Complications Following Intraosseous Injections of Calcium Phosphate Bone Cement in Subchondroplasty.

An alternative approach to the major problem of osteoarthritis that has begun to pique the interest of researchers focuses on the pathology of the subchondral bone, its constant cross-talk with the articular cartilage, and its interaction with the joint. The presence of bone marrow lesions, detectable on MRI scans, has proven to be a cause of pain as well as a predictor of the progression of degenerative changes. Subchondroplasty is a relatively new surgical procedure for the treatment of these lesions, in which injectable calcium phosphate bone cement is infused into the affected area percutaneously, under fluoroscopic guidance. In its use as a synthetic scaffold, calcium phosphate bone cement exhibits considerable osteoconductivity, bioabsorbability, and low toxicity, thus showing great potential for restoring subchondral biomechanical properties through structural remodeling. Although published results appear quite promising, there are certain complications that the surgeon should be aware of. We reviewed the published data regarding complications of the procedure, highlighting possible causes according to these data, and suggesting safety measures. Avascular necrosis of the talus is the most reported concern. Postsurgical pain, infection, and continuous wound drainage due to bone substitute material extravasation to the joint or soft tissue are also mentioned, necessitating further standardization of the procedure. There are no reports of permanent postoperative disability or fatal outcomes.

Long-Term Safety of Bone Regeneration Using Autologous Stromal Vascular Fraction and Calcium Phosphate Ceramics: A 10-Year Prospective Cohort Study.

This prospective cohort study aimed to assess long-term safety, dental implant survival, and clinical and radiological outcomes after maxillary sinus floor elevation (MSFE; lateral window technique) using freshly isolated autologous stromal vascular fraction (SVF) combined with calcium phosphate ceramics. All 10 patients previously participating in a phase I trial were included in a 10-year follow-up. They received either ß-tricalcium phosphate (ß-TCP; n = 5) or biphasic calcium phosphate (BCP; n = 5) with SVF-supplementation on one side (study). Bilaterally treated patients (6 of 10; 3 ß-TCP, 3 BCP) received only calcium phosphate on the opposite side (control). Clinical and radiological assessments were performed on 44 dental implants at 1-month pre-MSFE, and 0.5- to 10-year post-MSFE. Implants were placed 6 months post-MSFE. No adverse events or pathology was reported during a 10-year follow-up. Forty-three dental implants (98%) remained functional. Control and study sides showed similar peri-implant soft-tissue quality, sulcus bleeding index, probing depth, plaque index, keratinized mucosa width, as well as marginal bone loss (0-6 mm), graft height loss (0-6 mm), and graft volume reduction. Peri-implantitis was observed around 6 implants (control: 4; study: 2) in 3 patients. This study is the first to demonstrate the 10-year safety of SVF-supplementation in MSFE for jawbone reconstruction. SVF-supplementation showed enhanced bone regeneration in the short term (previous study) and led to no abnormalities clinically and radiologically in the long term.

Does Calcium Phosphate Cement Kyphoplasty Cause Intervertebral Disk Degeneration in Adolescents?

OBJECTIVE: Balloon kyphoplasty with polymethylmethacrylate (PMMA) represents the standard procedure for the treatment of thoracic and lumbar type A compression fractures. However, an increased degeneration in adjacent intervertebral disks following PMMA kyphoplasty has been demonstrated in elderly patients. Calcium phosphate cement (CPC) appears to be superior to PMMA for the intravertebral stabilization in younger patients. It remains unkown whether CPC kyphoplasty causes degeneration of adjacent disks in adolescents. DESIGN: Seven adolescents with thoracolumbar spine fractures underwent kyphoplasty at a mean age of 14.5 years (range 10-18). At a mean follow-up of 3.7 years (range 1 to 4.8) postoperatively, 3.0 Tesla magnetic resonance imaging (MRI) of the spine was performed to assess intervertebral disk degeneration by quantitative T2 relaxation maps and subjective ratings using modified Pfirrmann scores. A total of 56 intervertebral disks was analyzed. Initial computed tomography (CT) examinations served as basis to assess the severity of adjacent endplate injuries in terms of articular step-offs. RESULTS: Initial imaging detected 18 thoracolumbar vertebral body fractures of which 9 were treated with CPC kyphoplasty. Quantitative follow-up MRI revealed signs of degeneration in 10 (17.9%) of the examined 56 intervertebral disks, 7 of them adjacent to a previously fractured vertebral body. Signs of disk degeneration were significantly higher in caudal endplates with articular step-offs larger than 5 mm compared to fractured vertebral bodies without endplate step-offs. CONCLUSIONS: Quantitative MRI follow-ups did not suggest CPC-related intervertebral disk degradations following thoracolumbar kyphoplasty in adolescents, but indicated disk alterations correlating to adjacent endplate fracture severity.

