[Corrective osteotomies around the elbow in childhood and adolescence : Indications and techniques for posttraumatic deformities]. / Korrekturosteotomien rund um den Ellenbogen im Kindes- und Jugendalter : Indikationen und Techniken bei posttraumatischen Deformitäten.

Evidence-based literature on counseling and treatment of pediatric and adolescent patients with posttraumatic deformities is scarce; however, especially around the elbow with its low remodeling potential, the number of patients with malunions presenting in outpatient clinics is not rare at all. In this review the more frequent indications for corrective surgery around the pediatric elbow are described and treatment proposals are made from the perspective of an interregional reference center for pediatric and adolescent trauma.

[Treatment of femoral shaft fractures in children and adolescents ≥50 kg : A retrospective multicenter trial]. / Behandlung der Femurschaftfraktur bei Kindern und Jugendlichen mit einem Körpergewicht ≥50 kg : Eine retrospektive multizentrische Erhebung.

BACKGROUND: Operative treatment of diaphyseal fractures of the femur in older children and adolescents remains controversial due to multiple surgical options and higher complication rates in single-center studies compared to younger children. This retrospective multicenter study aimed to register early and late complications in day-by-day treatment. MATERIAL AND METHODS: Sixteen hospitals with particular expertise in pediatric orthopedic trauma participated in this study. Patients with diaphyseal femur fractures, a body weight ≥50 kg (aged 10-16 years) and treated between 2008 and 2012 were included. Age, weight, fracture type, and choice of operative treatment were correlated to complication rate and type. Patients with pathologic fractures and/or metabolic bone disorders were excluded. RESULTS: Fifty-three children (15 females and 38 males; mean age: 14.2 y [SD 1.4 y]; mean body weight: 60.5 kg [max. 95 kg]) with 54 fractures were included. Elastic stable intramedullary nailing (ESIN) was the treatment of choice in 31 of 42 fractures with open growth plates. In the subgroup with two nails, 7 of 12 patients experienced revision surgery due to instability or shortening. Three patients with ESIN and end caps had no complications. In the subgroup with three inserted nails (11 patients), one patient was converted to external fixation. Nine patients received primary or secondary plate osteosyntheses. Within this group, two patients had deep infections; one implant failure, and one peri-implant fracture were recorded. Adolescent lateral femoral nailing (ALFN), when used as the primary treatment option in two patients, was free of complications. When used as a secondary treatment option in three patients, one patient had a pseudarthrosis and one an infection. Both were treated in further operative procedures. In a group of eight patients with closed physes, regular intramedullary nailing as primary or secondary treatment of choice resulted in one locking screw change. As late complications, leg length discrepancy (LLD) over 15 mm (n = 2) and loss of range of motion (ROM) (n = 4; two knee and three hip) were noted in patients receiving multiple revisions or serious postoperative complication. CONCLUSIONS: Children older than 10 years of age with a body weight ≥50 kg and open physes are prone to complications regardless of treatment choice. A smaller revision rate occurred in patients treated with ESIN and end caps or a third nail compared to the other treatment options. When physes are closed, rigid intramedullary nailing is the treatment of choice.

[Bony injuries of the knee region in childhood and adolescence]. / Knöcherne Verletzungen der Knieregion im Kindes- und Jugendalter.

Fractures of the knee region in childhood and adolescence are rare but are an important group of injuries due to the high incidence of secondary complications from growth disturbances. Meticulous primary diagnostics and fracture treatment with clear indications for surgical treatment are essential for avoiding posttraumatic deformities, although these can occur even despite correct primary treatment and are therefore inherent to specific fractures and therefore often unavoidable. In cases of growth disturbance where a deformity is imminent or has already taken place, watchful waiting until closure of the growth plate is only rarely indicated due to the progress made in directing growth via surgical means. Even surgeons who are primarily working in the field of fracture treatment must be aware of current strategies for correction of posttraumatic deformities in order to prevent or treat them in time or at least be able to prophylactically inform patients and parents during primary fracture treatment.

[Diametaphyseal forearm fracture in childhood. Pitfalls and recommendations for treatment]. / Die diametaphysäre Unterarmfraktur im Kindesalter. Pitfalls und Empfehlungen in der Behandlung.

The optimal treatment for fractures in the diametaphyseal transition zone of the forearm is still a matter of debate. Stable fractures should be immobilized or treated by closed reduction when non-tolerably displaced. Unstable and displaced fractures can be treated by various operative techniques, which are all characterized by technical impracticability or disadvantages for the patient. In younger patients transepiphyseal intramedullary K-wire fixation represents a minimally invasive, quick and technically easy treatment option but requires additional immobilisation. In adolescent patients volar locking plate osteosynthesis constitutes an immobilisation-free treatment option, but is combined with high invasiveness. Percutaneous K-wire fixation and elastic stable intramedullary nailing may lead to poor results in the diametaphyseal region due to technical or biomechanical problems associated with the implant. The external fixator is indicated in some multifragmentary fractures. The choice of treatment option often results from an individual decision based on the patient's age, complexity and stability of the fracture and interest of the patient. The priority objective of all treatment modalities is a fully functional upper extremity, i.e. full range of motion.

