Femoral neck fracture after femoral head necrosis: a case report and review of the literature.

INTRODUCTION: Pathological fractures of the femoral neck caused by necrosis of the femoral head are extremely rare. Here, we report a rare case of bilateral femoral head osteonecrosis extending to the femoral neck, with bilateral pathological fractures of the femoral neck occurring within a short period of time. CASE REPORT: A 65-year-old male with a 25-year history of daily consumption of 750 ml of liquor, presented with right hip pain after labor for 1 month. He subsequently sustained a right femoral neck fracture without trauma and underwent a right total hip arthroplasty. Two months later, he suffered a non-traumatic left femoral neck fracture and underwent a left total hip arthroplasty. Histopathological examination revealed osteonecrosis of the femoral head and neck, along with the presence of osteoclasts and granulomatous inflammation. Bone mineral density testing also showed osteoporosis. The bilateral femoral neck fractures were ruled out to be caused by any other pathological factors. DISCUSSION: This is the first report of pathological fractures of the bilateral femoral neck caused by femoral head necrosis. During the literature review process, we found that this case conforms to the histological characteristics of rapidly destructive hip disease and analyzed the etiology of femoral head necrosis and the pathogenesis of femoral neck fractures.

Association between ACE gene I/D polymorphism and knee osteoarthritis in a Chinese population.

Osteoarthritis (OA) is a degenerative joint disease characterized by joint destruction with cartilage loss and occasional gross derangement of joint integrity. In recent years, several studies have reported the association between angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism and knee OA. However, the results were conflicting. To determine the association between ACE gene I/D polymorphism and knee OA, we conducted a hospital-based case-control study with 282 knee OA cases and 316 controls to investigate the association between ACE gene I/D polymorphism and knee OA susceptibility in a Chinese Han population. The present study found that DD genotype or D allele carriers of ACE gene I/D polymorphism increased the risk of knee OA. Stratification analyses of sex, age, and body mass index (BMI) showed significant associations amongst the groups of females, ≥55 years, and abnormal BMI. In addition, the present study made analysis between ACE I/D polymorphism and some clinical features of OA, and found DD genotype of I/D polymorphism was associated with arthralgia. Furthermore, we undertook a meta-analysis together with the present study between this single nucleotide polymorphism (SNP) and knee OA risk. This meta-analysis found that ACE gene I/D polymorphism was associated with increased risk for OA. Stratification analysis of ethnicity in this meta-analysis indicated that I/D polymorphism increased the risk of knee OA amongst the Asians and Caucasians. In conclusion, this case-control study and meta-analysis suggest that ACE gene I/D polymorphism is associated with increased risk for knee OA.

Associations between polymorphisms of the PDLIM4 gene and susceptibility to osteoporotic fracture in an elderly population of Han Chinese.

The aim of the present study was to investigate the associations between single nucleotide polymorphisms (SNPs) in the PDZ and LIM domain protein 4 (PDLIM4) gene and susceptibility to osteoporotic fracture in an elderly Han Chinese population. Seven SNPs of PDLIM4, including rs77584624, rs78418541, rs270611, rs3900945, rs77486529, rs71583465, and rs366512, were examined in 540 elderly Chinese patients with osteoporotic fractures (case group) and 540 healthy Chinese subjects (control group) using Sanger sequencing. A-allele carriers of rs270611 in PDLIM4 had a significantly high risk of osteoporotic fracture (adjusted odds ratio [OR] = 1.34; 95% confidence interval [CI]: 1.24-1.46; P<0.001). Similarly, individuals carrying the C-allele at PDLIM4 rs3900945 were predisposed to osteoporotic fracture (adjusted OR = 1.45; 95% CI: 1.05-1.25; P<0.001). In contrast, the T-allele at rs366512 appeared to be a protective genetic factor against osteoporotic fracture (adjusted OR = 0.84; 95% CI: 0.74-0.95; P<0.01). Consistently, the serum levels of N-terminal propeptide of type I procollagen (PINP) and C-telopeptide fragments of Collagen type I α1 chains (ß-CTx) were higher in A-allele carriers of rs270611 and C-allele carriers of rs3900945, while T-allele carriers of rs366512 had lower PINP and ß-CTx levels. Corresponding well with published findings, the A-allele of rs270611 and C-allele of rs3900945 were associated with reduced bone marrow density (BMD) at the fracture site, while T-allele carriers of rs366512 were shown to have normal BMD. Our study provides supportive evidence for the contribution of PDLIM4 gene polymorphisms to the susceptibility to osteoporotic fracture and suggests that rs270611 and rs3900945 are genetic risk factors, while rs366512 might be a genetic protective factor against osteoporotic fracture in elderly Han individuals.