The Antioxidant Supplementation with Filipendula ulmaria Extract Attenuates the Systemic Adverse Effects of Nanosized Calcium Phosphates in Rats.

The aim of this study was to investigate and compare the systemic toxicity of three nanosized calcium phosphates (CaPs): hydroxyapatite (HA), tricalcium phosphate (TCP), and amorphous calcium phosphate (ACP) in rats. Since those metallic compounds are widely used as bone replacement materials, including their use in oral surgery, CaPs were applied (per os) equimollary (17.8 mg/kg, 11 mg/kg, and 9.65 mg/kg b.w., respectively) for 30 days in order to mimic the previously described release rate from dental composites. Also, we employed antioxidant supplementation with Filipendula ulmaria (FU) extract. All the applied CaPs significantly increased serum calcium, triglycerides, LDL, and LDH, while serum levels of testosterone and LH declined, with no alterations in the liver enzymes. The evaluation of oxidative stress markers (in the liver, kidney, and testicle) showed an increase in TBARS values, while SOD and CAT activities and GSH levels were significantly reduced. The relative gene expression of Bax and Bcl-2 was shifted to proapoptotic action, accompanied by intense characteristic histological changes in architecture in all investigated organs. The toxic effects were most prominent in groups treated by ACP. FU administration attenuated the majority of nanosized CaP-induced adverse effects, thus recommending this therapeutic approach to minimize nano-CaP systemic toxicities.

Talar Avascular Necrosis After Calcium Phosphate Injection Treatment of Talar Bone Marrow Lesions: A Report of 2 Cases.

CASE: We report on 2 patients who developed avascular necrosis (AVN) of the talus and poor patient outcomes after undergoing calcium phosphate injection into talar dome bone marrow lesions. CONCLUSION: Subchondroplasty, defined as calcium phosphate injection for the treatment of articular bone marrow edema, is a recently described procedure for use in the ankle joint. In our opinion, the limited available research is of poor quality and describes equivocal improvement in patient symptoms after this procedure. Given the debilitating outcomes and extensive AVN we observed in 2 patients, we strongly advise caution in the use of this procedure in the talus.

High failure rate after Beta-tricalcium phosphate grafting for the treatment of femoral head osteonecrosis: a retrospective analysis.

BACKGROUND: Non-vascularized bone grafting is a promising head-preserving technique for younger patients diagnosed as non-traumatic osteonecrosis of the femoral head (NONFH). Among the various types of bone grafting techniques, "light-bulb" procedure grafting with synthetic bone substitute is an attractive option. We aimed to assess the effectiveness of using beta-tricalcium phosphate (ß-TCP) for the treatment of pre-collapse and early post-collapse lesions NONFH. METHODS: From April 2010 to June 2014, 33 patients (47 hips) with NONFH were treated using the afore-mentioned technique. The clinical and radiological outcomes were recorded and compared statistically between pre- and post-operation. Harris hip score (HHS) was used to evaluate the clinical results, and Association Research Circulation Osseous (ARCO) stage was applied to assess the radiological outcomes. RESULTS: The 5-years survival rate of using ß-TCP grafting was accounting for 25.5%. HHS was decreased from 78.47 to 52.87 points, and a very significant worsening of radiological results were revealed (P <  0.05). Two hips collapsed more than 2 mm were awaiting for THA, and 33 of the 47 hips had converted to THAs in an average time to failure of 24.24 months postoperatively. Meanwhile, only 4 hips survived without collapse, and 8 hips collapsed less than 2 mm. After surgery, the time onset of head collapse was 3.65 months on average, and the first conversion to THA was performed at 5 months postoperative. CONCLUSIONS: Our results suggest that "light-bulb" procedure grafting with ß-TCP sticks presented with a high failure rate in the early postoperative period. It is not proposed for the treatment of pre-collapse and early post-collapse lesions NONFH.

