China
Africa
Explore chapters and articles related to this topic
Pathophysiology of Fluorosis and Calcium Dose Prediction for Its Reversal in Children: Mathematical Modeling, Analysis, and Simulation of Three Clinical Case Studies
Published in P. Mereena Luke, K. R. Dhanya, Didier Rouxel, Nandakumar Kalarikkal, Sabu Thomas, Advanced Studies in Experimental and Clinical Medicine, 2021
Suja George, A. B. Gupta, Mayank Mehta, Akshara Goyal
The presence of increased PTH in the blood stream is responsible for the following two major body mechanisms: Significant Loss of Bone Mass: Bone loss is due to increase in the number of osteoblasts and the increase of their activity [9, 10] which causes the stimulation of bone resorption and depletion of bone mass as well as its formation. Osteoclast is a type of bone cell that resorbs bone tissue. Under the normal conditions, where there is an increase in bone resorption, it gets coupled with an effective compensatory increase in an equal magnitude of bone formation and therefore no net bone mass is depleted in the skeletal system. However, during the adjustor mechanism if there is a demand to mobilize calcium from skeletal system to counteract the effects of hypocalcemia, then the bone coupling process gets compromised.Depletion of Bone Formation: It has been reported that despite the effectiveness in a significant increase in bone resorption, bone formation decreased and was significantly inhibited due to PTH [9]. Therefore, the combination of various combined actions such as calcium depletion, bone resorption and decrease in its formation led to a significant loss of bone mass [9].
Pathogenesis: Molecular mechanisms of osteoporosis
Published in Peter V. Giannoudis, Thomas A. Einhorn, Surgical and Medical Treatment of Osteoporosis, 2020
Anastasia E. Markatseli, Theodora E. Markatseli, Alexandros A. Drosos
Osteoclasts are primarily responsible for bone resorption. Osteoclasts are multinucleated giant cells derived from precursor cells of the monocyte-macrophage lineage (39,40). Mononuclear cells are attracted to the point of the bone surface that will be absorbed and proliferate and differentiate into preosteoclasts. The fusion of mononuclear preosteoclasts follows, which results in the creation of the multinucleated osteoclast. First, the mature osteoclast is firmly adhered to the bone with the help of specialized podosomes, which are rich in actin. Among the highly corrugated surface of the osteoclast and the bone surface, a closed cavity is formed. The osteoclast secretes proteolytic enzymes (cathepsin K) and hydrochloric acid (hydrogen ions) into the cavity (41). Proteolytic enzymes contribute to the fragmentation of the organic phase, while the hydrogen ions dissolve the inorganic phase. It should be noted that the carbonic anhydrase II is an enzyme found in the cytoplasm of the osteoclast and contributes to the production of hydrogen ions. Therefore, the main function of osteoclasts is the absorption of the matrix, which is achieved through the creation of absorption cavities (Howship lacunae) (40). The process of bone resorption is completed with the apoptosis of osteoclast. Throughout the absorption, osteoclasts release substances, and bone tissue also releases local factors that ultimately inhibit the action of osteoclasts and induce osteoblast activity (signals are transmitted to osteoblasts in order to present in the absorption cavities) (42).
Infection-driven periodontal disease
Published in Phillip D. Smith, Richard S. Blumberg, Thomas T. MacDonald, Principles of Mucosal Immunology, 2020
Thomas E. Van Dyke, Mike Curtis
A major consequence of the inflammatory response associated with periodontal disease is resorption of alveolar bone. Under normal conditions, bone is periodically resorbed while new bone forms. In the case of periodontal disease, there is a shift to bone resorption due to an increase in inflammatory cells and cytokines, and an increase in osteoclasts in the local tissue. (Osteoclasts are large, multinucleated cells derived from the monocyte-macrophage lineage, whose major function is to resorb bone.) Differentiation of osteoclasts is regulated by macrophage colony-stimulating factor (M-CSF) and receptor activator of NF-κB ligand (RANKL) found on several cell types including T cells and osteoblasts. M-CSF promotes proliferation and survival of osteoclast progenitors, whereas RANKL promotes cells to differentiate along the osteoclast lineage and acts as an activating and survival factor for mature osteoclasts. RANKL binds to RANK present on osteoclast precursors and mature osteoclasts resulting in the recruitment of TNF receptor-associated factor (TRAF) family proteins, especially TRAF6, which leads to activation of various signaling pathways and transcription factors, and the secretion of bone-degrading factors.
