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1.  Regulation of bone destruction in rheumatoid arthritis through RANKL-RANK pathways 
Recent studies have demonstrated that osteoclasts, the primary cells responsible for bone resorption, are mainly involved in bone and joint destruction in rheumatoid arthritis (RA) patients. Recent progress in bone cell biology has revealed the molecular mechanism of osteoclast differentiation and bone resorption by mature osteoclasts. We highlight here the potential role of the receptor activator of nuclear factor κB ligand (RANKL)-RANK pathways in bone destruction in RA and review recent clinical trials treating RA by targeting RANKL.
doi:10.5312/wjo.v4.i1.1
PMCID: PMC3557316  PMID: 23362468
Rheumatoid arthritis; Osteoclast; Receptor activator of nuclear factor κB ligand; Bisphosphonate; Denosumab
2.  Anterior muscle sparing approach for total hip arthroplasty 
World Journal of Orthopedics  2013;4(1):12-18.
The purpose of this review is to examine the validity of positive claims regarding the direct anterior approach (DAA) with a fracture table for total hip arthroplasty. Recent literature regarding the DAA was searched and specific claims investigated including improved early outcomes, speed of recovery, component placement, dislocation rates, and complication rates. Recent literature is positive regarding the effects of total hip arthroplasty with the anterior approach. While the data is not definitive at present, patients receiving the anterior approach for total hip arthroplasty tend to recover more quickly and have improved early outcomes. Component placement with the anterior approach is more often in the “safe zone” than with other approaches. Dislocation rates tend to be less than 1% with the anterior approach. Complication rates vary widely in the published literature. A possible explanation is that the variance is due to surgeon and institutional experience with the anterior approach procedure. Concerns remain regarding the “learning curve” for both surgeons and institutions. In conclusion, it is not a matter of should this approach be used, but how should it be implemented.
doi:10.5312/wjo.v4.i1.12
PMCID: PMC3557317  PMID: 23362470
Total hip arthroplasty; Anterior approach; Hip; Arthritis; Joint replacement
3.  Access related complications during anterior exposure of the lumbar spine 
World Journal of Orthopedics  2013;4(1):19-23.
The new millennium has witnessed the emergence of minimally invasive, non-posterior based surgery of the lumbar spine, in particular via lateral based methodologies to discectomy and fusion. In contrast, and perhaps for a variety of reasons, anterior motion preservation (non-fusion) technologies are playing a comparatively lesser, though incompletely defined, role at present. Lateral based motion preservation technologies await definition of their eventual role in the armamentarium of minimally invasive surgical therapies of the lumbar spine. While injury to the major vascular structures remains the most serious and feared complication of the anterior approach, this occurrence has been nearly eliminated by the use of lateral based approaches for discectomy and fusion cephalad to L5-S1. Whether anterior or lateral based, non-posterior approaches to the lumbar spine share certain access related pitfalls and complications, including damage to the urologic and neurologic structures, as well as gastrointestinal and abdominal wall issues. This review will focus on the recognition, management and prevention of these anterior and lateral access related complications.
doi:10.5312/wjo.v4.i1.19
PMCID: PMC3557318  PMID: 23362471
Anterior spinal exposure; Lumbar spine; Complications
4.  Finger movement at birth in brachial plexus birth palsy 
World Journal of Orthopedics  2013;4(1):24-28.
AIM: To investigate whether the finger movement at birth is a better predictor of the brachial plexus birth injury.
METHODS: We conducted a retrospective study reviewing pre-surgical records of 87 patients with residual obstetric brachial plexus palsy in study 1. Posterior subluxation of the humeral head (PHHA), and glenoid retroversion were measured from computed tomography or Magnetic resonance imaging, and correlated with the finger movement at birth. The study 2 consisted of 141 obstetric brachial plexus injury patients, who underwent primary surgeries and/or secondary surgery at the Texas Nerve and Paralysis Institute. Information regarding finger movement was obtained from the patient’s parent or guardian during the initial evaluation.
RESULTS: Among 87 patients, 9 (10.3%) patients who lacked finger movement at birth had a PHHA > 40%, and glenoid retroversion < -12°, whereas only 1 patient (1.1%) with finger movement had a PHHA > 40%, and retroversion < -8° in study 1. The improvement in glenohumeral deformity (PHHA, 31.8% ± 14.3%; and glenoid retroversion 22.0° ± 15.0°) was significantly higher in patients, who have not had any primary surgeries and had finger movement at birth (group 1), when compared to those patients, who had primary surgeries (nerve and muscle surgeries), and lacked finger movement at birth (group 2), (PHHA 10.7% ± 15.8%; Version -8.0° ± 8.4°, P = 0.005 and P = 0.030, respectively) in study 2. No finger movement at birth was observed in 55% of the patients in this study group.