Association of interleukin 1 gene polymorphism with intervertebral disc degeneration risk in the Chinese Han population.

Intervertebral disc degeneration (IDD) is a major pathological process implicated in low back pain and is a prerequisite to disk herniation. Interleukin-1 α (IL-1α) was thought to be involved in the pathogenesis of disc degeneration by increasing the production of extracellular matrix degradation enzymes and by inhibiting extracellular matrix synthesis. IL-1α may provide insight about the etiology of IDD. We performed a hospital-based case-control study involving 200 IDD patients and 200 controls in the Chinese Han population. Genotyping was performed using a custom-by-design 48-Plex single nucleotide polymorphism Scan™ Kit. Our study indicated that IL-1α -899C/T polymorphism could increase the risk of IDD under the homozygous, recessive, and allelic models. Subsequently, we validated this significant association by a meta-analysis. Stratification analysis of ethnicity in this meta-analysis also obtained a significant association among Asians and Caucasians. In conclusion, the present study finds that IL-1α -899C/T polymorphism is associated with the risk of IDD. Larger studies with more diverse ethnic populations are needed to confirm these results.

[Case control study on clinical effects of arthroscopic treatment for stenosing tenosynovitis of radial styloid process].

OBJECTIVE: To investigate the clinical effect of arthroscopic treatment for stenosing tenosynovitis of radial styloid process. METHODS: Ninety nine patients diagnosed as stenosing tenosynovitis of radial styloid process from August, 2009 to July, 2013 were divided into three groups, including arthroscopic treatment group(32 cases), traditional operation group (34 cases) and local blocking therapy group(33 cases). Ache, tenderness, swollen situations and movement degrees of wrist joints and thumbs were observed before treatment and one week and one month after treatment. Total effective rates were calculated. RESULTS: Pain score of the wrist and thumb in activity state was lower in arthroscopic treatment group and traditional operation group than that in local blocking therapy group one week and one month after treatment(P=0.044, 0.039). Local pain score was lower in arthroscopic treatment group and traditional operation group than that in local blocking therapy group one month after treatment(P=0.017). The total symptom score was lower in arthroscopic treatment group and traditional operation group than that in local blocking therapy group one week and one month after treatment(P=0.007, 0.015). The effective rates one week after treatment in arthroscopic treatment group, traditional operation group and local blocking therapy group were respectively 96.9%, 94.1% and 84.8%, without significant differences(P=0.213). The effective rates one month after treatment in these three groups were respectively 93.8%, 97.1% and 72.7%, with significant differences(P=0.006). CONCLUSIONS: Compared with traditional operation and local blocking therapy, arthroscopic treatment has certain effects for the treatment of stenosing tenosynovitis of radial styloid process, with less operation trauma and complications, and it is worthy of clinical promotion.

[Case-control study on superior labrum from anterior to posterior repair and biceps tenodesis for the treatment of type II SLAP injury].

