BACKGROUND

Osteogenesis imperfecta (OI) is a group of connective tissue disease characterized by propensity to fractures following minimal trauma. OI is a lifelong inheritable disease and currently has no definitive cure. Management goals are directed towards prevention of fractures, controlling the symptoms, maximizing independent mobility, and developing optimal bone mass and muscle strength. Bisphosphonates are the mainstay of pharmacologic fracture-prevention therapy for most forms of OI. The University of the Philippines-Philippine General Hospital Bisphosphonate Treatment Program for OI was started in 2006 by the Clinical Genetics Service. For more than a decade now, the program has been serving more than 50 OI patients. This study evaluated the clinical outcomes of the patients who were included in the program to add to the body of knowledge on Filipino patients with OI.

This study sought to determine the clinical outcomes of children with OI on intravenous pamidronate treatment at the Philippine General Hospital (PGH) from January 2010 to December 2018.

The study utilized a retrospective review of medical records of 24 patients diagnosed with OI on pamidronate therapy seen at the PGH from January 2010 to December 2018. Descriptive statistics were used to summarize the demographic and baseline clinical characteristics of the patients. Median annualized fracture rates before and during treatment were calculated and compared. The patient functional mobility before and during pamidronate infusion was classified accordingly based on the Gross Motor Function Classification System (GMFCS) and were compared.

Twenty-four patients, which include seven males and 17 females, with ages at the time of conduct of the study ranging from four years to 11 years, fulfilled the inclusion criteria. There were four patients with OI type I, six with OI type III, 11 with OI type IV and three with OI type V. The annualized long bone fracture rate decreased significantly from a median of 2.0/year (range 1-2.75) to 0.75/year (range 0-1) after more than a year on pamidronate infusion (pCONCLUSION

Cyclic intravenous pamidronate treatment in young children with moderate-severe OI is well tolerated and associated with reduced fracture frequency with a tendency to improvement of gross functional mobility.

Osteoporotic fractures(OPF) refer to the fractures caused by minor violence in the state of osteoporosis, seriously threatening the life and health of elderly patients. Drug and surgical therapies have limitations such as single targets, diverse adverse reactions, and poor prognosis. Kidney-tonifying traditional Chinese medicine(TCM) has good potential in the treatment of OPF. TCM can promote the healing of OPF by promoting angiogenesis in the early stage of bone healing, promoting osteogenic differentiation of bone marrow mesenchymal stem cells in the stage of bone repair, maintaining the balance of osteogenic and osteoclastic system in the stage of bone remodeling, and regulating the oxidative stress responses throughout the process of OPF healing. TCM can alleviate the pathological state of osteoporosis and promote fracture healing in OPF patients via multiple pathways and targets, demonstrating the advantages and potential of biphasic regulation.
Humans ; Drugs, Chinese Herbal/therapeutic use* ; Osteoporotic Fractures/metabolism* ; Animals ; Fracture Healing/drug effects* ; Medicine, Chinese Traditional ; Kidney/metabolism* ; Osteogenesis/drug effects*

This paper aims to explore the effect of electrical stimulation of triboelectric nanogenerators (TENGs) on the osteogenic and other biological behaviors of mouse embryonic osteoblast precursor cells (MC3T3-E1 cells) on titanium surfaces. First, an origami-type TENG was fabricated, and its electrical output performance was tested. The optimal current of the generator and the feasibility of the experiment were verified by the CCK-8 assay and scratch assay. At the optimal current, the osteogenic conditions of the cells in each group were determined by quantitative analysis of the total protein content, alkaline phosphatase (ALP) activity, and alizarin red staining (ARS) on the titanium surface. Finally, the adhesion and spreading of cells on the titanium surface after electrical stimulation were observed. The results showed that the TENG had good electrical output performance, with an open-circuit voltage of 65 V and a short-circuit current of 42 μA. Compared with the rest of the current, a current strength of 30 μA significantly improved cell proliferation and migration, osteogenesis, and adhesion and spreading capabilities. The above results confirm the safety and operability of TENG in biomedical applications, laying the foundation for future TENG applications in reducing the time of bone integration around titanium implants after surgery.
Titanium/chemistry* ; Osteogenesis ; Animals ; Mice ; Osteoblasts/cytology* ; Electric Stimulation/instrumentation* ; Cell Adhesion ; Cell Proliferation ; Surface Properties ; Cell Differentiation ; Nanotechnology

