The inhibitory effect of tocilizumab on systemic bone loss and tendon inflammation in a juvenile Collagen-Induced arthritis rat model.

PURPOSE OF THE STUDY: Reduced Bone Mineral Density (BMD) is a prevalent comorbidity in Juvenile Idiopathic Arthritis (JIA). Enthesitis and other tendon abnormalities, such as tenosynovitis, tendinitis and tendon ruptures are, also, common extra-articular manifestations of the disease. The aim of the present study was to investigate the effect of tocilizumab, an antibody that binds the Interleukin-6 (IL-6) Receptor, on inflammation-related bone loss and tendon inflammation in an animal model of JIA. MATERIALS AND METHODS: The Collagen-Induced Arthritis (CIA) model was induced in male rats followed by intraperitoneal administration of tocilizumab for 8 weeks. Methotrexate, the most widely used Disease-Modifying Antirheumatic Drug in the management of JIA, was, also, administered, either as a monotherapy or as an add-on therapy to tocilizumab. BMD was evaluated with Micro-Computed Tomography (Micro-CT) and histopathological examination. Tendon damage was, also, assessed histologically. Finally, two pro-inflammatory cytokines, Tumor Necrosis Factor-alpha (TNF-a) and Interleukin-23 (IL-23) were quantified in tendon tissues by ELISA analysis. RESULTS: Tocilizumab-treated animals exhibited a significantly improved trabecular microarchitecture on micro-CT analysis and histological examination. Tendon morphology was also improved. Anti-IL-6 treatment led to a significant decrease in TNF-a and IL-23 expression in tendon tissue. CONCLUSIONS: The results of the present study provide evidence that tocilizumab reduces inflammation-related bone loss and suppresses tendon inflammation in a juvenile CIA rat model. These findings offer perspectives for the management of osteoporosis and enthesitis in JIA.

Efficacy and safety of anti-sclerostin antibodies in the treatment of osteoporosis: A meta-analysis and systematic review.

Osteoporosis is a chronic disease with an increasing prevalence. Anti-sclerostin antibodies are being investigated for the treatment of osteoporosis. The aim of this systematic review and meta-analysis is to evaluate the efficacy and safety of antis-sclerostin antibodies compared to placebo and conventional therapies (alendronate and teriparatide) in the treatment of osteoporosis. Randomized controlled trials were searched from PubMed, EMBASE and Cochrane Central Register of Controlled Trails (CENTRAL) from their inception up to June 2021 by using Medical Subject Headings terms "anti-sclerostin antibody", "romosozumab", "blosozumab", "AMG 785″, "LY2541546", and "osteoporosis". Two investigators independently screened eligible studies, assessed the risk of bias and extracted the data from each study. The I2 index was used to assess heterogeneity. Meta-analysis was conducted using the Review Manager Software (RevMan, Version 5.4). The GRADE approach was used to rate the quality of evidence for all the pooled outcomes. 8 RCTs with 12,416 patients met the inclusion criteria. Anti-sclerostin antibodies significantly increased lumbar spine, total hip and femoral neck bone mineral density compared to placebo, alendronate and teriparatide at both 6 and 12 mo. Adverse events were comparable between anti-sclerostin antibodies and other treatments, except for the incidence of injection-site reactions that was higher in the anti-sclerostin antibody groups. Anti-sclerostin antibodies represent a valid theurapeutic option in the treatment of osteoporosis. Further studies with longer duration and follow-up are needed to confirm the results of this meta-analysis.

Infliximab prevents systemic bone loss and suppresses tendon inflammation in a collagen-induced arthritis rat model.

