Piezo1 expression in chondrocytes controls endochondral ossification and osteoarthritis development.

Piezo proteins are mechanically activated ion channels, which are required for mechanosensing functions in a variety of cell types. While we and others have previously demonstrated that the expression of Piezo1 in osteoblast lineage cells is essential for bone-anabolic processes, there was only suggestive evidence indicating a role of Piezo1 and/or Piezo2 in cartilage. Here we addressed the question if and how chondrocyte expression of the mechanosensitive proteins Piezo1 or Piezo2 controls physiological endochondral ossification and pathological osteoarthritis (OA) development. Mice with chondrocyte-specific inactivation of Piezo1 (Piezo1Col2a1Cre), but not of Piezo2, developed a near absence of trabecular bone below the chondrogenic growth plate postnatally. Moreover, all Piezo1Col2a1Cre animals displayed multiple fractures of rib bones at 7 days of age, which were located close to the growth plates. While skeletal growth was only mildly affected in these mice, OA pathologies were markedly less pronounced compared to littermate controls at 60 weeks of age. Likewise, when OA was induced by anterior cruciate ligament transection, only the chondrocyte inactivation of Piezo1, not of Piezo2, resulted in attenuated articular cartilage degeneration. Importantly, osteophyte formation and maturation were also reduced in Piezo1Col2a1Cre mice. We further observed increased Piezo1 protein abundance in cartilaginous zones of human osteophytes. Finally, we identified Ptgs2 and Ccn2 as potentially relevant Piezo1 downstream genes in chondrocytes. Collectively, our data do not only demonstrate that Piezo1 is a critical regulator of physiological and pathological endochondral ossification processes, but also suggest that Piezo1 antagonists may be established as a novel approach to limit osteophyte formation in OA.

[Infectious, pathologic humeral fracture in a patient with sickle cell disease-A rare case?] / Infizierte, pathologische Humerusfraktur bei Sichelzellanämie ­ noch ein Einzelfall?

The vaso-occlusive crises of sickle cell disease are accompanied by bone necrosis, which favors endogenous bacterial colonization and thus osteomyelitis. This poses a major challenge for eradication and fracture management.A 22-year-old patient with sickle cell disease sustained a multifragmentary, humeral shaft fracture. During surgical management, pus drained from the fracture site and further diagnostic work-up revealed osteomyelitis with evidence of Klebsiella aerogenes. Septicemia due to Klebsiella aerogenes had been treated 5 months prior to the accident, which occured because of a vaso-occlusive crisis. This is associated with clustered bone necrosis and endogenous germ colonization. Eradication of the germs and fracture care become a challenge. Repeated surgical procedures with segmental transfer can be a successful treatment option.

Fracture healing in a mouse model of Hajdu-Cheney-Syndrome with high turnover osteopenia results in decreased biomechanical stability.

Notch signaling regulates cell fate in multiple tissues including the skeleton. Hajdu-Cheney-Syndrome (HCS), caused by gain-of-function mutations in the Notch2 gene, is a rare inherited disease featuring early-onset osteoporosis and increased risk for fractures and non-union. As the impact of Notch2 overactivation on fracture healing is unknown, we studied bone regeneration in mice harboring a human HCS mutation. HCS mice, displaying high turnover osteopenia in the non-fractured skeleton, exhibited only minor morphologic alterations in the progression of bone regeneration, evidenced by static radiological and histological outcome measurements. Histomorphometry showed increased osteoclast parameters in the callus of HCS mice, which was accompanied by an increased expression of osteoclast and osteoblast markers. These observations were accompanied by inferior biomechanical stability of healed femora in HCS mice. Together, our data demonstrate that structural indices of bone regeneration are normal in HCS mice, which, however, exhibit signs of increased callus turnover and display impaired biomechanical stability of healed fractures.

The influence of 3D printing on inter- and intrarater reliability on the classification of tibial plateau fractures.

PURPOSE: Tibial plateau fractures continue to be a challenging task in clinical practice and current outcomes seem to provide the potential for further improvement. Especially presurgical understanding of the orientation of fracture lines and fracture severity is an essential key to sufficient surgical treatment. The object of this study was to evaluate the reliability of modern axial CT-based classification systems for tibial plateau fractures. In addition, the diagnostic-added value of 3D printing on the classification systems was investigated. METHODS: 22 raters were asked to classify 22 tibial plateau fractures (11 AO B- and 11 AO C-fractures) with the AO, the 10-Segment and the Revisited Schatzker classification in a three-step evaluation: first only using CT scans, second with 3D volumetric reconstructions and last with 3D-printed fracture models. Inter- and intraobserver agreement and the subjective certainty were analyzed. Statistics were done using kappa values, percentage match and a univariant one-way analysis of variance. RESULTS: The AO classifications interobserver percentage match and kappa values improved for all raters and recorded an overall value of 0.34, respectively, 43% for the 3D print. The 10-Segment classification interobserver agreement also improved with the 3D-printed models and scored an overall kappa value of 0.18 and a percentage match of 79%. Equally the Revisited Schatzker classification increased its values to 0.31 and 35%. The intraobserver agreement showed a moderate agreement for the AO (0.44) and Revisited Schatzker classification (0.42) whereas the 10-Segment classification showed a fair agreement (0.27). Additionally, the raters changed their classification in 36% of the cases after evaluating the fracture with the 3D-printed models and the subjective certainty regarding the decisions improved as categories of self-reliant diagnostic choices were selected 18% (p < 0.05) more often after using the 3D-printed models. CONCLUSION: Based on the measured outcomes it was concluded that the new classification systems show an overall slight to fair reliability and the use of 3D printing proved to be beneficial for the preoperative diagnostics of tibial plateau fractures. The 10-Segment classification system showed the highest percentage match evaluation of all classification systems demonstrating its high clinical value across all levels of user experience.

