One-Stage Total Hip Arthroplasty with Modular S-ROM Stem for Patients with Bilateral Crowe Type IV Developmental Dysplasia.

OBJECTIVE: The aim of the present paper was to evaluate the results of one-stage total hip arthroplasty (THA) for patients with bilateral Crowe type IV developmental dysplasia of the hip (DDH). METHODS: Data for 58 patients (116 hips) with bilateral Crowe type IV DDH who had one-stage THA performed by the same surgeon during the period of April 2008 to February 2019 were retrospectively reviewed. The mean age of the patients was 37.3 years; 5 were men and 53 were women. All patients underwent THA through the posterolateral approach using the Pinnacle acetabular cup, a ceramic-on-ceramic bearing, and the modular S-ROM stem. Subtrochanteric shortening osteotomy was performed on 86/116 hips. Intraoperative conditions were recorded. Radiographic and functional outcomes were evaluated, and complications were recorded. RESULTS: All patients were followed up for an average of 71.3 ± 37.6 months (range, 12-140). The mean operative time was 276.5 ± 57.9 min (range, 175-540). The mean intraoperative blood loss was 933.6 ± 400.8 mL (range, 300-2000). The mean transfusion requirement was 1778 ± 798.0 mL (range, 575-4550). The mean length of hospital stay was 8.6 ± 3.7 days (range, 5-22). At the final follow-up, no loosening of acetabular and femoral components was observed. No osteolysis and heterotopic ossification occurred. The mean Harris hip scores were improved from 55.4 ± 14.3 preoperatively to 91.3 ± 4.2 postoperatively (P < 0.001) In terms of complications, no perioperative deaths were recorded. Deep vein thrombosis occurred in 1 hip, with no pulmonary embolism. Intraoperative femur fracture occurred in 3 hips, nerve injury in 1 hip, and leg length discrepancy in 1 patient. Postoperative dislocation occurred in 5 hips and nonunion in 1 hip. CONCLUSION: Our data demonstrated that one-stage bilateral THA for bilateral Crowe type IV DDH is feasible and can effectively restore hip function.

Three-dimensional distribution of cystic lesions in osteonecrosis of the femoral head.

PURPOSE: The aim of this study was to investigate the location characteristics of cystic lesions in a three-dimensional context and discuss the mechanism of formation. METHODS: A total of 155 femoral head computed tomography images from 94 patients diagnosed with stage II and III osteonecrosis of the femoral head were retrospectively reviewed. Three-dimensional structures of the femoral head including the cystic lesions and necrotic area were reconstructed. We divided each femoral head into eight regions to observe the positional relationship of the cystic lesions, normal areas, and necrotic areas. RESULTS: The regional distribution revealed 14 (13%), 35 (32%), 9 (8%), 25 (23%), 6 (6%), 15 (14%), 4 (4%), and 0 (0%) cystic lesions in regions Ⅰ, Ⅱ, Ⅲ, Ⅳ, Ⅴ, Ⅵ, Ⅶ, and Ⅷ, respectively. The anteromedial zone, A (Ⅰ â€‹+ â€‹â…¢), contained 22% of the lesions, anterolateral zone, B (Ⅱ â€‹+ â€‹â…£), contained 54%, posteromedial zone, C (Ⅴ +Ⅶ), contained 9% of the lesions, and posterolateral zone, D (Ⅵ â€‹+ â€‹â…§), contained 15% of the lesions. Most of the cystic lesions (78%) were located between the normal and necrotic areas; 18% of cystic lesions were in the necrotic area â€‹and 4% were in the normal area. CONCLUSIONS: Cystic lesions most often occur at the junction of the necrotic â€‹and normal areas and are most commonly located in the anterolateral femoral head, which is similar to the distribution of the stress concentration region. THE TRANSLATIONAL POTENTIAL OF THIS ARTICLE: The study showed the location characteristics of cystic lesions in osteonecrosis of femoral head, which suggested that the formation of cystic lesions may be related to stress and could accelerate the collapse of femoral head. The results can support further research on cystic lesions and provide a reference for doctors' treatment strategies for patients with osteonecrosis of femoral head.

