Mid-term efficacy and safety of Escherichia coli-derived rhBMP-2/hydroxyapatite carrier in lumbar posterolateral fusion: a randomized, multicenter study.

PURPOSE: This study aimed to evaluate the mid-term efficacy and safety of Escherichia coli-derived bone morphogenetic protein-2 (E.BMP-2)/hydroxyapatite (HA) in lumbar posterolateral fusion (PLF). METHODS: This multicenter, evaluator-blinded, observational study utilized prospectively collected clinical data. We enrolled 74 patients who underwent lumbar PLF and had previously participated in the BA06-CP01 clinical study, which compared the short-term outcomes of E.BMP-2 with an auto-iliac bone graft (AIBG). Radiographs and CT scans were analyzed to evaluate fusion grade at 12, 24, and 36 months. Visual analog scale (VAS), Oswestry disability index (ODI), and Short Form-36 (SF-36) scores were measured preoperatively and at 36 months after surgery. All adverse events in this study were assessed for its relationship with E.BMP-2. RESULTS: The fusion grade of the E.BMP-2 group (4.91 ± 0.41) was superior to that of the AIBG group (4.25 ± 1.26) in CT scans at 36 months after surgery (p = 0.007). Non-union cases were 4.3% in the E.BMP-2 and 16.7% in the AIBG. Both groups showed improvement in pain VAS, ODI, and SF-36 scores when compared to the baseline values, and there were no statistically significant differences between the two groups. No treatment-related serious adverse reactions were observed in either group. No neoplasm-related adverse events occurred in the E.BMP-2 group. CONCLUSIONS: The fusion quality of E.BMP-2/HA was superior to that of AIBG. E.BMP-2/HA showed comparable mid-term outcomes to that of AIBG in terms of efficacy and safety in one-level lumbar PLF surgery.

Efficacy of the erector spinae plane block with sedation for unilateral biportal endoscopic spine surgery and comparison with other anesthetic methods.

BACKGROUND: Erector spinae plane block (ESPB) is a new regional anesthesia. Unilateral biportal endoscopic (UBE) spine surgery, a minimal invasive technique, has been performed under not only general anesthesia (GA) but regional anesthesia including spinal anesthesia (SA). The aims of this study were to evaluate the efficacy of ESPB with sedation for UBE lumbar decompression and compare it with GA and SA. METHOD: A retrospective age matched case-control study design was performed. Three groups (20 patients in each group) of patients who underwent UBE lumbar decompressions under each anesthetic method (GA, SA, or ESPB) were formed. The total anesthesia time excluding operation time, postoperative analgesia effects, hospital days, and complications related to anesthetic methods were evaluated. RESULTS: In the ESPB group, all the operations were performed without change of anesthetic methods and without anesthetic complications. But there were no anesthetic effects in the epidural space, which resulted in additional intravenous fentanyl usage. The mean of time from initiation of anesthesia to completion of surgical preparation was 23.3 ± 4.7 min in the ESPB group, which was shorter than 32.3 ± 10.8 min in the GA (p value = 0.001) or 33.3 ± 6.7 min in the SA group (p < 0.001). The proportion of patients requiring first rescue analgesia within 30 min was 30% in the ESPB group, which was lower than 85% in the GA (p < 0.001), but no significant different with 10% in the SA (p = 0.11). The mean of total hospital days in the ESPB was 3.0 ± 0.8, shorter than 3.7 ± 1.8 in the GA (p = 0.02) or 3.8 ± 1.1 in the SA group (p = 0.01). There was no case of postoperative nausea and vomiting in the ESBB even without prophylactic antiemesis. CONCLUSION: ESPB with sedation is a viable anesthetic option for UBE lumbar decompression.

Effect of Muscularity and Fatty Infiltration of Paraspinal Muscles on Outcome of Lumbar Interbody Fusion.

