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Since December 2019, the COVID-19 pandemic has had a significant impact on healthcare systems worldwide, prompting policymakers to implement measures of isolation and eventually adopt strict national lockdowns, which affected mobility, healthcare-seeking behavior, and services, in an unprecedented manner. This study aimed to analyze the effects of these lockdowns on hip-fracture epidemiology and care services, compared to nonpandemic periods in previous years. We retrospectively collected data from electronic patient records of two major hospitals in Western Greece and included patients who suffered a fragility hip fracture and were admitted during the two 5-week lockdown periods in 2020, compared to time-matched patients from 2017–2019. The results showed a drop in hip-fracture incidence, which varied among hospitals and lockdown periods, and conflicting impacts on time to surgery, time to discharge after surgery, and total hospitalization time. The study also found that differences between the two differently organized units were exaggerated during the COVID-19 lockdown periods, highlighting the impact of compliance with social-distancing measures and the reallocation of resources on the quality of healthcare services. Further research is needed to fully understand the specific variations and patterns of geriatric hip-fracture care during emergency health crises characterized by limited resources and behavioral changes.

Introduction: Knee arthrodesis is a limb salvage intervention for persistent periprosthetic joint infection (PJI) when revision total knee arthroplasty fails. Conventional arthrodesis techniques are associated with the increased rate of complications, especially in patients with extensive bone loss and extensor tendon deficiency. Methods: Eight patients with a modular silver-coated arthrodesis implant after failed exchange arthroplasty for infection, were retrospectively reviewed. All patients had significant bone loss, while 5 displayed extensor tendon deficiency. Survivorship, complications, leg length discrepancy, median Visual Analogue Scale (VAS) and Oxford Knee score (OKS) were evaluated. Results: The median follow up was 32 months (range 24–59 months). The survivorship rate of the prosthesis was 86% during the minimum time of follow up of 24 months. In one patient recurrence of the infection was observed and above-knee amputation was performed. The median postoperative leg length discrepancy was 2.07 ± 0.67 cm. Patients were able to ambulate with mild or no pain. The median VAS and OKS was 2.14 ± 0.9 and 34.7 ± 9.3, respectively. Conclusions: The results of our study demonstrated that knee arthrodesis with a silver coated arthrodesis implant, performed for persistent PJI in patients with significant bone loss and extensor tendon deficit, provided a stable construct, allowed eradication of infection and was associated with good functional outcome.

Introduction:Neurofibromatosis Type 1 (Nf1), also termed von Recklinghausen disease, is a rare autosomal dominant genetic disorder accompanied by several osseous and skeletal manifestations. In NF, hypophosphatemia linked to secondary hyperparathyroidism due to Vitamin D deficiency and low calcium intake has been reported as a risk factor for low bone mass density (BMD), but reports of NF1 associated oncogenic hypophosphatemic osteomalacia (HO) are extremely rare. Case Report: We report a patient with NF1 associated with intracranial low-grade gliomas and congenital renal agenesis suffering from HO. Bone defects and deformities such as generalized bone pains located in feet, ankles and lower limbs, thoracic scoliosis, mild bowing of long bones of lower limbs, stress fractures, and old fractures as well as with altered bone metabolic serum markers were present. After 8 weeks of follow-up, it was observed that the combination of oral administration of phosphate and Vitamin D improved her medical symptoms without significant changes in phosphate levels or BMD. Conclusion: Although renal agenesis is not correlated with hypophosphatemia, the coexistence of NF1, renal congenital deformities, and low-grade gliomas may contribute to disease severity. Conventional treatment with high doses of oral calcitriol associated with phosphate is efficient to improve the clinical and laboratory symptoms of the disease. Keywords: Bone pains, scoliosis, bone mass density, stress fractures, vitamin D.

Below-knee amputation is the treatment of choice for distal tibia malignancies, considering the specific anatomic features of the distal leg and ankle. However, advances in imaging modalities and adjuvant therapies and improved surgical techniques have made limb salvage surgery increasingly possible. The distal tibia is an uncommon location for malignant bone tumors, and there is limited information about limb salvage and reconstruction. Currently, 3-dimensional printed implants may successfully address reconstruction challenges after tumor resection. We present a patient with high-grade osteosarcoma of the distal tibia who underwent limb salvage and distal tibia and ankle joint replacement with a 3-dimensional printed endoprosthesis. [ Orthopedics . 2022;45(6):e348–e352.]

Prosthetic reconstruction after wide resection of tumors of the proximal humerus presents a unique challenge. The shoulder is a complex articulation, and patients have high expectations for postoperative function. The goal of this study is to compare functional outcomes, oncologic outcomes, and complication rates for 2 reconstructive methods. Forty patients with proximal humeral tumors were reviewed retrospectively. Proximal humeral endoprosthesis (PHE) was used for 21 patients, and reverse shoulder arthroplasty (RSA) was used for 19 patients. Clinical results, oncologic outcomes, and complication rates were assessed. The functional outcomes of the patients were assessed with the Musculoskeletal Tumor Society scoring system (MSTS), the shortened version of the Disabilities of the Arm, Shoulder and Hand (QuickDASH) score, and shoulder range of motion. The mean follow-up was 62±15 months. Shoulder dislocations occurred among 8 patients with PHE and 1 patient with RSA ( P =.021). The other complication rates were similar for the 2 groups ( P P =.72). However, the QuickDASH score was significantly better ( P =.031) for those with RSA (mean, 19±6.3) compared with patients with PHE (mean, 30±4.8). Additionally, shoulder active abduction and forward flexion were significantly greater for the RSA group ( P =.04 and P =.03, respectively). Five patients had local recurrence. Prosthetic reconstruction after oncologic re-section of the proximal humerus is associated with significant limitation of shoulder range of motion and a high rate of revision surgery. However, in this study, RSA was associated with fewer dislocations, improved Quick-DASH score, and greater abduction and forward flexion compared with PHE. [ Orthopedics . 2022;45(6):e335–e341.]

