Two-stage multi-task deep learning framework for simultaneous pelvic bone segmentation and landmark detection from CT images.

PURPOSE: Pelvic bone segmentation and landmark definition from computed tomography (CT) images are prerequisite steps for the preoperative planning of total hip arthroplasty. In clinical applications, the diseased pelvic anatomy usually degrades the accuracies of bone segmentation and landmark detection, leading to improper surgery planning and potential operative complications. METHODS: This work proposes a two-stage multi-task algorithm to improve the accuracy of pelvic bone segmentation and landmark detection, especially for the diseased cases. The two-stage framework uses a coarse-to-fine strategy which first conducts global-scale bone segmentation and landmark detection and then focuses on the important local region to further refine the accuracy. For the global stage, a dual-task network is designed to share the common features between the segmentation and detection tasks, so that the two tasks mutually reinforce each other's performance. For the local-scale segmentation, an edge-enhanced dual-task network is designed for simultaneous bone segmentation and edge detection, leading to the more accurate delineation of the acetabulum boundary. RESULTS: This method was evaluated via threefold cross-validation based on 81 CT images (including 31 diseased and 50 healthy cases). The first stage achieved DSC scores of 0.94, 0.97, and 0.97 for the sacrum, left and right hips, respectively, and an average distance error of 3.24 mm for the bone landmarks. The second stage further improved the DSC of the acetabulum by 5.42%, and this accuracy outperforms the state-of-the-arts (SOTA) methods by 0.63%. Our method also accurately segmented the diseased acetabulum boundaries. The entire workflow took ~ 10 s, which was only half of the U-Net run time. CONCLUSION: Using the multi-task networks and the coarse-to-fine strategy, this method achieved more accurate bone segmentation and landmark detection than the SOTA method, especially for diseased hip images. Our work contributes to accurate and rapid design of acetabular cup prostheses.

Deep learning-based workflow for hip joint morphometric parameter measurement from CT images.

Objective.Precise hip joint morphometry measurement from CT images is crucial for successful preoperative arthroplasty planning and biomechanical simulations. Although deep learning approaches have been applied to clinical bone surgery planning, there is still a lack of relevant research on quantifying hip joint morphometric parameters from CT images.Approach.This paper proposes a deep learning workflow for CT-based hip morphometry measurement. For the first step, a coarse-to-fine deep learning model is designed for accurate reconstruction of the hip geometry (3D bone models and key landmark points). Based on the geometric models, a robust measurement method is developed to calculate a full set of morphometric parameters, including the acetabular anteversion and inclination, the femoral neck shaft angle and the inclination, etc. Our methods were validated on two datasets with different imaging protocol parameters and further compared with the conventional 2D x-ray-based measurement method.Main results. The proposed method yields high bone segmentation accuracies (Dice coefficients of 98.18% and 97.85%, respectively) and low landmark prediction errors (1.55 mm and 1.65 mm) on both datasets. The automated measurements agree well with the radiologists' manual measurements (Pearson correlation coefficients between 0.47 and 0.99 and intraclass correlation coefficients between 0.46 and 0.98). This method provides more accurate measurements than the conventional 2D x-ray-based measurement method, reducing the error of acetabular cup size from over 2 mm to less than 1 mm. Moreover, our morphometry measurement method is robust against the error of the previous bone segmentation step. As we tested different deep learning methods for the prerequisite bone segmentation, our method produced consistent final measurement results, with only a 0.37 mm maximum inter-method difference in the cup size.Significance. This study proposes a deep learning approach with improved robustness and accuracy for pelvis arthroplasty planning.

Lateral-Opening Injection Tool Used in Percutaneous Vertebroplasty to Treat Asymptomatic Osteoporotic Vertebral Burst Fractures: A Retrospective Study.