OBJECTIVE: To compare clinical outcomes of superior labrum from anterior to posterior (SLAP) repair and biceps tenodesis in treating type I SLAP injury. METHODS: From March 2009 to March 2012, 38 patients with type II SLAP injury were treated with SLAP repair and biceps tenodesis, and all patients were unilateral SLAP injury. Sixteen patients treated with biceps tenodesis included 8 males and 7 females with an average age of (49.3±3.7) years old (ranged, 45 to 54); 10 cases were on the left side and 6 cases on the right side; 10 cases were caused by falling down, 2 cases were caused by throwing damage and 4 cases were caused by daily life damage; the time from injury to operation were from 3 to 8 weeks. Twenty-two patients treated with SLAP repair included 14 males and 8 females with an average age of (49.0±2.8) years old (ranged, 44 to 56); 13 cases were on the left side and 9 cases were on the right side; 14 cases were caused by falling down, 5 cases were caused by throwing damage and 3 cases were caused by daily life damage; the time from injury to operation were from 3 to 7 weeks. Preoperative, postoperative at 6 months, 1 year and 2 years' UCLA and SST score were compared between two groups. RESULTS: There was no significant differences in UCLA and SST score between two groups before operation. At 6 months after operation, UCLA and SST score in biceps tenodesis group was higher than SLAP group, and action,range of anteflexion, strength of anteflexion, degree of satisfaction in biceps tenodesis group was higher than SLAP group. There was no significant meaning in SST and UCLA score between two groups at 1 and 2 years after operation. CONCLUSION: Short-term efficacy of biceps tenodesis for SLAP injury is better than SLAP repair, but long-term efficacy is fairly.

Altered microRNA expression profile in synovial fluid from patients with knee osteoarthritis with treatment of hyaluronic acid.

OBJECTIVE: The aim of this study was to investigate the microRNA (miRNA) expression pattern in synovial fluid from patients with knee osteoarthritis (OA) after treatment with intra-articular injection of hyaluronan (HA). METHODS: Twelve OA patients were enrolled in accordance with the Kellgren-Lawrence classification of knee OA. All patients received intra-articular injection of HA once a week for 5 weeks and were evaluated with the Western Ontario and McMaster Universities (WOMAC) index at baseline. TaqMan miRNA assay profiling was performed on synovial fluid RNAs extracted from OA patients pre-injection and after 5 weeks of treatment with HA. Validation was performed using independent samples, including ten healthy controls and ten matched OA patients. RESULTS: Forty-three miRNAs (21 overexpressed miRNAs and 22 underexpressed miRNAs) were differentially expressed in OA patients before and after treatment with HA (P < 0.05, false discovery rate corrected). Further bioinformatics prediction by mirPath indicated that the differential miRNA signatures in synovial fluid extracted from the OA patients demonstrated primarily upregulation of the PI3K-Akt signaling pathway, mitogen-activated protein kinase signaling pathway, regulation of autophagy, mRNA surveillance pathway, and B cell receptor signaling pathway. In addition, TaqMan real-time reverse transcription polymerase chain reaction was performed for validation on miR-146a, miR-155, let-7a, miR-181a, miR-454, and let-7b, which were significantly changed in abundance, using an independent cohort of ten healthy controls and ten OA patients as compared with those with intra-articular injection of HA. CONCLUSION: Our results demonstrated that dysregulation in miRNAs in synovial fluid from OA patients and their affected biologic cellular processes might play important role in OA pathogenesis and HA-mediated therapeutics.

CD47 blockade inhibits tumor progression human osteosarcoma in xenograft models.

Osteosarcoma is the most common bone tumors in children and adolescents. Despite intensive chemotherapy, patients with advanced disease still have a poor prognosis, illustrating the need for alternative therapies. In this study, we explored the use of antibodies that block CD47 with a tumor growth suppressive effect on osteosarcoma. We first found that up-regulation of CD47 mRNA levels in the tumorous tissues from eight patients with osteosarcoma when compared with that in adjacent non-tumorous tissues. Further western-blot (WB) and immunohistochemistry (IHC) demonstrated that CD47 protein level was highly expressed in osteosarcoma compared to normal osteoblastic cells and adjacent non-tumorous tissues. Osteosarcoma cancer stem cell markers staining shown that the majority of CD44+ cells expressed CD47 albeit with different percentages (ranging from 80% to 99%). Furthermore, high CD47 mRNA expression levels were associated with a decreased probability of progression-free and overall survival. In addition, blockade of CD47 by specific Abs suppresses the invasive ability of osteosarcoma tumor cells and further inhibits spontaneous pulmonary metastasis of KRIB osteosarcoma cells in vivo. Finally, CD47 blockade increases macrophage phagocytosis of osteosarcoma tumor cells.In conclusion, our findings demonstrate that CD47 is a critical regulator in the metastasis of osteosarcoma and suggest that targeted inhibition of this antigen by anti-CD47 may be a novel immunotherapeutic approach in the management of this tumor.