Achieving enhanced bone regeneration using monetite granules with bone anabolic drug conjugates (C3 and C6) in rat mandibular defects.

Bone grafting procedures are commonly used to manage bone defects in the craniofacial region. Monetite is an excellent biomaterial option for bone grafting, however, it is limited by lack of osteoinduction. Several molecules can be incorporated within the monetite matrix to promote bone regeneration. The aim was to investigate whether incorporating bone forming drug conjugates (C3 and C6) within monetite can improve their ability to regenerate bone in bone defects. Bilateral bone defects were created in the mandible of 24 Sprague-Dawley rats and were then packed with monetite control, monetite+C3 or monetite+C6. After 2 and 4 weeks, post-mortem samples were analyzed using microcomputed tomography, histology and back-scattered electron microscopy to calculate the percentages of bone formation and remaining graft material. At 2 and 4 weeks, monetite with C3 and C6 demonstrated higher bone formation than monetite control, while monetite+C6 had the highest bone formation percentage at 4 weeks. There were no significant differences in the remaining graft material between the groups at 2 or 4 weeks. Incorporating these anabolic drug conjugates within the degradable matrix of monetite present a promising bone graft alternative for bone regeneration and repair in orthopedic as well as oral and maxillofacial applications.

[Basal ganglia calcification]. / Calcifications des noyaux gris centraux.

Calcifications of the basal ganglia are frequently seen on the cerebral CT scans and particularly in the globus pallidus. Their frequency increases physiologically with age after 50 years old. However, pathological processes can also be associated with calcium deposits in the gray nuclei, posterior fossa or white matter. Unilateral calcification is often related to an acquired origin whereas bilateral ones are mostly linked to an acquired or genetic origin that will be sought after eliminating a perturbation of phosphocalcic metabolism. In pathological contexts, these calcifications may be accompanied by neurological symptoms related to the underlying disease: Parkinson's syndrome, psychiatric and cognitive disorders, epilepsy or headache. The purpose of this article is to provide a diagnostic aid, in addition to clinical and biology, through the analysis of calcification topography and the study of different MRI sequences.

Dipyridamole-loaded 3D-printed bioceramic scaffolds stimulate pediatric bone regeneration in vivo without disruption of craniofacial growth through facial maturity.

This study investigates a comprehensive model of bone regeneration capacity of dypiridamole-loaded 3D-printed bioceramic (DIPY-3DPBC) scaffolds composed of 100% beta-tricalcium phosphate (ß -TCP) in an immature rabbit model through the time of facial maturity. The efficacy of this construct was compared to autologous bone graft, the clinical standard of care in pediatric craniofacial reconstruction, with attention paid to volume of regenerated bone by 3D reconstruction, histologic and mechanical properties of regenerated bone, and long-term safety regarding potential craniofacial growth restriction. Additionally, long-term degradation of scaffold constructs was evaluated. At 24 weeks in vivo, DIPY-3DPBC scaffolds demonstrated volumetrically significant osteogenic regeneration of calvarial and alveolar defects comparable to autogenous bone graft with favorable biodegradation of the bioactive ceramic component in vivo. Characterization of regenerated bone reveals osteogenesis of organized, vascularized bone with histologic and mechanical characteristics comparable to native bone. Radiographic and histologic analyses were consistent with patent craniofacial sutures. Lastly, through application of 3D morphometric facial surface analysis, our results support that DIPY-3DPBC scaffolds do not cause premature closure of sutures and preserve normal craniofacial growth. Based on this novel evaluation model, this DIPY-3DPBC scaffold strategy is a promising candidate as a safe, efficacious pediatric bone tissue engineering strategy.

Maxillary sinus floor elevation using Beta-Tricalcium-Phosphate (beta-TCP) or natural bone: same inflammatory response.