Introduction: Implant-associated infections are a major problem in orthopaedic surgery. Local delivery systems of antimicrobial agents on the implant surface have attracted great interest recently. The purpose of this study was to identify antimicrobial coatings currently used in clinical practice, examining their safety and effectiveness in reducing post-operative infection rates.Materials and Methods: A systematic review was conducted in four databases (Medline, Embase, Cochrane, Cinahl) according to the Preferred Reporting Items for Systematic reviews and Meta-analysis (PRISMA) guidelines up to December 2019, using the key words “orthopaedic implant coated”, “coated implant infection”, “silver coating ” and “antibiotic coating”.Results: Seven articles involving 1307 patients (561 with coated implants and 746 controls who were not) comparing the incidence of periprosthetic infections after the application of internal fracture fixation, total arthroplasties and endoprostheses were evaluated. Three different coating technologies were identified: gentamicin coating for tibia nail and total arthroplasties; silver technology and povidone-iodine coating for tumour endoprostheses and titanium implants. Meta-analysis demonstrated that patients who were treated with antimicrobial coated implants presented lower infection rates compared to controls over the seven studies (Q = 6.1232, I2 = 0.00, 95% CI: 1.717 to 4.986, OR: 2.926, Z= 3.949, pConclusion: All technologies were reported to have good biocompatibility and were effective in the reduction of post-operative peri-prosthetic infection rates.

Soft tissue tumours of the elbow are mostly benign. Malignant tumours in this area, although uncommon, often present unique clinical and histopathological characteristics that are helpful for diagnosis. Management of soft tissue tumours around the elbow may be challenging because of their rarity and the proximity to neurovascular structures. Careful staging, histological diagnosis and treatment are essential to optimize clinical outcome. A missed or delayed diagnosis or an improperly executed biopsy may have devastating consequences for the patient. This article reviews the most common benign and malignant soft tissue tumours of the elbow and discusses the clinicopathological findings, imaging features and current therapeutic concepts.Cite this article: EFORT Open Rev 2019;4:668-677. DOI: 10.1302/2058-5241.4.190002

Osteoarthritis is a degenerative joint disease affecting middle-aged and elderly patients. It mainly involves weight-bearing joints such as the hip, knee and spine as well as the basilar joint of the thumb, causing dysfunction and painful symptoms. Often, joint arthritis is accompanied by cartilage defects, joint space narrowing, osteophytes, bone sclerosis and subchondral bone cysts (SBC). The aim of the present study was to explore the pathophysiology responsible for the development of SBCs as well as the association between SBCs and disease progress, the level of clinical symptoms and their impact on postoperative outcomes and risk of possible complications following joint replacements if left untreated. A literature review on PubMed articles was conducted to retrieve and evaluate all available evidence related to the main objective mentioned above. A few theories have been put forth to explain the formation process of SBCs. These involve MMPs secretion, angiogenesis, and enhanced bone turnover as a biological response to abnormal mechanical loads causing repeated injuries on cartilage and subchondral tissue during the development of arthritis. However, the application of novel therapeutics, celecoxib-coated microspheres, local administration of IGF-1 and activated chondrocytes following surgical debridement of SBCs hinders the expansion of SBCs and prevents the progression of osteoarthritis.

Sclerostin has been identified as an important regulator of bone homeostasis through inhibition of the canonical Wnt-signaling pathway, and it is involved in the pathogenesis of many different skeletal diseases. Many studies have been published in the last few years regarding sclerostin’s origin, regulation, and mechanism of action. The ongoing research emphasizes the potential therapeutic implications of sclerostin in many pathological conditions with or without skeletal involvement. Antisclerostin antibodies have recently been approved for the treatment of osteoporosis, and several animal studies and clinical trials are currently under way to evaluate the effectiveness of antisclerostin antibodies in the treatment of other than osteoporosis skeletal disorders and cancer with promising results. Understanding the exact role of sclerostin may lead to new therapeutic approaches for the treatment of skeletal disorders.

Background: Parosteal osteosarcoma (PAO), which is a surface osteosarcoma, can be treated with wide excision and endoprosthetic or allograft application. However, due to the low local recurrence and metastasis rate, when it appears in the posterior surface of the distal femur, can be managed with hemicortical wide resection and biological reconstruction with hemicortical allograft.The purpose of this study was to evaluate the oncological and functional outcomes of patients with parosteal osteosarcoma (PAO) of the posterior cortex of the distal femur who underwent biological reconstruction after hemicortical resection. Methods: Eleven patients who underwent wide tumor resection and defect reconstruction of the posterior surface of the distal femur using hemicortical allograft were studied retrospectively. Local recurrence, metastasis, complications and the functional outcome using the Musculoskeletal Tumor Society scoring system (MSTS Score) were evaluated.Results: The average postoperative follow-up period was 53.64 months (range, 30 to 84 months). At the latest follow up, all patients were free of the disease without appearing any metastases. A patient with local recurrence underwent revision surgery with fibula autograft reconstruction. The mean MSTS score was 93.45 ± 3.56. Conclusions: In patients with PAO of the posterior aspect of the distal femur the treatment of hemicortical resection and allograft reconstruction has satisfactory oncological and functional outcomes and low complication rates.