OBJECTIVE: The adequate management of asymptomatic osteoporotic vertebral burst fractures (OVBFs) was still controversial. Percutaneous vertebroplasty (PVP) could achieve quick recovery with minor trauma, but there were certain safety problems by traditional bone cement injection method. Thus, the aim of this study was to assess the efficacy of lateral-opening injection tool used in PVP treating patients with asymptomatic OVBFs. METHODS: This was a retrospective study of OVBFs treated in our institute from March 2016 to March 2020. A total of 66 patients (mean age 72.10 ± 7.98 years, with 21 men and 45 women) who were diagnosed with acute asymptomatic OVBFs with mild spinal canal compromise were treated with PVP by using a lateral-opening injection tool. Two puncture needles were simultaneously placed transpedicularly in the fractured vertebra, and the inner core was removed, and the lateral-opening injection tool was inserted. The adjustment of lateral hole was to improve the distribution height of bone cement and avoid the entry of bone cement into the posterior wall of vertebral body. Related clinical outcomes and images were assessed, including back pain (visual analog scale [VAS]), vertebral height ratio (fractured vertebral height/average adjacent nonfractured vertebral height), kyphosis Cobb angle, union of the fractured vertebral posterior wall, distribution of bone cement, surgical data, and complications. RESULTS: The average follow-up time of all cases was 21.23 ± 9.35 months. The mean amount of bone cement was 3.28 ± 0.35 ml in the vertebrae and the mean operative time was 34.02 ± 5.23 min. There were 60 cases of bone cement that contacted the upper and lower endplates on at least one side. There was no cement leakage into the spinal canal or fracture displacement of the posterior wall of the vertebral body in all cases. The VAS scores were 3.78 ± 0.42 at 1 day postoperatively and 0.53 ± 0.40 at the last follow-up, significantly lower than 8.40 ± 0.48 preoperatively (p < 0.05). The average height ratio of anterior, middle, and posterior vertebral body after operation increased compared with that pre-operation (p < 0.05), and the postoperative kyphosis angle decreased (p < 0.05). At 6 months follow-up, there was no significant height loss of the vertebral body. Computed tomography examination 3 months postoperatively showed that the fracture of posterior vertebral wall healed well in all cases. There were seven cases of bone cement leakage without clinical symptoms and two adjacent vertebral fractures caused by falling. There were no cases of deep vein embolism, lower limb muscle atrophy, pneumonia, decubitus. CONCLUSION: The lateral opening tool can be safely and effectively used in the PVP treatment on asymptomatic OVBFs with mild spinal canal compromise.

Estrogen Regulation of the Expression of Pain Factor NGF in Rat Chondrocytes.

OBJECTIVE: Pain is the main symptom of osteoarthritis (OA). Nerve growth factor (NGF) plays a crucial role in the generation of OA pain. And estrogen-alone used resulted in a sustained joint pain reduction in postmenopausal women. So we aim to find whether estrogen alters chondrocytes' NGF level, affecting OA pain. METHODS: Primary chondrocytes and cartilage explants isolated from Sprague Dawley rat knees were cultured with physiological concentrations of estrogen (17ß-Estradiol ≥ 98%, E2), Estrogen Receptor α (ERα) inhibitor and stimulants. Then, chondrocytes NGF mRNA expression and protein release were analyzed by a quantitative real-time polymerase chain reaction (qPCR) and enzyme-linked immunosorbent assay (ELISA) respectively. Additionally, cultures were pre-incubated with MEK-ERK inhibitor to identify the signaling pathway that estrogen alters NGF mRNA and protein levels. RESULTS: We found that chondrocytes NGF expression and release were decreased by E2. E2 also reduced chondrocytes IL-1ß-stimulated or TGF-ß1-stimulated NGF expression. Phosphorylated extracellular signal-regulated kinasep1/2 (p-ERK1/2) signals were detected stronger than the control group by Western Blotting (WB). When we cultured chondrocytes with PD98059 (MEK-ERK inhibitor, PD), NGF mRNA expression was added to 1.41Ct (2.07±0.1 fold). CONCLUSION: We showed that E2 reduces chondrocytes NGF expression significantly, even after stimulation by TGF-ß1 or IL-1ß. MEK-ERK signaling is involved in this process.

The Effect of Early Limited Activity after Bipedicular Percutaneous Vertebroplasty to Treat Acute Painful Osteoporotic Vertebral Compression Fractures.