Association of GPR126 gene polymorphism with adolescent idiopathic scoliosis in Chinese populations.

Idiopathic scoliosis is the most common pediatric spinal deformity affecting 1% to 3% of the population, and adolescent idiopathic scoliosis (AIS) accounts for approximately 80% of these cases; however, the etiology and pathogenesis of AIS are still uncertain. The current study aims to identify the relationship between G protein-coupled receptor 126 (GPR126) gene and AIS predisposition, to identify the relationship between the genotypes of the GPR126 SNPs and the clinical phenotypes of AIS. We conducted a case-control study and genotyped twenty SNPs of GPR126 gene including ten exonic SNPs and ten intronic polymorphisms in 352 Chinese sporadic AIS patients and 149 healthy controls. We provided evidence for strong association of three intronic SNPs of the GPR126 gene with AIS susceptibility: rs6570507 A > G (p =0 .0035, OR = 1.729), rs7774095 A > C (p = 0.0078, OR = 1.687), and rs7755109 A > G (p = 0.0078, OR = 1.687). However, we did not identify any significant association between ten exonic SNPs of GPR126 and AIS. Linkage disequilibrium analysis indicated that rs7774095 A > C and rs7755109 A > G could be parsed into one block. The association between the intronic haplotype and AIS was further confirmed in an independent population with 110 AIS individuals and 130 healthy controls (p = 0.046, OR = 1.680). Furthermore, molecular mechanisms underlying intronic SNP regulation of GPR126 gene were studied. Although intronic SNPs associated with AIS didn't influence GPR126 mRNA alternative splicing, there was a strong association of rs7755109 A > G with decreased GPR126 mRNA level and protein levels. Our findings indicate that genetic variants of GPR126 gene are associated with AIS susceptibility in Chinese populations. The genetic association of GPR126 gene and AIS might provide valuable insights into the pathogenesis of adolescent idiopathic scoliosis.

Altered microRNA expression profile in exosomes during osteogenic differentiation of human bone marrow-derived mesenchymal stem cells.

The physiological role of microRNAs (miRNAs) in osteoblast differentiation remains elusive. Exosomal miRNAs isolated from human bone marrow-derived mesenchymal stem cells (BMSCs) culture were profiled using miRNA arrays containing probes for 894 human matured miRNAs. Seventy-nine miRNAs (∼8.84%) could be detected in exosomes isolated from BMSC culture supernatants when normalized to endogenous control genes RNU44. Among them, nine exosomal miRNAs were up regulated and 4 miRNAs were under regulated significantly (Relative fold>2, p<0.05) when compared with the values at 0 day with maximum changes at 1 to 7 days. Five miRNAs (miR-199b, miR-218, miR-148a, miR-135b, and miR-221) were further validated and differentially expressed in the individual exosomal samples from hBMSCs cultured at different time points. Bioinformatic analysis by DIANA-mirPath demonstrated that RNA degradation, mRNA surveillance pathway, Wnt signaling pathway, RNA transport were the most prominent pathways enriched in quantiles with differential exosomal miRNA patterns related to osteogenic differentiation. These data demonstrated exosomal miRNA is a regulator of osteoblast differentiation.

[Effects of statins upon bone mineral density in postmenopausal women with hypercholesterolemia].