Idiopathic scoliosis is a disorder of unknown etiology. Bone biopsies from idiopathic scoliosis patients revealed changes at cellular and molecular level. Osteocytic sclerostin is downregulated, and serum level of sclerostin is decreased. Osteocytes in idiopathic scoliosis appear to be less active with abnormal canaliculi network. Differentiation of osteoblasts to osteocytes is decelerated, while Wnt/β-catenin signaling pathway is overactivated and affects normal bone mineralization that leads to inferior mechanical properties of the bone, which becomes susceptible to asymmetrical forces and causes deformity of the spinal column. Targeting bone metabolism during growth by stimulating sclerostin secretion from osteocytes and restoring normal function of Wnt/β-catenin signaling pathway could, in theory, increase bone strength and prevent deterioration of the scoliotic deformity.

Soft tissue and bone sarcomas represent a group of aggressive neoplasms often accompanied by dismal patient prognosis, especially when distant metastases are present. Moreover, effective treatment can pose a challenge, as recurrences are frequent and almost half of patients present with advanced disease. Researchers have unveiled the molecular abnormalities implicated in sarcomas’ carcinogenesis, paving the way for novel treatment strategies based on each individual tumor’s characteristics. Therefore, the development of new techniques aiding in early disease detection and tumor molecular profiling is imperative. Liquid biopsy refers to the sampling and analysis of patients’ fluids, such as blood, to identify tumor biomarkers, through a variety of methods, including qRT-PCR, qPCR, droplet digital PCR, magnetic microbeads and digital PCR. Assessment of circulating tumor cells (CTCs), circulating free DNA (ctDNA), micro RNAs (miRs), long non-coding RNAs (lncRNAs), exosomes and exosome–associated proteins can yield a plethora of information on tumor molecular signature, histologic type and disease stage. In addition, the minimal invasiveness of the procedure renders possible its wide application in the clinical setting, and, therefore, the early detection of the presence of tumors. In this review of the literature, we gathered information on biomarkers assessed through liquid biopsy in soft tissue and bone sarcoma patients and we present the information they can yield for each individual tumor type.

Υπόβαθρο: Η πλειοτροπίνη (ΡΤΝ) είναι ένας αυξητικός παράγοντας με υψηλή συγγένεια για την ηπαρίνη. Η ΡΤΝ εκφράζεται στον εμβρυικό και νεανικό χόνδρο, καθώς και στις επιφύσεις των οστών σε πειραματόζωα. Επιπλέον εκφράζεται και σε κύτταρα του μεσοσπονδύλιου δίσκου in vitro. Ασκεί τις βιολογικές της δράσεις με την σύνδεσή της στον υποδοχέα της Receptor Protein Tyrosine Phosphatase β/ζ (RPTPβ/ζ). Παρόλα αυτά ο ρόλος της παραμένει ακόμα ασαφής.Σκοπός: Σκοπός της έρευνάς μας είναι να μελετήσουμε την έκφραση της ΡΤΝ και του υποδοχέα της RPTPβ/ζ στην λειτουργική μονάδα τελικής πλάκας-μεσοσπονδύλιου δίσκου, κατά την ανάπτυξη σπονδυλικών παραμορφώσεων, που οφείλονται στην διαταραχή του μηχανικού περιβάλλοντος της σπονδυλικής στήλης.Υλικό και Μέθοδοι: Χρησιμοποιήθηκαν 64 επίμυες Sprague-Dawley, ηλικίας 8 εβδομάδων, εκ των οποίων 4 χρησιμοποιήθηκαν ως υγιείς μάρτυρες. Στις ουρές των πειραματόζωων εφαρμόστηκε μηχανική φόρτιση με την χρήση μιας mini συσκευής εξωτερική οστεοσύνθεσης τύπου Ilizarov. Η φόρτιση αντιστοιχούσε με 0 μοίρες μέτριας αξονικής συμπίεσης της τάξης των 5mm, και 10 , 30 και 50 μοιρών που ταξινομήθηκαν στις ομάδες 0, Ι, ΙΙ και ΙΙΙ, αντίστοιχα. Η έκφραση της ΡΤΝ, του RPTPβ/ζ και των πιθανόν αλληλεπιδράσεων μεταξύ τους ερευνήθηκαν με Western blot ανάλυση καθώς και με ανοσοϊστοχημικές μεθόδους.Αποτελέσματα: Η έκφραση της ΡΤΝ, στο control group, ήταν περιορισμένη στα χονδροκύτταρα της υπερτροφικής ζώνης της τελικής πλάκας. Στα group 0 – ΙΙ, η έκφραση της ΡΤΝ αυξάνονταν και εντοπίζονταν στα χονδροκύτταρα της υπερτροφικής ζώνης, της ζώνης πολλαπλασιασμού και στα οστεοκύτταρα και οσστεοβλαστικά κύτταρα της ζώνης οστεοποίησης των τελικών πλακών. Αύξηση της έκφρασης της ΡΤΝ παρατηρήθηκε και στα χονδροκύτταρα της περιφέρειας του ινώδους δακτυλίου. Στο group ΙΙΙ μόνο περιορισμένη έκφραση της ΡΤΝ παρατηρήθηκε κυρίως στα οστεοκύτταρα. Ο υποδοχέας RPTPβ/ζ εκφράστηκε με τις τρεις ισομορφές των > 250 kDa, 130 και 85 kDa. Η έκφραση του RPTPβ/ζ παρουσίαζε αύξηση κυρίως στο group 0 σε όλους τους τύπους των κυττάρων. Μικρής έντασης ανοσοχρώση για τον RPTPβ/ζ παρατηρήθηκε στα groups I και II, ενώ στο group ΙΙΙ η έκφρασή του ελαχιστοποιήθηκε.Συμπεράσματα: Η ΡΤΝ και ο υποδοχέας της RPTPβ/ζ εκφράζονται κατά την ανάπτυξη των σπονδυλικών παραμορφώσεων που οφείλονται στην άσκηση μηχανικής φόρτισης. Το ποσό της έκφρασή τους εξαρτάται από τον τύπο και την σοβαρότητα της παραμόρφωσης. Τα ανωτέρω τους καθιστούν σημαντικά μόρια στην παθοφυσιολογία της πάθησης αλλά και ως ενδιαφέροντες υποψήφιους στόχους για την ανάπτυξη θεραπευτικής προσέγγισης της νόσου.