CONCLUSION: Posterior subluxation and glenoid retroversion measurements indicated significantly severe shoulder deformities in children with finger movement at birth, in comparison with those lacked finger movement. However, the improvement after triangle tilt surgery was higher in patients who had finger movement at birth.
doi:10.5312/wjo.v4.i1.24
PMCID: PMC3557319  PMID: 23362472
Finger movement; Triangle tilt surgery; Brachial plexus birth palsy; Glenohumeral dysplasia; Pejorative sign
5.  Femoral impaction grafting 
Femoral impaction grafting is a reconstruction option applicable to both simple and complex femoral component revisions. It is one of the preferred techniques for reconstructing large femoral defects when the isthmus is non-supportive. The available level of evidence is primarily derived from case series, which shows a mean survivorship of 90.5%, with revision or re-operation as the end-point, with an average follow-up of 11 years. The rate of femoral fracture requiring re-operation or revision of the component varies between several large case series, ranging from 2.5% to 9%, with an average of 5.4%.
doi:10.5312/wjo.v4.i1.7
PMCID: PMC3557320  PMID: 23362469
Femoral impaction grafting; Femoral revision; Bone grafting; Revision total hip arthroplasty; Bone loss
6.  Single row rotator cuff repair with modified technique 
World Journal of Orthopedics  2012;3(12):199-203.
Rotator cuff tear is a common medical condition. We introduce various suture methods that can be used for arthroscopic rotator cuff repair, review the single row rotator cuff repair method with modified technique, and introduce the Ulsan-University (UU) stich. We compare the UU stitch with the modified Mason-Allen (MA) suture method. The UU stitch configuration is a simple alternative to the modified MA suture configuration for rotator cuff repair.
doi:10.5312/wjo.v3.i12.199
PMCID: PMC3557321  PMID: 23362463
Shoulder; Rotator Cuff Repair; Mason-Allen Stitch; Ulsan-University Stitch
7.  Current concepts in management of femoroacetabular impingement 
World Journal of Orthopedics  2012;3(12):204-211.
Femoroacetabular impingement (FAI) is an increasingly recognized condition, which is believed to contribute to degenerative changes of the hip. This correlation has led to a great deal of interested in diagnosis and treatment of FAI. FAI can be divided into two groups: cam and pincer type impingement. FAI can lead to chondral and labral pathologies, that if left untreated, can progress rapidly to osteoarthritis. The diagnosis of FAI involves a detailed history, physical exam, and radiographs of the pelvis. Surgical treatment is indicated in anatomic variants known to cause FAI. The primary goal of surgical treatment is to increase joint clearance and decrease destructive forces being transmitted through the joint. Treatment has been evolving rapidly over the past decade and includes three primary techniques: open surgical dislocation, mini-open, and arthroscopic surgery. Open surgical dislocation is a technique for dislocating the femoral head from the acetabulum with a low risk of avascular necrosis in order to reshape the neck or acetabular rim to improve joint clearance. Mini-open treatment is performed using the distal portion of an anterior approach to the hip to visualize and to correct acetabular and femoral head and neck junction deformities. This does not involve frank dislocation. Recently, arthroscopic treatment has gained popularity. This however does have a steep learning curve and is best done by an experienced surgeon. Short- to mid-term results have shown relatively equal success with all techniques in patients with no or only mild evidence of degenerative changes. Additionally, all techniques have demonstrated low rates of complications.
doi:10.5312/wjo.v3.i12.204
PMCID: PMC3557322  PMID: 23362464
Femoroacetabular impingement; Pincer; Cam; Mini-open; Hip arthroscopy; Surgical dislocation; Osteochondroplasty
8.  Osteoclast fusion and regulation by RANKL-dependent and independent factors 
World Journal of Orthopedics  2012;3(12):212-222.
