Osteogenesis imperfecta - multi-systemic and life-long disease that affects whole family [Osteogenesis imperfecta - više-sustavna, doživotna bolest i njen utjecaj na obitelj]

Osteogenesis imperfecta or brittle bone disease, a heritable disorder of connective tissue, is the most common of the inherited disorders primarily affecting bone. There are approximately 400 individuals with OI in Croatia alone. It is estimated that twice that number is present, represented by individuals with mild OI in whom the diagnosis has not been made. Due to the relatively low number of patients in the general population, treating physicians have limited experience with this disease, either with children or adults. The basis of this disease in European populations is mostly the result of defects in the structure or processing of collagen type I, an important protein of the extracellular matrix of many tissues. Presently, molecular defects in 16 different genes have been discovered to result in at least one type of OI of which 14 are not COL1 mutation loci. Although fractures occurring with no injury or minor injury are the hallmark of OI, other non-mineralized tissues can be affected as well and the pathological changes can be present in skin, tendons, eyes, teeth and blood vessels. Clinical manifestations are very heterogeneous and numerous signs and symptoms such as blue sclera, deafness, abnormal teeth development, joint hypermobility, increased risk of hernias, capillary fragility, aneurysms etc. Although there is no cure for this disease, there are specific therapies that can reduce the pain and complications associated with OI. The purpose of this review is to provide a brief overview of the molecular basis of this disease, describe clinical presentations, as well as to present orthopaedic therapeutic modalities for the patients with OI

Osteogenesis Imperfecta – Multi-Systemic and Life-Long Disease that Affects Whole Family

Osteogenesis imperfecta or brittle bone disease, a heritable disorder of connective tissue, is the most common of the inherited disorders primarily affecting bone. There are approximately 400 individuals with OI in Croatia alone. It is estimated that twice that number is present, represented by individuals with mild OI in whom the diagnosis has not been made. Due to the relatively low number of patients in the general population, treating physicians have limited experience with this disease, either with children or adults. The basis of this disease in European populations is mostly the result of defects in the structure or processing of collagen type I, an important protein of the extracellular matrix of many tissues. Presently, molecular defects in 16 different genes have been discovered to result in at least one type of OI of which 14 are not COL1 mutation loci. Although fractures occurring with no injury or minor injury are the hallmark of OI, other non-mineralized tissues can be affected as well and the pathological changes can be present in skin, tendons, eyes, teeth and blood vessels. Clinical manifestations are very heterogeneous and numerous signs and symptoms such as blue sclera, deafness, abnormal teeth development, joint hypermobility, increased risk of hernias, capillary fragility, aneurysms etc. Although there is no cure for this disease, there are specific therapies that can reduce the pain and complications associated with OI. The purpose of this review is to provide a brief overview of the molecular basis of this disease, describe clinical presentations, as well as to present orthopaedic therapeutic modalities for the patients with OI

Groin Pain

Entezitis tetiva aduktora longusa i/ili trbušnih mišića definiramo kao sindrom bolne prepone. Jedan od čestih uzroka nastanka sindroma bolne prepone jest slabost trbušne stijenke. Za nj danas postoji uvriježeni naziv sportska hernija. Sindrom bolne prepone najčešće se pojavljuje u nogometaša (u Hrvatskoj 6,24%). Inicijalno se pojavljuju mukle boli u području preponske regije kao rezultat opterećenja tokom sportske aktivnosti. U kliničkom pregledu osobito je važan aduktorski test. Liječenje sindroma bolne prepone je složeno, kao i uzroci nastanka sindroma. U početku treba smanjiti intenzitet treninga ili potpuno prestati sa sportskom aktivnošću. Primjenjuju se nesteroidni protuupalni lijekovi i miorelaksansi. Provode se vježbe istezanja i jačanja aduktora, trbušne muskulature, iliopsoasa, kvadricepsa te mišića stražnje lože natkoljenice. Ako konzervativno liječenje ne dovodi do poboljšanja, potrebno je kirurško liječenje.Groin pain is defined as tendon enthesitis of adductor longus muscle and/or abdominal muscles that may lead to degenerative arthropathy of pubic symphisis in an advanced stage. Pubic region is a point where kinematic forces cross. The balance between the adductor and abdominal muscles is of great importance, as well as the elasticity of pubic symphisis which enables movement of up to 2 mm and rotation of up to 3 degrees. The weakness of the abdominal muscle wall, known as the sportsman\u27s hernia, is the most common cause of painful groin. Groin pain is the most common in soccer players (6.24% in Croatia). Most authors believe that the main cause of groin pain is the adductor muscle overload. When active, sportsmen start to feel a dull pain in the groin region. The adductor test is of great importance for physical examination; the patient should be lying supine with his hips abducted and flexed at 80 degrees. The test is positive if the patient, while attempting to pull his/her legs against pressing in the opposite direction, feels a sharp pain in the groins. The treatment of groin pain is complex and individual, as its causes may vary from patient to patient. Gradual physical therapy combined with pharmacotherapy should be effective in most cases. The latter includes nonsteroid anti-inflammatory drugs and muscle relaxants. A physical therapy programme usually involves stretching and strengthening of adductor muscles, abdominal wall muscles, iliopsoas muscle, quadriceps, and hamstrings. In case that physical therapy and pharmacotherapy fail, surgery is needed, depending on the cause