Osteoarthritis (ΟΑ) is characterized by cartilage breakdown and subchondral sclerosis. Micro-fractures of the calcified tissues have been, also, detected, but their exact role has not been elucidated yet. This study was to examine the frequency of cracks during OA progression and to correlate them with the underlying cellular modifications and matrix metalloproteinase-2 (MMP-2) expression using histological/immunohistological methods.Overall, 20 patients and 3 controls (9 specimens per patient), aged 60-89 years, diagnosed with hip/knee OA were included. The development of cracks was examined in 138 sections, whereas the expression of MMP-2 was examined in 69 additional sections.Based on Mankin score, three groups of OA severity were analyzed: Group I (mild) was constituted of sections with score 1-5 while Groups II (moderate) and III (severe) with score 6-7 and greater or equal to 8, respectively. Demographic characteristics did not reveal any association between the number of microdefects and age or body mass index (BMI). Cartilage micro-cracks were increased during moderate and severe OA, while bone cracks were increased during mild and severe OA. In knee OA, cartilage cracks were not correlated with Mankin score, whereas in hip OA they appeared association with severity score. Bone cracks were positively correlated with matrix apoptotic osteocytes and osteoblastic cells, but not with osteoclasts. MMP-2 immunostaining was increasing by OA severity in the osteochondral unit. Similarly, MMP-2 was expressed on the microcracks' wall mainly in Group III.Our data displayed that bone cracks during primary OA stages, represent an early adaptative mechanism aiming to maintain cartilage integrity. Accumulation of bone defects and concomitant increase of apoptotic osteocytes activated an abnormal remodeling due to osteoblastic activity, in which MMP-2 played a pivotal role, leading to subchondral sclerosis promoting further osteochondral deformities.

Background: Long bone fractures display significant non-union rates, but the exact biological mechanisms implicated in this devastating complication remain unclear. The combination of osteogenetic and angiogenetic factors at the fracture site is an essential prerequisite for successful bone regeneration. The aim of this study is to investigate the results of the clinical implantation of growth factors for intraoperative enhancement of osteogenesis for the treatment of long bone fractures and non-unions. Methods: A systematic literature review search was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines in the PubMed and Web of Science databases from the date of inception of each database through to 10 January 2022. Specific inclusion and exclusion criteria were applied in order to identify relevant studies reporting on the treatment of upper and lower limb long bone non-unions treated with osteoinductive or cellular factors. Results: Overall, 18 studies met the inclusion criteria and examined the effectiveness of the application of Bone Morphogenetic Proteins-2 and -7 (BMPs), platelet rich plasma (PRP) and mesenchymal stem cells (MSCs). Despite the existence of limitations in the studies analysed (containing mixed groups of open and close fractures, different types of fractures, variability of treatment protocols, different selection criteria and follow-up periods amongst others), their overall effectiveness was found significantly increased in patients who received them compared with the controls (I2 = 60%, 95% CI = 1.59 [0.99–2.54], Z =1.93, p = 0.05). Conclusion: Administration of BMP-2 and -7, PRP and MSCs were considered effective and safe methods in fracture treatment, increasing bone consolidation, reducing time to repair and being linked to satisfactory postoperative functional scores.

Pleiotrophin (PTN) is a growth factor that appears to play an important role in prostate cancer growth and angiogenesis. We have previously shown that decreased PTN expression in human prostate cancer PC3 cells leads to decreased adhesion of prostate cancer cells to osteoblasts, suggesting that PTN mediates this interaction. In the current work, using peptides that correspond to different regions of the PTN protein, we identified that a domain responsible for the adhesion of prostate cancer cells to osteoblasts corresponds to amino acids 16-24 of the mature PTN protein. Given that a synthetic PTN

Objectives The increasing number of hip arthroplasties (HA), due to the growing elderly population, is associated with the risk of femoral periprosthetic fractures (FPFs). The purpose of this study was to identify potential risk factors for the development of FPFs after HA. Methods A systematic review was conducted in five data bases (Medline, Embase, Cochrane, Cinahl, ICTRP) according to the Preferred Reporting Items for Systematic reviews and Meta-analysis (PRISMA) guidelines up to May 2019, using the key words “risk factor,” “periprosthetic fracture,” and “hip replacement or arthroplasty.” Meta-analysis of the clinical outcomes of HA and subgroup analysis based on the factors that were implicated in FPFs was performed. Results Sixteen studies were included (sample size: 599,551 HA patients, 4253 FPFs, incidence 0.71%). Risk factors statistically associated with increased incidence of FPFs were female gender (+ 40%), previous revision arthroplasty surgery (× 3 times), and the presence of rheumatoid arthritis (× 2.1 times), while osteoarthritis (− 57%), cement application (− 59%), and insertion of Biomet (− 68%) or Thompson’s prosthesis (− 75%) were correlated with low prevalence of FPFs. Obesity, cardiac diseases, advanced age, bad general health (ASA grade ≥ 3), and use of Exeter or Lubinus prosthesis were not linked to the appearance of FPFs. Conclusion This meta-analysis suggested that female gender, rheumatoid arthritis, and revision arthroplasty are major risk factors for the development of FPFs after a HA. In those patients, frequent follow-ups should be planned. Further prospective studies are necessary to clarify all the risk factors contributing to the appearance of FPFs after HA.

