisolone. These patients were collected prospectively and with excellent long term follow-up. Results. The HA responder rates were good at 12 weeks and better at the later time points (6 to 9 months) while the methylprednisolone rate decreased significantly by 26 weeks. Conclusion. HA appears to be a reasonable mid to long term solution for patients with Kellgren grade 1 and 2 arthritis. It lasts longer than steroids and has what appears to be a cost-effective advantage

Introduction: The aim of this study was to investigate if steroids enhance the vasoconstrictive effect of nor-adrenaline on femoral arteries, which may result in femoral head blood flow reduction. Materials and Methods: Ten male Wistar rats 62 to 88 days of age, 254 to 318 g of body weight, were used. Twenty femoral artery segments were harvested. These arterial segments were mounted as ring preparations on a small vessel myograph for isometric force measurements. The arteries were stimulated cumulatively with noradrenaline before and after incubation with methylprednisolone (5 μg/ml). Isometric wall tension was plotted and quantified by the EC50, the vasoconstrictor concentration resulting in halfmaximal contraction. Results: The noradrenaline dose-response curve displayed a shift to the left for the steroid group in relation to the controls. This was reflected by a significantly lower EC50 of 9.5*10. −7. M ± 5.1*10. −7. M for the steroid vessels compared to 2.5*10. −6. M ± 1.1*10. −6. M for the control vessels (mean ± SD; p< 0.005). Discussion: This study showed that incubation with methylprednisolone enhanced noradrenaline-mediated contraction of femoral arteries. Enhanced contraction of femoral arteries can diminish blood flow within the vascular bed supplying the femoral head. This may be a relevant cofactor in the early pathogenesis of steroid-associated femoral head necrosis

Summary. Corticosteroids (CS) are commonly administered by intra-articular injection to control the symptoms of osteoarthritis; however, CSs also suppress articular chondrocyte matrix synthesis. Both triamcinolone and methylprednisolone acetate significantly suppressed BMPs −2 and −7, and TGF-b1 expression, suggesting a mechanism by which CSs suppress articular chondrocyte matrix synthesis and cartilage homeostasis. Introduction. Osteoarthritis (OA) is a common and debilitating disease that affects approximately 30% of the US population and is also a major clinical problem in companion animals. There are many drugs available to manage the symptoms of OA. Of these, intra-articular corticosteroid (CS) administration is a common and very effective anti-arthritic therapy, and is frequently administered to equine athletes. CSs exert their potent anti-inflammatory effects by blocking phospholipase A and reducing inflammatory mediator production; however, CSs also suppress matrix-biosynthetic activity of articular chondrocytes. This activity, along with ther increased joint use that symptomatic relief allows, has been linked to ‘steroid arthropathy’; a progression of arthritis driven by compromised chondrocyte homeostatic capacity. Several lines of experimental and clinical evidence emphasise the importance of TGF-b and BMP autocrine/paracrine activity in maintaining the homeostatic status of articular chondrocytes (reviewed in Oshin and Stewart 2007). This study was carried out to address the following objectives: 1) To assess the effects of CS on expression of chondro-protective TGF-β and BMP ligands in equine articular chondrocytes, and 2) To determine if exogenous BMP ligand administration can mitigate the suppressive effects of CSs on articular chondrocyte synthesis of collagen type II (Coll II) and glycosaminoglycans (sGAG). Methods. Articular cartilage was collected from clinically normal joints of adult horses, euthanased for reasons other than musculoskeletal disease. Articular chondrocytes were isolated by collagenase digestion and cultured as aggregates in serum-free medium under non-adherent conditions (Stewart et al 2000). Triamcinolone acetate (TA) or methylprednisolone acetate (MPA) was added to the articular chondrocyte cultures at 10. −10. M, 10. −7. M, and 10. −5. M; comparable to in vivo exposure concentrations. Effects on Coll II, aggrecan/sGAG, BMP and TGF-b ligand expression were assessed by QPCR, Coll II ELISAs and DMMB assays. In a separate series of experiments, exogenous BMP-2 was administered to chondrocyte cultures exposed to CS supplementation, to determine whether BMP can prevent or mitigate CS-mediated suppression of matrix synthesis. Results. BMP-2 and BMP-7 mRNA levels were significantly down-regulated by both CS treatments. In contrast, expression of BMPs-4 and 6 was not affected at any of the CS doses tested. TGF-b1 mRNA levels were significantly suppressed by both CSs at all doses tested. Somewhat surprisingly, TGF-b2 expression was increased by CS administration, though not significantly, while TGF-b3 expression was not affected. Exogenous BMP-2 administration (1–100 ng/ml) increased Coll II expression in the control groups but did not prevent the suppression of Coll II or sGAG synthesis in CS-treated chondrocytes. Discussion/Conclusions. Both TA and MPA down-regulated BMP-2, BMP-7 and TGF-b1 mRNA expression in articular chondrocytes. These CS-mediated effects appear to be gene-specific, since BMPs-4 and 6, and TGF-bs 2 and 3 were not similarly affected. Although exogenous BMP-2 administration increased Coll II production under control conditions, this did not effectively prevent CS-mediated suppressive effects on cartilage matrix synthesis. This suggests that other elements of the articular chondrocyte BMP and/or TGF-b signaling pathways are also affected by CS administration