Anterior cruciate ligament reconstruction with anterolateral stabilization by a modified Lemaire technique in adolescent professional football player: a case report

Background: Anterior cruciate ligament (ACL) tear is one of the most common injuries in professional athletes. Additional procedures, such as anterolateral ligament reconstruction and lateral extra-articular tenodesis attempt to reduce rotational instability, the most common cause of re-injury in patients with a nonisolated ACL tear. Case study: A 17-year-old professional football player suffered a right knee injury in a direct hit to the lateral side of the knee. Magnetic resonance imaging showed anterior cruciate ligament tear and lateral knee structures soft tissue contusion. Due to the injury of the lateral structures and the increased risk of ACL rerupture, it was decided to perform ACL reconstruction with additional anterolateral stabilization by a modified Lemaire technique without additional screw fixation in the area of the lateral femoral epicondyle, which could damage the epiphyseal plate and, concurrently, impair bone growth. Conclusion: The addition of lateral extra-articular tenodesis by a modified Lemaire technique prevents rotational instability in a patient with expressed pivotshift before the surgery, without overconstraint of the knee and additional damage to the epiphyseal plate

Early results of intra-articular micro-fragmented lipoaspirate treatment in patients with late stages knee osteoarthritis: a prospective study

Aim To analyze clinical and functional effects of intra-articular injection of autologous micro-fragmented lipoaspirate (MLA) in patients with late stage knee osteoarthritis (KOA). Secondary aims included classifying cell types contributing to the treatment effect, performing detailed MRIbased classification of KOA, and elucidating the predictors for functional outcomes. Methods This prospective, non-randomized study was conducted from June 2016 to February 2018 and enrolled 20 patients with late stage symptomatic KOA (Kellgren Lawrence grade III, n = 4; and IV, n = 16) who received an intra-articular injection of autologous MLA in the index knee joint. At baseline radiological KOA grade and MRI were assessed in order to classify the morphology of KOA changes. Stromal vascular fraction cells obtained from MLA samples were stained with antibodies specific for cell surface markers. Patients were evaluated at baseline and 12-months after treatment with visual analog scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Knee Injury and Osteoarthritis Outcome Score (KOOS).Results Three patients (15%) received a total knee replacement and were not followed up completely. Seventeen patients (85%) showed a substantial pattern of KOOS and WOMAC improvement, significant in all accounts. KOOS score improved from 46 to 176% when compared with baseline, WOMAC decreased from 40 to 45%, while VAS rating decreased from 54% to 82% (all P values were <0.001). MLA contained endothelial progenitor cells, pericytes, and supra-adventitial adipose stromal cells as most abundant cell phenotypes. Conclusion This study is among the first to show a positive effect of MLA on patients with late stages KOA