BACKGROUND: Although percutaneous vertebroplasty (PVP) can effectively relieve the pain for patients with acute osteoporotic vertebral compression fractures (OVCFs), many patients still complain of mild back pain in the early postoperative period. OBJECTIVES: The aim of this study was to assess the effect of early limited activity (LA) on prognosis after bipedicular small-cement-volume (i.e., PVP) to treat single-segment acute OVCFs. STUDY DESIGN: A prospective study and retrospective observations were performed on 125 patients with a minimum of 1 year of follow-up. SETTING: A university hospital orthopedics and pathology departments. METHODS: All patients were allocated into an LA group (n = 64) and an unlimited activity group (ULA group, n = 61). Patients in the LA group were suggested to keep time of off-bed activity < 4 hours per day in the first 3 weeks postoperatively. Patients in the ULA group did not limit activity. The demographic, clinical, and radiologic outcomes were assessed, such as pain intensity Numeric Rating Scale (NRS-11) and vertebral height ratio (i.e., fractured vertebral height/adjacent nonfractured vertebral height). Based on outcomes following surgery, all patients were classified as responders (NRS-11 score 1-day postoperation < 50% of preoperative NRS-11 score) or low responders (NRS-11 score 1-day postoperation >= 50% of preoperative NRS-11 score). RESULTS: The demographic results and complications were similar. In the LA group, NRS-11 scores at 1 and 3 months postoperation respectively were 2.23 ± 0.42 and 1.46 ± 0.40, and corresponding scores respectively were 2.85 ± 0.80 and 1.73 ± 0.77 in the ULA group, and there was a difference in the 2 groups in both time points (P < 0.05). At 12 months postoperation, anterior and middle vertebral height ratio respectively were 78.42% ± 3.52% and 82.37% ± 3.49% in the LA group, which were higher than 76.87% ± 3.68% and 81.10% ± 3.31% in the ULA group (P < 0.05). Thirty-two cases were low responders. Among those, NRS-11 scores at 1 and 3 months postoperation respectively were 2.29 ± 0.45 and 1.53 ± 0.46 in the LA group, which were lower than 3.67 ± 0.80 and 2.56 ± 0.79 in the ULA group (P < 0.05), and at 12 months postoperation, anterior vertebral height ratio was 79.81% ± 3.25% in the LA group and 75.60% ± 3.50% in the ULA group (P < 0.05). LIMITATIONS: First, some patients lacked the results of bone mineral density during follow-up; second, the limited time in our study was chosen from our previous working experience, which may lack an objective basis; third, NRS-11 is solely used as an indicator of clinical outcomes in our study; finally, our next studies can increase the sample size to improve the clinically difference. CONCLUSIONS: LA in the early period after PVP can help patients achieve more pain relief postoperatively and maintain better vertebral shape, especially for low responders. KEY WORDS: Osteoporotic vertebral compression fractures, percutaneous vertebroplasty, Numeric Rating Scale, vertebral height, responders, low responders, limited activity, complications.

Bone Mesenchymal Stem Cell-Enriched ß-Tricalcium Phosphate Scaffold Processed by the Screen-Enrich-Combine Circulating System Promotes Regeneration of Diaphyseal Bone Non-Union.

Bone non-union after fracture, considered a therapeutic challenge for orthopedics, always needs a reversion surgery, including autograft transplantation (AGT). However, adverse events related to autograft harvest cannot be ignored. Our group designed a novel system called the bone marrow stem cell Screen-Enrich-Combine Circulating System (SECCS) by seeding mesenchymal stem cells (MSCs) into ß-tricalcium phosphate (ß-TCP) during surgery to thereafter rapidly process bioactive bone implantation. In this retrospective case-control study, 30 non-union patients who accepted SECCS therapy and 20 non-union patients who accepted AGT were enrolled. By SECCS therapy, the MSC-enriched ß-TCP particles were implanted into the non-union gap. During the enrichment procedure, a significant proportion of MSCs were screened and enriched from bone marrow into porous ß-TCP particles, and the cells possessed the capacity for three-line differentiation and were CD90+/CD105+/CD34-/CD45-. Approximately 82.0±10.7% of MSCs were enriched from 60 mL bone marrow without damaging cell viability, and approximately 11,444.0±6,018 MSCs were transplanted per patient. No implant-related infections occurred in any case. After 9 months of follow-up, 27 patients (90%) in the SECCS group acquired clinical union, compared with 18 patients (90%) in the AGT group (clinical union time, P = 0.064), and postoperative radiographic union score at 9 months post-operation was similar between the two groups. In conclusion, the SECCS could concentrate a large proportion of MSCs from bone marrow to acquire enough effective cells for therapy without in vitro cell culture. Bone substitutes processed by SECCS demonstrated encouraging promotion of bone regeneration and showed a satisfactory clinical curative effect for diaphyseal bone non-union, which was non-inferior to AGT.