Therapeutic potential of RUNX1 and RUNX2 in bone metastasis of breast cancer
Published in Expert Opinion on Therapeutic Targets, 2023
Scientists mainly focus on two aspects of osteoclasts and osteoblasts in the process of bone metastasis for target identification and targeted drug development. For osteoclasts, their role in driving bone metastasis in breast cancer is widely recognized. In the vicious cycle of bone metastasis, as osteoclasts are activated directly or indirectly by tumor cells, they promote enhanced bone metastasis. During metastasis, RANK/RANKL and CSF-1/CSF-1 R activate key transcription factors, which can regulate the expression of key genes (DC-STAMP, TRAP, histone K, MMP9, calcitonin receptor, and avb3) that enhance osteoclast function. Therefore, scientists are currently developing targeted drugs for these essential genes or substances. Osteoblasts, on the other hand, play a crucial role in the process of bone metastasis. Its two targets RUNX1 and RUNX2 are involved in tumor development. Currently, there are some targeted drugs, such as AI-1047, CADD522, XRK3F2, L-Quebrachitol, Muramyl dipeptide, and L-ascorbic acid 2-phosphate sesquimagnesium salt. These drugs are primarily for RUNX1 and RUNX2, but they are not yet officially available for breast cancer and their use in cancer has not been pioneered. As we learn more about breast cancer development and bone metastasis, the pathogenesis of RUNX family and treatment resistance would require further research.
Effects of osthole on osteoporotic rats: a systematic review and meta-analysis
Published in Pharmaceutical Biology, 2022
Bin Wu, Xiu-Fang Zhu, Xiao-Qiang Yang, Wei-Yi Wang, Jian-Hua Lu
Bone remodelling is tightly regulated by bone-forming osteoblasts and bone-resorbing osteoclasts (Kim et al. 2020). When bone resorption is greater than bone formation, there is a net loss of bone tissue (Alippe et al. 2017), which can lead to osteoporosis. Osteoclasts are multinucleated cells derived from monocyte/macrophage lineage and are the only cells capable of bone resorption (Udagawa et al. 2021). The proliferation and differentiation of osteoclasts are regulated by cytokines, transcription factors and osteoclast-related genes such as macrophage-colony stimulating factor and tumour necrosis factor. The OPG/RANKL/RANK pathway is the critically important signalling pathway in the process (Meng et al. 2020). Receptor activator of nuclear factor kappa-Β ligand binds to receptors on the osteoclast surface; it regulates NF-κB signalling, activates nuclear factor of activated T-cells 1, and activates osteoclast-specific molecules (e.g., cathepsin K, matrix metalloproteinase-9, and tartrate-resistant acid phosphatase). Previous in vitro experiments demonstrated that osthole inhibits bone resorption by suppressing proliferation of osteoclasts and expression of osteoclast-specific genes (Zhai et al. 2014; Lv et al. 2016; Ma et al. 2019). The results of this meta-analysis confirmed that osthole had similar effects in vivo, presumably through increased expression of OPG/RANKL (Zhai et al. 2014; Li et al. 2016).
Risk factors for hypocalcemia in dialysis patients with refractory secondary hyperparathyroidism after parathyroidectomy: a meta-analysis
Published in Renal Failure, 2022
Dan Gao, Yan Lou, Yingchun Cui, Shengmao Liu, Wenpeng Cui, Guangdong Sun
Numerous studies have confirmed that preoperative iPTH concentrations and the magnitude of postoperative iPTH reduction in patients with HBS are higher than those in patients without HBS. This finding is consistent with the physiological functions of iPTH. Under stimulation by excessive iPTH, both bone formation and bone resorption exhibited an increase despite a marked negative balance [35–37]. Upon rapid decrease in iPTH level, the activity of osteoclasts in vivo decreases. This stops the osteolytic action, with a concurrent increase in osteoblast activity. A large amount of circulating calcium ions are then transferred to the bone to participate in osteogenesis. Thereafter, the serum calcium level declined after PTX, which was confirmed in a previous in vitro study [38–41]. Based on the results of this meta-analysis, it was concluded that a high preoperative iPTH level was a risk factor for postoperative hypocalcemia. Moreover, the reasons for high heterogeneity might be similar to that of ALP, including factors such as definition, surgical method, and continuous variables. However, all included studies consistently suggested that a high preoperative iPTH level was a risk factor for postoperative hypocalcemia, which also confirmed our conclusion. Clinicians should be aware of the important predictive role of preoperative iPTH level, better understand the postoperative course, and improve perioperative management to avoid the occurrence of hypocalcemia and minimize any adverse consequences.