Reduced Bone Mineral Density (BMD) and tendon abnormalities, such as tenosynovitis and enthesitis, are prevalent comorbidities in patients with rheumatoid arthritis (RA). The aim of the present study was to investigate the effect of chronic treatment with infliximab on BMD and tendon inflammation in an animal model of inflammatory arthritis. Collagen-Induced Arthritis (CIA) was induced in rats, followed by long-term intraperitoneal administration of infliximab. Two additional groups of animals received methotrexate either as a monotherapy or as a co-treatment to infliximab. BMD was evaluated by Micro-Computed Tomography (Micro-CT) and bone histological examination. Tendon inflammation was assessed histologically and by quantitative ELISA analysis of pro-inflammatory cytokines in tendon tissues. Both methotrexate and infliximab treatment alleviated joint inflammation and reduced paw edema. Infliximab-treated animals exhibited an improved trabecular microarchitecture on micro-CT and histological analysis compared to both non-treated and methotrexate-treated animals. Infliximab almost reversed the pathological changes in tendons induced by CIA. Finally, we observed statistically significant declines in tendon TNF-a and IL-23 levels after infliximab treatment. Our study provides evidence that infliximab prevents arthritis-related osteoporosis and suppresses tendon inflammation in an animal model of inflammatory arthritis, in addition to controlling disease activity. These findings offer perspectives for the management of osteoporosis and enthesitis in RA.

The Use of Collagen-Induced Arthritis Animal Model on Studying Bone Metabolism.

CIA is a well-studied animal model of autoimmune arthritis. It resembles rheumatoid arthritis as far as histopathological changes and molecular pathogenesis are concerned. CIA is induced by immunization with collagen type II in susceptible strains. The purpose of this review is to assess the use of CIA animal model on bone metabolism and the potential therapeutic agents that could reverse this effect. A database search from their inception to 2019 was conducted to identify experimental animal studies pertinent to CIA model and bone examination. Studies including ovariectomy or without a direct comparison between control and CIA groups were excluded. Forty-eight articles were considered suitable for inclusion. Imaging techniques, biomechanical analysis, histopathological studies, and molecular biology techniques were employed. A decrease in bone mineral density in CII arthritic animals was established. Bone loss was either periarticular, generalized or both. Although trabecular bone loss was clear, the effect on cortical bone is yet to be determined. The proposed mechanism is an imbalance between bone formation and resorption as a result of osteoclast activation. The signal pathways implicated appear to be the RANKL/RANK/OPG and the Wnt pathway. Many therapeutic targets were investigated with promising results.

Postural and muscle responses to galvanic vestibular stimulation reveal a vestibular deficit in adolescents with idiopathic scoliosis.

One of the most appealing hypotheses around the aetiopathogenesis of adolescent idiopathic scoliosis attributes the development of the spine deformity to an imbalance in the descending vestibulospinal drive to the muscles resulting in a differential mechanical pull on the spine during the early life stages. In this study, we explored this hypothesis by examining postural and muscle responses to binaural bipolar galvanic vestibular stimulation (GVS) of randomly alternating polarity. Adolescents diagnosed with idiopathic scoliosis (n = 12) and healthy age-matched controls (n = 12) stood quietly with feet together (stance duration 66-102 s), eyes closed and facing forward, while 10 short (2s), transmastoidal, bipolar square wave GVS pulses (0.3-2.0 mA) of randomly alternating polarity were delivered at varying time intervals. Responses depicted in the electromyographic (EMG) activity of bilateral axial and appendicular muscles, vertical reaction forces and segment kinematics were recorded and analysed. Scoliotic patients demonstrated smaller ankle muscle responses and a delayed postural shift to the right relative to controls during anode right/cathode left GVS. When GVS polarity was reversed, patients had a greater soleus short-latency response on the left anodal side, while the rest of the muscle and postural responses were similar between groups. Vestibular stimulation also evoked greater head and upper trunk sway in scoliotic compared with healthy adolescents irrespective of stimulus polarity. Results provide new preliminary evidence for a vestibular imbalance in adolescents with idiopathic scoliosis that is compensated by somatosensory, load-related afferent feedback from the lower limbs during the latter part of the response.

Postoperative MRI findings 5 years after lumbar microdiscectomy.