BACKGROUND: Lumbar paraspinal muscles play an important role in maintaining global spinal alignment and are associated with lower back pain; however, only a few studies on the effect of the paraspinal muscles on the surgical outcome exist. Therefore, this study aimed to analyze the association of preoperative muscularity and fatty infiltration (FI) of paraspinal muscles with the outcome of lumbar interbody fusion. METHODS: Postoperative clinical and radiographic outcomes were analyzed in 206 patients who underwent surgery for a degenerative lumbar disease. The preoperative diagnosis was spinal stenosis or low-grade spondylolisthesis, and the surgery performed was posterior lumbar interbody fusion or minimally invasive transforaminal lumbar interbody fusion. Indications for surgery were a complaint of severe radiating pain that did not improve with conservative treatment and neurological symptoms accompanied by lower extremity motor weakness. Patients with fractures, infections, tumors, or a history of lumbar surgery were excluded from this study. Clinical outcome measures included functional status, measured using the Oswestry disability index (ODI) and visual analog scale (VAS) score for lower back and leg pain. Other radiographic parameters included measures of spinal alignment, including lumbar lordosis, pelvic tilt, sacral slope, pelvic incidence, C7 sagittal vertical axis, and pelvic incidence-lumbar lordosis mismatch. Lumbar muscularity (LM) and FI were measured preoperatively using a lumbar magnetic resonance image (MRI). RESULTS: The high LM group showed more significant improvement in VAS score for lower back pain than the low LM group. In contrast, the VAS score for leg pain demonstrated no statistical significance. The high LM group showed more significant improvement in ODI postoperatively than the medium group. The severe FI group showed more significant improvement in ODI postoperatively, whereas the less severe FI group showed more significant improvement in the sagittal balance postoperatively. CONCLUSION: Patients with high LM and mild FI ratio observed on preoperative MRI demonstrated more favorable clinical and radiographic outcomes after lumbar interbody fusion. Therefore, preoperative paraspinal muscle condition should be considered when planning lumbar interbody fusion.

BMP-2 Induced Signaling Pathways and Phenotypes: Comparisons Between Senescent and Non-senescent Bone Marrow Mesenchymal Stem Cells.

The use of BMP-2 in orthopedic surgery is limited by uncertainty surrounding its effects on the differentiation of mesenchymal stem cells (MSCs) and how this is affected by cellular aging. This study compared the effects of recombinant human BMP-2 (rhBMP-2) on osteogenic and adipogenic differentiation between senescent and non-senescent MSCs. Senescent and non-senescent MSCs were cultured in osteogenic and adipogenic differentiation medium containing various concentrations of rhBMP-2. The phenotypes of these cells were compared by performing a calcium assay, adipogenesis assay, staining, real-time PCR, western blotting, and microarray analysis. rhBMP-2 induced osteogenic differentiation to a lesser extent (P < 0.001 and P = 0.005 for alkaline phosphatase activity and Ca2+ release) in senescent MSCs regardless of dose-dependent increase in both cells. However, the induction of adipogenic differentiation by rhBMP-2 was comparable between them. There was no difference between these two groups of cells in the adipogenesis assay (P = 0.279) and their expression levels of PPARγ were similar. Several genes such as CHRDL1, NOG, SMAD1, SMAD7, and FST encoding transcription factors were proposed to underlie the different responses of senescent and non-senescent MSCs to rhBMP-2 in microarray analyses. Furthermore, inflammatory, adipogenic, or cell death-related signaling pathways such as NF-kB or p38-MAPK pathways were upregulated by BMP-2 in senescent MSCs, whereas bone forming signaling pathways involving BMP, SMAD, and TGF- ß were upregulated in non-senescent MSCs as expected. This phenomenon explains bone forming dominance by non-senescent MSCs and possible frequent complications such as seroma, osteolysis, or neuritis in senescent MSCs during BMP-2 use in orthopedic surgery.

Differences between simple trapeziectomy and trapeziectomy with ligament reconstruction and tendon interposition for the treatment of trapeziometacarpal osteoarthritis: a systematic review and meta-analysis.