Osteoclasts are the bone resorbing cells essential for bone remodeling. Osteoclasts are formed from hematopoietic progenitors in the monocyte/macrophage lineage. Osteoclastogenesis is composed of several steps including progenitor survival, differentiation to mono-nuclear pre-osteoclasts, fusion to multi-nuclear mature osteoclasts, and activation to bone resorbing osteoclasts. The regulation of osteoclastogenesis has been extensively studied, in which the receptor activator of NF-κB ligand (RANKL)-mediated signaling pathway and downstream transcription factors play essential roles. However, less is known about osteoclast fusion, which is a property of mature osteoclasts and is required for osteoclasts to resorb bone. Several proteins that affect cell fusion have been identified. Among them, dendritic cell-specific transmembrane protein (DC-STAMP) is directly associated to osteoclast fusion in vivo. Cytokines and factors influence osteoclast fusion through regulation of DC-STAMP. Here we review the recently discovered new factors that regulate osteoclast fusion with specific focus on DC-STAMP. A better understanding of the mechanistic basis of osteoclast fusion will lead to the development of a new therapeutic strategy for bone disorders due to elevated osteoclast bone resorption. Cell-cell fusion is essential for a variety of cellular biological processes. In mammals, there is a limited number of cell types that fuse to form multinucleated cells, such as the fusion of myoblasts for the formation of skeletal muscle and the fusion of cells of the monocyte/macrophage lineage for the formation of multinucleated osteoclasts and giant cells. In most cases, cell-cell fusion is beneficial for cells by enhancing function. Myoblast fusion increases myofiber size and diameter and thereby increases contractile strength. Multinucleated osteoclasts have far more bone resorbing activity than their mono-nuclear counterparts. Multinucleated giant cells are much more efficient in the removal of implanted materials and bacteria due to chronic infection than macrophages. Therefore, they are also called foreign-body giant cells. Cell fusion is a complicated process involving cell migration, chemotaxis, cell-cell recognition and attachment, as well as changes into a fusion-competent status. All of these steps are regulated by multiple factors. In this review, we will discuss osteoclast fusion and regulation.
doi:10.5312/wjo.v3.i12.212
PMCID: PMC3557323  PMID: 23362465
Osteoclasts; Fusion; Dendritic cell-specific transmembrane protein; Receptor activator of NF-κB ligand; Bone resorption.
9.  Male osteoporosis: A review 
World Journal of Orthopedics  2012;3(12):223-234.
Osteoporosis in men is a heterogeneous disease that has received little attention. However, one third of worldwide hip fractures occur in the male population. This problem is more prevalent in people over 70 years of age. The etiology can be idiopathic or secondary to hypogonadism, vitamin D deficiency and inadequate calcium intake, hormonal treatments for prostate cancer, use of toxic and every disease or drug use that alters bone metabolism.
Risk factors such as a previous history of fragility fracture should be assessed for the diagnosis. However, risk factors in men are very heterogeneous. There are significant differences in the pharmacological treatment of osteoporosis between men and women fundamentally due to the level of evidence in published trials supporting each treatment. New treatments will offer new therapeutic prospects. The goal of this work is a revision of the present status knowledge about male osteoporosis.
doi:10.5312/wjo.v3.i12.223
PMCID: PMC3557324  PMID: 23362466
Male osteoporosis; Skeleton involution; Etiology; Fracture risk; Osteoporosis; Non-pharmacological treatments; Pharmacological treatments
10.  Do osteoporosis-related vertebral fractures precede hip fractures? 
World Journal of Orthopedics  2012;3(12):235-238.
AIM: To evaluate the relationship between a vertebral fracture and a hip fracture in Saudi Arabians with osteoporosis.
METHODS: In this retrospective study, 154 Saudi Arabian patients with osteoporosis-related hip fractures were analyzed for the presence of a vertebral fracture. Radiographs were retrieved from the IPAC (Image Picture Archiving and Computing) System, an imaging retrieval system, and were reviewed independently by two of the authors, Abid Hussain Gullenpet, and Mir Sadat-Ali, and later reviewed jointly. Patients admitted with proximal hip fracture who were ≥ 50 years and had undergone Thoraco-lumber imaging and a dual energy X-ray absorptiometry (DEXA) scan were included in the study. Patients with a history of significant trauma to the spine and those with a malignancy or connective tissue disorder were excluded from the analysis.
RESULTS: Out of 154 patients with hip fractures, 78 had a fracture of the femoral neck while 76 had an intertrochanteric hip fracture. Of the 111 patients who were finally included in the study, after applying inclusion and exclusion criteria, 76 patients with an average age of 67.28 ± 12 years had no fractures of the spine. Thirty-five patients with an average age of 76.9 ± 14.5 years (31.53%) had a total of 49 vertebral fractures. Patients with vertebral fractures were significantly older than those without fractures P < 0.001. Overall, 24.7% of these patients had an asymptomatic vertebral fracture. Further analysis showed that 11 males (18.96%) and 24 females (45.28%) had suffered a previous asymptomatic vertebral fracture. Interestingly, all women who participated in this study and who presented with a femoral neck fracture had experienced a prior asymptomatic vertebral fracture.