To assess the implantation effectiveness of porous scaffolds, it is essential to consider not only their mechanical properties but also their biological performance. Given the high cost, long duration and low reproducibility of biological experiments, simulation studies as a virtual alternative, have become a widely adopted and efficient evaluation method. In this study, based on the secondary development environment of finite element analysis software, the strain energy density growth criterion for bone tissue was introduced to simulate and analyze the cell proliferation-promoting effects of four different lattice porous scaffolds under cyclic compressive loading. The biological performance of these scaffolds was evaluated accordingly. The computational results indicated that in the early stages of bone growth, the differences in bone tissue formation among the scaffold groups were not significant. However, as bone growth progressed, the scaffold with a porosity of 70% and a pore size of 900 μm demonstrated markedly superior bone formation compared to other porosity groups and pore size groups. These results suggested that the scaffold with a porosity of 70% and a pore size of 900 μm was most conducive to bone tissue growth and could be regarded as the optimal structural parameter for bone repair scaffold. In conclusion, this study used a visualized simulation approach to pre-evaluate the osteogenic potential of porous scaffolds, aiming to provide reliable data support for the optimized design and clinical application of implantable scaffolds.
Tissue Scaffolds/chemistry* ; Porosity ; Finite Element Analysis ; Tissue Engineering/methods* ; Computer Simulation ; Bone Development ; Osteogenesis ; Humans ; Cell Proliferation

The three-dimensional (3D) printed bone tissue repair guide scaffold is considered a promising method for treating bone defect repair. In this experiment, chitosan (CS), sodium alginate (SA), and mineralized collagen (MC) were combined and 3D printed to form scaffolds. The experimental results showed that the printability of the scaffold was improved with the increase of chitosan concentration. Infrared spectroscopy analysis confirmed that the scaffold formed a cross-linked network through electrostatic interaction between chitosan and sodium alginate under acidic conditions, and X-ray diffraction results showed the presence of characteristic peaks of hydroxyapatite, indicating the incorporation of mineralized collagen into the scaffold system. In the in vitro collagen release experiments, a weakly alkaline environment was found to accelerate the release rate of collagen, and the release amount increased significantly with a lower concentration of chitosan. Cell experiments showed that scaffolds loaded with mineralized collagen could significantly promote cell proliferation activity and alkaline phosphatase expression. The subcutaneous implantation experiment further verified the biocompatibility of the material, and the implantation of printed scaffolds did not cause significant inflammatory reactions. Histological analysis showed no abnormal pathological changes in the surrounding tissues. Therefore, incorporating mineralized collagen into sodium alginate/chitosan scaffolds is believed to be a new tissue engineering and regeneration strategy for achieving enhanced osteogenic differentiation through the slow release of collagen.
Chitosan/chemistry* ; Alginates/chemistry* ; Tissue Scaffolds/chemistry* ; Printing, Three-Dimensional ; Osteogenesis ; Collagen/chemistry* ; Cell Differentiation ; Animals ; Tissue Engineering/methods* ; Cell Proliferation ; Biocompatible Materials ; Glucuronic Acid/chemistry* ; Hexuronic Acids/chemistry*

OBJECTIVE: To summarize the research progress of bioactive scaffolds in the repair and regeneration of osteoporotic bone defects. METHODS: Recent literature on bioactive scaffolds for the repair of osteoporotic bone defects was reviewed to summarize various types of bioactive scaffolds and their associated repair methods. RESULTS: The application of bioactive scaffolds provides a new idea for the repair and regeneration of osteoporotic bone defects. For example, calcium phosphate ceramics scaffolds, hydrogel scaffolds, three-dimensional (3D)-printed biological scaffolds, metal scaffolds, as well as polymer material scaffolds and bone organoids, have all demonstrated good bone repair-promoting effects. However, in the pathological bone microenvironment of osteoporosis, the function of single-material scaffolds to promote bone regeneration is insufficient. Therefore, the design of bioactive scaffolds must consider multiple factors, including material biocompatibility, mechanical properties, bioactivity, bone conductivity, and osteogenic induction. Furthermore, physical and chemical surface modifications, along with advanced biotechnological approaches, can help to improve the osteogenic microenvironment and promote the differentiation of bone cells. CONCLUSION With advancements in technology, the synergistic application of 3D bioprinting, bone organoids technologies, and advanced biotechnologies holds promise for providing more efficient bioactive scaffolds for the repair and regeneration of osteoporotic bone defects.
Humans ; Tissue Scaffolds/chemistry* ; Bone Regeneration ; Osteoporosis/therapy* ; Tissue Engineering/methods* ; Biocompatible Materials/chemistry* ; Printing, Three-Dimensional ; Calcium Phosphates/chemistry* ; Osteogenesis ; Ceramics ; Cell Differentiation ; Hydrogels ; Bioprinting ; Bone and Bones