OBJECTIVE: To explore the effects of statins upon bone mineral density (BMD) and bone metabolic markers in postmenopausal women with hypercholesterolemia. METHODS: A prospective study was conducted for 100 women receiving treatment from January 2011 to August 2012 and meeting the inclusion criteria of osteopenia or osteoporosis with hypercholesterolemia postmenopausal. They were randomly divided into treatment group on atorvastatin 10 mg once daily and control group. The parameters of lumbar BMD, bone resorption markers of type I collagen cross-linked C-telopeptide (CTX) , bone synthesis markers procollagen type I N-terminal peptide (PINP) were compared between two groups after half a year and one year. RESULTS: There was an upward trend of lumbar spine BMD and PINP in the treatment group at half a year and one year compared with the control group. And two groups had significant difference (P < 0.05). Although two groups had no significant difference in all parameters at half a year, the values of lumbar spine BMD and PINP were higher in the treatment group at one year than the control group. Two groups had significant difference (P < 0.05). CONCLUSIONS: Statins can help maintain or increase bone mass of hypercholesterolemic menopausal women through promoting bone synthesis.

Effect of combination therapy with alginate dressing and mouse epidermal growth factor on epidermal stem cells in patients with refractory wounds.

BACKGROUND: The aim of this research was to determine the efficacy of combination therapy using an alginate dressing and mouse epidermal growth factor (mEGF) on proliferation and differentiation of epidermal stem cells (ESCs) in patients with refractory wounds. METHODS: Eighteen patients (12 males and 6 females, aged from 18 to 61 years (mean 36.4 years)) with various skin wounds, were treated by dressing changing for one month. The wounds were located in the foot (11), calf (3), thigh (2) and forearm (2). The patients were randomly divided into 3 groups: alginate dressing and mEGF (group A; n = 6), mEGF (group B; n = 6) and control (group C; n = 6). Wound closure indexes were measured at 7, 14, 21 and 28 days. Samples were harvested for pathologic examination, at 7 and 14 days following treatment. Cytokeratin 10 (CK10) and cytokeratin 15 (CK15) positive cells were evaluated using the super-sensitivity (SP) immunohistochemical staining technique. RESULTS: Wound healing was promoted in groups A and B. In group A, the wound closure index was increased significantly (P < 0.05), and in one case the maximum cure area reached 102 cm(2). Pathological examination identified a thicker epidermis, active angiogenesis and enhanced granulation in group A compared with groups B and C. Using the SP immunohistochemical staining technique, we showed that ESCs in group A were bigger in size and larger in number than in groups B and C. Overall, there was a significant difference in ESCs proliferation and differentiation between group A and group B (or C). CONCLUSIONS: Combination therapy using an alginate dressing and mEGF shows increased proliferation and differentiation of ESCs in patients with refractory wounds compared with those treated with mEGF alone.

[Application value of FS-3D-FISP sequence in the diagnosis of ankle cartilage injury].

OBJECTIVE: To compare several sequences of MRI and arthroscopy for detecting the ankle articular cartilage lesions and to evaluate the clinical outcome of special sequence of FS-3D-FISP. METHODS: Forty patients (41 ankles) with iterative ankle pain who were scheduled for arthroscopy underwent MR scanning, including FS-3D-FISP, FSE T2WI and FSE PDWI sequences. The results of each sequence were then compared with the arthroscopic findings. RESULTS: Using arthroscopic results as the standard of reference, the FS-3D-FISP images had the higher sensitivity (92.86%) than the other two sequences. The FS-3D-FISP sequence was well consistent with the result of arthroscopy. Kappa value (0.7590) was higher than the other two sequences (P < 0.01). CONCLUSION: As a favorable scanning sequence, FS-3D-FISP imaging can show the early-stage pathological changes of articular cartilage and it has an excellent correlation with the arthroscopic findings. A 3-D reconstruction is helpful to determine the location and the degree of lesion and obtain a more accurate classification to guide clinical decisions.