CONCLUSION: We recommend that all elderly patients who go to the radiology department for a chest X-ray also have a DEXA scan and a lateral thoracic spine radiograph.
doi:10.5312/wjo.v3.i12.235
PMCID: PMC3557325  PMID: 23362467
Fragility fracture; Osteoporosis; Vertebral fractures; Hip fractures; Saudi Arabia
11.  Molecular mechanisms of triggering, amplifying and targeting RANK signaling in osteoclasts 
World Journal of Orthopedics  2012;3(11):167-174.
Osteoclast differentiation depends on receptor activator of nuclear factor-κB (RANK) signaling, which can be divided into triggering, amplifying and targeting phases based on how active the master regulator nuclear factor of activated T-cells cytoplasmic 1 (NFATc1) is. The triggering phase is characterized by immediate-early RANK signaling induced by RANK ligand (RANKL) stimulation mediated by three adaptor proteins, tumor necrosis factor receptor-associated factor 6, Grb-2-associated binder-2 and phospholipase C (PLC)γ2, leading to activation of IκB kinase, mitogen-activated protein kinases and the transcription factors nuclear factor (NF)-κB and activator protein-1 (AP-1). Mice lacking NF-κB p50/p52 or the AP-1 subunit c-Fos (encoded by Fos) exhibit severe osteopetrosis due to a differentiation block in the osteoclast lineage. The amplification phase occurs about 24 h later in a RANKL-induced osteoclastogenic culture when Ca2+ oscillation starts and the transcription factor NFATc1 is abundantly produced. In addition to Ca2+ oscillation-dependent nuclear translocation and transcriptional auto-induction of NFATc1, a Ca2+ oscillation-independent, osteoblast-dependent mechanism stabilizes NFATc1 protein in differentiating osteoclasts. Osteoclast precursors lacking PLCγ2, inositol-1,4,5-trisphosphate receptors, regulator of G-protein signaling 10, or NFATc1 show an impaired transition from the triggering to amplifying phases. The final targeting phase is mediated by activation of numerous NFATc1 target genes responsible for cell-cell fusion and regulation of bone-resorptive function. This review focuses on molecular mechanisms for each of the three phases of RANK signaling during osteoclast differentiation.
doi:10.5312/wjo.v3.i11.167
PMCID: PMC3547110  PMID: 23330071
Receptor activator of nuclear factor-κB ligand; Tumor necrosis factor receptor-associated factor 6; c-Fos; Nuclear factor of activated T-cells cytoplasmic 1; Immunoreceptor tyrosine-based activation motif; Ca2+ oscillation
12.  New roles of osteoblasts involved in osteoclast differentiation 
World Journal of Orthopedics  2012;3(11):175-181.
Bone-resorbing osteoclasts are formed from a monocyte/macrophage lineage under the strict control of bone-forming osteoblasts. So far, macrophage colony-stimulating factor (M-CSF), receptor activator of nuclear factor-κB ligand (RANKL), and osteoprotegerin (OPG) produced by osteoblasts play major roles in the regulation of osteoclast differentiation. Recent studies have shown that osteoblasts regulate osteoclastogenesis through several mechanisms independent of M-CSF, RANKL, and OPG production. Identification of osteoclast-committed precursors in vivo demonstrated that osteoblasts are involved in the distribution of osteoclast precursors in bone. Interleukin 34 (IL-34), a novel ligand for c-Fms, plays a pivotal role in maintaining the splenic reservoir of osteoclast-committed precursors in M-CSF deficient mice. IL-34 is also able to act as a substitute for osteoblast-producing M-CSF in osteoclastogenesis. Wnt5a, produced by osteoblasts, enhances osteoclast differentiation by upregulating RANK expression through activation of the non-canonical Wnt pathway. Semaphorin 3A produced by osteoblasts inhibits RANKL-induced osteoclast differentiation through the suppression of immunoreceptor tyrosine-based activation motif signals. Thus, recent findings show that osteoclast differentiation is tightly regulated by osteoblasts through several different mechanisms. These newly identified molecules are expected to be promising targets of therapeutic agents in bone-related diseases.
doi:10.5312/wjo.v3.i11.175
PMCID: PMC3547111  PMID: 23330072
Osteoclast; Osteoblast; Receptor activator of nuclear factor-κB ligand; Wnt5a; Semaphorin 3A; Interleukin 34
13.  Management of postoperative spinal infections 
World Journal of Orthopedics  2012;3(11):182-189.