BACKGROUND: The optimal management of trapeziometacarpal osteoarthritis remains controversial. This systematic review and meta-analysis assessed the subjective and objective outcomes and complications of simple trapeziectomy (T) versus trapeziectomy with ligament reconstruction and tendon interposition (T + LRTI). METHODS: The PubMed, Embase, Web of science, and Cochrane electronic databases were searched from inception to Aug 31, 2020. Key words included "osteoarthrosis", "carpometacarpal joint", and "trapeziectomy". Randomized controlled trials (RCTs) and controlled clinical trials (CCTs) including patients treated for trapeziometacarpal osteoarthritis were included. The subjective outcomes (visual analog scale [VAS] and disabilities of the arm, shoulder, and hand questionnaire scores), objective outcomes (grip strength, tip, and key pinch strength) and complications were extracted. The methodological quality of each was assessed independently. Meta-analysis was performed for comparative trials. The protocol for this meta-analysis is available in PROSPERO (CRD42020195752). RESULTS: From the 8 included studies (7 RCTs, 1 CCT), 656 cases were divided into T (n = 325) and T + LRTI (n = 331) groups. Compared with the T group, grip and tip pinch strength was better in the T + LRTI group (SMD = - 2.74, 95% confidence interval (CI) (- 3.46 to - 2.02), P < 0.00001) and (SMD = - 0.21, 95% CI (- 0.34 to - 0.08), P = 0.002), respectively, but there were significantly more complications 3 months after operation in the T + LRTI group (RR = 0.50, 95% CI (0.31 to 0.80), P = 0.004). The VAS score (SMD = 0.33, 95% CI (- 0.39 to 1.04), P = 0.37), DASH (SMD = - 1.86, 95% CI (- 7.59 to 3.87), P = 0.52), key pinch strength (SMD = - 0.13, 95% CI (- 0.28 to 0.01), P = 0.07), and incidence of complications 1 year after operation (RR = 0.83, 95% CI (0.53-1.29), P = 0.41) were not significantly different between the two groups. CONCLUSION: While the T + LRTI group demonstrated a better effect in grip and tip pinch strength at the one-year follow-up, there was no statistical difference in key pinch strength, pain relief, and DASH. Furthermore, T + LRTI has more latrogenic injury, more short-term postoperative complications, and higher surgical costs. Considered comprehensively, if there is no special strength requirement, we recommend simple trapeziectomy.

Efficacy of various core decompression techniques versus non-operative treatment for osteonecrosis of the femoral head: a systemic review and network meta-analysis of randomized controlled trials.

BACKGROUND: Various Joint-preserving therapy (JPT) methods have been performed and tried in recent decades, but their results and efficacy were inconsistent and controversial. The purpose of this study is to evaluate its effectiveness and whether there are statistical differences in treatment between different interventions based on published RCT studies. METHODS: Following the PRISMA-NMA checklist, Medline, EMBASE, Web of Science, and Cochrane Library databases were searched and collected related RCT studies. The sources were searched from inception up to October 30, 2020. The primary outcomes including the rate of radiographic progression and conversion to THA and the secondary outcome -Harris Hip Scores (HHS) were extracted and compared in a Network meta-analysis. RESULTS: Seventeen RCT studies involving 784 patients (918 hips) with seven interventions including CD (core decompression), CD + BG (bone graft), CD + TI (tantalum rod implantation), CD + CT (Cell therapy), CD + BG + CT, VBG (vascularized bone graft), and nonsurgical or conservative treatment for ONFH were evaluated. In the radiographic progression results, CD + CT showed a relatively better result than CD, CD + BG and non-surgical treatment, the surface under the cumulative ranking curve (SUCRA) plot displayed that CD + CT (96.4%) was the best, followed by CD (64.1%).In conversion to THA results, there were no significant differences between the JPT methods and non-surgical treatment. In HHS, there was also no significant difference, other than CD + BG showed a statistical difference than non-surgical treatment only in terms of Cis, but the SUCRA was highest in non-surgical treatment (80.5%) followed by CD + CT (72.8%). CONCLUSIONS: This Net-work meta-analysis demonstrated that there was no statistical difference in the outcome of radiographic progression and conversion to THA, also in HHS, other than CD + CT showed a relatively superior result in radiographic progression than nonsurgical treatment, namely, it's maybe an effective method for delaying disease progression or reducing disease development based on current evidence.