Sinus elevation is a common procedure to increase bone volume in the atrophic maxilla to allow placement of dental implants. Autogenous bone is the gold standard but is limited in quantity and causes morbidity at the donor site. ß-TCP is a synthetic biomaterial commonly used in that purpose. It appears to induce a poor inflammatory response. This study aimed to evaluate the degree of edema of the sinus mucosa after sinus lift surgery according to the type of biomaterial. Forty sinuses (20 patients) were included retrospectively and divided into 2 groups according to the biomaterial that was used: synthetic biomaterial (BTCP group), natural bone (BONE group). A control group (CTRL group) was constituted by the non-grafted maxillary sinuses. Twelve measurements per sinus were realized on pre- and post-operative computed tomography and averaged to provide the sinus membrane thickness value (SM.Th). SM.Th was thicker post-operatively in the BTCP and BONE groups in comparison with the CTRL group and in comparison with pre-operative measurements. No difference was found post operatively between the BTCP and BONE groups. We found that a synthetic biomaterial (ß-TCP) induced the same degree of edema, and thus of inflammation, as natural bone. It constitutes therefore an interesting alternative to autogenous bone for maxillary sinus lifts.

[The effect of procyanidin on periprosthetic osteolysis caused by TCP wear particles in the mouse calvaria and its mechanism].

OBJECTIVE: To investigate the protective effects of procyanidin on periprosthetic osteolysis caused by tricalcium phosphate (TCP) wear particles in the mouse calvaria and its mechanism. METHODS: Forty-eight male ICR mice were randomly divided into sham group, TCP group, and procyanidin (0.2 mg/kg, 1 mg/kg, 5 mg/kg)-treated group (n=12). A periprosthetic osteolysis model in the mouse calvaria was established by implanting 30 mg of TCP wear particles onto the surface of bilateral parietal bones following removal of the periosteum. On the 2nd day post-operation, procyanidin (1 mg/kg, 5 mg/kg) was locally injected to the calvaria under the periosteum every other day. After 2 weeks, all the mice were sacrificed to collect the blood samples and the calvaria. Periprosthetic osteolysis and osteoclastogenesis in the mouse calvaria were observed by tartrate resistant acid phosphatase (TRAP) staining and HE staining. mRNA levels of TRAP, capthesin K, c-Fos and NFATc1 in the periprosthestic bone tissue were examined by real-time fluorescence quantitative PCR. Serum contents of total anti-oxidation capacity (T-AOC) and MDA, and superoxide dismutase (SOD) activity were determined by chemical colorimetry. Protein expressions of autophagic biomarkers such as Beclin-1 and LC-3 in periprosthetic bone tissue of the calvaria were examined by Western blot. RESULTS: Compared with sham group, periprosthetic osteolysis, osteoclastogenesis, mRNA levels of TRAP, capthesin K, c-Fos and NFATc1, and serum MDA content were increased significantly in the TCP group (P＜0.05), whereas serum T-AOC level and SOD activity were decreased. The protein expressions of Beclin-1 and LC-3, and the conversion of LC3-II from LC3-I were both up-regulated markedly in the mouse calvaria of TCP group (P＜0.05). Compared with TCP group, osteolysis, osteoclastogenesis, mRNA levels of TRAP, capthesin K, c-Fos and NFATc1 and serum MDA content were decreased obviously in the procyanidine group (P＜0.05), serum T-AOC level and SOD activity were increased, the expressions of Beclin-1 and LC-3, and the conversion of LC3-II from LC3-I were down-regulated obviously in the mouse calvaria of procyanidin group (P＜0.05). CONCLUSION: Procyanidin has a protective effect of periprosthetic osteolysis caused by TCP wear particles in the mouse calvaia, its mechanism may be mediated by inhibition of oxidative stress and autophagy.

A unidirectional porous beta-tricalcium phosphate material (Affinos®) for reconstruction of bony defects after excision of fibular bone for spinal surgery graft.