Postoperative surgical site infection (SSI) is a common complication after posterior lumbar spine surgery. This review details an approach to the prevention, diagnosis and treatment of SSIs. Factors contributing to the development of a SSI can be split into three categories: (1) microbiological factors; (2) factors related to the patient and their spinal pathology; and (3) factors relating to the surgical procedure. SSI is most commonly caused by Staphylococcus aureus. The virulence of the organism causing the SSI can affect its presentation. SSI can be prevented by careful adherence to aseptic technique, prophylactic antibiotics, avoiding myonecrosis by frequently releasing retractors and preoperatively optimizing modifiable patient factors. Increasing pain is commonly the only symptom of a SSI and can lead to a delay in diagnosis. C-reactive protein and magnetic resonance imaging can help establish the diagnosis. Treatment requires acquiring intra-operative cultures to guide future antibiotic therapy and surgical debridement of all necrotic tissue. A SSI can usually be adequately treated without removing spinal instrumentation. A multidisciplinary approach to SSIs is important. It is useful to involve an infectious disease specialist and use minimum serial bactericidal titers to enhance the effectiveness of antibiotic therapy. A plastic surgeon should also be involved in those cases of severe infection that require repeat debridement and delayed closure.
doi:10.5312/wjo.v3.i11.182
PMCID: PMC3547112  PMID: 23330073
Surgical site infection; Spine surgery; Discitis; Postoperative infection
14.  Energy metabolism and the skeleton: Reciprocal interplay 
World Journal of Orthopedics  2012;3(11):190-198.
The relation between bone remodelling and energy expenditure is an intriguing, and yet unexplained, challenge of the past ten years. In fact, it was only in the last few years that the skeleton was found to function, not only in its obvious roles of body support and protection, but also as an important part of the endocrine system. In particular, bone produces different hormones, like osteocalcin (OC), which influences energy expenditure in humans. The undercarboxylated form of OC has a reduced affinity for hydroxyapatite; hence it enters the systemic circulation more easily and exerts its metabolic functions for the proliferation of pancreatic β-cells, insulin secretion, sensitivity, and glucose tolerance. Leptin, a hormone synthesized by adipocytes, also has an effect on both bone remodelling and energy expenditure; in fact it inhibits appetite through hypothalamic influence and, in bone, stimulates osteoblastic differentiation and inhibits apoptosis. Leptin and serotonin exert opposite influences on bone mass accrual, but several features suggest that they might operate in the same pathway through a sympathetic tone. Serotonin, in fact, acts via two opposite pathways in controlling bone remodelling: central and peripheral. Serotonin product by the gastrointestinal tract (95%) augments bone formation by osteoblast, whereas brain-derived serotonin influences low bone mineral density and its decrease leads to an increase in bone resorption parameters. Finally, amylin (AMY) acts as a hormone that alters physiological responses related to feeding, and plays a role as a growth factor in bone. In vitro AMY stimulates the proliferation of osteoblasts, and osteoclast differentiation. Here we summarize the evidence that links energy expenditure and bone remodelling, with particular regard to humans.
doi:10.5312/wjo.v3.i11.190
PMCID: PMC3547113  PMID: 23330074
Leptin; Osteocalcin; Serotonin; Amylin; Bone mass; Energy metabolism
15.  Pulmonary complications after spine surgery 
World Journal of Orthopedics  2012;3(10):156-161.
Spine surgery is one of the fastest growing branches of orthopedic surgery. Patients often present with a relatively high acuity and, depending on surgical approach, morbidity and mortality can be comparatively high. Among the most prevalent and most frequently fatality-bound perioperative complications are those affecting the pulmonary system; evidence of clinical or subclinical lung injury triggered by spine surgical procedures is emerging. Increasing burden of comorbidity among the patient population further increases the likelihood of adverse outcome. This review is intended to give an overview over some of the most important causes of pulmonary complications after spine surgery, their pathophysiology and possible ways to reduce harm associated with those conditions. We discuss factors surrounding surgical trauma, timing of surgery, bone marrow and debris embolization, transfusion associated lung injury, and ventilator associated lung injury.
doi:10.5312/wjo.v3.i10.156
PMCID: PMC3536857  PMID: 23293756
Spine surgery; Complications; Pulmonary; Pulmonary embolism; Transfusion-associated lung injury; Ventilator-associated lung injury
16.  Intraprosthetic fixation techniques in the treatment of periprosthetic fractures-A biomechanical study 
World Journal of Orthopedics  2012;3(10):162-166.
AIM: To develop new fixation techniques for the treatment of periprosthetic fractures using intraprosthetic screw fixation with inserted threaded liners.
METHODS: A Vancouver B1 periprosthetic fracture was simulated in femur prosthesis constructs using sawbones and cemented regular straight hip stems. Fixation was then performed with either unicortical locked-screw plating using the less invasive stabilization system-plate or with intraprosthetic screw fixation using inserted liners. Two experimental groups were formed using either prostheses made of titanium alloy or prostheses made of cobalt chrome alloy. Fixation stability was compared in an axial load-to-failure model. Drilling was performed using a specially invented prosthesis drill with constantly applied internal cooling.