Saline Solution Lavage and Reaspiration for Culture with a Blood Culture System Is a Feasible Method for Diagnosing Periprosthetic Joint Infection in Patients with Insufficient Synovial Fluid.

BACKGROUND: Culture is a key step for detecting periprosthetic joint infection (PJI) before surgery. However, using saline solution lavage and reaspiration in patients with insufficient synovial fluid remains controversial. The objective of this study was to evaluate this technique. METHODS: This study included 286 aspirations performed by 1 surgeon in patients after total joint arthroplasty during the period of April 2015 to August 2018. If >1.0 mL of synovial fluid was obtained, then we directly used the fluid for culture. For cases in which ≤1.0 mL of synovial fluid was aspirated, 10 mL of saline solution was injected and the joint was reaspirated for culture. The samples were injected into 2 blood culture bottles for anaerobic bacterial culture and aerobic bacterial and fungal culture, and were inoculated for 14 days in a BACT/ALERT 3D blood culture system unless microorganisms were detected. A PJI diagnosis was determined on the basis of the modified Musculoskeletal Infection Society criteria. RESULTS: Saline solution lavage and reaspiration were used in 82 cases (47 PJI cases and 35 non-PJI cases), while direct aspiration was used in 204 cases (99 PJI cases and 105 non-PJI cases). The overall rate for the use of saline solution lavage was 28.7% (82 of 286). Among knee cases, the saline solution lavage rate was 15.0% (21 of 140), and among hip cases, the rate was 41.8% (61 of 146). The overall sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of culture were 0.795 (95% confidence interval [CI], 0.720 to 0.857), 0.957 (95% CI, 0.909 to 0.984), 0.951 (95% CI, 0.896 to 0.982), and 0.817 (95% CI, 0.749 to 0.873); and for "dry tap" cases, they were 0.851 (95% CI, 0.717 to 0.938), 0.857 (95% CI, 0.697 to 0.952), 0.889 (95% CI, 0.760 to 0.963), and 0.811 (95% CI, 0.648 to 0.920), respectively. CONCLUSIONS: Saline solution lavage and reaspiration for culture in patients with insufficient synovial fluid before surgery may be a sound practice. LEVEL OF EVIDENCE: Diagnostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Aligned fibers enhance nerve guide conduits when bridging peripheral nerve defects focused on early repair stage.

Nerve conduits enhance nerve regeneration in the repair of long-distance peripheral nerve defects. To help optimize the effectiveness of nerve conduits for nerve repair, we developed a multi-step electrospinning process for constructing nerve guide conduits with aligned nanofibers. The alignment of the nerve guide conduits was characterized by scanning electron microscopy and fast Fourier transform. The mechanical performance of the nerve guide conduits was assessed by testing for tensile strength and compression resistance. The biological performance of the aligned fibers was examined using Schwann cells, PC12 cells and dorsal root ganglia in vitro. Immunohistochemistry was performed for the Schwann cell marker S100 and for the neurofilament protein NF200 in PC12 cells and dorsal root ganglia. In the in vivo experiment, a 1.5-cm defect model of the right sciatic nerve in adult female Sprague-Dawley rats was produced and bridged with an aligned nerve guide conduit. Hematoxylin-eosin staining and immunohistochemistry were used to observe the expression of ATF3 and cleaved caspase-3 in the regenerating matrix. The recovery of motor function was evaluated using the static sciatic nerve index. The number of myelinated fibers, axon diameter, fiber diameter, and myelin thickness in the distal nerve were observed by electron microscopy. Gastrocnemius muscle mass ratio was also determined. The analyses revealed that aligned nanofiber nerve guide conduits have good mechanical properties and can induce Schwann cells, PC12 cells and dorsal root ganglia to aggregate along the length of the nanofibers, and promote the growth of longer axons in the latter two (neuronal) cell types. The aligned fiber nerve conduits increased the expression of ATF3 and cleaved caspase-3 at the middle of the regenerative matrix and at the distal nerve segment, improved sciatic nerve function, increased muscle mass of the gastrocnemius muscle, and enhanced recovery of distal nerve ultrastructure. Collectively, the results show that highly aligned nanofibers improve the performance of the nerve conduit bridge, and enhance its effectiveness in repairing peripheral nerve defects.