Differential expression of neuroleukin in osseous tissues and its involvement in mineralization during osteoblast differentiation.

Osteoblast differentiation is a multistep process that involves critical spatial and temporal regulation of cellular processes marked by the presence of a large number of differentially expressed molecules. To identify key functional molecules, we used differential messenger RNA (mRNA) display and compared RNA populations isolated from the defined transition phases (proliferation, matrix formation, and mineralization) of the MC3T3-E1 osteoblast-like cell line. Using this approach, a complementary DNA (cDNA) fragment was isolated and identified as neuroleukin (NLK), a multifunctional cytokine also known as autocrine motility factor (AMF), phosphoglucose isomerase (PGI; phosphohexose isomerase [PHI]), and maturation factor (MF). Northern analysis showed NLK temporal expression during MC3T3-E1 cell differentiation with a 3.5-fold increase during matrix formation and mineralization. Immunocytochemical studies revealed the presence of NLK in MC3T3-E1 cells as well as in the surrounding matrix, consistent with a secreted molecule. In contrast, the NLK receptor protein was detected primarily on the cell membrane. In subsequent studies, a high level of NLK expression was identified in osteoblasts and superficial articular chondrocytes in bone of 1-, 4-, and 8-month-old normal mice, as well as in fibroblasts, proliferating chondrocytes, and osteoblasts within a fracture callus. However, NLK was not evident in hypertrophic chondrocytes or osteocytes. In addition, treatment of MC3T3 cells with 6-phosphogluconic acid (6PGA; a NLK inhibitor) resulted in diminishing alkaline phosphatase (ALP) activity and mineralization in MC3T3-E1 cells, especially during the matrix formation stage of differentiating cells. Taken together, these data show specific expression of NLK in discrete populations of bone and cartilage cells and suggest a possible role for this secreted protein in bone development and regeneration.

Non-adrenergic, non-cholinergic regulation of stone-diseased and stone-free human gallbladders.

OBJECTIVE: The aim of this study was to determine the role of nitric oxide (NO), as the primary neurotransmitter of non-adrenergic, non-cholinergic (NANC) innervation, in stone-diseased and stone-free human gallbladders. METHODS: Human gallbladder muscle strips were mounted in modified Krebs-Henseleit solution with atropine (1 mM), guanethidine sulfate (5 mM) and aerated with Carbogen. Electric field stimulation (EFS) (70 V, 0.5 ms, 100 pulses) was used to activate NANC nerves. N-omega-nitro-L-arginine (L-NNA, 100 mM) and L-arginine (L-Arg, 120 mM) were used to manipulate the NO-synthase. Gallbladder slices were stained by using the alkaline phosphatase, anti-alkaline phosphatase (APAAP) method for histological examination. RESULTS: In the control group (basal tone, 8.94 +/- 1.17 mN) caused a frequency-dependent reduction of basal tone (1 Hz = 5.73 +/- 0.81 mN; 3 Hz = 5.18 +/- 0.65 mN; 10 Hz = 4.63 +/- 0.49 mN), inhibition of NO-synthesis with L-NNA increased the tone (7.63 +/- 0.76 mN). Stone-diseased groups were divided into two groups (contractor and subcontractor), according to their ability to contract by CCK. Under the influence of EFS the contractor group (basal tone = 7.79 +/- 0.93 mN) reacted like the control group, but was frequency-independent and, additionally, showed spontaneous phasic contractions. In the sub-contractor group (basal tone 4.13 +/- 0.65 mN) EFS only decreased the frequency of spontaneous phasic contractions. L-NNA caused an increase in tone (5.97 +/- 0.84 mN) and frequency. L-arginine, the substrate for NO-synthase, significantly reversed this effect, indicating the dependence on NO. Histologically, the contractor group showed a wrinkled mucosal membrane and low-grade inflammation. Shallow mucosa, necrosis and high-grade inflammation were found in the sub-contractor group. CONCLUSIONS: In vitro, NANC relaxation of human gallbladder is NO dependent. The motility of stone-diseased gallbladders is modulated by NO and seems to depend on the degree of scarification.

Elastic stable intramedullary nailing (ESIN) in the adolescent patient-perils, pearls, and pitfalls.