The worldwide increasing frequency of mass casualty situations after combat and terrorist explosion or natural disasters is characterized by large number of casualties, variety of injuries, dangerous environmental conditions, and raised medical involvement demands. Ocular, cardiovascular, respiratory, neurological, and musculoskeletal systems are severely affected and are managed differently. Pelvic and spinal injuries are very common during these situations, and they require immediate and effective therapeutic approaches. Comprehension of injury physiology in conjunction with focused medical history, targeted physical examination, and radiographic findings allow early and accurate diagnosis and treatment. Primary cervical, spinal, and pelvic immobilization with external fixation systems and damage control resuscitation must be performed. Additional treatment priorities are the management of open wounds and soft tissue traumas and the prevention of infections and sepsis. The coordination between different medical specialization teams may increase the therapeutic efficacy. Awareness of diagnostic and management protocols for these injuries is absolutely necessary for the emergency medical staff.

Neurofibromatosis type 1 (NF1), which is the most common phacomatoses, is an autosomal dominant disorder characterized by clinical presentations in various tissues and organs, such as the skin, eyes and nervous and skeletal systems. The musculoskeletal implications of NF1 include a variety of deformities, including scoliosis, kyphoscoliosis, spondylolistheses, congenital bony bowing, pseudarthrosis and bone dysplasia. Scoliosis is the most common skeletal problem, affecting 10–30% of NF1 patients. Although the pathophysiology of spinal deformities has not been elucidated yet, defects in bone metabolism have been implicated in the progression of scoliotic curves. Measurements of Bone Mineral Density (BMD) in the lumbar spine by using dual energy absorptiometry (DXA) and quantitative computer tomography (QCT) have demonstrated a marked reduction in Z-score and osteoporosis. Additionally, serum bone metabolic markers, such as vitamin D, calcium, phosphorus, osteocalcin and alkaline phosphatase, have been found to be abnormal. Intraoperative and histological vertebral analysis confirmed that alterations of the trabecular microarchitecture are associated with inadequate bone turnover, indicating generalized bone metabolic defects. At the molecular level, loss of function of neurofibromin dysregulates Ras and Transforming Growth factor-β1 (TGF-β1) signaling and leads to altered osteoclastic proliferation, osteoblastic activity and collagen production. Correlation between clinical characteristics and molecular pathways may provide targets for novel therapeutic approaches in NF1.

As a result of the increasing numbers of joint replacement surgeries and other implant-associated procedures performed, the incidences of periprosthetic joint infections and osteomyelitis are on the rise. Antibiotic resistance to gram-positive species, which are mostly isolated from such infections, is a significant obstacle in clinical practice. Promising clinical outcomes have been reported with the use of novel antibiotics for patients with periprosthetic joint infections and osteomyelitis. Further research is necessary for the establishment of these novel antibiotic therapies in routine clinical practice. [ Orthopedics . 2018; 41(6):323–328.]

Hyperbaric oxygen has been used as an adjunctive measure in the treatment of chronic osteomyelitis. The aim of this systematic literature review was to analyze the outcome and the complications of hyperbaric oxygen for chronic osteomyelitis. Forty-five of 96 studies reporting the use of hyper-baric oxygen for 460 patients with chronic osteomyelitis met the inclusion criteria and were analyzed qualitatively. All patients previously received antibiotics and surgical debridement. Mixed bacterial flora was detected in most of the studies. Staphylococcus aureus was the isolated pathogen in 12 (60%) of the 20 cohort and in 4 (20%) of the 20 case studies. Adjuvant hyperbaric oxygen was effective in 16 (80%) of the 20 cohort and 19 (95%) of the 20 case studies. Overall, 308 (73.5%) of 419 patients with complete data had a successful outcome and no reported relapse. Available evidence supports a potentially beneficial role of adjunctive hyperbaric oxygen, especially in refractory cases of chronic osteomyelitis. [ Orthopedics. 2018; 41(4):193–199.]

Treatment of bone sarcomas in children is associated with wide tumor re-section and segmental reconstruction. The optimal surgical approach is still under debate in the literature. During the past decade, the application of expandable prostheses has gained remarkable attention because it improves patients' appearance and allows limb growth preventing leg length discrepancy. A systematic review of the literature was performed to identify studies focusing on the functional and surgical outcomes of the application of expandable endoprostheses. [ Orthopedics . 2019; 42(4):184–190.]

Bone Marrow Oedema Syndrome during childhood is a rare benign transient condition without clear pathophysiology. It usually resolves after conservative treatment, but resolution may exceed up to 8 months. A 12-year-old child with bone marrow oedema of the left foot which was diagnosed by magnetic resonance imaging (MRI) is reported. She presented with a six week subacute pain and mild swelling on the dorsal surface of the foot. Routine plain radiographs, blood tests, biochemical and serological tests were normal with the exception of serum Vitamin D levels that were reduced. The management of the child included partial weight-bearing, administration of anti-inflammatory drugs and supplementation of Vitamin D due to insufficient Vitamin D intake. After six months the child did not have any clinical symptoms and MRI showed complete resolution of the oedema. This is the first report of a juvenile bone marrow oedema correlated with hypovitaminosis D that was successfully treated with Vitamin D administration.