Dislocation of a McMinn-Like Prosthesis with Distinctive Metallosis and Fracture of the Os Ilium.

Osteoarthritis of the hip joint (coxarthrosis) is the most common hip disease in adults. Since the 1960s, total hip arthroplasty (THA) has made great progress and is nowadays one of the most frequently used procedures in orthopedic surgery. Different bearing concepts exist in various implant designs. A metal-on-metal bearing can create metal debris and lead to metallosis. We present a unique case of a 78-year old woman, who received hip resurfacing with a McMinn-like prosthesis 15 years ago. Over the cause of time, metallosis developed and created a bone cyst in the Os ilium, and osteolysis led to a dislocation of the femoral implant. A minor stumble fall led to a fracture of the Os ilium. We present our treatment method with implantation of a cemented THA and refill of the bone cyst with bone from allogene femoral heads. The surgery led to a reconstruction of the physiological center of rotation in the hip. Consequently, to the inpatient stay, the patient took part in a follow-up treatment with intensive physiotherapy. Taken together, the results after total hip arthroplasty are more superior to other hip surface replacements in terms of longevity and patient satisfaction. Especially, metal-on-metal bearing couples carry a great risk of metallosis, which goes a long with pseudotumors, osteolysis, and the elevated metal ions in the blood. Since this case is unique in the literature, no guidelines are noted for surgical treatment. In our opinion, a periprosthetic fracture of this type should be performed in a hospital using extensive endoprosthetic expertise.

Glucose Metabolism in Osteoblasts in Healthy and Pathophysiological Conditions.

Bone tissue in vertebrates is essential to performing movements, to protecting internal organs and to regulating calcium homeostasis. Moreover, bone has also been suggested to contribute to whole-body physiology as an endocrine organ, affecting male fertility; brain development and cognition; and glucose metabolism. A main determinant of bone quality is the constant remodeling carried out by osteoblasts and osteoclasts, a process consuming vast amounts of energy. In turn, clinical conditions associated with impaired glucose metabolism, including type I and type II diabetes and anorexia nervosa, are associated with impaired bone turnover. As osteoblasts are required for collagen synthesis and matrix mineralization, they represent one of the most important targets for pharmacological augmentation of bone mass. To fulfill their function, osteoblasts primarily utilize glucose through aerobic glycolysis, a process which is regulated by various molecular switches and generates adenosine triphosphate rapidly. In this regard, researchers have been investigating the complex processes of energy utilization in osteoblasts in recent years, not only to improve bone turnover in metabolic disease, but also to identify novel treatment options for primary bone diseases. This review focuses on the metabolism of glucose in osteoblasts in physiological and pathophysiological conditions.

Third day laboratory follow-up: mandatory for surgical site infections of tibial plateau fractures.

INTRODUCTION: Tibial plateau fractures are common fractures in adults and can be extremely challenging for surgeons. State-of-the-art therapy is open reduction and internal fixation (ORIF), although major complications of ORIF are surgical site infections (SSIs). This is especially critical on the proximal tibia, which is only sparsely covered by soft tissue and has a close relation to the knee joint. We analyzed SSIs after ORIF to correlate established laboratory parameters to the occurrence of SSIs. METHODS: A monocentric case-control study in a Level 1 Trauma Center was conducted. Data were acquired from electronic medical records from 2011 until 2016. White blood cell count (WBC) and C-reactive protein (CRP) were used as laboratory parameters and statistically analyzed. RESULTS: In total, 97 patients were included, with four patients suffering from SSIs. Patients with SSIs had a significantly increased WBC count and CRP levels on the third postoperative day. Infection was diagnosed after rehospitalization, 12 ± 4 weeks after initial surgery. Furthermore, a large bony destruction through trauma coincides with a rise of WBC count with no influence on CRP level. CONCLUSION: We highly recommend a laboratory analysis with WBC count and CRP on the third day after ORIF. Patients with a CRP level above 100 mg/l should be closely watched, even if laboratory parameters few days later are adequate-since a one-time increase above this landmark might be a hint regarding the development of a SSI.

Extended approach to the lateral tibial plateau with central meniscal subluxation in fracture repair: feasibility and first clinical and radiographic results.

PURPOSE: Anatomic reduction in tibial plateau fractures remains to be demanding. For further visualisation of and approach to the joint surface an extended lateral approach using a lateral femoral epicondyle osteotomy and subluxation of the lateral meniscus was recently described. First clinical and radiographic mid-term results of this technique are presented in this feasibility study. METHOD: Ten complex tibial plateau fractures treated with extended lateral approach and lateral meniscal subluxation were prospectively analysed. Clinical and radiographic results were objectified according to the Rasmussen scores. RESULTS: After a median follow-up of 8.6 (IQR 4.3) months good to excellent clinical and radiographic results were noted. The clinical Rasmussen Score showed a median of 25 (IQR 2.8) and radiographic a median of 17 (IQR 2.0) points. CONCLUSION: Good to excellent clinical and radiological scores were obtained after using an extended lateral approach with lateral femoral epicondyle osteotomy and central meniscus subluxation. No approach specific complications could be observed.