Stem cell therapy for treating osteonecrosis of the femoral head: From clinical applications to related basic research.

Osteonecrosis of the femoral head (ONFH) is a refractory disease that is associated with collapse of the femoral head, with a risk of hip arthroplasty in younger populations. Thus, there has been an increased focus on early interventions for ONFH that aim to preserve the native articulation. Stem cell therapy is a promising treatment, and an increasing number of recent studies have focused on this topic. Many clinical studies have reported positive outcomes of stem cell therapy for the treatment of ONFH. To improve the therapeutic effects of this approach, many related basic research studies have also been performed. However, some issues must be further explored, such as the appropriate patient selection procedure, the optimal stem cell selection protocol, the ideal injection number, and the safety of stem cell therapy. The purpose of this review is to summarize the available clinical studies and basic research related to stem cell therapy for ONFH.

Differentiation of adipose-derived stem cells into Schwann cell-like cells through intermittent induction: potential advantage of cellular transient memory function.

BACKGROUND: Peripheral nerve injury (PNI) is a worldwide issue associated with severe social and economic burden. Autologous nerve grafting, the gold standard treatment for peripheral nerve defects, still has a number of technical limitations. Tissue engineering technology is a novel therapeutic strategy, and mesenchymal stromal cells (MSCs) are promising seed cells for nerve tissue engineering. However, the efficiency of traditional methods for inducing the differentiation of MSCs to Schwann cell-like cells (SCLCs) remains unsatisfactory. METHODS: Here, we propose an intermittent induction method with alternate use of complete and incomplete induction medium to induce differentiation of adipose-derived stem cells (ASCs) to SCLCs. The time dependence of traditional induction methods and the efficiency of the intermittent induction method and traditional induction methods were evaluated and compared using immunocytochemistry, quantitative reverse transcription polymerase chain reaction (qRT-PCR), enzyme-linked immunosorbent assay (ELISA), and co-culture with the dorsal root ganglion (DRG) in vitro. Cell transplantation was used to compare the effects of the traditional induction method and the intermittent induction method in repairing sciatic nerve defects in vivo. RESULTS: The results of the present study indicated that the intermittent induction method is more efficient than traditional methods for inducing ASCs to differentiate into SCLCs. In addition, SCLCs induced by this method were closer to mature myelinating Schwann cells and were capable of secreting neurotrophins and promoting DRG axon regeneration in vitro. Furthermore, SCLCs induced by the intermittent induction method could repair sciatic nerve defects in rats by cell transplantation in vivo more effectively than those produced by traditional methods. CONCLUSION: Intermittent induction represents a novel strategy for obtaining seed cells for use in nerve tissue engineering.

Centrifugation May Change the Results of Leukocyte Esterase Strip Testing in the Diagnosis of Periprosthetic Joint Infection.

BACKGROUND: Centrifugation is used to remove the color interference by erythrocytes in blood-synovial fluid samples before leukocyte esterase (LE) strip testing. However, the impact of centrifugation requires further study. METHODS: From April 2016 to October 2017, 133 (53 infected and 80 noninfected) patients were included in this study. One drop of synovial fluid was applied to LE strips before and after centrifugation in 110 cases. The other 23 cases could not be read without centrifugation due to the color disturbance caused by blood contamination. The results were recorded after approximately 3 minutes according to different color grades on a color chart, including grade 3 (++), grade 2 (+), and grade 1 (others). RESULTS: After centrifugation, almost every sample was lighter in color than before. Although most results changed inconspicuously and remained in the same grade, 18.6% (8/43) and 17.9% (12/67) of cases were downgraded in the periprosthetic joint infection and non-periprosthetic joint infection groups, respectively. Before centrifugation, when grade 3 (++) was used as the positive threshold, the sensitivity and specificity were 97.7% (86.2%-99.9%) and 100% (94.3%-100%), respectively. After centrifugation, when grades 2 and 3 (+ and ++, respectively) were used as the positive threshold, the sensitivity and specificity were 92.5% (80.9%-97.6%) and 100% (94.3%-100%), respectively. CONCLUSIONS: The influence of centrifugation should be considered when interpreting the LE strip test results. For cases without centrifugation, we recommended using ++ as the positive threshold, while for cases using centrifugation, the threshold should be reduced to both ++ and +.