Coexisting Spine Lesions on Whole Spine T2 Sagittal MRI in Evaluating Spinal Degenerative Disease.

BACKGROUND: Studies have reported on the usefulness of whole spine magnetic resonance imaging (MRI) in evaluating specific diseases such as spinal tuberculosis, spinal trauma, spondyloarthropathies, and multiple myeloma. In studies concerning degenerative spinal disease, sample sizes were small and some did not provide information on how symptomatic coexisting lesions were treated. We evaluated the types and prevalence of coexisting spine lesions found on whole spine T2 sagittal screening performed at the time of routine cervical and lumbar spine MRI and evaluated the efficacy of such screening in degenerative diseases of the cervical and lumbar spine. METHODS: We reviewed 1,757 and 2,266 consecutive cases where whole spine T2 sagittal screening had been performed with routine cervical and lumbar spine MRI, respectively, in patients with cervical and lumbar spinal degenerative diseases. Coexisting spine lesions were documented and statistical analysis was performed to investigate significant differences according to sex, age, and initial diagnosis. Electronic medical records were reviewed to determine whether additional interventions were necessary following such findings. RESULTS: We reviewed 1,252 and 1,689 consecutive cases of routine cervical and lumbar spine MRI respectively, with whole spine T2 sagittal screening. Of the 1,252, 419 (33.5%) patients with cervical spinal degenerative disease had coexisting lesions in the thoracolumbar spine. Patients with ligament ossification disease of the cervical spine showed a higher prevalence of coexisting spine lesions. Sixty of the 419 (14.3%) patients with coexisting spine lesions warranted additional intervention or surgical treatment. Four hundred and eighty-one of 1,689 (28.5%) patients with lumbar degenerative disease had coexisting spine lesions in the cervicothoracic spine. Forty-eight of the 481 (10.0%) patients with coexisting spine lesions warranted additional intervention. In both patient groups, older patients showed a significantly higher prevalence of coexisting spine lesions than younger patients. CONCLUSION: Considering the minimal extra time and cost in performing whole spine screening, its application to routine spine MRI can be considered in evaluating cervical and lumbar spinal degenerative diseases.

The toxicological effect of 4-week repeated intravenous injection of activin a/BMP-2 chimera and 2-week recovery study in Beagle dog.

The purposes of this study was to determine the toxicological effect of repeated intravenous administration of Activin A/BMP-2 chimera (AB204) in beagle dogs for a long period of four weeks and evaluate two-week recovery. AB204 was administered at doses of 0.08, 0.16, or 0.32 mg/kg/day to three male and three female beagle dogs for 4 weeks as the experimental group. For the control group, sterile saline was administered to three male and three female beagle dogs. For the two-week recovery test, two male and two female beagle dogs were randomly selected from the control group and the 0.32 mg/kg/day administered experimental group. General symptoms, body weight, food consumption, ophthalmological examination, electrocardiogram, urinalysis, hematology and blood biochemistry, organ weights, autopsy, and histopathological examination were observed or conducted. No animals died. There was no significant difference in any parameter evaluated between the experimental group and the control group. Histopathological examination revealed compound inflammation at the administration site in both the experimental group and the control group. The inflammation disappeared during the two-week recovery. These results indicated that repetitive intravenous injection of AB204 in beagle dog for a long period of four weeks did not show any toxicity. Therefore, no observed adverse effects level (NOAEL) of AB204 was 0.32 mg/kg/day in big animal model.

Madelung Disease Epidemiology and Clinical Characteristics: a Systemic Review.

