Michail E. Klontzas

Bone and cartilage regeneration with the use of umbilical cord mesenchymal stem cells.

Introduction: The production of functional alternatives to bone autografts and the development new treatment strategies for cartilage defects are great challenges that could be addressed by the field of tissue engineering. Umbilical cord mesenchymal stem cells (MSCs) can be used to produce cost-effective, atraumatic and possibly autologous bone and cartilage grafts. Areas covered: MSCs can be isolated from umbilical cord Wharton’s jelly, perivascular tissue and blood using various techniques. Those cells have been characterized and phenotypic similarities with bone marrow-derived MSCs (BM-MSCs) and embryonic stem cells have been found. Findings on their differentiation into the osteogenic and chondrogenic lineage differ between studies and are not as consistent as for BM-MSCs. Expert opinion: MSCs from umbilical cords have to be more extensively studied and the mechanisms underlying their differentiation have to be clarified. To date, they seem to be an attractive alternative to BM-MSCs. However, further research with suitable scaffolds and growth factors as well as with novel scaffold fabrication and culture technology should be conducted before they are introduced to clinical practice and replace BM-MSCs.

Investigational drugs for fracture healing: preclinical & clinical data.

ABSTRACT Introduction: The need for fracture healing enhancement for the management of fracture complications such as non-union and for the achievement of early function in fracture patients is constantly increasing. Therefore, the development and evaluation of novel pharmaceutical agents is mandatory in order to accelerate the process and increase bone union rates. Areas covered: This review summarizes the most recent knowledge on the pharmacological enhancement of fracture repair. It provides a synopsis of the most important preclinical and clinical studies published over the past five years on long bone fracture healing. Expert opinion: To date, limited drugs seem to have the potential for clinical use in fracture healing enhancement and the field is progressing very slowly. Among anti-osteoporotic drugs, only PTH and anti-sclerostin antibodies have such a potential but further research is needed before clinical use. The same applies also to BMPs, the use of which still carries major drawbacks that should be overcome before their widespread clinical utilization. Other drugs and growth factors, such as statins, VEGF, FGF, EPO, could be future key players in fracture healing but evidence is still lacking. Further in depth understanding of the healing process is essential in order to identify novel effective pharmacological agents.

Fibronectin stimulates the osteogenic differentiation of murine embryonic stem cells.

Conditioned medium from human hepatocarcinoma cells (HepG2‐CM) has been shown to stimulate the osteogenic/chondrogenic differentiation of murine embryonic stem cells (mESCs). HepG2‐CM is considered to contain visceral endoderm (VE)‐like signals and attempts have recently been made to characterize it, using proteomic profiling, with fibronectin being identified as one promising candidate. Herein, we investigated whether fibronectin is able to mimic the activities of HepG2‐CM during the osteogenic differentiation of mESCs. Specifically, the addition of RGD peptides and heparin in HepG2‐CM significantly reduced the growth‐ and adhesion‐promoting effects of HepG2‐CM, in addition to suppressing its osteogenic‐inductive activity. Furthermore, direct addition of fibronectin to basal medium was able to reproduce, at least partially, the function of HepG2‐CM. In particular, fibronectin induced the early onset of osteogenic differentiation in mESCs, as confirmed by gene expression of osteogenic markers, and resulted in the three‐fold higher calcium deposition at day 11 of osteogenic culture compared to the control group. These data clearly suggest that fibronectin contributes to the biological activities of HepG2‐CM and plays a stimulatory role during the process of osteogenesis in mESCs. Copyright

Rotational Knee Laxity in Anterior Cruciate Ligament Deficiency: An Additional Secondary Sign on MRI.

OBJECTIVE The objective of this study was to evaluate the accuracy of tibial rotation measurement as a secondary sign for diagnosing anterior cruciate ligament (ACL) tears with the use of MRI. MATERIALS AND METHODS A total of 893 MRI studies were retrospectively reviewed, and 239 patients were identified as having either an intact ACL (group 1; n = 182), an arthroscopically confirmed acutely torn ACL (group 2; n = 22), or a chronically torn ACL (group 3; n = 35). Tibial rotation was estimated by measuring the femorotibial angle (FTA). RESULTS The mean (± SD) FTA was significantly higher in group 2 (10.7° ± 4.8°) and group 3 (11° ± 5.5°) than in group 1 (3.2° ± 3.3°) (p < 0.001, for all cases). An FTA of 4.9° was the optimal threshold (sensitivity, 93%; specificity, 80%) for separating completely torn ACLs from intact ACLs. An FTA ranging from 4.9° to 5.5° (sensitivity, 95%; specificity, 80%) indicated a complete acute ACL tear, whereas an FTA of 5.6° or greater (sensitivity, 91.4%; specificity, 83.5%) suggested a complete chronic ACL tear. CONCLUSION An increased FTA indicates alteration in the femorotibial anatomic relationship and could be of value in assessing ACL tears in patients with equivocal signs on MRI.