OBJECTIVE: To summarize the latest research progress of graphene and its derivatives (GDs) in bone repair. METHODS: The relevant research literature at home and abroad in recent years was extensively accessed. The properties of GDs in bone repair materials, including mechanical properties, electrical conductivity, and antibacterial properties, were systematically summarized, and the unique advantages of GDs in material preparation, functionalization, and application, as well as the contributions and challenges to bone tissue engineering, were discussed. RESULTS: The application of GDs in bone repair materials has broad prospects, and the functionalization and modification technology effectively improve the osteogenic activity and material properties of GDs. GDs can induce osteogenic differentiation of stem cells through specific signaling pathways and promote osteogenic activity through immunomodulatory mechanisms. In addition, the parameters of GDs have significant effects on the cytotoxicity and degradation behavior. CONCLUSION GDs has great potential in the field of bone repair because of its excellent physical and chemical properties and biological properties. However, the cytotoxicity, biodegradability, and functionalization strategies of GDs still need to be further studied in order to achieve a wider application in the field of bone tissue engineering.
Graphite/pharmacology* ; Tissue Engineering/methods* ; Humans ; Osteogenesis/drug effects* ; Biocompatible Materials/pharmacology* ; Bone Regeneration ; Tissue Scaffolds/chemistry* ; Cell Differentiation ; Bone and Bones ; Bone Substitutes/chemistry* ; Animals

OBJECTIVE: To describe the characteristics of short arm deformity in patients with achondroplasia, and summarize the progress of its lenthening and reconstruction, so as to provide reference for clinical diagnosis and treatment. METHODS: The literature on the lenthening of upper limb with achondroplastic short arm deformity at home and abroad in recent years was reviewed, and the characteristics, extension methods, postoperative management, effectiveness evaluation, and related complications of short arm deformity were summarized. RESULTS: Achondroplastic short arm deformity affect the patient's daily perineal hygiene activities. Although the upper limb is proportionately shortened, the humerus is mainly short limb deformity. Bilateral humeral lengthening is a common treatment method, and the traditional lengthening tools are mainly external fixation, guided by Ilizarov distraction osteogenesis concept; intramedullary lengthening is the latest treatment method. Lengthening percentage and healing index are commonly used for clinical evaluation indexes, and complications such as nerve injury may occur during upper limb lengthening. CONCLUSION In addition to appearance improvement, achondroplastic short arm lengthening is of great significance in achieving self-management of individual perineal hygiene. Lenthening and reconstruction methods are constantly being innovated and improved.
Humans ; Achondroplasia/surgery* ; Osteogenesis, Distraction/methods* ; Bone Lengthening/methods* ; Plastic Surgery Procedures/methods* ; Humerus/abnormalities* ; Treatment Outcome ; Ilizarov Technique ; Arm/abnormalities*

