Introduction The prevalence of patients with osteoporosis continues to increase in aging societies, including Japan. The first choice for managing osteoporotic vertebral compression fracture (OVF) is conservative treatment. Failure in conservative treatment for OVF may lead to non-union or vertebral collapse, resulting in neurological deficit and subsequently requiring surgical intervention. This multicenter nationwide study in Japan was conducted to comprehensively understand the outcomes of surgical treatments for OVF non-union. Methods This multicenter, retrospective study included 403 patients (89 males, 314 females, mean age 73.8 ± 7.8 years, mean follow-up 3.9 ± 1.7 years) with neurological deficit due to vertebral collapse or non-union after OVF at T10-L5 who underwent fusion surgery with a minimum 1-year follow-up. Radiological and clinical outcomes at baseline and at the final follow-up (FU) were evaluated. Results OVF was present at a thoracolumbar junction such as T12 (124 patients) and L1 (117 patients). A majority of OVF occurred after a minor trauma, such as falling down (55.3%) or lifting objects (8.4%). Short segment fusion, including affected vertebra, was conducted (mean 4.0 ± 2.0 vertebrae) with 256.8 minutes of surgery and 676.1 g of blood loss. A posterior approach was employed in 86.6% of the patients, followed by a combined anterior and posterior (8.7%), and an anterior (4.7%) approach. Perioperative complications and implant failures were observed in 18.1% and 41.2%, respectively. VAS scores of low back pain (74.7 to 30.8 mm) and leg pain (56.8 to 20.7 mm) improved significantly at FU. Preoperatively, 52.6% of the patients were unable to walk and the rate of non-ambulatory patients decreased to 7.5% at FU. Conclusions This study demonstrated that substantial improvement in activity of daily living (ADL) was achieved by fusion surgery. Although there was a considerable rate of complications, fusion surgery is beneficial for elderly OVF patients with non-union.
Background To date, there have been little published data on surgical outcomes for patients with PD with thoracolumbar OVF. We conducted a retrospective multicenter study of registry data to investigate the outcomes of fusion surgery for patients with Parkinson’s disease (PD) with osteoporotic vertebral fracture (OVF) in the thoracolumbar junction. Methods Retrospectively registered data were collected from 27 universities and their affiliated hospitals in Japan. In total, 26 patients with PD (mean age, 76 years; 3 men and 23 women) with thoracolumbar OVF who underwent spinal fusion with a minimum of 2 years of follow-up were included (PD group). Surgical invasion, perioperative complications, radiographic sagittal alignment, mechanical failure (MF) related to instrumentation, and clinical outcomes were evaluated. A control group of 296 non-PD patients (non-PD group) matched for age, sex, distribution of surgical procedures, number of fused segments, and follow-up period were used for comparison. Results The PD group showed higher rates of perioperative complications ( p < 0.01) and frequency of delirium than the non-PD group (p < 0.01). There were no significant differences in the degree of kyphosis correction, frequency of MF, visual analog scale of the symptoms, and improvement according to the Japanese Orthopaedic Association scoring system between the two groups. However, the PD group showed a higher proportion of non-ambulators and dependent ambulators with walkers at the final follow-up (p < 0.01). Conclusions A similar surgical strategy can be applicable to patients with PD with OVF in the thoracolumbar junction. However, physicians should pay extra attention to intensive perioperative care to prevent various adverse events and implement a rehabilitation regimen to regain walking ability. Electronic supplementary material The online version of this article (10.1186/s12891-019-2473-8) contains supplementary material, which is available to authorized users.
This study aimed to evaluate the in vitro pharmacological activity of growth factors (GFs) in freeze-dried platelet-rich plasma (FD-PRP) after storage for 4 weeks. Overview of Literature: Freshly prepared PRP is a rich source of many GFs. We reported that FD-PRP stored for 8 weeks accelerated bone union in a rat posterolateral fusion model equally well as fresh-PRP. However, the pharmacological activity of FD-PRP after longterm storage has not been shown in vitro. Methods: Immediately after preparation, as well as 4 weeks after freeze-dried storage, the platelet count was measured. Human osteoblasts were treated with fresh-PRP and FD-PRP, respectively. Western blotting was used to assess the phosphorylation of the platelet-derived growth factor (PDGF) receptor (PDGFR) and its downstream target, extracellular signal-regulated kinase (ERK). The proliferation rates of osteoblasts were investigated by immunocytochemistry and MTT cell viability assays. Furthermore, we used western blotting to evaluate the effect of PDGFR knockdown on the phosphorylation of ERK stimulated with fresh-PRP and FD-PRP. Results: Platelet counts in both the fresh-PRP and FD-PRP samples were approximately 10-fold higher than in peripheral blood samples. The phosphorylation and activation of the PDGFR and ERK were evenly induced by fresh-PRP and FD-PRP stimulation. Both fresh-PRP and FD-PRP significantly induced osteoblast proliferation in MTT cell viability assays. Furthermore, osteoblast PDGFR knockdown attenuated the downstream ERK activation by fresh PRP and FD-PRP. Conclusions: We demonstrated the pharmacological activity of PDGF in FD-PRP in vitro after 4 weeks of storage.