BACKGROUND: Madelung disease is a rare lipid metabolic disorder, and most cases are sporadically reported. There are currently no systematic reviews summarizing the epidemiological and clinical characteristics of this disease. The purpose of the current article is to extract and analyze the existing evidence concerning Madelung disease derived from case series in order to provide adequate treatments for patients based on a more comprehensive understanding of the disease. METHODS: PubMed, Embase, and Web of Science databases were queried for relevant articles using the search terms "Madelung disease," "multiple symmetric lipomatosis," "Launois-Bensaude syndrome" and synonyms until Aug 31,2020. Data statistics of Madelung disease epidemiology and clinical characteristics are summarized in different tables or charts with Microsoft Office software. RESULTS: Patients exhibiting Madelung disease were mostly located in Europe, although some records existed in Asia as well. Average patient age was between 45 and 65 years old. Type I was the most common form of the disease, and the neck was the most common location for tumors. Madelung disease is associated with various metabolic disorders, and hematoma and seroma were the most common complications. Overall recurrence rate was 18.3%, with similar recurrence rates after lipectomy and liposuction. Fewer complications occurred after liposuction compared with lipectomy, but relapse was more common after liposuction. CONCLUSION: Madelung disease consists of specific epidemiological and clinical characteristics, knowledge of which can be helpful for diagnosis and cognition. Lipectomy and liposuction are considered to be the most effective treatment methods for Madelung disease; however, choice of surgery should be based on comprehensive consideration of the disease, such as severity, mass location, and patient expectations. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Macular Pigment Optical Density in the Korean Population: a Cross Sectional Study.

BACKGROUND: To evaluate the macular pigment optical density (MPOD) with age in the Korean population using the Macular Pigment Screener II (MPSII®). METHODS: One hundred and twenty-six eyes were retrospectively reviewed. MPOD was measured using MPSII®, which uses a heterochromatic flicker photometry method, and the estimated values were analyzed. Spearman's correlation test was used to evaluate correlations between MPOD and age. The association between MPOD and age was determined using a simple linear regression analysis. MPODs among the four groups were compared via the post hoc analysis with Bonferroni correction, MPODs between the age-related macular degeneration (AMD) group and aged-matched healthy subjects were compared via the Mann-Whitney U test. Other risk factors for AMD were identified via a logistic regression analysis. RESULTS: Estimated MPOD decreased significantly with increasing age in the general population. In the simple regression analysis, a statistically significant linear regression model was observed, and the estimated values of MPOD decreased by ?0.005 as age increased by 1 year. Aged (> 50 years) showed lower MPOD than younger (30-49 years) subjects. But, in the healthy population, the estimated MPOD values exhibited a decreasing trend with age, but there were no significant differences according to age, after excluding patients with AMD. MPOD was significantly lower in patients with AMD than in aged healthy controls. Furthermore, hypertension, dyslipidemia, and smoking were identified as risk factors for AMD. CONCLUSION: MPOD measured with MPSII® reflects the MP density in healthy individuals and patients with dry AMD. Aging was not significantly associated with low MPOD in healthy population, but the presence of dry AMD was significantly associated with low MPOD. Then, low MPOD may be a risk factor for development of dry AMD. Furthermore, routine screening with MPS II® for ages 50 and older is thought to help detect early low MPOD and identify individuals who should take supplements.

Umbilical Cord Mesenchymal Stem Cell-Derived Nanovesicles Potentiate the Bone-Formation Efficacy of Bone Morphogenetic Protein 2.

Recombinant human bone morphogenetic protein 2 (rhBMP-2) is one of the most potent osteogenic factors used to treat bone loss. However, at higher doses, rhBMP-2 does not necessarily increase bone formation but rather increases the incidence of adverse side effects. Here, we investigated whether umbilical cord mesenchymal stem cell (UCMSC)-derived nanovesicles (NVs) further increase the in vivo bone formation at high doses of rhBMP-2. In the presence of UCMSC-derived NVs, proliferation, migration, and tube formation of human umbilical vein endothelial cells were stimulated in vitro. Furthermore, migration and osteogenesis of human bone marrow-derived mesenchymal stem cells were stimulated. To examine the efficacy of UCMSC-derived NVs on in vivo bone formation, collagen sponges soaked with rhBMP-2 and UCMSC-derived NVs were used in athymic nude mice with calvarial defects. At a high rhBMP-2 dosage (500 ng/mL), UCMSC-derived NVs significantly promoted bone formation in calvarial defects; however, the UCMSC-derived NVs alone did not induce in vivo bone formation. Our results indicate that UCMSC-derived NVs can potentiate the bone formation efficacy of rhBMP-2 at a high dosage.