Extracellular matrix from human umbilical cord-derived mesenchymal stem cells as a scaffold for peripheral nerve regeneration.

The extracellular matrix, which includes collagens, laminin, or fibronectin, plays an important role in peripheral nerve regeneration. Recently, a Schwann cell-derived extracellular matrix with classical biomaterial was used to mimic the neural niche. However, extensive clinical use of Schwann cells remains limited because of the limited origin, loss of an autologous nerve, and extended in vitro culture times. In the present study, human umbilical cord-derived mesenchymal stem cells (hUCMSCs), which are easily accessible and more proliferative than Schwann cells, were used to prepare an extracellular matrix. We identified the morphology and function of hUCMSCs and investigated their effect on peripheral nerve regeneration. Compared with a non-coated dish tissue culture, the hUCMSC-derived extracellular matrix enhanced Schwann cell proliferation, upregulated gene and protein expression levels of brain-derived neurotrophic factor, glial cell-derived neurotrophic factor, and vascular endothelial growth factor in Schwann cells, and enhanced neurite outgrowth from dorsal root ganglion neurons. These findings suggest that the hUCMSC-derived extracellular matrix promotes peripheral nerve repair and can be used as a basis for the rational design of engineered neural niches.

A radiographic simulation study of fixed superior pubic ramus fractures with retrograde screw insertion.

OBJECTIVES: The study's aim is to calculate the parameters for retrograde insertion points for fixed superior pubic ramus fractures. METHODS: From the pubic symphysis, diameter and length of the screw were measured, as well as the angle between the screw axis and the 3 planes. RESULTS: When the diameter was fixed at 4.5 mm, the maximum lengths were 125 mm and 119 mm. CONCLUSIONS: When the fracture occurs in Zone I, the penetration point could be selected in the pubic symphysis pubis angle to ensure that medial fracture fragments have sufficient screw channel length.

Use of electrospinning to construct biomaterials for peripheral nerve regeneration.

A number of limitations associated with the use of hollow nerve guidance conduits (NGCs) require further discussion. Most importantly, the functional recovery outcomes after the placement of hollow NGCs are poor even after the successful bridging of peripheral nerve injuries. However, nerve regeneration scaffolds built using electric spinning have several advantages that may improve functional recovery. Thus, the present study summarizes recent developments in this area, including the key cells that are combined with the scaffold and associated with nerve regeneration, the structure and configuration of the electrospinning design (which determines the performance of the electrospinning scaffold), the materials the electrospinning fibers are composed of, and the methods used to control the morphology of a single fiber. Additionally, this study also discusses the processes underlying peripheral nerve regeneration. The primary goals of the present review were to evaluate and consolidate the findings of studies that used scaffolding biomaterials built by electrospinning used for peripheral nerve regeneration support. It is amazing that the field of peripheral nerve regeneration continues to consistently produce such a wide variety of innovative techniques and novel types of equipment, because the introduction of every new process creates an opportunity for advances in materials for nerve repair.

Identification of Changes in Gene expression of rats after Sensory and Motor Nerves Injury.

Wallerian degeneration is a sequence of events in the distal stump of axotomized nerves. Despite large numbers of researches concentrating on WD, the biological mechanism still remains unclear. Hence we constructed a rat model with both motor and sensory nerves injury and then conducted a RNA-seq analysis. Here the rats were divided into the 4 following groups: normal motor nerves (NMN), injured motor nerves (IMN), normal sensory nerves (NSN) and injured sensory nerves (ISN). The transcriptomes of rats were sequenced by the Illumina HiSeq. The differentially expressed genes (DEGs) of 4 combinations including NMN vs. IMN, NSN vs. ISN, NMN vs. NSN and IMN vs. ISN were identified respectively. For the above 4 combinations, we identified 1666, 1514, 95 and 17 DEGs. We found that NMN vs. IMN shared the most common genes with NSN vs. ISN indicating common mechanisms between motor nerves injury and sensory nerves injury. At last, we performed an enrichment analysis and observed that the DEGs of NMN vs IMN and NSN vs. ISN were significantly associated with binding and activity, immune response, biosynthesis, metabolism and development. We hope our study may shed light on the molecular mechanisms of nerves degeneration and regeneration during WD.