Normal Magnetic Resonance Imaging Anatomy of the Anterolateral Knee Ligament With a T2/T1-Weighted 3-Dimensional Sequence: A Feasibility Study

Purpose The anatomy of the lateral knee compartment has been recently further explored with description of the anterolateral knee ligament (ALL). The purpose of this study was to confirm the presence of ALL on cadaveric knees and to describe its normal anatomy in young healthy volunteers, utilizing a high-resolution 3-dimensional (3D) pulse sequence. Methods Dissection was performed on 9 cadaveric knees in order to confirm the presence of ALL. Conventional 2-dimensional sequences of 10 knees at 1.5 T and 10 knees at 3 T, with a slice thickness of 2-4 mm, were reviewed for the presence of ALL. A 3D T2/T1-weighted gradient echo sequence (constructive interference in steady state [CISS]), yielding in-plane resolution of 0.4 mm × 0.4 mm × 0.4 mm, was applied in 14 healthy volunteers (26 knees). All 3D images were manipulated using multiplanar reconstruction (MPR) and the presence and width of ALL were recorded. Results Cadaveric dissection disclosed the presence of ALL in 8 of 9 knees. Conventional knee MR imaging depicted ALL only on coronal images (18 of 20) whereas the CISS revealed ALL on 24 of 26 studied knees (92.3%). ALL has a mean thickness of 1.1 ± 0.27 mm measured on coronal MR images. Conclusions ALL can be thoroughly assessed in young healthy individuals with the use of high-resolution 3D MR imaging with MPR at 1.5 T.

Hydroxyapatite deposition disease around the hip: outcomes of CT-guided treatment.

PURPOSE Hydroxyapatite deposition disease (HADD) around the hip joint is a self-limiting condition usually treated conservatively. The aim of the present study is to directly compare the outcomes of CT-guided and conservative treatments in cases of refractory hip HADD. METHODS Two groups of patients with refractory hip HADD were prospectively constructed from a pool of 484 patients referred for greater trochanter pain syndrome, based on the presence of calcifications around the hip and the failure of conservative treatment. Study group included 22 hips, which underwent CT-guided barbotage and steroid injection treatment, whereas control group consisted of 28 hips that were treated conservatively. Evaluation of the outcome of both groups was performed over a one-year follow-up period with the use of a score measuring clinical improvement in terms of pain and functional impairment. RESULTS Three weeks after the initiation of treatment, study group exhibited significantly higher scores compared with the control group (P < 0.001). Improvement scores of the control group were similar to the study group after three months of treatment (P > 0.1). CONCLUSION CT-guided treatment provides relief of debilitating symptoms in the acute phase.

MR imaging findings of medial tibial crest friction

OBJECTIVE Medial tibial condyle bone marrow edema (BME), associated with soft tissue edema (STe) surrounding the medial collateral ligament, was incidentally observed in MRI examinations of young and athletic individuals. The aim of the present study was to 1. Prospectively investigate the association between these findings and coexistence of localized pain, and 2. Explore the possible contribution of the tibial morphology to its pathogenesis. METHODS The medial tibial condyle crest was evaluated in 632 knee MRI examinations. The angle and depth were measured by two separate evaluators. The presence of STe and BME was recorded. A third evaluator blindly assessed the presence of pain at this site. RESULTS BME associated with STe was found in 24 patients (with no history of previous trauma, osteoarthritis, tumor or pes anserine bursitis). The mean crest angle was 151.3° (95%CI 147.4-155.3°) compared to 159.4° (95%CI 158.8-160°) in controls (Mann-Whitney test, P<0.0001). MRI findings were highly predictive of localized pain (sensitivity 92% specificity 99%, Fishers exact test, P<0.0001). CONCLUSION Friction at the medial tibial condyle crest is a painful syndrome. MRI is a highly specific and sensitive imaging modality for its diagnosis.

Imaging of Impingement Syndromes around the Hip Joint

Impingement syndromes are increasingly recognised as significant causes of hip pain and dysfunction. A broad spectrum of intraarticular and extraarticular conditions has been implicated in their pathophysiology. Physical examination is often inconclusive as clinical findings may be unclear or misleading, often simulating other disorders. With current improvements in imaging techniques and better understanding of hip impingement related pathomechanisms, these entities can be accurately diagnosed. In addition, preoperative imaging has allowed for targeted treatment planning. This article provides an overview of the various types of hip impingement, including femoroacetabular impingement, ischiofemoral impingement, snapping hip syndrome, greater trochanteric-pelvic and subspine impingement. Current literature data regarding their pathogenesis, clinical manifestation and imaging work-up are discussed.

Reply to “The Half-Moon Sign of the Femoral Neck Is Nonspecific for the Diagnosis of Osteoid Osteoma.”

AJR 2016; 206:W55 0361–803X/16/2063–W55

THA Following Pediatric Hip Diseases (Legg-Calvé-Perthes/Slipped Capital Femoral Epiphysis)

Legg-Calve-Perthes disease (LCPD) represents a type of idiopathic avascular necrosis of the femoral head which typically develops during childhood [1, 2]. Its etiology is considered to be multifactorial but is generally unknown; genetic, constitutional, and environmental factors have been implicated [3]. Despite receiving treatment, some patients initially develop morphological changes in the femoral head and secondarily acetabular deformity, femoroacetabular in congruency, and the abnormal hip movement that could lead to early-onset secondary osteoarthritis [1, 4]. In a current prospective cohort, 5% of LCPD patients underwent THA at 20 years after nonoperative treatment [5]. Stulberg classification is used as prognostic tool of hip osteoarthritis at skeletal maturity [2]; Stulberg types III–V are more susceptible to the development of early secondary hip osteoarthritis [1].