Serum-derived exosomes from neurofibromatosis type 1 congenital tibial pseudarthrosis impaired bone by promoting osteoclastogenesis and inhibiting osteogenesis.

Treatment of congenital pseudarthrosis of the tibia (CPT) still is full of challenges in pediatric orthopedist. Serum-derived exosomes (SDEs) have been proven to be participated in bone remodeling. However, the molecular changes in SDEs of CPT children and their pathologies have not been elucidated. In this study, SDEs were isolated and purified from CPT patients (CPT-SDEs) associated with neurofibromatosis type 1 (NF1) and normal children (Norm-SDEs). Then we obtained the proteomics profile of SDEs by combining liquid chromatography-tandem mass spectrometry (LC-MS/MS) and tandem mass tag label-based quantitation. In vitro, the efficacy of SDEs on osteoblastic differentiation of MC3T3-E1 cells and osteoclastogenesis ability of RAW264.7 cells were evaluated by quantitative real-time PCR (qRT-PCR) and cytochemical staining. In vivo, we used micro-CT to assess cortical bone mass and trabecular microstructures to reflect the influence of SDEs on bone remodeling after injection into the tail vein of rats. Based on proteomics analysis, 410 differentially expressed proteins, including 289 downregulated proteins and 121 upregulated proteins, were identified in the CPT-SDEs. These proteins have multiple biological functions associated with cellular metabolic processes, catalytic activity, and protein binding, which are important for cell differentiation and proliferation. In vitro, CPT-SDEs decreased the osteogenic differentiation of MC3T3-E1 cells and promoted the osteoclastogenesis of RAW264.7 cells. Injection of CPT-SDEs into the tail vein for two months resulted in bone loss in rats, as indicated by the decrease in trabecular and cortical bone mass. Our findings demonstrated the differences in proteins in SDEs between normal and CPT children with NF1. These differentially expressed proteins in CPT-SDEs contributed to deteriorating trabecular bone microstructures by inhibiting bone formation and stimulating bone resorption.

Preoperative Assessment of Bone Quality in Spine Deformity Surgery: Correlation With Clinical Practice and Published Recommendations.

STUDY DESIGN: Retrospective cohort study. OBJECTIVE: The goals of this study were to (A) evaluate preoperative bone quality assessment and intervention practice over time and (B) review the current evidence for bone evaluation in spine fusion surgery. SUMMARY OF BACKGROUND DATA: Deformity spine surgery has demonstrated improved quality of life in patients; however, its cost has made it controversial. If preoperative bone quality can be optimized then potentially these treatments could be more durable; however, at present, no clinical practice guidelines have been published by professional spine surgical organizations. METHODS: A retrospective cohort review was performed on patients who underwent a minimum five-level primary or revision fusion. Preoperative bone quality metrics were evaluated over time from 2012 to 2017 to find potential trends. Subgroup analysis was conducted based on age, sex, preoperative diagnosis, and spine fusion region. RESULTS: Patient characteristics including preoperative rates of pseudarthrosis and junctional failure did not change. An increasing trend of physician bone health documentation was noted (P = 0.045) but changes in other metrics were not significant. A sex bias favored females who had higher rates of preoperative DXA studies (P = 0.001), Vitamin D 25-OH serum labs (P = 0.005), Vitamin D supplementation (P = 0.022), calcium supplementation (P < 0.001), antiresorptive therapy (P = 0.016), and surgeon clinical documentation of bone health (P = 0.008) compared with men. CONCLUSION: Our spine surgeons have increased documentation of bone health discussions but this has not affected bone quality interventions. A discrepancy exists favoring females over males in nearly all preoperative bone quality assessment metrics. Preoperative vitamin D level and BMD assessment should be considered in patients undergoing long fusion constructs; however, the data for bone anabolic and resorptive agents have less support. Clinical practice guidelines on preoperative bone quality assessment spine patients should be defined. LEVEL OF EVIDENCE: 4.

[Concentration of several osteotropic growth factors, markers of osteogenesis and biologically active molecules in the blood serum of patients with congenital pseudarthrosis of tibia during orthopaedic treatment with combined technologies]. / Soderzhanie nekotorykh osteotropnykh faktorov rosta, markerov osteogeneza i biologicheski aktivnykh molekul v krovi patsientov s vrozhdennym lozhnym sustavom goleni pri ortopedicheskom lechenii s ispol'zovaniem kombinirovannykh tekhnologii.

Congenital pseudarthrosis of tibia is a genetic, systemic pathology with impaired bone remodeling and unknown pathogenetic mechanisms. Orthopaedic treatment of the disease can fail in some cases. The process of bone remodeling is known to occur under control of local and systemic growth factors, and we sought to explore several osteotropic growth factors, markers of osteogenesis and biologically active molecules in the blood serum of patients with congenital pseudarthrosis of tibia. The study included 12 patients with congenital pseudarthrosis of tibia and anatomical shortening of 2.5±1.1 cm. The' age of patients ranged from 7 years to 18 years. Blood serum was used for enzyme immunoassay analysis. The own blood serum levels of 103 conditionally healthy individuals (of mean age of 13.0±0.27 years) were considered as the norm. Greater changes in the concentration were detected among vascular endothelial and transforming growth factors. The patients showed imbalance in serum TGF, low reparative potential of bone tissue due to osteoclast activation prevailing over differentiation of osteoblasts, progenitor and mesenchymal cells. Dynamics in serum concentration of IGF at the time of frame removal indicated to terminating osteoblast activation and collagen synthesis and concomitant active bone restructuring.

[Metabolic status and bone mineral density in patients with pseudarthrosis of long bones in hyperhomocysteinemia].

In article described research of the metabolic status and bone mineral density in 153 patients with with pseudarthrosis of long bones, in individuals with consolidated fractures and healthy people. The violations of reparative osteogenesis at hyperhomocysteinemia are accompanied by disturbances of the functional state of bone tissue, inhibition of biosynthetic and increased destruction processes, reduced bone mineral density in the formation of osteopenia and osteoporosis. The degree and direction of change of bone depends on the type of violation of reparative osteogenesis.

The rate of pseudarthrosis (surgical nonunion) in patients who are smokers and patients who are nonsmokers: a comparison study.

To investigate the relationship of smoking with the rate of pseudarthrosis (surgical nonunion), 50 patients, who were smokers, and 50 patients, who were not, and who had had a two-level laminectomy and fusion during 1977 and 1978 were randomly selected for this study. Most of those participating had sustained job-related injuries whereas the others had no common etiology for their back dysfunction. Most of the patients were from the southeastern United States. Ages ranged from 23 to 62 years, with a mean age of 42.4 years for smokers and 42.7 years for nonsmokers. There was an equal representation of males and females, with minorities represented according to their general percentage in the population. Examination 1 to 2 years after surgery revealed that 40% (20) of the smokers had developed a pseudarthrosis, whereas among nonsmokers, the rate was 8% (4). This finding appears to be independent of age, sex, or race and was statistically significant (chi 2 = 14.035, P = .001). It was hypothesized that the higher incidence of surgical nonunion among smokers may be related to blood gas levels. Nonsmokers showed no significant deficiencies, whereas smokers showed a mean PO2 level of 78.5% (normal = 95-97) and a mean O2 saturation level of 92.9% (normal = 95 or above). Implications and suggestions for further research are also discussed.