Therapeutic potential of hyaluronic acid/chitosan nanoparticles for the delivery of curcuminoid in knee osteoarthritis and an in vitro evaluation in chondrocytes.

Knee osteoarthritis (OA) is the main cause of leg pain in middle­aged and elderly individuals. Hyaluronic acid (HA), as well as curcuminoid, has been used in the treatment of knee OA. In the present study, HA/chitosan nanoparticles (CNPs) were prepared for the delivery of curcuminoid, in order to investigate whether HA and curcuminoid can act synergistically as a better treatment option. The knee OA model was established by the Hulth method, and a knee OA chondrocyte model was constructed by the co­induction of interleukin­1ß and tumor necrosis factor (TNF)­α. The drug loading capacity of HA/CNP for the delivery of curcuminoid was measured by an ultraviolet assay, and the cytotoxicity to chondrocytes was measured by an MTT assay. Collagen II was detected by immunofluorescence, and the expression levels of nuclear factor (NF)­κB and inflammation­related genes in cartilage tissue and chondrocytes were detected. Chondrocyte proliferation was determined by an EdU assay, and chondrocyte apoptosis was determined by flow cytometry. The Mankin pathological score of the Outerbridge classification was obtained. The results demonstrated that the optimum drug loading capacity of HA/CNP for the delivery of curcuminoid was 38.44%, with a good sustained release function. HA/CNP treatment resulted in inhibition of the NF­κB pathway, as well as the expression of matrix metalloproteinase (MMP)­1 and MMP­13, but it increased collagen II expression. HA/CNP for the delivery of curcuminoid significantly decreased the Outerbridge classification and Mankin pathological scores to close to normal until the 4th week. Furthermore, it was also observed that all the effects of HA/CNP on the delivery of curcuminoid were more prominent compared with the effects of HA or curcuminoid treatment individually. Taken together, these findings demonstrated that HA/CNP for the delivery of curcuminoid may suppress inflammation and chondrocyte apoptosis in knee OA via repression of the NF­κB pathway.

Aldehyde dehydrogenase 2 overexpression inhibits neuronal apoptosis after spinal cord ischemia/reperfusion injury.

Aldehyde dehydrogenase 2 (ALDH2) is an important factor in inhibiting oxidative stress and has been shown to protect against renal ischemia/reperfusion injury. Therefore, we hypothesized that ALDH2 could reduce spinal cord ischemia/reperfusion injury. Spinal cord ischemia/reperfusion injury was induced in rats using the modified Zivin's method of clamping the abdominal aorta. After successful model establishment, the agonist group was administered a daily consumption of 2.5% alcohol. At 7 days post-surgery, the Basso, Beattie, and Bresnahan score significantly increased in the agonist group compared with the spinal cord ischemia/reperfusion injury group. ALDH2 expression also significantly increased and the number of apoptotic cells significantly decreased in the agonist group than in the spinal cord ischemia/reperfusion injury group. Correlation analysis revealed that ALDH2 expression negatively correlated with the percentage of TUNEL-positive cells (r = -0.485, P < 0.01). In summary, increased ALDH2 expression protected the rat spinal cord against ischemia/reperfusion injury by inhibiting apoptosis.

Regulation of type II collagen, matrix metalloproteinase-13 and cell proliferation by interleukin-1ß is mediated by curcumin via inhibition of NF-κB signaling in rat chondrocytes.

