Arthritis is inflammation of the joints accompanied by osteochondral destruction. It can take many forms, including osteoarthritis, rheumatoid arthritis, and psoriatic arthritis. These diseases share one commonality—osteochondral destruction based on inflammation. The background includes a close interaction between osseous tissues and immune cells through various inflammatory cytokines. However, the tissues and cytokines that play major roles are different in each disease, and as a result, the mechanism of osteochondral destruction also differs. In recent years, there have been many findings regarding not only extracellular signaling pathways but also intracellular signaling pathways. In particular, we anticipate that the intracellular signals of osteoclasts, which play a central role in bone destruction, will become novel therapeutic targets. In this review, we have summarized the pathology of arthritis and the latest findings on the mechanism of osteochondral destruction, as well as present and future therapeutic strategies for these targets.
Osteoporosis is an unavoidable public health problem in an aging or aged society. Anti-resorptive agents (calcitonin, estrogen, and selective estrogen-receptor modulators, bisphosphonates, anti-receptor activator of nuclear factor κB ligand antibody along with calcium and vitamin D supplementations) and anabolic agents (parathyroid hormone and related peptide analogs, sclerostin inhibitors) have major roles in current treatment regimens and are used alone or in combination based on the pathological condition. Recent advancements in the molecular understanding of bone metabolism and in bioengineering will open the door to future treatment paradigms for osteoporosis, including antibody agents, stem cells, and gene therapies. This review provides an overview of the molecular mechanisms, clinical evidence, and potential adverse effects of drugs that are currently used or under development for the treatment of osteoporosis to aid clinicians in deciding how to select the best treatment option.
Although bone morphogenetic protein (BMP) has potent osteoinductivity, the potential adverse events attributed to its burst release prevent its widespread clinical application. Therefore, there is a strong need for BMP delivery systems that maximize osteoinductivity while preventing adverse effects. We evaluated the bone-regenerating potential of NOVOSIS putty (NP), a novel composite combining hydroxyapatite, beta-tricalcium phosphate microsphere/poloxamer 407-based hydrogel, and recombinant human (rh) BMP-2. In vitro assessment of release kinetics by enzyme-linked immunosorbent assay demonstrated sustained release of rhBMP-2 from NP and burst release from collagen sponge (CS), and in vivo assessment of release kinetics by longitudinal tracking of fluorescently labeled rhBMP-2 showed a longer biological half-life of rhBMP-2 with NP than with CS. Furthermore, osteogenic gene expression in MC3T3-E1 cells was significantly higher after co-culture with NP than after co-culture with CS, suggesting that the sustained release of rhBMP-2 from NP effectively contributed to the differentiation of osteoblasts. In a rat spinal fusion model, the volume and quality of newly formed bone was higher in the NP group than in the CS group. Use of NP results in efficient bone regeneration through sustained release of rhBMP-2 and improves the quality of BMP-induced bone.
In this era of aging societies, the number of elderly individuals who undergo spinal arthrodesis for various degenerative diseases is increasing. Poor bone quality and osteogenic ability in older patients, due to osteoporosis, often interfere with achieving bone fusion after spinal arthrodesis. Enhancement of bone fusion requires shifting bone homeostasis toward increased bone formation and reduced resorption. Several biological enhancement strategies of bone formation have been conducted in animal models of spinal arthrodesis and human clinical trials. Pharmacological agents for osteoporosis have also been shown to be effective in enhancing bone fusion. Cytokines, which activate bone formation, such as bone morphogenetic proteins, have already been clinically used to enhance bone fusion for spinal arthrodesis. Recently, stem cells have attracted considerable attention as a cell source of osteoblasts, promising effects in enhancing bone fusion. Drug delivery systems will also need to be further developed to assure the safe delivery of bone-enhancing agents to the site of spinal arthrodesis. Our aim in this review is to appraise the current state of knowledge and evidence regarding bone enhancement strategies for spinal fusion for degenerative spinal disorders, and to identify future directions for biological bone enhancement strategies, including pharmacological, cell and gene therapy approaches.
Background:Intraspinal extradural lipomas are very rare and should be differentiated from spinal epidural lipomatosis (SEL) and/or angiolipomas.Case Description:A 76-year-old male presented with left lower extremity radiculopathy. The magnetic resonance imaging (MRI) revealed hyperplasia of epidural fat at the L2–3 and L3–4 levels accompanied by a lipomatous L4–5 mass. Following resection of this mass and hyperplastic epidural fat, the histological examination was consistent with an intraspinal extradural lipoma and SEL.Conclusion:This case indicates that asymmetrical compression of the dural sac may be attributed to an intraspinal extradural lipoma vs. just SEL and/or an angiolipoma.
The number of studies on bone metastasis (BM) from gastric cancer (GC) is currently limited. Therefore, the aim of the present study was to investigate the characteristics, skeletal-related events (SREs) and prognosis of GC in patients with BMs. Data from 60 patients with BMs from GC were retrospectively retrieved and patient-, tumor-and BM-related characteristics were analyzed. Kaplan-Meier survival curves were analyzed using the univariate log-rank test. Multivariate analyses were conducted using the Cox proportional hazards model. The median patient age was 63.5 years (range, 26-83 years). Visceral or brain metastases were observed at BM diagnosis in 61.7% of the patients. Multiple BMs were detected in 83.3% and SREs occurred in 76.7% of the patients. The median overall survival (OS) after BM diagnosis and SRE occurrence was 9 months (range, 0-43 months) and 5 months (range, 0-36 months), respectively. On multivariate analysis, poor Eastern Cooperative Oncology Group performance status (P=0.030), the administration of chemotherapy prior to BM diagnosis (P<0.001) and no chemotherapy after BM diagnosis (P= 0.002) were significant prognostic factors for unfavorable OS, whereas the non-use of bone-modifying agents (BMAs) was the only independent prognostic factor for poor SRE-free survival (SRS; P=0.022). Among patients without SREs at BM diagnosis, the median SRS duration was 7 months (range, 0-43 months). In conclusion, chemotherapy may confer a survival benefit in GC patients with BMs. In addition, the prognosis for GC patients with BMs presenting with SREs is poor, but treatment with BMAs may prevent or delay the development of SREs.
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