RESULTS: The intraprosthetic fixation model with titanium prostheses was superior to the unicortical locked-screw fixation in all tested devices. The intraprosthetic fixation model required 10 456 N ± 1892 N for failure and the unicortical locked-screw plating required 7649 N ± 653 N (P < 0.05). There was no significant difference between the second experimental group and the control group.
CONCLUSION: Intraprosthetic screw anchorage with special threaded liners enhances the primary stability in treating periprosthetic fractures by internal fixation.
doi:10.5312/wjo.v3.i10.162
PMCID: PMC3536858  PMID: 23326763
Periprosthetic fracture; Less invasive stabilization system; Plate fixation; Intraprosthetic screw fixation; Material science; Biomechanical testing; Axial load-to-failure
17.  Strategy for prevention of hip fractures in patients with Parkinson’s disease 
World Journal of Orthopedics  2012;3(9):137-141.
Hypovitaminosis D and K due to malnutrition or sunlight deprivation, increased bone resorption due to immobilization, low bone mineral density (BMD) and an increased risk of falls may contribute to an increased risk of hip fractures in patients with Parkinson’s disease. The purpose of the present study was to clarify the efficacy of interventions intended to prevent hip fractures in elderly patients with Parkinson’s disease. PubMed was used to search the literature for randomized controlled trials (RCTs) regarding Parkinson’s disease and hip fractures. The inclusion criteria were 50 or more subjects per group and a study period of 1 year or longer. Five RCTs were identified and the relative risk and 95% confidence interval were calculated for individual RCTs. Sunlight exposure increased serum hydroxyvitamin D [25(OH)D] concentration, improved motor function, decreased bone resorption and increased BMD. Alendronate or risedronate with vitamin D supplementation increased serum 25(OH)D concentration, strongly decreased bone resorption and increased BMD. Menatetrenone (vitamin K2) decreased serum undercarboxylated osteocalcin concentration, decreased bone resorption and increased BMD. Sunlight exposure (men and women), menatetrenone (women), alendronate and risedronate with vitamin D supplementation (women) significantly reduced the incidence of hip fractures. The respective RRs (95% confidence intervals) according to the intention-to-treat analysis were 0.27 (0.08, 0.96), 0.13 (0.02, 0.97), 0.29 (0.10, 0.85) and 0.20 (0.06, 0.68). Interventions, including sunlight exposure, menatetrenone and oral bisphosphonates with vitamin D supplementation, have a protective effect against hip fractures elderly patients with Parkinson’s disease.
doi:10.5312/wjo.v3.i9.137
PMCID: PMC3502609  PMID: 23173109
Vitamin D; Vitamin K; Hip fractures; Parkinson’s disease; Mortality
18.  RANKL-RANK interaction in immune regulatory systems 
World Journal of Orthopedics  2012;3(9):142-150.
The interaction between the receptor activator of NF-κB ligand (RANKL) and its receptor RANK plays a critical role in the development and function of diverse tissues. This review summarizes the studies regarding the functions of RANKL signaling in immune regulatory systems. Previous in vitro and in vivo studies have indicated that the RANKL signal promotes the survival of dendritic cells (DCs), thereby activating the immune response. In addition, RANKL signaling to DCs in the body surface barriers controls self-tolerance and oral-tolerance through regulatory T cell functions. In addition to regulating DC functions, the RANKL and RANK interaction is critical for the development and organization of several lymphoid organs. The RANKL signal initiates the formation of clusters of lymphoid tissue inducer cells, which is crucial for lymph node organogenesis. Moreover, the RANKL-RANK interaction controls the differentiation of M cells, specialized epithelial cells in mucosal tissues, that take up and transcytose antigen particles to control the immune response to pathogens or commensal bacterium. The development of epithelial cells localized in the thymic medulla (mTECs) is also regulated by the RANKL-RANK signal. Given that the unique property of mTECs to express a wide variety of tissue-specific self-antigens is critical for the elimination of self-antigen reactive T cells in the thymus, the RANKL-RANK interaction contributes to the suppression of autoimmunity. Future studies on the roles of the RANKL-RANK system in immune regulatory functions would be informative for the development and application of inhibitors of RANKL signaling for disease treatment.
doi:10.5312/wjo.v3.i9.142
PMCID: PMC3502610  PMID: 23173110
RANKL; T cells; Dendritic cells; Thymus; Medullary thymic epithelial cells; Lymphoid tissue inducer cells; Lymph node; M cells; Peyer’s patches
19.  Injury patterns of seniors in traffic accidents: A technical and medical analysis 
World Journal of Orthopedics  2012;3(9):151-155.