Bone has an enormous capacity for growth, regeneration, and remodelling, largely due to induction of osteoblasts that are recruited to the site of bone formation. Although the pathways involved have not been fully elucidated, it is well accepted that the immediate environment of the cells is likely to play a role via cell–matrix interactions, mediated by several growth factors. Formation of new blood vessels is also significant and interdependent to bone formation, suggesting that enhancement of angiogenesis could be beneficial during the process of bone repair. Pleiotrophin (PTN), also called osteoblast-specific factor 1, is a heparin-binding angiogenic growth factor, with a well-defined and significant role in both physiological and pathological angiogenesis. In this review we summarise the existing evidence on the role of PTN in bone repair.

Summary Background Subchondral bone cyst (SBC) formation is often identified in patients with osteoarthritis. Furthermore, several studies have shown that expression of matrix metalloproteinases (MMPs) is elevated in patients with OA. Objectives The aim of our study is to correlate the presence of SBCs and MMP-1 expression with the osteochondral alterations during OA progression. Methods We studied the cartilage and subchondral bone of 15 patients who had undergone total knee or hip replacement due to primary OA. As controls, we used the femoral heads of three patients without macroscopic OA changes. We evaluated three specimens per patient. Results Specimens were divided in four groups based on the Mankin histological severity score. Using immunohistochemistry, we noted SBCs at the site of greatest disease severity. Specifically, these were present more frequently in group III (Mankin score: 6–7) and IV (Mankin: ≥ 8), compared with group I (Mankin: 1–3) and II (Mankin: 4–5). Mild OA stages (Mankin: 1–6) were characterized by degeneration and thinning of the cartilage, followed by increased osteoblast and osteoclast activity of the subjacent bone and the subsequent appearance of SBCs. Simultaneously, we observed expression of MMP-1 in groups I and II in the cartilage and III and IV in both the cartilage and the subchondral bone. Moreover, osteoblast-like cells in the lining of the SBCs showed an increased expression of MMP-1 in stages III and IV. Conclusion Our study provides immunohistological evidence that SBCs accumulate in advanced OA and contain activated cells, which express MMP-1, suggesting that they may thus participate in the osteochondral changes of OA. Level of evidence Level III; prospective comparative study.

Objectives Pleiotrophin is a heparin-binding growth factor expressed in embryonic but not mature cartilage, suggesting a role in cartilage development. Elucidation of the molecular changes observed during the remodelling process in osteoarthritis is of paramount importance. This study aimed to investigate serum pleiotrophin levels and expression of pleiotrophin and its receptor protein tyrosine phosphatase beta/zeta in the cartilage and subchondral bone of osteoarthritis patients. Methods Serum samples derived from 16 osteoarthritis patients and 18 healthy donors. Pleiotrophin and receptor protein tyrosine phosphatase beta/zeta in the cartilage and subchondral bone were studied in 29 patients who had undergone total knee or hip replacement for primary osteoarthritis and in 10 control patients without macroscopic osteoarthritis changes. Results Serum pleiotrophin levels and expression of pleiotrophin in chondrocytes and subchondral bone osteocytes significantly increased in osteoarthritis patients graded Ahlback II to III. Receptor protein tyrosine phosphatase beta/zeta was mainly detected in the subchondral bone osteocytes of patients with moderate osteoarthritis and as disease severity increased, in the osteocytes and bone lining cells of the distant trabeculae. Conclusions These data render pleiotrophin and receptor protein tyrosine phosphatase beta/zeta promising candidates for further studies towards developing targeted therapeutic schemes for osteoarthritis.

The most prevalent musculoskeletal disorder of childhood with unclear aetiology is growing pains (GPs). Anatomic deformities and factors that change bone turnover are implicated in GP pathophysiology. Perinatal risk factors alter the bone metabolism affecting the bone mineral density and content. The aim of our study was to analyze the relationship between GPs, knock knees and perinatal factors. The examined population consisted of 276 children aged 3–7 years. Among them, ten pairs of dizygotic twins were evaluated. The data were collected by using a combination of semi-structured questionnaires, clinical examinations and medical charts of the children and the obstetric history of the mothers. A total of 78 children presenting GPs met Peterson’s criteria. Genu valgum severity was a significant factor for GP manifestation and for their increased frequency and intensity. Subsequently, perinatal factors regarding gestational age, Apgar score, head circumference (lower than 33 cm) and birth length or weight (smaller than 50 cm and 3000 g, respectively) made a remarkable contribution to the development of GPs. Conversely, antenatal corticosteroid treatment, increased maternal age and maternal smoking during pregnancy were not predictive of the disorder. Our data are potentially supportive for the “bone strength” theory and for the contribution of anatomical disturbances in GP appearance.