The aim of this study was to elucidate the bone regeneration-inducing capability of Affinos®, a newly developed, high-porosity unidirectional porous ß-TCP artificial bone. We compared the ability of Affinos® and OSferion®, a commercially available ß-TCP product, to induce bone regeneration following implantation into bony defects left after fibula harvesting for spinal fusion surgery. Study subjects underwent surgery to harvest non-vascularized fibula grafts for spinal fusion surgery and were implanted with either Affinos® (19 patients) or OSferion® (15 patients, control group) at the defect site. The minimal and mean follow up periods were 6 and 11 months after surgery, respectively. X-rays of the lower leg taken 1-2 weeks after surgery and at the final follow-up visit were used to evaluate fibular-ß-TCP continuity and fibula defect filling ratio. There was no significant difference in radiographic continuity in the fibula between the two groups. The fibula defect filling ratio for the Affinos® group decreased from 0.94 ±â€¯0.17 at 1-2 weeks to 0.77 ±â€¯0.14 at 10 months. For the OSferion® control group, the fibula defect filling ratio decreased from 0.94 ±â€¯0.14 at 1-2 weeks to 0.52 ±â€¯0.27 at final follow-up. The Affinos® group showed a significantly higher fibula defect filling ratio compared to that for the OSferion® group (p = 0.003). These results indicate that Affinos® has slow absorption rates and significant defect filling activity compared with OSferion®. Thus, Affinos® could be a suitable substitute to fill bony defects induced by fibula harvesting for spinal reconstruction surgery.

[Effects of bergapten on damages of osteocytes MLO-Y4 induced by TCP wear particles and its mechanism].

OBJECTIVE: To study the effects of bergapten (BP) on damages of osteocytes MLO-Y4 induced by tricalcium phosphate (TCP) wear particles and its mechanism. ;Methods: MLO-Y4 cells were treated with TCP wear particles for 48 h to establish the model of osteocytes injuries in vitro. The MLO-Y4 cells were divided into the following five groups: control group, TCP wear particles treated (0.1 mg/ml) group, bergapten (1, 5 and 20 µmol/L) treated groups. MTT assay and Calcein-AM staining were used to determine the viability of MLO-Y4 cells; Hoechst 33342 staining and the flow cytometry were applied to detect the apoptosis of MLO-Y4; real-time PCR was performed to examine the mRNA levels of dentin matrix protein1 (DMP-1), sclerostin (SOST) and fibroblast growth factor23 (FGF23); Western blot was performed to examine protein expressions of glucose-regulated protein 78 (GRP78), protein kinase R-like ER kinase (PERK) phospho-PERK (p-PERK), eukaryotic initiation factor 2α (eIF2α), phospho-eIF2α (p-eIF2α), activating transcription factor 4 (AFT4), C/EBP homologous protein (CHOP) and caspase-3 in MLO-Y4 cells. ;Results: Compared with control group, the MLO-Y4 viability and DMP-1 mRNA level in TCP group were decreased significantly (P＜0.05), while the percentage of apoptosis and mRNA levels of SOST and FGF23 were obviously increased (P＜0.05), and protein expressions of GRP78, AFT4, CHOP, p-PERK/PERK and p-eIF2α/eIF2α were up-regulated significantly in MLO-Y4 cells (P＜0.05). Compared with TCP group, the damages of MLO-Y4 and cell apoptosis in bergapten treated groups were decrease obviously (P＜0.05), the expressions of GRP78, AFT4, CHOP, p-PERK/PERK and p-eIF2α/eIF2α were down-regulated remarkably (P＜0.05). ;Conclusion: Bergapten can inhibit osteocytes damages induced by TCP wear particles, which may be related to reducing ER stress and PERK pathway activation.

Calcium crystal deposition diseases - beyond gout.

The most common types of calcium-containing crystals that are associated with joint and periarticular disorders are calcium pyrophosphate dihydrate (CPP) and basic calcium phosphate (BCP) crystals. Several diverse but difficult-to-treat acute and chronic arthropathies and other clinical syndromes are associated with the deposition of these crystals. Although the pathogenic mechanism of calcium crystal deposition is partially understood, much remains to be investigated, as no drug is available to prevent crystal deposition, permit crystal dissolution or specifically target the pathogenic effects that result in the clinical manifestations. In this Review, the main clinical manifestations of CPP and BCP crystal deposition are discussed, along with the biological effects of these crystals, current therapeutic approaches and future directions in therapy.

Review of potential health risks associated with nanoscopic calcium phosphate.