AIM: To investigate the actual injury situation of seniors in traffic accidents and to evaluate the different injury patterns.
METHODS: Injury data, environmental circumstances and crash circumstances of accidents were collected shortly after the accident event at the scene. With these data, a technical and medical analysis was performed, including Injury Severity Score, Abbreviated Injury Scale and Maximum Abbreviated Injury Scale. The method of data collection is named the German In-Depth Accident Study and can be seen as representative.
RESULTS: A total of 4430 injured seniors in traffic accidents were evaluated. The incidence of sustaining severe injuries to extremities, head and maxillofacial region was significantly higher in the group of elderly people compared to a younger age (P < 0.05). The number of accident-related injuries was higher in the group of seniors compared to other groups.
CONCLUSION: Seniors are more likely to be involved in traffic injuries and to sustain serious to severe injuries compared to other groups.
doi:10.5312/wjo.v3.i9.151
PMCID: PMC3502611  PMID: 23173111
Traffic accidents; Seniors; Head injury; Injury severity score; Abbreviated injury scale
20.  Complications in the management of metastatic spinal disease 
World Journal of Orthopedics  2012;3(8):114-121.
Metastatic spine disease accounts for 10% to 30% of new cancer diagnoses annually. The most frequent presentation is axial spinal pain. No treatment has been proven to increase the life expectancy of patients with spinal metastasis. The goals of therapy are pain control and functional preservation. The most important prognostic indicator for spinal metastases is the initial functional score. Treatment is multidisciplinary, and virtually all treatment is palliative. Management is guided by three key issues; neurologic compromise, spinal instability, and individual patient factors. Site-directed radiation, with or without chemotherapy is the most commonly used treatment modality for those patients presenting with spinal pain, causative by tumours which are not impinging on neural elements. Operative intervention has, until recently been advocated for establishing a tissue diagnosis, mechanical stabilization and for reduction of tumor burden but not for a curative approach. It is treatment of choice patients with diseaseadvancement despite radiotherapy and in those with known radiotherapy-resistant tumors. Vertebral resection and anterior stabilization with methacrylate or hardware (e.g., cages) has been advocated.Surgical decompression and stabilization, however, along with radiotherapy, may provide the most promising treatment. It stabilizes the metastatic deposited areaand allows ambulation with pain relief. In general, patients who are nonambulatory at diagnosis do poorly, as do patients in whom more than one vertebra is involved. Surgical intervention is indicated in patients with radiation-resistant tumors, spinal instability, spinal compression with bone or disk fragments, progressive neurologic deterioration, previous radiation exposure, and uncertain diagnosis that requires tissue diagnosis. The main goal in the management of spinal metastatic deposits is always palliative rather than curative, with the primary aim being pain relief and improved mobility. This however, does not come without complications, regardless of the surgical intervention technique used. These complication range from the general surgical complications of bleeding, infection, damage to surrounding structures and post operative DT/PE to spinal specific complications of persistent neurologic deficit and paralysis.
doi:10.5312/wjo.v3.i8.114
PMCID: PMC3425630  PMID: 22919567
Metastases; Spine; Complications
21.  Instability after total hip arthroplasty 
World Journal of Orthopedics  2012;3(8):122-130.
Instability following total hip arthroplasty (THA) is an unfortunately frequent and serious problem that requires thorough evaluation and preoperative planning before surgical intervention. Prevention through optimal index surgery is of great importance, as the management of an unstable THA is challenging even for an experienced joints surgeon. However, even after well-planned surgery, a significant incidence of recurrent instability still exists. Non-operative management is often successful if the components are well-fixed and correctly positioned in the absence of neurocognitive disorders. If conservative management fails, surgical options include revision of malpositioned components; exchange of modular components such as the femoral head and acetabular liner; bipolar arthroplasty; tripolar arthroplasty; use of a larger femoral head; use of a constrained liner; soft tissue reinforcement and advancement of the greater trochanter.
doi:10.5312/wjo.v3.i8.122
PMCID: PMC3425631  PMID: 22919568
Instability; Total hip arthroplasty; Revision; Constrained liner; Bipolar arthroplasty; Large femoral head
22.  Hip joint center localisation: A biomechanical application to hip arthroplasty population 
World Journal of Orthopedics  2012;3(8):131-136.
AIM: To determine hip joint center (HJC) location on hip arthroplasty population comparing predictive and functional approaches with radiographic measurements.