Bracing has been widely used for the treatment of adolescent idiopathic scoliosis (AIS). However, effectiveness of brace treatment remains controversial. A systematic review was conducted to investigate evidence that brace treatment is effective in the treatment of AIS. A total of 20 studies, including randomized controlled trials, nonrandomized clinical controlled trials, or case-control studies, were included. Studies comparing the results of brace treatment with no-treatment, other conservative treatments, or surgical treatment were included. Outcomes of the studies included radiological curve progression, incidence of surgery, pulmonary function, quality of life (QOL), and psychological state. The results from the systematic review are difficult to interpret. There are quite a number of varying parameters between studies that make it very difficult to reach any firm conclusions. In addition, the quality of evidence is limited because most of the studies included in this review were of low methodological quality. However, the available data suggest that, compared to observation, bracing is more potent in preventing the progression of scoliosis and may not have a negative impact on patients' QOL. Therefore, bracing can be recommended for the treatment of AIS, at least for female patients with a Cobb angle of 25-35°. Compared to other conservative treatments, bracing seems to be more effective than electrical stimulation, although an advantage of bracing over side-shift exercise or casting has not been established. Comparison between bracing and surgery is difficult because in most studies, the curve magnitude at baseline was considerably larger in the surgery group. We recommend that future studies have clearer and more consistent guidelines.

Idiopathic scoliosis (IS) is characterized by the lateral deviation of the spine and constitutes a three-dimensional distortion that leads to geometric and morphological lesions in the spine and thoracic cage. The most widespread method of conservative management is to use spinal orthoses or body braces. These are usually recommended in patients with skeletal immaturity with a Risser sign 2 or less and with curves ranging from 25° to 45°. Of these, perhaps one of the most popular in recent years is the Boston Brace. It was developed in the early 1970s, and its design is based on symmetry, consisting of extensions and pads, with each of them exerting corrective forces and has a specific role depending on the type of scoliosis. It is important that the treatment group, the patient, and the family environment should work as a team consistently and be well trained to achieve the best result. Various studies published in international literature have observed beneficial effects from the use of the Boston system. Nevertheless, there are still issues that need further investigation regarding its effectiveness depending on the type of curves, the duration of application, the gender, and BMI of patients to whom it is applied. However, without question, if all these factors are taken into account and with the compliance of the therapy group with the instructions, the main goal can be achieved, which is the stability of the spine, and the ultimate result of clinical-radiological and aesthetic improvement, which is directly linked to the psychological satisfaction of the patient.

Objectives: In contrast to what was believed in the past, nonspecific low back pain is a fairly frequent condition in children, whose pathophysiology remains unclear as yet. Although many factors have been implicated in its development, results are often contradictory. Methods: Our study aims to examine most of the reasons investigated in the international literature, as well as the previously unexamined impact of passive smoking in its clinical appearance. It is a retrospective study that investigates the symptom of nonspecific low back pain during a 12-month period before the visit of children to our department. The research included 692 children aged 7.5 to 14 years. The data were collected using a semistructured questionnaire, which included a mix of open and closed questions, followed by physical examination during their visit. Results: A total of 153 children were considered to present nonspecific low back pain during the previous year. The determinant factors appear to be greater age, the male sex, larger height, increased weight, dissatisfaction with school chairs, the clinical presentation of back pain in at least 1 parent, and coexisting anatomic orthopedic conditions. On the contrary, the weight of the school bag, the way in which it was carried and participation in sports, as well as the time spent by children in front of the TV or PC playing video or play station games, did not appear to have a statistically significant correlation with its appearance. In general, passive smoking does not appear to be a risk factor (Pr 0.341), and does not seem to play a leading role in the etiology of the condition. Furthermore, even the heaviness of parental smoking (over 20 cigarettes a day) does not seem to alter the appearance of the disease. The effect of nonspecific low back pain in children’s activities was measured using Hannover Functional Ability and Rolland Morris questionnaires, appropriately modified to childhood, where he found a moderate or severe restriction of activity in 23.52% (score 5) and 19.61% (score 6), respectively. Conclusions: The data analysis shows that nonspecific low back pain in children is a benign disorder with an unknown pathophysiological mechanism. Many anthropometric characteristics and environmental factors are implicated, but to a different degree each time. Passive smoking as well as the heaviness thereof does not appeal to play in important role in its clinical presentation. Further investigation is deemed necessary to determine the existence of other risk factors, as well as the level of their participation in the condition’s pathophysiology.

Resume Objectifs Les douleurs recidivantes des membres inferieurs (douleurs de croissance) constituent la cause la plus frequente de douleurs musculo-squelettiques chez l’enfant. Bien que depuis des annees, la litterature internationale ait decrit de nombreux cas a l’origine d’hypotheses variees sur la nature exacte de la maladie et son etiologie, celles-ci restent encore inconnues. Methodes L’objectif de notre etude est d’etablir a la fois le profil des enfants atteints par la maladie et la nature de leur prise en charge par les parents ou les specialistes medicaux. De plus, nous avons essaye de correler les theories existantes a nos observations afin de savoir si celles ci etaient verifiables par les donnees epidemiologiques. Cette etude retrospective a recherche l’apparition de douleurs des membres inferieurs dans les 12 mois precedents la consultation de l’enfant dans notre service. L’etude a inclus 532 enfants, âges de quatre a 12 ans. Les donnees ont ete obtenues par des sondages semi-structures comprenant a la fois des questions ouvertes et fermees. Resultats Cent trente enfants ont presente des douleurs de croissance, satisfaisant aux criteres de Petersen. La frequence des symptomes etait de 24,5 %. La plupart du temps, ces douleurs apparaissaient apres un exercice physique intense, sans rapport avec l’IMC de l’enfant. La principale mesure therapeutique utilisee par les parents etait le massage des membres inferieurs douloureux et, dans un moindre degre, l’administration d’anti-inflammatoires. Conclusions L’analyse des donnees montre qu’il s’agit d’une affection benigne dont le mecanisme phathogenique est inconnu. De plus, la presence de ces douleurs n’est pas fortement correlee a des maladies anatomiques ou orthopediques, ce qui va a l’encontre d’une theorie anatomique. Au contraire, leur apparition, apres un exercice physique intense dans 78,5 % des cas, nous a conduit a l’hypothese qu’il s’agissait d’un syndrome d’« overuse » du membre inferieur, ce qui semble etre en accord avec nombre de donnees experimentales de la litterature internationale.