Calcium phosphate is applied in many products in biomedicine, but also in toothpastes and cosmetics. In some cases, it is present in nanoparticulate form, either on purpose or after degradation or mechanical abrasion. Possible concerns are related to the biological effect of such nanoparticles. A thorough literature review shows that calcium phosphate nanoparticles as such have no inherent toxicity but can lead to an increase of the intracellular calcium concentration after endosomal uptake and lysosomal degradation. However, cells are able to clear the calcium from the cytoplasm within a few hours, unless very high doses of calcium phosphate are applied. The observed cytotoxicity in some cell culture studies, mainly for unfunctionalized particles, is probably due to particle agglomeration and subsequent sedimentation onto the cell layer, leading to a very high local particle concentration, a high particle uptake, and subsequent cell death. There is no risk from an oral uptake of calcium phosphate nanoparticles due to their rapid dissolution in the stomach. The risk from dermal or mucosal uptake is very low. Calcium phosphate nanoparticles can enter the bloodstream by inhalation, but no adverse effects have been observed, except for a prolonged exposition to high particle doses. Calcium phosphate nanoparticles inside the body (e.g. after implantation or due to abrasion) do not pose a risk as they are typically resorbed and dissolved by osteoclasts and macrophages. There is no indication for a significant influence of the calcium phosphate phase or the particle shape (e.g. spherical or rod-like) on the biological response. In summary, the risk associated with an exposition to nanoparticulate calcium phosphate in doses that are usually applied in biomedicine, health care products, and cosmetics is very low and most likely not present at all. STATEMENT OF SIGNIFICANCE: Calcium phosphate is a well-established biomaterial. However, there are occasions when it occurs in a nanoparticulate form (e.g. as nanoparticle or as nanoparticulate bone substitution material) or after abrasion from a calcium phosphate-coated metal implant. In the light of the current discussion on the safety of nanoparticles, there have been concerns about potential adverse effects of nano-calcium phosphate, e.g. in a statement of a EU study group from 2016 about possible dangers associated with non-spherical nano-hydroxyapatite in cosmetics. In the US, there was a discussion in 2016 about the dangers of nano-calcium phosphate in babyfood. In this review, the potential exposition routes for nano-calcium phosphate are reviewed, with special emphasis on its application as biomaterial.

[TCP wear particles causes injury of periprosthetic osteocytes in the mouse calvaria].

OBJECTIVE: To study whether tricalcium phosphate(TCP) wear particles cause injuries of periprosthetic osteocytes in the mouse calvaria, and to explain its molecular mechanism. METHODS: Thirty six-week(ICR)male mice were randomly divided into sham group, model (TCP) group and 3-methyladenine (3-MA) group. A murine calvarial model of osteolysis was established by 30 mg of TCP wear particles implantation over the periosteum around the middle suture of calvaria in mice. On the second postoperative day, the autophagy specific inhibitor 3-MA (1.0 mg/kg) was subcutaneously injected to the calvaria in the 3-MA-treated mice every other day. After 2 weeks, blood and the calvaria were obtained. Micro-CT was used to detect bone mineral density(BMD), bone volume fraction (BVF) and porosity number. HE staining and flow cytometry were performed to analyze the viability and apoptosis of periprosthetic osteocytes. The serum levels of dentin matrix protein 1(DMP-1) and sclerostin (SOST) were determined by ELISA. The proteins expressions of DMP-1, SOST, Beclin-1 and microtuble-associated protein 1 light chain 3 (LC-3) were detected by Western blot in the calvaria osteocytes. RESULTS: Compared with the sham group, the mice in the TCP group showed that a significant decrease in the viability of periprosthetic osteocytes, but obvious increases in number of osteocytes death and osteocytes apoptosis (P<0.05), and in serum level and protein expression of SOST; significant decreases in serum level and protein expression of DMP-1 (P<0.05), and remarkable up-regulation of autophagy-related factors beclin-1 and the conversion of LC3-Ⅱ from LC3-I in the calvaria osteocytes. Compared with TCP group, the mice in the 3-MA group showed that injuries of calvaria osteocytes were obviously aggravated, and osteocytes apoptosis was significantly increased (P<0.05). CONCLUSIONS: TCP wear particles can cause injuries of periprosthetic osteocytes via activation of apoptosis and autophagy, which promotes osteolysis around the prosthesis osteolysis and joint aseptic loosening.

Hip osteonecroses treated with calcium sulfate-calcium phosphate bone graft substitute have different results according to the cause of osteonecrosis: alcohol abuse or corticosteroid-induced.