OBJECTIVE: To investigate the effects of sodium valproate (VPA) in inhibiting Erastin-induced ferroptosis in bone marrow mesenchymal stem cells (BMSCs) and its underlying mechanisms. METHODS: BMSCs were isolated from bone marrow of 8-week-old Spragur Dawley rats and identified [cell surface antigens CD90, CD44, and CD45 were analyzed by flow cytometry, and osteogenic and adipogenic differentiation abilities were assessed by alizarin red S (ARS) and oil red O staining, respectively]. Cells of passage 3 were used for the Erastin-induced ferroptosis model, with different concentrations of VPA for intervention. The optimal drug concentration was determined using the cell counting kit 8 assay. The experiment was divided into 4 groups: group A, cells were cultured in osteogenic induction medium for 24 hours; group B, cells were cultured in osteogenic induction medium containing optimal concentration Erastin for 24 hours; group C, cells were cultured in osteogenic induction medium containing optimal concentration Erastin and VPA for 24 hours; group D, cells were cultured in osteogenic induction medium containing optimal concentration Erastin and VPA, and 8 μmol/L EX527 for 24 hours. The mitochondrial state of the cells was evaluated, including the levels of malondialdehyde (MDA), glutathione (GSH), and reactive oxygen species (ROS). Osteogenic capacity was assessed by alkaline phosphatase (ALP) activity and ARS staining. Western blot analysis was performed to detect the expressions of osteogenic-related proteins [Runt-related transcription factor 2 (RUNX2) and osteopontin (OPN)], ferroptosis-related proteins [glutathione peroxidase 4 (GPX4), ferritin heavy chain 1 (FTH1), and solute carrier family 7 member 11 (SLC7A11)], and pathway-related proteins [adenosine monophosphate-activated protein kinase (AMPK) and Sirtuin 1 (SIRT1)]. RESULTS: The cultured cells were identified as BMSCs. VPA inhibited Erastin-induced ferroptosis and the decline of osteogenic ability in BMSCs, acting through the activation of the AMPK/SIRT1 pathway. VPA significantly reduced the levels of ROS and MDA in Erastin-treated BMSCs and significantly increased GSH levels. Additionally, the expression levels of ferroptosis-related proteins (GPX4, FTH1, and SLC7A11) significantly decreased. VPA also upregulated the expressions of osteogenic-related proteins (RUNX2 and OPN), enhanced mineralization and osteogenic differentiation, and increased the expressions of pathway-related proteins (AMPK and SIRT1). These effects could be reversed by the SIRT1 inhibitor EX527. CONCLUSION VPA inhibits ferroptosis in BMSCs through the AMPK/SIRT1 axis and promotes osteogenesis.
Mesenchymal Stem Cells/metabolism* ; Ferroptosis/drug effects* ; Animals ; Valproic Acid/pharmacology* ; Rats ; Rats, Sprague-Dawley ; Sirtuin 1/metabolism* ; Cell Differentiation/drug effects* ; Cells, Cultured ; AMP-Activated Protein Kinases/metabolism* ; Osteogenesis/drug effects* ; Piperazines/pharmacology* ; Bone Marrow Cells/cytology* ; Reactive Oxygen Species/metabolism* ; Signal Transduction/drug effects*

OBJECTIVE: To report the clinical experience of using Ilizarov wrist joint distraction technique in the treatment of a case of rheumatoid arthritis of the wrist. METHODS: In January 2019, a 49-year-old female patient with rheumatoid arthritis of the left wrist, complicated by ulnar impaction syndrome, was admitted for treatment. Preoperatively, the active range of motion of the left wrist was as follows: extension 0°-flexion 0°, pronation 65°-supination 35°, and grip strength of 4.0 kg. The visual analogue scale (VAS) score was 9, and the Cooney wrist function score was 15, indicating poor function. As conservative treatment failed to achieve symptom relief, Ilizarov wrist joint distraction surgery was performed. Postoperatively, joint distraction was applied at 2 mm increments on postoperative days 2 and 7, in 4 separate sessions. RESULTS: Postoperative X-ray film examination at 7 days revealed a distraction of 3.6 mm in the affected wrist joint compared to the contralateral side. The external fixator was removed 2.5 months postoperatively. At 22 months postoperatively, X-ray film and MRI examinations revealed that the joint space of the left wrist had returned to near-normal, with significant reduction in joint effusion and synovial proliferation. The active range of motion of the left wrist improved to extension 15°- flexion 30°, pronation 90°-supination 90°, with a grip strength of 18.0 kg. The wrist pain VAS score decreased to 0, and the Cooney wrist function score improved to 90, indicating excellent function. At 50 months postoperatively, follow-up X-ray film, MRI, and functional assessments showed the results similar to those at 22 months. CONCLUSION Ilizarov wrist joint distraction may be a viable treatment option for rheumatoid arthritis of the wrist.
Humans ; Female ; Middle Aged ; Wrist Joint/physiopathology* ; Arthritis, Rheumatoid/physiopathology* ; Range of Motion, Articular ; Ilizarov Technique ; Treatment Outcome ; Osteogenesis, Distraction/methods*