Objectives Recurrent lower limb pains (growing pains) constitute the most frequent cause of musculoskeletal pain in children. Despite the fact that the international literature has presented numerous cases over the years, which have led to various hypotheses and theories, the disorder's exact nature and aetiology remain unclear. Methods Our study aims to examine both the epidemiological profile of the children affected by the disorder and the measures taken by parents or medical specialists for their management. In addition, we tried to link the existing theories with the findings of our study, to ascertain whether these were verified by the epidemiological findings. This retrospective study investigated the appearance of lower limbs in the 12-month period before the visit of the children to our department. The study included a total of 532 children, aged 4–12, while the data were collected through semi-structured interviews including a mix of open and closed questions. Results One hundred and thirty of these children presented growing pains, meeting Petersen's criteria. The frequency of the disorder was 24.5%. Most times, they appeared after intensive physical exercise, while their development was not linked to the children's BMI. The main therapeutic approach used by parents was massaging the painful lower limbs and, to a lesser extent, the administration of anti-inflammatory agents. Conclusions The data analysis proves that this is a benign disorder with an unknown pathophysiological mechanism. In addition, their presence is not strongly related to anatomic or orthopaedic disorders, a fact opposing anatomical theory. On the contrary, their appearance after intensive physical exercise at a percentage of up to 78.5% leads us to hypothesise that it is a lower local extremity overuse syndrome, which seems in accordance with many experimental data in international literature.

Recurrent pains of the lower extremities (growth pains) constitute the most frequent cause of musculoskeletal pains in children. The disorder’s pathophysiological mechanism remains unclear. Numerous researchers have tried to ascertain this by studying the anthropometrical characteristics of the children they examined, their family history and levels of physical activity, even their psychological background. To date though, no study has looked into whether breastfeeding may avert their appearance or limit their intensity and duration. Aiming to investigate the above theory, we conducted interviews with the mothers of 532 children, using a semiconstructed questionnaire. According to Petersen’s criteria, 130 children presented growth pains during the last year. Specifically, 32.5% of non-breastfed children presented recurrent lower extremity pains, whereas such pains were identified in only 19.6% of breastfed children (p value = 0.001

Mechanical loading of the spine is a major causative factor of degenerative changes and causes molecular and structural changes in the intervertebral disc (IVD) and the vertebrae end plate (EP). Pleiotrophin (PTN) is a growth factor with a putative role in bone remodeling through its receptor protein tyrosine phosphatase beta/zeta (RPTPβ/ζ). The present study investigates the effects of strain on PTN and RPTPβ/ζ protein expression in vivo. Tails of eight weeks old Sprague-Dawley rats were subjected to mechanical loading using a mini Ilizarov external apparatus. Rat tails untreated (control) or after 0 degrees of compression and 10°, 30° and 50° of angulation (groups 0, I, II and III respectively) were studied. PTN and RPTPβ/ζ expression were evaluated using immunohistochemistry and Western blot analysis. In the control group, PTN was mostly expressed by the EP hypertrophic chondrocytes. In groups 0 to II, PTN expression was increased in the chondrocytes of hypertrophic and proliferating zones, as well as in osteocytes and osteoblast-like cells of the ossification zone. In group III, only limited PTN expression was observed in osteocytes. RPTPβ/ζ expression was increased mainly in group 0, but also in group I, in all types of cells. Low intensity RPTPβ/ζ immunostaining was observed in groups II and III. Collectively, PTN and RPTPβ/ζ are expressed in spinal deformities caused by mechanical loading, and their expression depends on the type and severity of the applied strain.

Background: Metalloproteinase 12 (MMP-12) is induced in chondrocytes during fetal development and malignant transformation. Objectives: The aim of our study is to examine the expression of MMP-12 in the cartilage and the subchondral bone of patients with osteoarthritis (OA) and to correlate its expression with disease severity and anthropometric characteristics. Methods: Overall, 60 sections from 20 patients with idiopathic OA, were examined for the immunolocalization of MMP-12. As controls, we used the femoral heads of 4 patients treated with seniarthroplasty after fracture. Demographic characteristics and Body Mass Index (BMI) were calculated for all subjects. Results: Specimens were divided into four groups based on the Mankin histological severity score. The immunohistochemical study showed MMP-12 expression in the cartilage and subchonral bone of OA patients, while there was no expression in normal controls. At the moderate OA changes (Mankin score: 6–7), MMP-12 was detected mainly at the matrix of fibrocartilage tissue. During disease progression, MMP-12 was expressed at the sides of the cartilage and bone erosion and in the bone cysts. Furthermore, it was traced in the osteocytes of the subchondral bone. Osteoblast-like cells and bone lining cells express MMP-12 during the stage of severe OA (Mankin: ≥8). Osteoclasts expressing MMP-12 were also detected in the group of severe OA. Interestingly, MMP-12 expression was positively correlated with the age and the BMI of OA patients. Conclusion: The increased expression of MMP-12 in the bone-cartilage unit of OA patients suggests a possible role in OA pathogenesis and progression. Level of evidence III, prospective comparative study.