INTRODUCTION: The aim of the study was to assess the factors influencing the final results of treatment of the femoral head osteonecrosis (ONFH) with core decompression and bone substitute grafting. The special interest was focused on comparison between alcohol- and steroid-induced ONFHs. MATERIAL AND METHODS: In this prospective study, a total of 53 patients (58 hips) in the mean age of 35.5 years were included: 29 had a history of alcohol use (32 hips) and 24 of steroid use (26 hips). The mean follow-up was 4.2 years (minimum 3 years). RESULTS: At last follow-up, significant improvements were noted in the Harris Hip Score (HHS) (mean 44.0 vs 55.9 points, p < 0.00002) and VAS scores (mean 7.0 vs 5.8 points, p < 0.0002) for the whole ONFH cohort, comparing to pre-operative status. The degree of improvement did not differ between Ficat and Arlet grade II and grade III (mean 14.9 vs 6.2 points, respectively, p = 0.1). No change was found between the final and initial results in this group in the steroid group (HHS mean 42.2 vs 45.5 points, p = 0.5 and VAS mean 6.8 vs 6.5 points, p = 0.5), but the improvement was noted in the alcohol group (HHS mean 45.5 vs 64.4 points, p < 0.0001; VAS mean 7.1 vs 5.2 points, p < 0.0001) comparing to pre-operative status. CONCLUSIONS: Presented treatment of ONFH significantly improves hip function, offers pain reduction, and gives similar functional improvement for hips scoring grade II and III on the Ficat and Arlet scale. A good response to operative treatment is seen in patients with alcohol-induced ONFH, but not in those with steroid-induced ONFH.

The synthesis of amphiphilic polyethyleneimine/calcium phosphate composites for bispecific T-cell engager based immunogene therapy.

Bispecific T-cell engagers (BiTEs) are single chain variable fragments with specific structures, which could connect the surface antigen on cancer cells and CD3 ligands on T cells, and then engage the T cells for cancer immunotherapy. In this report, a novel organic-inorganic hybrid gene delivery system composed of stearic acid modified polyethyleneimine (stPEI) and calcium phosphate (CaP) was used to deliver MC.DNA into cells to express BiTE antibodies. This gene delivery system exhibits high transfection efficiency, long-term effects and low cytotoxicity in vitro. Furthermore, the gene production, anti-IGF1R/CD3 bispecific T-cell engager, exhibited a rapid redirection activity in T cells to induce cancer cell apoptosis. In summary, the results confirmed that stPEI-CaP could be an efficient gene delivery system for BiTE encoding MC.DNA based gene immunotherapy.

Crystal arthritides - gout and calcium pyrophosphate arthritis : Part 1: Epidemiology and pathophysiology.

Gout and calcium pyrophosphate deposition disease (CPPD, pseudogout) are still the most frequent inflammatory arthritides in multimorbid elderly patients. Gout and CPPD are different diseases and based on different pathophysiological principles. Gout is closely associated with the metabolic syndrome and is an independent risk factor for cardiovascular mortality. The prevalence of asymptomatic hyperuricemia is estimated to be 10-20% of adults in industrial nations and prevalence is strongly associated with age. More than 7% of persons aged over 65 years suffer from clinically manifest gout. The underlying pathophysiological principle is an imbalance between the formation and elimination of uric acid. The degradation of the purine bases adenine and guanosine to uric acid is catalysed by xanthine oxidase and genetic polymorphisms and mutations play an important role in absorption and excretion processes. Furthermore, carrier proteins, such as URAT-1 or OAT-4 also have an influence on these processes. An imbalance of the physiological processes results in the solubility product being exceeded, which in consequence leads to crystallization of urate. This induces a cascade of massive inflammatory reactions at the molecular and cellular level with the activation of cytokines. The inflammatory process can be stopped by neutrophil extracellular traps (NETs) that modulate aggregation and degradation of chemokines and cytokines and partitioning of crystallized urate against immune cells. Calcium pyrophosphate dehydrate (CPP) crystals are formed in the cartilage and CPP deposition can be found in 30% of people aged over 80 years. Inorganic pyrophosphate (PPi) is synthesized in chondrocytes and plays an important part in the formation of calcium pyrophosphate crystals. The degradation is catalyzed by inorganic pyrophosphatases. If there is dysregulation of this homeostasis more PPi is produced, which ultimately contributes to the formation of the CPP crystals.