PURPOSE: Elastic stable intramedullary nailing (ESIN) has become the treatment of choice for diaphyseal long-bone fractures in children. This paper reviews the complications and limitations of this method which can occur when applying this osteosynthesis to patients within the adolescent age group. METHODS: Each topographic site where ESIN is used was analyzed individually and systematically. Technical errors, indicational problems, and mistakes during the rehabilitation process are pointed out and recommendations are given on how to avoid failure. RESULTS: ESIN can be safe and efficacious within certain limits also in the adolescent age group. Whenever errors and mistakes occur in combination, e.g., applying ESIN to a patient with a multi-fragmented fracture and a high body mass index (BMI), the adolescent age group is less forgiving to indicational "stretching" than the pediatric age group. CONCLUSIONS: The best prophylaxis for failure of ESIN is a stable and symmetric construct with correctly sized implants. This holds even more true for the adolescent patient. Using ESIN in difficult situations such as longitudinally unstable fractures, patients with a body weight >50 kg, or away from the diaphysis should be considered and followed up carefully. If possible, these patients should be treated in specialized pediatric trauma centers.

[Severely displaced radial neck fractures after minimally invasive joystick reduction and Prévot nailing: long-term course in childhood]. / Stark dislozierte Radiushalsfrakturen nach minimal-invasiver Joystick-Reposition und Prévot-Nagelung: Langzeitverlauf im Kindesalter.

Significantly displaced radial neck fractures in children are at risk for functional problems due to malaligned healing or growth disturbances at the proximal growth plate. Anatomic reduction is needed, especially in older children (aged 10+ years). Elastic stable intramedullary nailing (ESIN) (1993 Metaizeau) is the preferred method. When closed reduction is not possible, we use a joystick technique to fully reduce the radial head. The aim of this study was to challenge the hypothesis that this manipulation leads to secondary complications by affecting blood flow. Also, we asked the question to which extent an additional injury to the growth plate leads to functional problems concerning range of motion in the elbow joint. We undertook a retrospective analysis of children with severely displaced radial head fractures that occurred as isolated incidents or in combination with complex elbow fractures who had been treated by us with this technique between 1998 and 2004. We collected data on the clinical and radiological healing process.

Biology of bone and how it orchestrates the form and function of the skeleton.

The principal role of the skeleton is to provide structural support for the body. While the skeleton also serves as the body's mineral reservoir, the mineralized structure is the very basis of posture, opposes muscular contraction resulting in motion, withstands functional load bearing, and protects internal organs. Although the mass and morphology of the skeleton is defined, to some extent, by genetic determinants, it is the tissue's ability to remodel--the local resorption and formation of bone--which is responsible for achieving this intricate balance between competing responsibilities. The aim of this review is to address bone's form-function relationship, beginning with extensive research in the musculoskeletal disciplines, and focusing on several recent cellular and molecular discoveries which help understand the complex interdependence of bone cells, growth factors, physical stimuli, metabolic demands, and structural responsibilities. With a clinical and spine-oriented audience in mind, the principles of bone cell and molecular biology and physiology are presented, and an attempt has been made to incorporate epidemiologic data and therapeutic implications. Bone research remains interdisciplinary by nature, and a deeper understanding of bone biology will ultimately lead to advances in the treatment of diseases and injuries to bone itself.

Inhibition of osteopenia by low magnitude, high-frequency mechanical stimuli.

The identification of anabolic agents for the treatment of metabolic bone disease is a highly prized, and elusive, goal. In searching for the osteogenic (bone-producing) constituents within mechanical stimuli, it was determined that high frequency (10-100 Hz) and low magnitude (<10 microstrain) stimuli were capable of augmenting bone mass and morphology, thereby benefiting both bone quantity and quality. Using animal models, it is shown that these mechanical signals can double bone-formation rates, inhibit disuse osteoporosis and increase the strength of trabecular bone by 25%. Considering that the magnitude of these mechanical signals are several orders of magnitude below those which cause damage to the bone tissue, it is proposed that this modality could be useful in the treatment of metabolic bone diseases.

Differential phosphorylation of paxillin in response to surface-bound serum proteins during early osteoblast adhesion.

An early signaling event during the adhesion and spreading of cells is integrin-mediated tyrosine phosphorylation of the cytoskeletal adaptor protein paxillin and the non-receptor tyrosine kinase pp125(FAK) at focal contacts. To determine the influence of surface-charge and -adsorbed adhesion proteins on this signaling pathway, paxillin phosphorylation was examined during attachment of MC3T3-E1 osteoblast-like cell onto charged and uncharged polystyrene, and on adsorbed layers of serum proteins, fibronectin (Fn), vitronectin (Vn), a mixture of Fn and Vn, and albumin. Paxillin phosphorylation was induced 2.4-fold (P < 0.05) on charged vs uncharged polystyrene only in the presence of serum proteins. Activation of paxillin via Fn or Vn alone, or in combination, resulted in significantly lower phosphorylation signals compared to whole serum (41 +/- 6.9%, P < 0.05, 45 +/- 5.9%, P < 0.05, and 76 +/- 9.8%, P < 0.075, respectively). Confocal laser microscopy confirmed increased co-localization of phosphotyrosine and paxillin at protruding lamellopodia of spreading osteoblasts on charged vs uncharged serum-pretreated polystyrene. Taken together, these data suggest that subtle differences in surface characteristics mediate effects on adhering cells via adsorbed serum proteins involving the cytoskeletal adaptor protein paxillin.