Curcumin possesses strong anti-inflammatory, anti-rheumatoid and anti-oxidative activities, and has the potential to inhibit nuclear factor­κB (NF­κB) signaling. Cartilage damage in osteoarthritis (OA) is largely mediated by interleukin-1ß (IL-1ß) via activation of various transcription factors, including NF­κB and activator protein­1. The aim of the present study was to determine whether IL­1ß induces matrix metalloproteinase-13 (MMP-13) expression and inhibits type II collagen expression, as well as to examine whether cell proliferation may be inhibited by curcumin through the inhibition of NF­κB signaling. The effects of curcumin were investigated in rat articular chondrocyte cell cultures treated with IL­1ß in the presence or absence of curcumin or the NF­κB inhibitor pyrrolidine dithiocarbamate. Western blotting and reverse transcription­quantitative polymerase chain reaction were conducted to evaluate protein and mRNA expression levels of type II collagen, MMP­13, NF­κB inhibitor α (IκBα), phosphorylated­IκBα and NF­κB subunit p65/RelA. Western blotting and immunofluorescence were performed to examine the effects of curcumin on the expression, phosphorylation and nuclear translocation of NF­κB­associated proteins. The effects of curcumin on cell proliferation were evaluated by Cell Counting Kit­8 (CCK­8). Curcumin was demonstrated to inhibit the IL­1ß­induced activation of NF­κB by suppressing IκBα phosphorylation and p65/RelA nuclear translocation. These events were associated with the downregulation of MMP­13 expression and the upregulation of type II collagen expression, both of which are considered to be NF­κB targets. CCK­8 assays revealed that co­treatment with curcumin resulted in increased proliferation in IL­1ß­treated chondrocytes. These findings implicated curcumin as a naturally occurring anti­inflammatory agent for the treatment of OA via inhibition of NF­κB signaling.

Treatment of osteoporosis with eldecalcitol, a new vitamin D analog: a comprehensive review and meta-analysis of randomized clinical trials.

OBJECTIVE: Eldecalcitol (ELD) is an active form of vitamin D analog that has been approved for the treatment of osteoporosis in Japan. Over recent years, a number of multicenter, randomized controlled clinical trials have been conducted. Our goal is to comprehensively summarize the results from these studies. METHODS: We searched the databases MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials up to February 28, 2015. Each database was searched using search terms "Eldecalcitol" and "ED-71" and the results were combined. The retrieved data from three independent clinical trials included a total of 1,332 patients with osteoporosis. After the data were pooled from three trials, RevMan software was used to conduct meta-analyses to determine the effects of ELD on bone mineral density (BMD) and bone turnover marker (BTM) type I collagen amino-terminal telopeptide (NTX). Effects of ELD on some of the bone formation and bone resorption parameters, incidence of vertebral fractures at the lower spine, and health-related quality of life (HRQOL) in patients with osteoporosis were also summarized. RESULTS: With a test for overall effect Z=6.35, ELD could increase lumbar BMD (P<0.00001). In comparison with alphacalcidol, ELD suppressed the NTX level to a greater degree (test for overall effect Z=3.82,P<0.0001). ELD was also found to suppress bone alkaline phosphatase (BALP) by 19% (P<0.01) and osteocalcin by 19% (P<0.01) at the dose of 0.75 µg/day. Compared to alfacalcidol, ELD showed higher potency in suppressing serum BALP (26±9 vs 32±11 U/L,P<0.05) and amino-terminal propeptide of procollagen I (PINP) (42±15 vs 59±23 ng/mL,P<0.05). In addition, ELD was found to be more effective in reducing the incidence of vertebral fractures at the lower spine (P=0.029). CONCLUSION: Our meta-analysis showed that ELD was more potent than alphacalcidol in reducing BTM (NTX). Clinical data together suggest that ELD is efficient in treating osteoporosis by increasing lumbar BMD; suppressing BTMs, including NTX, BALP, osteocalcin, and PINP; resulting in the reduction in the incidence of vertebral fractures at the lower spine; and increasing the HRQOL in patients with osteoporosis.

Histone deacetylase inhibitors repress chondrosarcoma cell proliferation.