Escherichia coli BMP-2 showed comparable osteoinductivity with Chinese hamster ovary derived BMP-2 with demineralized bone matrix as carrier.

Escherichia coli bone morphogenetic protein-2 (ErhBMP-2) had a larger yield but less osteoinductivity than Chinese hamster ovary cell bone morphogenetic protein-2 (CrhBMP-2). Since the release profile of rhBMP-2 affects its osteoinductivity, an appropriate carrier could improve the effect of ErhBMP-2. Demineralized bone matrix (DBM) was one of the most widely used bone substitutes, but few studies evaluated the osteoinductivity of ErhBMP-2 while it was carried by DBM. Therefore, we compared the osteoinductivity of ErhBMP-2 with CrhBMP-2 with DBM as the carrier of each. In vitro results showed ErhBMP-2 had slightly less osteoinductivity than CrhBMP-2. However, with DBM as the carrier, ErhBMP-2 induced significantly more bone regeneration in rat calvaria defects. Therefore, ErhBMP-2 might have comparable osteoinductivity with CrhBMP-2 while carried by DBM.

Assessment of patient-reported outcomes (PROs): treatment satisfaction, medication adherence, and quality of life (QoL) and the associated factors in postmenopausal osteoporosis (PMO) patients in Korea.

Patient-reported outcomes (PROs) provide practical guides for treatment; however, studies that have evaluated PROs of women in Korea with postmenopausal osteoporosis (PMO) are lacking. This cross-sectional, multi-center (29 nationwide hospitals) study, performed from March 2013 to July 2014, aimed to assess PROs related to treatment satisfaction, medication adherence, and quality of life (QoL) in Korean PMO women using osteoporosis medication for prevention/treatment. Patient demographics, clinical characteristics, treatment patterns, PROs, and experience using medication were collected. The 14-item Treatment Satisfaction Questionnaire for Medication (TSQM) (score-range, 0-100; domains: effectiveness, side effects, convenience, global satisfaction), Osteoporosis-Specific Morisky Medication Adherence Scale (OS-MMAS) (score-range, 0-8), and EuroQol-5 dimensions questionnaire (index score range, - 0.22 to 1.0; EuroQol visual analog scale score range, 0-100) were used. To investigate factors associated with PROs, linear (treatment satisfaction/QoL) or logistic (medication adherence) regression analyses were conducted. A total of 1804 patients (age, 62 years) were investigated; 60.1% used bisphosphonate, with the majority (67.2%) using weekly medication, 27.8% used daily hormone replacement therapy, and 12.1% used daily selective estrogen receptor modulator. Several patients reported gastrointestinal (GI) events (31.6%) and dental visits due to problems (24.1%) while using medication. Factors associated with the highest OS-MMAS domain scores were convenience and global satisfaction. GI events were associated with non-adherence. TSQM scores for effectiveness, side effects, and GI risk factors were significantly associated with QoL. Our study elaborately assessed the factors associated with PROs of Korean PMO women. Based on our findings, appropriate treatment-related adjustments such as frequency/choice of medications and GI risk management may improve PROs.

Effect of medications on prevention of secondary osteoporotic vertebral compression fracture, non-vertebral fracture, and discontinuation due to adverse events: a meta-analysis of randomized controlled trials.