BACKGROUND: Lumbar microdiscectomy is a common procedure with satisfactory results; however, postoperative events like progressive adjacent level degeneration and perineural fibrosis can contribute to long-term pain. The purpose of the study was to evaluate MRI changes 5 years after lumbar microdiscectomy and assess their association with clinical parameters. MATERIALS AND METHODS: A prospective study enrolling 61 patients who underwent microdiscectomy. Changes between preoperative and postoperative MRI findings were recorded, and these findings were tested for associations with demographic, clinical and perioperative parameters. The measured imaging parameters were degeneration of the operated and adjacent discs and endplates, morphology of the disc herniation, facet joints arthritis and the presence of postoperative perineural fibrosis. RESULTS: Statistically significant differences were found between preoperative and postoperative morphology of the operated disc, facet joints arthritis and degeneration of the operated and caudal adjacent disc. There were no differences between preoperative and postoperative disc degeneration of the superior adjacent disc and in degeneration of the operated and adjacent endplates. Postoperatively perineural fibrosis was common; however, thecal sac compression and nerve root impingement were reduced. Age at the time of surgery was the only parameter associated with postoperative changes. CONCLUSION: Five years after microdiscectomy, several postoperative MRI changes including operated disc's morphology, facet joints arthritis and degeneration of the operated and caudal adjacent disc were shown. Taking into consideration that participants were on average middle-aged, these changes could be attributed not only to the impact of the surgery but also to the natural history of lumbar spine degeneration.

Lower back and neck pain among dentistry students: a cross-sectional study in dentistry students in Northern Greece.

INTRODUCTION: Dentistry students and dentists comprise a unique group of professionals, whose everyday professional activity requires long hours of standing and working in a position considered unhealthy for the lower back and neck. Our aim was to explore the factors involved in the appearance of low back and neck pain in dentistry students as well as the impact of the pain on the students' professional and everyday activities. MATERIALS AND METHODS: A questionnaire was given to all dentistry students of the 4th and 5th year of our university. The questionnaire included 43 questions regarding demographic data, history (spinal injury, other comorbidities), daily activities (exercise, smoking, alcohol and caffeine consumption, use of cell phone), professional activities (length and type of dental work), pattern and intensity of pain, and personal pain evaluation. A statistical analysis of the gathered data was performed. RESULTS: All students having suffered a spinal trauma or indicating any other comorbidity that could cause severe pain of the spine were excluded from the study. Fifty-five students (21 male, 34 female) were included. Our data showed that increased alcohol consumption and prolonged use of cell phone were connected to increased levels of pain. The students reported that the most frequent onset of pain was 1 h after starting to work in a standing position, while the majority believed that their working habits were involved in the appearance and the intensity of neck and low-back pain. CONCLUSION: Our findings indicate that among dentistry students appears to be a causative relationship between their professional activities and the experienced spinal pain. These findings may be useful in a possible future restructuring of the educational program in dental schools, as well as in improving the ergonomics of dentistry working units.

Periprosthetic giant cell tumour of the tibia: en bloc resection and megaprosthesis revision.

We present a case detailing the diagnosis and management of a periprosthetic giant cell tumour in a female patient in her 70s, who had undergone total knee arthroplasty (TKA) for primary osteoarthritis in her right knee 7 years prior. The patient reported 4 months of painful weight-bearing. Various imaging modalities, including plain radiographs, CT scans and MRI, revealed a sizeable lytic lesion beneath the TKA prosthesis, along with loosening of the tibial component.Blood tests and analyses of synovial fluid ruled out periprosthetic joint infection, and a biopsy confirmed the diagnosis of a giant cell tumour of the bone. Treatment entailed en bloc resection of the tumour and revision of the TKA using a hinged, oncological-type megaprosthesis. Surgical procedures involved careful resection of the proximal tibia, preservation of vasculature and the creation of a medial gastrocnemius muscle flap. Following surgery, the patient underwent supervised rehabilitation with a functional brace.

Minimally invasive outpatient management of iliopsoas muscle abscess in complicated spondylodiscitis.