METHODS: The distance between the HJC and the mid-pelvis was calculated and compared between the three approaches. The localisation error between the predictive and functional approach was compared using the radiographic measurements as the reference. The operated leg was compared to the non-operated leg.
RESULTS: A significant difference was found for the distance between the HJC and the mid-pelvis when comparing the predictive and functional method. The functional method leads to fewer errors. A statistical difference was found for the localization error between the predictive and functional method. The functional method is twice more precise.
CONCLUSION: Although being more individualized, the functional method improves HJC localization and should be used in three-dimensional gait analysis.
doi:10.5312/wjo.v3.i8.131
PMCID: PMC3425632  PMID: 22919569
Hip arthroplasty; Hip joint center localization; Predictive approach; Functional approach; Radiographic measurements
23.  Establishing proof of concept: Platelet-rich plasma and bone marrow aspirate concentrate may improve cartilage repair following surgical treatment for osteochondral lesions of the talus 
World Journal of Orthopedics  2012;3(7):101-108.
Osteochondral lesions of the talus are common injuries in the athletic patient. They present a challenging clinical problem as cartilage has a poor potential for healing. Current surgical treatments consist of reparative (microfracture) or replacement (autologous osteochondral graft) strategies and demonstrate good clinical outcomes at the short and medium term follow-up. Radiological findings and second-look arthroscopy however, indicate possible poor cartilage repair with evidence of fibrous infill and fissuring of the regenerative tissue following microfracture. Longer-term follow-up echoes these findings as it demonstrates a decline in clinical outcome. The nature of the cartilage repair that occurs for an osteochondral graft to become integrated with the native surround tissue is also of concern. Studies have shown evidence of poor cartilage integration, with chondrocyte death at the periphery of the graft, possibly causing cyst formation due to synovial fluid ingress. Biological adjuncts, in the form of platelet-rich plasma (PRP) and bone marrow aspirate concentrate (BMAC), have been investigated with regard to their potential in improving cartilage repair in both in vitro and in vitro settings. The in vitro literature indicates that these biological adjuncts may increase chondrocyte proliferation as well as synthetic capability, while limiting the catabolic effects of an inflammatory joint environment. These findings have been extrapolated to in vitro animal models, with results showing that both PRP and BMAC improve cartilage repair. The basic science literature therefore establishes the proof of concept that biological adjuncts may improve cartilage repair when used in conjunction with reparative and replacement treatment strategies for osteochondral lesions of the talus.
doi:10.5312/wjo.v3.i7.101
PMCID: PMC3399015  PMID: 22816065
Osteochondral lesion; Cartilage repair; Platelet-rich plasma; Bone marrow aspirate concentrate
24.  Giant pseudomeningocele after spinal surgery: A case report 
World Journal of Orthopedics  2012;3(7):109-113.
Very few reports have described giant pseudomeningoceles ≥ 8 cm in diameter. We report this case of the biggest giant pseudomeningocele at the unusual cervicothoracic level. A 59 year old man who underwent cervicothoracic laminectomy had a giant pseudomeningocele detected and the lesion gradually grew to about 15 cm in diameter by 2 years postoperatively. Cerebrospinal fluid leak closure was performed and the postoperative course was favorable. We present this case, review the literature and discuss the size and portion, mechanism of formation, symptoms and treatments of giant pseudomeningocele.
doi:10.5312/wjo.v3.i7.109
PMCID: PMC3399016  PMID: 22816066
Pseudomeningocele; Spinal surgery; Dura tear; Cerebrospinal fluid; Complication
25.  Reconstruction options for acetabular revision 
World Journal of Orthopedics  2012;3(7):95-100.
This article summarizes reconstruction options available for acetabular revision following total hip arthroplasty. A thoughtful methodology to the evaluation and treatment of patients with implant failure after joint replacement is essential to guarantee accurate diagnoses, appropriate triage to reconstruction options, and optimal clinical outcomes. In the majority of patients who undergo acetabular revision, factors such as bone loss and pelvic discontinuity provide a challenge in the selection and implementation of the proper reconstruction option. With advanced evaluation algorithms, imaging techniques, and implant designs, techniques have evolved to rebuild the compromised acetabulum at the time of revision surgery. However, clinical outcomes data for these techniques continue to lag behind the exponential increase in revision hip arthroplasty cases predicted to occur over the next several years. We encourage those involved in the treatment of patients undergoing hip replacement surgery to participate in well-designed clinical studies to enhance evidence-based knowledge regarding revision acetabular reconstruction options.
doi:10.5312/wjo.v3.i7.95
PMCID: PMC3399017  PMID: 22816064
Hip; Arthoplasty; Revision; Acetabulum; Tantalum

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