Unidirectional porous hydroxyapatite (UDPHAp) is an artificial bone substitute with a unique microstructure consisting of 100–300-µm oval pores that present the material unidirectionally. UDPHAp has a compression strength of 14 MPa and a porosity of 75%, which promotes cell migration and capillary formation within the material. Despite these advantageous properties, bone remodeling and bone formation with UDPHAp remain unclear. To examine long-term remodeling and differences in bone formation based on the defect site, trapezoidal prism-shaped UDPHAp blocks were implanted into rectangular-shaped cortical bone defects in the proximal tibia of Japanese white rabbits. Histological analysis performed at 52 and 104 weeks after implantation revealed that bone and capillaries had formed within the implanted UDPHAp material. Bone formed within the UDPHAp implanted in the cortical defect of rabbit tibia and remodel up to two years. The percentage of new bone area within UDPHAp was larger in cortical lesions than that in medullary lesions. These findings suggest that UDPHAp is a promising material for the repair of non-critical-sized cortical bone defects.
Unidirectional porous hydroxyapatite (UDPHAp) bone substitute comprises a microstructure of cross‐sectionally oval pores with diameters ranging from 30 to 300 µm. Bone remodeling within the UDPHAp is expected upon implantation into bone; however, the mechanism and factors influencing this bone growth remain unclear. The objectives of the present study were to assess the vasculature and microstructure of newly formed bone and to determine how bone formation is affected by load transfer and UDPHAp pore size. Formation of osteon‐like structures, defined by the presence of lacunae, canaliculi and a central lumen containing capillaries, was observed within the implanted UDPHAp material in all animals after six weeks. The number of osteocytes and osteon‐like structures in areas adjacent to the cortex of recipient bone was significantly higher than in areas next to the medullary cavity throughout the recovery period. Notably, osteon‐like structures tended to form in smaller diameter pores. Continuous bone remodeling might be promoted by the rapid formation of unidirectional capillaries and the osteocyte lacunae‐canalicular system. Load transfer and smaller pore size could positively affect cortical bone regeneration. © 2018 The Authors Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 2665–2672, 2018.
Background: The optimal treatment of osteoporosis after reconstruction surgery for osteoporotic vertebral fractures (OVF) remains unclear. In this multicentre retrospective study, we investigated the effects of typically used agents for osteoporosis, namely, bisphosphonates (BP) and teriparatide (TP), on surgical results in patients with osteoporotic vertebral fractures. Methods: Retrospectively registered data were collected from 27 universities and affiliated hospitals in Japan. We compared the effects of BP vs TP on postoperative mechanical complication rates, implant-related reoperation rates, and clinical outcomes in patients who underwent posterior instrumented fusion for OVF. Data were analysed according to whether the osteoporosis was primary or glucocorticoid-induced.
Osteosarcoma (OS) is the most common malignant bone tumor, and its sensitivity to preoperative chemotherapy is a significant prognostic factor. The present study aimed to identify potential genomic markers for the prediction of chemosensitivity in patients with OS using a genomic approach. A total of 50 pediatric and adolescent patients diagnosed with high-grade OS were selected. Each pre-therapeutic biopsy sample was subjected to comparative genomic hybridization array analysis and targeted exome sequencing. Although no recurrent gene mutation was observed in chemoresistant tumors, copy number analysis detected recurrent gain of chromosome 12q14.1, which was significantly more frequent (5/21; 24%) in the poor responder cohort than in the good responder cohort (0/29; 0%; P<0.01). Subsequent expression analysis revealed that CDK4 was the only gene in the 12q14.1 gained region with an expression level that was positively associated with copy number gains. In order to elucidate the effect of CDK4 on drug sensitivity, CDK4-overexpressing OS cell lines were treated with cisplatin (CDDP); significant attenuation of CDDP sensitivity, demonstrated by increased cell viability and decreased expression of cleaved caspase-9, was induced by enforced expression of CDK4. In addition, treatment with CDK4/6 inhibitor palbociclib in CDK4-overexpressing U2OS cells facilitated apoptosis and a significant decrease in cell viability in a dose-dependent manner. In conclusion, the results of the present study showed that higher expression and amplification of CDK4 in tumors is a predictive biomarker for resistance to conventional chemotherapy in patients with OS and that palbociclib is a promising drug for this therapeutically challenging cohort.
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