BACKGROUND: Iliopsoas muscle abscess (IPA) and spondylodiscitis are two clinical conditions often related to atypical presentation and challenging management. They are both frequently related to underlying conditions, such as immunosuppression, and in many cases they are combined. IPA can be primary due to the hematogenous spread of a microorganism to the muscle or secondary from a direct expansion of an inflammatory process, including spondylodiscitis. Computed tomography-guided percutaneous drainage has been established in the current management of this condition. AIM: To present a retrospective analysis of a series of 8 immunocompromised patients suffering from spondylodiscitis complicated with IPA and treated with percutaneous computed tomography-guided drainage and drain insertion in an outpatient setting. METHODS: Patient demographics, clinical presentation, underlying conditions, isolated microorganisms, antibiotic regimes used, abscess size, days until the withdrawal of the catheter, and final treatment outcomes were recorded and analyzed. RESULTS: All patients presented with night back pain and local stiffness with no fever. The laboratory tests revealed elevated inflammatory markers. Radiological findings of spondylodiscitis with unilateral or bilateral IPA were present in all cases. Staphylococcus aureus was isolated in 3 patients and Mycobacterium tuberculosis in 2 patients. Negative cultures were found in the remaining 3 patients. The treatment protocol included percutaneous computed tomography-guided abscess drainage and drain insertion along with a course of targeted or empiric antibiotic therapy. All procedures were done in an outpatient setting with no need for patient hospitalization. CONCLUSION: The minimally invasive outpatient management of IPA is a safe and effective approach with a high success rate and low morbidity.

Gaucher Disease: An Unusual Cause of Knee Pain.

INTRODUCTION: Gaucher disease (GD) is a genetic lysosomal disorder leading to storage of the glycolipid molecule glucocerebroside in macrophages, causing multiorgan dysfunction. Bone marrow involvement may result in painful bone crisis and hematologic disturbance. CASE REPORT: We present a case of a 13-year-old adolescent boy with right knee pain. Radiograph and magnetic resonance imaging of the distal femur indicated possible osteomyelitis or bone tumor. However, histologic examination of bone biopsy material suggested the diagnosis of GD, which was confirmed by detection of decreased ß-glucocerebrosidase activity and identification of the exact gene mutation. DISCUSSION: Many visceral and bone abnormalities of GD have been described. The diagnosis of GD is based on clinical and laboratory findings and is established by the measurement of ß-glucocerebrosidase dysfunction and the study of GBA gene mutations. Treatment is currently based on enzyme replacement and substrate reduction. CONCLUSION: This is a rare case of GD presenting initially with knee pain. Because early diagnosis is important for the treatment of this condition, orthopaedic surgeons should consider this uncommon cause in the differential diagnosis of joint pain.

Are venotonic drugs effective for decreasing acute posttraumatic oedema following ankle sprain? A prospective randomized clinical trial.

OBJECTIVE: Lower leg oedema after trauma may cause various degrees of pain, disability and delay in patient recovery. In this prospective randomized study, we hypothesized that venotonic drugs had no effect in clinical outcome of patients with ankle sprain. PATIENTS AND METHODS: Eighty-one patients with type II and III ankle sprain were screened and randomly assigned for receiving standard conservative treatment alone (control group, 39 patients) or with oral intake of a venotonic drug (micronized purified flavonoid fraction, Daflon 1,000 mg × 3) for 20 days (study group, 42 patients). Measurement of the circumference of ankle region in two different locations and assessment of pain intensity with the Visual Analogue Score were performed at the time of patients' admission and during the 7th and 20th posttraumatic day. RESULTS: Patients demographics were comparable in both groups. There were no significant differences between the two groups regarding the values of perimeter of ankle joint or pain intensity at all the examined time points. CONCLUSIONS: Venotonic drugs seem not to decrease the posttraumatic oedema or pain in patients who suffer from moderate or severe ankle sprain.