Comparisons of Emu Necrotic Femoral Head Micro Structure Repaired in Two Different Methods.

OBJECTIVE: To compare emu necrotic femoral head micro structure repaired in two different methods. METHODS: Fifteen adult emus were divided into 3 groups (all n=5), and the right femoral head was selected to research. The first group was the control group; in the second group, femoral head necrosis was made by cryogen with liquid nitrogen; and in the third group, femoral head necrosis was made by local pure ethanol injection. Right femurs were taken for micro CT examination,then femoral head micro structures were compared among these three groups. RESULTS: No infection or unexpected death was found in all groups. Compared with normal group, necrotic femoral heads in cryogen group showed that bone mineral density significantly reduced after repaire (P=0.015), trabecular space significantly reduced (P=0.001), bone volume fraction significantly enlarged (P=0.036), bone surface/volume fraction (P=0.032) and trabecular numbers (P=0.002) significantly enlarged; trabecular thickness showed no significant difference (P=0.060). Compared with control group, necrotic femoral heads in ethanol group showed that bone mineral density significantly enlarged after repaire (P=0.001), trabecular thickness (P=0.003) and bone surface/volume fraction (P=0.022) significantly enlarged, trabecular space (P=0.001) and bone volume fraction (P=0.001) significantly reduced; the trabecular numbers showed no significant difference (P=0.143). Compared with ethanol group, necrotic femoral heads in cryogen group showed significant lower bone mineral density after repair (P=0.001), significantly lower bone volume fraction (P=0.001), significantly lower trabecular thickness (P=0.001), significantly higher bone surface/volume fraction (P=0.022) and higher trabecular numbers (P=0.003); the trabecular space showed no significant difference (P=0.398). CONCLUSION: Different repair methods make reconstructed femoral head weight bearing area have different bone structure and bone mineral density, along with different bone trabecular quality.

MicroRNAs' Involvement in Osteoarthritis and the Prospects for Treatments.

Osteoarthritis (OA) is a chronic disease and its etiology is complex. With increasing OA incidence, more and more people are facing heavy financial and social burdens from the disease. Genetics-related aspects of OA pathogenesis are not well understood. Recent reports have examined the molecular mechanisms and genes related to OA. It has been realized that genetic changes in articular cartilage and bone may contribute to OA's development. Osteoclasts, osteoblasts, osteocytes, and chondrocytes in joints must express appropriate genes to achieve tissue homeostasis, and errors in this can cause OA. MicroRNAs (miRNAs) are small noncoding RNAs that have been discovered to be overarching regulators of gene expression. Their ability to repress many target genes and their target-binding specificity indicate a complex network of interactions, which is still being defined. Many studies have focused on the role of miRNAs in bone and cartilage and have identified numbers of miRNAs that play important roles in regulating bone and cartilage homeostasis. Those miRNAs may also be involved in the pathology of OA, which is the focus of this review. Future studies on the role of miRNAs in OA will provide important clues leading to a better understanding of the mechanism(s) of OA and, more particularly, to the development of therapeutic targets for OA.

Application of bone marrow mesenchymal stem cells to the treatment of osteonecrosis of the femoral head.

Osteonecrosis of the femoral head (ONFH) is a type of common and refractory disease in the orthopedic clinic that is primarily caused by a partial obstruction of the blood supply to the femoral head, resulting in a series of pathological processes. Mesenchymal stem cells (MSCs) comprise a mixture of various stem cells in myeloid tissue with multipotential differentiation capacity. They can differentiate into bone cells under specific conditions and can be used to treat ONFH through cell transplantation. This review summarizes research on MSCs in the field of ONFH in recent years, reveals the inner characteristics of MSCs, describes their potential to treat osteonecrosis disease, and analyzes the existing challenges of using MSCs in clinical applications.

Mesenchymal Stem Cells for Treating Articular Cartilage Defects and Osteoarthritis.