PURPOSE: Due to the high resistance to conventional therapy, there is still no convincingly effective treatment for chondrosarcoma. As a promising new treatment strategy, histone deacetylase inhibitors (HDACIs) have been reported to induce cell arrest, apoptosis and differentiation in some kinds of malignancies, but how HDACi exert their effects on chondrosarcoma is not well understood yet. METHODS: We investigated the effects of HDACIs trichostatin A (TSA) and sodium valproate (VPA) on chondrosarcoma cells in vitro and in vivo. The cell proliferation and cell cycle were examined in two chondrosarcoma cell lines, SW1353 and JJ012, by MTS and flow cytometry assays, respectively. The in vivo effects of HDACIs were investigated by assessing the chondrosarcoma growth in a mouse xenograft model. RESULTS: Our results showed that TSA and VPA significantly repressed the proliferation of chondrosarcoma cells in a concentration-dependent manner. Flow cytometry indicated that TSA arrested the cell cycle in G2/M phase and VPA arrested the cell cycle in G1 phase. The tumor growth was markedly suppressed in mice treated with TSA and VPA. CONCLUSIONS: HDACIs significantly repress the proliferation of chondrosarcoma cells in vitro and in vivo. Our findings imply that HDACIs may provide a novel therapeutic target for the treatment of chondrosarcoma.

Ara-C increases gastric cancer cell invasion by upregulating CD-147-MMP-2/MMP­9 via the ERK signaling pathway.

Gastric cancer cell are not particularly sensitive to Ara-C, a deoxycytidine analog that affects DNA synthesis. In the present study, AGS and MKN-45 gastric cancer cell lines were treated with Ara-C to determine its role in cell prolife-ration and apoptosis. The antiproliferative effect of Ara-C was assessed using the Cell Counting kit-8. Gelatinase zymography was utilized to detect the activity of MMP-2 and MMP-9, and an in vitro invasion assay was performed. Using RT-PCR, CD-147, MMP-2 and MPP-9 mRNA levels were assessed in AGS cells with various doses of Ara-C treatment. CD-147, MMP-2 and MMP-9 protein levels were analysed in Ara-C­treated AGS and MKN-45 cells. AGS cells were treated with or without U-0126 or siRNA-CD147 and/or Ara-C for 24 h, and an in vitro invasion assay was performed. Although low-dose Ara-C had no obvious effect on cell proliferation, it upregulated the expression of MMP-2, MMP-9 and CD-147 and ERK activation. Low-dose Ara-C increased gastric cancer cell invasion. U-0126 and siRNA-CD-147 inhibited the induction of Ara-C in gastric cancer cell invasion. Therefore, Ara-C enhances the invasiveness of gastric cancer cells by expression of CD-147 /MMP-2 and MMP-9 via the ERK signaling pathway. The results are therefore useful in the prevention of Ara-C collateral damage associated with standard, conventional protocols of chemotherapy administration.

[Experimental study on the treatment of femur head necrosis with tricalcium phosphate and platelet-rich plasma].

OBJECTIVE: To study the mechanism of compound of calcium phosphate (TCP) and platelet-rich plasma(PRP) in the treatment of femoral head necrosis. METHODS: The left femoral heads of 48 New Zealand white rabbits were frozen by liquid nitrogen as to make the model of femoral head necrosis. Twenty-four rabbits were randomly chosen as the experimental group and their femoral heads were filled with TCP/PRP. The other 24 rabbits were used as the control group and their femoral heads were filled only with TCP. They were sacrificed at 2, 4, 8, 12 weeks after operation. The specimens were examined with X-ray and histological study. RESULTS: At 2 weeks after operation, there was no significant difference in femoral head density between the two groups. Four weeks after operation, femoral head density decreased in both groups, while it decreased more in the control group. At 8, 12 weeks after operation, the density of the femoral heads in both groups increased, and it was higher in the experimental group. Histology examination showed that there was no difference between the two groups 2 weeks after operation. The head became flat at 4 weeks. Control group had more defects. At 4, 8, 12 weeks, more repairs were observed in the experimental group than that in the control group. The amount and maturity of osteogenesis in experimental group were much more greater than those in control group. Bone histomorphometry showed that the volume of the trabecular was larger in the experimental group (36.65% +/- 7.22%, 38.29% +/- 4.28%, 39.24% +/- 3.42%) than that of control group (P < 0. 05). CONCLUSION: TCP/PRP does not only provide osteoblasts scaffold, but also promotes bone formation and the head repair. TCP/PRP is a good biomaterial for the treatment of femur head necrosis.