BACKGROUND: Bone loss with aging and menopause increases the risk of fragile vertebral fracture, osteoporotic vertebral compression fracture (OVCF). The fracture causes severe pain, impedes respiratory function, lower the quality of life, and increases the risk of new fractures and deaths. Various medications have been prescribed to prevent a secondary fracture, but few study summarized their effects. Therefore, we investigated their effects on preventing subsequent OVCF via meta-analyses of randomized controlled trials. METHODS: Electronic databases, including MEDLINE, EMBASE, CENTRAL, and Web of Science were searched for published randomized controlled trials from June 2015 to June 2019. The trials that recruited participants with at least one OVCF were included. We assessed the risk of bias of every study, estimated relative risk ratio of secondary OVCF, non-vertebral fracture, gastrointestinal complaints and discontinuation due to adverse events. Finally, we evaluated the quality of evidence. RESULTS: Forty-one articles were included. Moderate to high quality evidence proved the effectiveness of zoledronate (Relative Risk, RR: 0.34; 95% CI, 0.17-0.69, p = 0.003), alendronate (RR: 0.54; 95% CI: 0.43-0.68; p < 0.0001), risedronate (RR: 0.61; 95% CI: 0.51-0.73; p < 0.0001), etidronate (RR, 0.50; 95% CI, 0.29-0.87, p < 0.01), ibandronate (RR: 0.52; 95% CI: 0.38-0.71; p < 0.0001), parathyroid hormone (RR: 0.31; 95% CI: 0.23-0.41; p < 0.0001), denosumab (RR, 0.41; 95% CI, 0.29-0.57; p < 0.0001) and selective estrogen receptor modulators (Raloxifene, RR: 0.58; 95% CI: 0.44-0.76; p < 0.0001; Bazedoxifene, RR: 0.66; 95% CI: 0.53-0.82; p = 0.0002) in preventing secondary fractures. Moderate quality evidence proved romosozumab had better effect than alendronate (Romosozumab vs. alendronate, RR: 0.64; 95% CI: 0.49-0.84; p = 0.001) and high quality evidence proved that teriparatide had better effect than risedronate (risedronate vs. teriparatide, RR: 1.98; 95% CI: 1.44-2.70; p < 0.0001). CONCLUSION: Zoledronate, alendronate, risedronate, etidronate, ibandronate, parathyroid hormone, denosumab and selective estrogen receptor modulators had significant secondary prevention effects on OVCF. Moderate quality evidence proved romosozumab had better effect than alendronate. High quality evidence proved PTH had better effect than risedronate, but with higher risk of adverse events.

In vitro and in vivo evaluation of osteoinductivity and bone fusion ability of an activin a/BMP2 chimera (AB204): a comparison study between AB204 and rhBMP-2.

This study compared osteoinductivity and osteogenic capacity between AB204 and rhBMP-2 using hMSCs in vitro and a beagle's posterolateral spinal fusion model. Cultured hMSCs were treated with AB204 or rhBMP-2 with low to high doses. Three male beagles were performed posterolateral spinal fusion with biphasic calcium phosphate (2 ml) + AB204 or rhBMP-2 (20, 50 or 200 µg). They were euthanized after 8 weeks. The fusion rate and bone formation of spine samples were examined. AB204 had higher alkaline phosphatase activity, mineralization and osteogenic-related gene expression than rhBMP-2. Fusion rates in all rhBMP-2 groups were 0. They were 100% for 50 µg and 200 µg AB204 groups. Therefore, AB204 showed higher osteogenicity than rhBMP-2. It could be a better bone graft substitute.

Anti-adhesive effect of poloxamer-based thermo-sensitive sol-gel in rabbit laminectomy model.

Poloxamer-based thermo-sensitive sol-gel has been developed to reduce the incidence of postoperative scar formation at the laminectomy site. The purpose of this study was to evaluate the anti-adhesive effect of poloxamer based thermo-sensitive sol-gel compared to hyaluronate based solution after laminectomy, using a rabbit model. A thermo-sensitive anti-adhesive with a property of sol-gel transition was manufactured by a physical mixture of Poloxamer188/407, Chitosan and Gelatin. The viscosity in different temperatures was assessed. 72 adult New Zealand rabbits underwent lumbar laminectomy and were randomly divided into experimental (treated with the newly developed agent), positive (treated with hyaluronate based solution), and negative control groups. Each group was subdivided into 1 and 4-week subgroups. Gross and histological evaluations were performed to assess the extent of epidural adhesion. The experimental group showed significantly higher viscosity compared to the positive control group and showed a significant increase of viscosity as the temperature increased. Gross evaluation showed no statistically significant differences between the 1- and 4-week subgroups. However, histologic evaluation showed significant differences both in 1- and 4-week subgroups. Although the 4-week histologic results of the experimental and the positive control subgroups showed no significant difference, both subgroups revealed higher value compared to the negative control subgroup with regard to the ratio of adhesion less than 50 %. The new poloxamer based thermo-sensitive agent showed superior efficacy over the hyaluronate based agent at 1 week postoperatively. At 4 weeks postoperatively, there were no statistically significant differences between the two agents, although both showed efficacy over the sham group.