Articular cartilage damage and osteoarthritis are the most common joint diseases. Joints are prone to damage caused by sports injuries or aging, and such damage regularly progresses to more serious joint disorders, including osteoarthritis, which is a degenerative disease characterized by the thinning and eventual wearing out of articular cartilage, ultimately leading to joint destruction. Osteoarthritis affects millions of people worldwide. Current approaches to repair of articular cartilage damage include mosaicplasty, microfracture, and injection of autologous chondrocytes. These treatments relieve pain and improve joint function, but the long-term results are unsatisfactory. The long-term success of cartilage repair depends on development of regenerative methodologies that restore articular cartilage to a near-native state. Two promising approaches are (i) implantation of engineered constructs of mesenchymal stem cell (MSC)-seeded scaffolds, and (ii) delivery of an appropriate population of MSCs by direct intra-articular injection. MSCs may be used as trophic producers of bioactive factors initiating regenerative activities in a defective joint. Current challenges in MSC therapy are the need to overcome current limitations in cartilage cell purity and to in vitro engineer tissue structures exhibiting the required biomechanical properties. This review outlines the current status of MSCs used in cartilage tissue engineering and in cell therapy seeking to repair articular cartilage defects and related problems. MSC-based technologies show promise when used to repair cartilage defects in joints.

Effect of cervus and cucumis peptides on osteoblast activity and fracture healing in osteoporotic bone.

Osteoporosis is associated with delayed and/or reduced fracture healing. As cervus and cucumis are the traditional Chinese treatments for rheumatoid arthritis, we investigated the effect of supplementation of these peptides (CCP) on bone fracture healing in ovariectomized (OVX) osteoporotic rats in vitro and in vivo. CCP enhanced osteoblast proliferation and increased alkaline phosphatase activity, matrix mineralization, and expression of runt-related transcription factor 2 (Runx2), bone morphogenetic protein 4 (BMP4), and osteopontin. In vivo, female Sprague-Dawley rats underwent ovariectomy and the right femora were fractured and fixed by intramedullary nailing 3 months later. Rats received intraperitoneal injections of either CCP (1.67 mg/kg) or physiological saline every day for 30 days. Fracture healing and callus formation were evaluated by radiography, micro-CT, biomechanical testing, and histology. At 12 weeks after fracture, calluses in CCP-treated bones showed significantly higher torsional strength and greater stiffness than control-treated bones. Bones in CCP-treated rats reunified and were thoroughly remodeled, while two saline-treated rats showed no bone union and incomplete remodeling. Taken together, these results indicate that use of CCP after fracture in osteoporotic rats accelerates mineralization and osteogenesis and improves fracture healing.

[Study of animal model of osteonecrosis induced by local ethanol injection in emu].

OBJECTIVE: To establish a new animal model of osteonecrosis of the femoral head by local ethanol injection in emu. METHODS: Eight milliliter ethanol was injected slowly to the operated femoral head with customized probe in twenty adult male emus. Postoperatively, hip magnetic resonance imaging was performed at 1, 4, 8, 12 weeks. After emus were sacrificed, the femurs were collected for micro-computed tomography and histological analysis. RESULTS: No emu demonstrated signs of infection or died unexpectedly. Magnetic resonance imaging examination showed broad edema at proximal femur at 1(th) week, and the edema decreased with time, till local edema at femoral head at the 12(th) week. Histological images showed human-like osteonecrotic changes with active bone repair. There were significant differences in trabecular structure and bone mineral density between the operated and intact femoral heads. No collapse was found 6 months after the operation. CONCLUSIONS: This emu model of femoral head osteonecrosis by local ethanol injection can progress to early stage osteonecrosis. The different repair methods may have certain correlation with the results of osteonecrosis of the femoral heads.

Bone microstructure and regional distribution of osteoblast and osteoclast activity in the osteonecrotic femoral head.