Functional protection of pentoxifylline against spinal cord ischemia/reperfusion injury in rabbits: necrosis and apoptosis effects.

BACKGROUND: Little is known about neuronal death mechanisms following spinal cord ischemia. The present study aimed to investigate the protective effect of pentoxifylline (PTX) against spinal cord ischemia/reperfusion (I/R) injury. METHODS: Rabbits sustained spinal cord ischemia following 45 minutes cross-clamping of the infrarenal aorta. Experimental groups were as follows: the first group of animals (sham, n = 8) underwent laparotomy alone and served as the sham group; the second group (I/R, n = 20) received carrier (3 ml saline solution) and served as the control group; the third group (PTX-A, n = 20) received PTX intravenously 10 minutes prior to ischemia; and the fourth group (PTX-B, n = 20) received PTX intravenously at the onset of reperfusion. Rabbits were evaluated for hind-limb motor function with the Tarlov scoring system at 48 hours. Serum was assayed with enzyme-linked immunosorbent assay for tumor necrosis factor alpha (TNF-alpha) and spinal cords were harvested for myeloperoxidase (MPO) activity, histopathological analysis, terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling staining, platelet/endothelial cell adhesion molecule-1 (PECAM-1) and caspase-3 immunohistochemistry, and the number of necrotic and apoptotic neuron were counted and data analyzed at 12, 24, 48 and 72 hours of reperfusion. Spinal cords were studied by electron microscopy. RESULTS: Improved Tarlov scores were seen in PTX-treated rabbits as compared with ischemic control rabbits at 48 hours. A significant reduction was found in TNF-alpha in serum, activity of MPO and immunoreactivity of the PECAM-1 and caspase-3 in PTX-treated rabbits. There were fewer apoptotic neurons than necrotic neurons (P < 0.05). A significant decrease in both necrotic and apoptotic neurons was observed in the PTX-treated groups (PTX-A and PTX-B) compared with the I/R group (P < 0.05). Both necrotic and apoptotic neurons were found with the electron microscope. CONCLUSIONS: PTX may induce protection against ischemia injury in the spinal cord, thereby preventing both necrosis and apoptosis. A major mode of cell death in spinal cord ischemia/reperfusion injury is necrosis while apoptosis is not dominant.

Comparative study on treatment of midshaft tibial fracture with expandable and interlocking intramedullary nails.

OBJECTIVE: To evaluate the clinical results of treatment of midshaft tibial fracture with expandable intramedullary nails compared with interlocking intramedullary nails. METHODS: From June 2003 to August 2005, 46 patients (27 males and 19 females, aged 20-74 years, mean=38.4 years) with midshaft tibial fracture were treated surgically in our department. The causes of fractures were traffic injury in 21 patients, fall injury in 6, tumbling injury in 11 and crushing injury in 8. According to AO/ASIF classification, Type A fracture was found in 16 patients, Type B in 11, Type C(1) in 5, and Type C(2) in 2. Open fractures were found in 12 patients, according to Gustilo classification, Type I in 9 patients and Type II in 3 patients. Based on the patients'consent, 24 patients were treated with expandable intramedullary nails (Group A) and 22 with interlocking intramedullary nails (Group B). The operation time, blood loss during operation, X-ray fluoroscopic times, hospitalization time, weight bearing time after operation, healing time of fracture and complications of all the patients were recorded. The clinical effects of all the cases were evaluated according to the criteria of Johner-Wruhs. RESULTS: All the patients were followed up for 12-34 months (mean equal to 16.2 months). The time of operation, the blood loss, X-ray fluoroscopic times, hospitalization time and healing time of fracture of Group A significantly decreased (P less than 0.05) compared with those of Group B, but the time for weight bearing after operation, the Johner-Wruhs degree of clinical effects and complications had no significant difference between Group A and Group B (P larger than 0.05). CONCLUSIONS: Expandable intramedullary nail can shorten operation time, decrease blood loss and reduce invasion, which is a safe and effective treatment method for tibial midshaft fracture.