Effects of Long-Term Methotrexate, Infliximab, and Tocilizumab Administration on Bone Microarchitecture and Tendon Morphology in Healthy Wistar Rats.

Objective Rheumatic diseases are associated with bone loss, both systemic and periarticular, and tendon abnormalities. The aim of this study is to examine the effect of three antiarthritic drugs, methotrexate, an anti-folate metabolite; infliximab, a Tumor Necrosis Factor-alpha (TNF-α) inhibitor; and tocilizumab, an antibody against Interleukin-6 (IL-6) receptor, on bone microarchitecture and tendon morphology in the absence of an inflammatory state. Materials and methods Thirty-five, 8- to 9-week-old, male, Wistar rats were randomly allocated into five groups: negative control (CTRL), vehicle (VEH), methotrexate (MTX), infliximab (INFX), and tocilizumab (TCZ). After 8 weeks of antiarthritic drug intraperitoneal administration, animals were euthanized and rat tibiae and patellar tendons were histologically examined. Results All sections exhibited normal bone microarchitecture. Histological scores in all groups corresponded to normal bone mineral density. No no apparent differences in tenocyte morphology and architecture of collagen fibers were observed. Conclusions The results of this study indicate that long-term administration of methotrexate, infliximab, and tocilizumab had no effect on bone microarchitecture and tendon morphology in rats in the absence of an inflammatory condition.

Running-Related Injury From an Engineering, Medical and Sport Science Perspective.

Etiologic factors associated to running injuries are reviewed, with an emphasis on the transient shock waves experienced during foot strike. In these terms, impact mechanics are analyzed from both, a biomechanical and medical standpoint and evaluated with respect injury etiology, precursors and morbidity. The complex interaction of runner specific characteristics on the employed footwear system are examined, providing insight into footwear selection that could act as a preventive measure against non-acute trauma incidence. In conclusion, and despite the vast literature on running-related injury-risks, only few records could be identified to consider the effect of shoe cushioning and anthropometric data on injury prevalence. Based on this literature, we would stress the importance of such considerations in future studies aspiring to provide insight into running related injury etiology and prevention.

Surgical management of closed tibiotalar dislocation: a case report and 2-year follow-up.

UNLABELLED: We report a case of a closed tibiotalar dislocation without an associated malleolar fracture, in the presence of medial malleolar hypoplasia, treated with closed reduction and surgical repair of the deltoid ligament, followed by cast immobilization. Post-reduction radiographs, before open repair of the deltoid ligament, revealed an Elisé test ratio of 0.43. The ruptured superficial and deep portions of the deltoid ligament and the anterior ankle capsule were primarily repaired with suture, after which cast immobilization and non-weight bearing were used before physiotherapy and rehabilitation. Two years after the injury, the patient was pain free with a full range of ankle motion, and there were no signs of residual instability or early osteoarthritis. Subjective clinical testing using a valid health measurement instrument revealed an excellent clinical outcome. Based on our experience in this case, closed ankle dislocation in the presence of a hypoplastic medial malleolus and stress manipulation evidence of medial instability indicates the need for primary repair of the deltoid ligament. LEVEL OF CLINICAL EVIDENCE: 4.

Intraoperative epidural application of steroid and local anaesthetic agent following lumbar discectomy: A prospective double blinded randomized controlled trial.