HISTOLOGIC ASSESSMENT OF TISSUE HEALING OF HYALINE CARTILAGE BY USE OF SEMIQUANTITATIVE EVALUATION SCALE

Kao avaskularno, alimfatično i aneuralno tkivo sa smanjenom mogućnošću cijeljenja, hijalina hrskavica je zanimljiv predmet istraživanja. Ispitivane su brojne metode kojima bi se potakla regeneracija oštećene hrskavice no niti jedna od njih ne daje idealne rezultate. Rezultate spomenutih metoda potrebno je odgovarajuće ocijeniti. Cilj ove studije bio je analizirati rezultate dobivene primjenom ugrušaka autologne koštane srži prethodno transduciranih faktorom rasta TGF-β1 na oštećenja zglobne hrskavice. Istraživanje je provedeno na 28 koštano zrelih ovaca koje su slučajnim odabirom podijeljene u 4 skupine te im je kirurški učinjeno oštećenje zglobne hrskavice na nosivoj površini medijalnog kondila bedrene kosti. U oštećenje je zatim ansplantiran autologni ugrušak koštane srži transduciran faktorom rasta - TGF-β1 (skupina TGF), zelenim fluorescentnim proteinom - GFP (skupina GFP), bez genetske promjene (skupina BM) ili nije postavljen nikakav transplantat (skupina NC). Uzorci su pregledani pomoću svjetlosnog kroskopa i ocijenjeni primjenom vizualno-histološke ocjenske ljestvice Međunarodnog društva za istraživanje hrskavice (ICRS-a). Statistička analiza pokazala je značajnu razliku između skupine TGF i NC. Rezultati pokazuju da je primjenom ove ljestvice moguće dobiti mjerljive histološke rezultate.Introduction: Articular cartilage is an avascular and aneural tissue lacking lymph drainage, hence its inability of spontaneous repair following injury. Thus, it offers an interesting model for scientific research. A number of methods have been suggested to enhance cartilage repair, but none has yet produced significant success. The possible application of the aforementioned methods has brought about the necessity to evaluate their results. The objective of this study was to analyze results of a study of the effects of the use of TGF-β gene transduced bone marrow clot on articular cartilage defects using ICRS visual histological assessment scale. Methods: The research was conducted on 28 skeletally mature sheep that were randomly assigned to four groups and surgically inflicted femoral chondral defects. The articular surfaces were then treated with TGF-β1 gene transduced bone marrow clot (TGF group), GFP transduced bone marrow clot (GFP group), untransduced bone marrow clot (BM group) or left untreated (NC group). The analysis was performed by visual examination of cartilage samples and results were obtained using ICRS visual histological assessment scale. The results were subsequently subjected to statistical assessment using Kruskal-Wallis and Mann-Whitney tests. Results: Kruskal-Wallis test yielded statistically significant difference with respect to cell distribution. Mann-Whitney test showed statistically significant difference between TGF and NC groups (P=0.002), as well as between BM and NC groups (P=0.002 with Bonferroni correction). Discussion: Twenty-six of the twenty-eight samples were subjected to histologic and subsequent statistical analysis; two were discarded due to faulty histology technique. Our results indicated a level of certainty as to the positive effect of TGF-β1 gene transduced bone marrow clot in restoration of articular cartilage defects. However, additional research is necessary in the field. One of the significant drawbacks on histologic assessment of cartilage samples were the errors in histologic preparation, for which some samples had to be discarded and significantly impaired the analytical quality of the others. Defects of structures surrounding the articular cartilage, e.g., subchondral bone or connective tissue, might also impair the quality of histologic analysis. Additional analyses, i.e. polarizing microscopy should be performed to determine the degree of integration of the newly formed tissue with the surrounding cartilage. The semiquantitative ICRS scale, although of great practical value, has limitations as to the objectivity of the assessment, taking into account the analytical ability of the evaluator, as well as the accuracy of emiquantitative analysis in comparison to the methods of quantitative analysis.Conclusion: Overall results of histologic analysis indicated that the application of TGF-β1 gene transduced bone marrow clot could have measurable clinical effects on articular cartilage repair. The ICRS visual histological assessment scale is a valuable analytical method for cartilage repair evaluation. In this respect, further analyses of the method value would be of great importance

Immunophenotyping of a Stromal Vascular Fraction from Microfragmented Lipoaspirate Used in Osteoarthritis Cartilage Treatment and Its Lipoaspirate Counterpart

Osteoarthritis (OA) is a degenerative joint disease accompanied by pain and loss of function. Adipose tissue harbors mesenchymal stem/stromal cells (MSC), or medicinal signaling cells as suggested by Caplan (Caplan, 2017), used in autologous transplantation in many clinical settings. The aim of the study was to characterize a stromal vascular fraction from microfragmented lipoaspirate (SVF-MLA) applied for cartilage treatment in OA and compare it to that of autologous lipoaspirate (SVF-LA). Samples were first stained using a DuraClone SC prototype tube for the surface detection of CD31, CD34, CD45, CD73, CD90, CD105, CD146 and LIVE/DEAD Yellow Fixable Stain for dead cell detection, followed by DRAQ7 cell nuclear dye staining, and analyzed by flow cytometry. In SVF-LA and SVF-MLA samples, the following population phenotypes were identified within the CD45- fraction: CD31+CD34+CD73±CD90±CD105±CD146± endothelial progenitors (EP), CD31+CD34-CD73±CD90±CD105-CD146± mature endothelial cells, CD31-CD34-CD73±CD90+CD105-CD146+ pericytes, CD31-CD34+CD73±CD90+CD105-CD146+ transitional pericytes, and CD31-CD34+CD73highCD90+CD105-CD146- supra-adventitial-adipose stromal cells (SA-ASC). The immunophenotyping profile of SVF-MLA was dominated by a reduction of leukocytes and SA-ASC, and an increase in EP, evidencing a marked enrichment of this cell population in the course of adipose tissue microfragmentation. The role of EP in pericyte-primed MSC-mediated tissue healing, as well as the observed hormonal implication, is yet to be investigated