Effect of Brace to Osteoporotic Vertebral Fracture: a Meta-Analysis.

Brace is one of the most commonly used interventions to manage osteoporotic vertebral fracture. However, its authentic effectiveness remains unclear. The aim of this study was to investigate the efficacy of brace in patients with osteoporotic vertebral fractures. We conducted a literature review and meta-analysis following the guideline and handbook of the Cochrane collaboration. Ten published articles were included in this study and data from 4 randomized controlled trials were analyzed. Low quality evidence proved using Spinomed brace could bring large and significant beneficial effect to patients with sub-acute osteoporotic vertebral fractures. Very low quality evidence proved no significant difference between Spinomed orthosis, rigid brace and soft brace when they were used in patients with acute fractures. Therefore, it might be applicable to recommend middle term use of Spinomed orthosis to patients with subacute fracture. In addition, this study emphasized the need for high quality randomized controlled trials.

The effects of a single intravenous injection of novel activin A/BMP-2 (AB204) on toxicity and the respiratory and central nervous systems.

The purpose of this study was to determine the effects of a single intravenous injection of a novel osteoinductive material, activin A/BMP-2 (AB204), to rodents on toxicity and their respiratory functions and central nervous system (CNS). A single intravenous injection of AB204 was given to Sprague-Dawley (SD) rats in doses of 0, 0.625, 2.5 and 10 mg/kg to observe the mortality rate, the general symptoms for 14 days. The experimental groups were also given 0.2, 0.4 and 0.8 mg/kg of AB204, respectively, and the respiration rate, the tidal volume and the minute volume were measured for 240 min. The experimental groups of imprinting control region (ICR) mice were given a single intravenous injection of 0.2, 0.4 and 0.8 mg/kg of AB204, respectively. Their body temperature was taken and general behaviors were observed to evaluate the effect of AB204 on the CNS for 240 min. The study on toxicity of a single intravenous injection found no death or abnormal symptoms, abnormal findings from autopsy, or abnormal body weight gain or loss in all the experimental groups. No abnormal variation associated with the test substance was observed in the respiration rate, the tidal volume, the minute volume, body temperature or the general behaviors. On the basis of these results, the approximate lethal dose of AB204 for a single intravenous injection exceeds 10 mg/kg for SD rats and a single intravenous injection of ≤0.8 mg/kg AB204 has no effect on their respiratory system for SD rat and no effect on their CNS for ICR mice.

The inhibitory effect of zoledronate on early-stage osteoinduction by recombinant human bone morphogenetic protein 2 in an osteoporosis model.

This study evaluated the effect of the combined treatment of intravenous zoledronic acid (ZA, 0.08 mg/kg) and rhBMP-2 (5 µg) on osteogenesis in a calvarial defect model of ovariectomized SD rats. New bone formation was evaluated 4 or 8 weeks after calvarial defect implantation using micro-CT and histology. Micro-CT results revealed that the rhBMP-2 group showed significantly higher calvarial defect coverage ratio compared with the ZA + rhBMP-2 group at 4 weeks. In addition, bone formation indices were significantly lower in ZA + rhBMP-2 group when compared with the rhBMP-2 group after 4 weeks, which indicates a negative effect of ZA on the initial bone formation and the bone quality. At 8 weeks, the negative effect induced by ZA treatment was alleviated as time passed. Histological examination showed similar results to the micro-CT measurements. In conclusion, although ZA treatment lowered the new bone formation induced by rhBMP-2 initially, as time passed, the negative effect was decreased.