OBJECTIVE: To detect and compare the bone microstructure and osteoblast and osteoclast activity in different regions of human osteonecrotic femoral heads. METHODS: Osteonecrotic femoral heads were obtained from 10 patients (6 males, 4 females; Ficat IV) undergoing total hip arthroplasty between 2011 and 2013. The samples were divided into subchondral bone, necrotic, sclerotic, and healthy regions based on micro-computed tomography (CT) images. The bone microstructure, micromechanics, and osteoblast and osteoclast activity were assessed using micro-CT, pathology, immunohistochemistry, nanoindentation, reverse transcription polymerase chain reaction (RT-PCR), tartrate-resistant acid phosphatase staining and Western blotting. RESULTS: (1) The spatial structure of the bone trabeculae differed markedly in the various regions of the osteonecrotic femoral heads. (2) The elastic modulus and hardness of the bone trabeculae in the healthy and necrotic regions did not differ significantly (P >0.05). (3) The subchondral bone and necrotic region were positive on TRAP staining, while the other regions were negative. (4) On immunohistochemical staining, RANK and RANKL staining intensities were increased significantly in the subchondral bone and necrotic region compared with the healthy region, while RUNX2 and BMP2 staining intensities were increased significantly in the sclerotic region compared with the necrotic region. (5) OPG, RANK, RANKL, RUNX2, BMP2, and BMP7 protein levels were greater in the necrotic and sclerotic region than in subchondral bone and the healthy region. CONCLUSION: The micromechanical properties of bone trabeculae in the necrotic region did not differ significantly from the healthy region. During the progress of osteonecrosis, the bone structure changed markedly. Osteoclast activity increased in subchondral bone and the necrotic region while osteoblast activity increased in the sclerotic region. We speculate that the altered osteoblast and osteoclast activity leads to a reduction in macroscopic mechanical strength.

Basic research and clinical applications of bisphosphonates in bone disease: what have we learned over the last 40 years?

It is now 40 years since bisphosphonates (BPs) were first used in the clinic. So, it is timely to provide a brief review of what we have learned about these agents in bone disease. BPs are bone-specific and have been classified into two major groups on the basis of their distinct molecular modes of action: amino-BPs and non-amino-BPs. The amino-BPs are more potent and they inhibit farnesyl pyrophosphate synthase (FPPS), a key enzyme of the mavalonate/cholesterol biosynthetic pathway, while the non-amino-BPs inhibit osteoclast activity, by incorporation into non-hydrolyzable analogs of ATP. Both amino-BPs and non-amino-BPs can protect osteoblasts and osteocytes against apoptosis. The BPs are widely used in the clinic to treat various diseases characterized by excessive bone resorption, including osteoporosis, myeloma, bone metastasis, Legg-Perthes disease, malignant hyperparathyroidism, and other conditions featuring bone fragility. This review provides insights into some of the adverse effects of BPs, such as gastric irritation, osteonecrosis of the jaw, atypical femoral fractures, esophageal cancer, atrial fibrillation, and ocular inflammation. In conclusion, this review covers the biochemical and molecular mechanisms of action of BPs in bone, particularly the discovery that BPs have direct anti-apoptotic effects on osteoblasts and osteocytes, and the current situation of BP use in the clinic.

[Combined effects of NEL-like type 1 gene and zoledronate in preventing collapse of the femoral head].

OBJECTIVE: To determine if combined therapy consisting of NEL-like type 1 gene (NELL-1) and zoledronate can prevent the collapse of the femoral head and stimulate the new bone formation in an animal model of osteonecrosis. METHODS: Ischemic osteonecrosis was surgically induced in 24 SD rats, whicih were equally randomly divided into three groups: combination group, treated with both NELL-1 and zoledronate; sham operation group; and placebo group, treated with normal saline solution. The animals were killed 5 weeks after surgery. Radiography, MicroCT, histology, and immunohistochemistry were performed to analyze the results. RESULTS: Morphologically, the femoral head was at good shape in the combination group, while mildly flattened femoral head was seen in the placebo group. No heterotopic ossifications were observed in each group. MicroCT assessment showed significantly higher total and bone mineral volume in the combination group than in the placebo group (P<0.01), whereas no such significant difference was found when compared with the sham operation group(P>0.05). Histological assessment showed more active osteoblast activity and reduced osteoclast activity in the combination group compared with placebo group. CONCLUSION: A combination of NELL-1 and zoledronate can decrease the femoral head deformity while stimulating bone formation in a traumatic rat osteonecrois model, showing a potential to reverse the osteonecrosis.