BACKGROUND: Postoperative pain management following lumbar discectomy is a key part of the procedure and various postoperative pain protocols including a wide range of agents are being used in daily practice worldwide. The aim of this study is to investigate the effect of intraoperative epidural infiltration of local anaesthetic and steroid compared with placebo (normal saline) following microscopic lumbar discectomy. METHODS: Sixty patients undergoing lumbar discectomy were randomized to intraoperative infiltration of 3 mg betamethoasone acetate and 18 mg ropivacaine (Group A) or normal saline (Group B). Infiltration was performed after discectomy and decompression and immediately prior to incision closure. Postoperatively a standard protocol of intravenous acetaminophen administration and physiotherapy was followed. Additional analgesia with tramadol was given only in patients who required further pain management. Postoperative pain was evaluated using VAS score. Opioid consumption was recorded. Primary outcome measures included immediate postoperative back pain VAS score, opioid consumption and infection rate. Patients were reviewed in clinic at 6 weeks, 6 months and 1 year postoperatively. RESULTS: None of the patients in Group A required further analgesia while 12 Group B patients required further treatment with tramadol (p = 0.01). At 3 h postoperatively the VAS score was significantly lower in Group A compared to Group B (p < 0.05). Fifty-seven patients completed the 1 year follow up (95%) and 2 patients (1 from each group) suffered a complication of postoperative radiculopathy. CONCLUSION: Intraoperative application of steroid and local anaesthetic agent is effective on pain reduction for only a short period after surgery, while there is no effect on infection rate or any other long-term outcome compared with placebo. Hence although it is a safe technique, its benefits are limited from the duration of action.

Spinal cord compression by a solitary metastasis from a low grade leydig cell tumour: a case report and review of the literature.

BACKGROUND: Leydig tumour is rare and there are only three cases with metastatic disease reported. CASE PRESENTATION: A 52 year-old Caucasian male was admitted, on emergency basis to the Orthopaedic Department with six weeks history of increasing midthoracic back pain, change in gait, poor balance, subjective weakness and numbness of the lower trunk and legs. MRI scan showed change in the signal intensity of T4 and T5 vertebral body but their height were maintained. Urgent T4 and T5 corpectomies, decompression of the spinal cord and reconstruction of the vertebral bodies were performed followed by radiotherapy. Neurological status significantly improved with a mild residual numbness over the dorsum of the right foot. The histology of the excised tumour was identical to the primary. At 2 years follow-up visit the patient is neurologically stable and disease free without other organs metastases. CONCLUSION: This is the first case in English literature, which shows that spinal metastases could occur even in the early stage of Leydig cell tumour, without other organs involvement. Aggressive surgical management of spinal metastases combined with post operative radiotherapy can give a better chance for long survivorship.

Acute management of clavicle fractures. A long term functional outcome study.

The purpose of this study was to evaluate the long-term results after acute treatment of clavicle fractures. We reviewed 139 patients with an average age of 39.3 years (range: 18 to 74) who sustained a clavicle fracture either isolated or as part of a polytrauma. Besides demographic data, both clinical result and residual symptoms were also recorded. The average follow-up was 7.2 years (range: 4 to 13). The fracture showed a higher prevalence in young men and older women. The most frequent mechanism of injury was a fall (39.6%) and coexisting injuries were found in 12.9% of patients. Conservatively treated fractures united in 96.9% of cases and the time to union was no different with a sling or figure-of-eight bandage. Fracture location did not influence the functional outcome. One third of patients were still complaining of mild pain and discomfort during overhead activities and polytrauma patients had a lower Constant score.

Pulsatile bleeding during closed vertebral biopsy.

Needle biopsy of the spine yields a higher diagnostic accuracy when large bore instruments are used. The Harlow Wood vertebral biopsy needle, for instance, has an internal diameter of 3 mm. However, pulsatile bleeding may occur, especially when a tumoral lesion is biopsied. The authors noted 9 pulsatile bleedings in 238 needle biopsies (3.8%). A piece of Surgicel, brought in with the trephine guide and the obturator, was an efficient treatment. A second piece of Surgicel, soaked in 1:10.000 adrenaline, was sometimes necessary.

Subcutaneous targeted neuromodulation technique for the treatment of intractable chronic postthoracotomy pain.

Subcutaneous targeted neuromodulation has been used successfully in chronic neuropathic pain. A 26 year-old patient with severe postthoracotomy pain and ipsilateral "wing scapula" due to intraoperative injury of the long thoracic nerve, is reported. Application of targeted neuromodulation resulted in immediate pain relief and marked improvement of shoulder function at one-year follow-up. The technique may be an effective alternative treatment of chronic and intractable postoperative painful conditions.