- Modulation Of Alendronate Release From A Calcium Phosphate Bone Cement: An In Vitro Osteoblast-Osteoclast Co-Culture Study. [Journal Article]
- IJInt J Pharm 2018 Nov 10
- In this study, we loaded a biomimetic calcium phosphate bone cement (CPC) with relatively high amounts of a bisphosphonate through the use of Solid Lipid Microparticles (MPs) and investigated bone ce...
In this study, we loaded a biomimetic calcium phosphate bone cement (CPC) with relatively high amounts of a bisphosphonate through the use of Solid Lipid Microparticles (MPs) and investigated bone cells response to the composite cements. 10, 20 and 30% w/w of Alendronate (AL) were successfully introduced into microparticles of Cutina HR and Precirol, which were prepared by means of spray-congealing technique. Addition of AL-loaded MPs to the cement composition provoked a lengthening of the setting and of the hardening processes. However, setting times were still in a range useful for clinical applications, except for the cements at the highest Alendronate content. The composite cements displayed a sustained drug release over time. Cements with the best performances in terms of setting, hardening, mechanical properties and drug release were submitted to in vitro tests using a co-culture model of osteoblast and osteoclast. The results showed that the use of MPs to enrich the cement composition with Alendronate provides materials able to inhibit osteoclast viability and activity, while promoting osteoblast viability and earlier differentiation, indicating that the MPs-cements are good delivery systems for bisphosphonates.
- Decreased microRNA-182-5p helps alendronate promote osteoblast proliferation and differentiation in osteoporosis via the Rap1/MAPK pathway. [Journal Article]
- BRBiosci Rep 2018 Nov 09
- Osteoporosis (OP) is a serious health problem that contributes to osteoporotic structural damage and bone fragility. MicroRNAs (miRNAs) can exert important functions over bone endocrinology. Therefor...
Osteoporosis (OP) is a serious health problem that contributes to osteoporotic structural damage and bone fragility. MicroRNAs (miRNAs) can exert important functions over bone endocrinology. Therefore, it is of substantial significance to clarify the expression and function of miRNAs in bone endocrine physiology and pathology to improve the potential therapeutic value for metabolism-related bone diseases. We explored the effect of microRNA-182-5p (miR-182-5p) on osteoblast proliferation and differentiation in OP rats after alendronate (ALN) treatment by targeting ADCY6 through the Rap1/mitogen-activated protein kinase (MAPK) signaling pathway. Rat models of OP were established to observe the effect of ALN on OP, and the expression of miR-182-5p, ADCY6 and the Rap1/MAPK signaling pathway-related genes was determined. To determine the roles of miR-182-5p and ADCY6 in OP after ALN treatment, the relationship between miR-182 and ADCY6 was initially verified. Osteoblasts were subsequently extracted and transfected with a miR-182-5p inhibitor, miR-182-5p mimic, si-ADCY6 and the MAPK signaling pathway inhibitor U0126. Cell proliferation, apoptosis and differentiation were also determined. ALN treatment was able to ease the symptoms of OP. miR-182-5p negatively targeted ADCY6 to inhibit the Rap1/MAPK signaling pathway. Cells transfected with miR-182 inhibitor decreased the expression of ALP, BGP and COL I, which indicated that the downregulation of miR-182-5p promoted cell differentiation and cell proliferation and inhibited cell apoptosis. In conclusion, this study shows that downregulated miR-182-5p promotes the proliferation and differentiation of osteoblasts in OP rats through Rap1/MAPK signaling pathway activation by upregulating ADCY6, which may represent a novel target for OP treatment.
- Modified Gelatin Nanoparticles for Gene Delivery. [Review]
- IJInt J Pharm 2018 Nov 05
- Gelatin nanoparticles (GNPs) are one of the most extensively used natural polymers for gene therapy. With advantages of being biodegradable, biocompatible, low cost and easily modified, gelatin holds...
Gelatin nanoparticles (GNPs) are one of the most extensively used natural polymers for gene therapy. With advantages of being biodegradable, biocompatible, low cost and easily modified, gelatin holds great promise as a non-viral system for gene delivery. This review examines various methods of preparation of modified gelatin nanoparticles and considers how these modifications apply to gene delivery. The article discusses cationic gelatin, PEGylated gelatin, thiolated gelatin, alendronate gelatin, and EGFR gelatin nanoparticles. This article also considers several advantages of these modifications and their contribution to the improvement in the efficiency of these systems, resulting in superior transfection and enhanced gene delivery in general.
- Novel mutations in BMP1 induce a rare type of osteogenesis imperfecta. [Journal Article]
- CCClin Chim Acta 2018 Nov 05
- CONCLUSIONS: We report for the first time that the novel pathogenic mutations in BMP1 can lead to the extremely rare OI type XIII, which exhibit unique characters of high bone mass, but with impaired bone microstructure and comprised bone strength. Alendronate is beneficial in increasing bone mineral density and decreasing bone resorption biomarkers, but concerns still remain whether it can reduce fracture incidence in this rare type of OI.
- Long-term control of Paget's disease of bone with low-dose, once-weekly, oral bisphosphonate preparations, in a "real world" setting. [Journal Article]
- EEndocrine 2018 Nov 08
- CONCLUSIONS: In a large proportion of "real world" PDB patients, remission can be achieved with once-weekly, "osteoporosis doses" of alendronate or risedronate.
- Cathepsin K inhibition preserves compressive load in lumbar vertebrae of osteoporotic monkeys. [Journal Article]
- BRBone Rep 2018; 9:159-164
- Anti-resorptive drugs treat bone loss by blocking osteoclast activity through a variety of mechanisms of action. Once significant bone loss has occurred, the ability to restore biomechanical function...
Anti-resorptive drugs treat bone loss by blocking osteoclast activity through a variety of mechanisms of action. Once significant bone loss has occurred, the ability to restore biomechanical function may differ based on the drug chosen. To assess this question, bisphosphonate (alendronate, ALN) and cathepsin K inhibitor (MK-0674, CatKi) were employed in treatment mode to compare the relative changes to cancellous bone microstructure and mechanical properties in ovariectomized (OVX) cynomolgus monkeys. Lumbar vertebrae (LV) bone mineral density (BMD) values taken two years post-surgery prior to drug treatment show a 10-15% decrease (p < 0.05) for all OVX animals. OVX animals were then treated with vehicle (VEH), ALN (0.03 mg/kg weekly), or CatKi MK-0674 (0.6 or 2.5 mg/kg daily, CatKi-L and H respectively) for two years and compared to a control Sham surgery group. Ex-vivo microcomputed tomography (μCT) of LV2 and compression testing of LV4-6 were used to measure cancellous bone microstructure and changes in bone mechanics, respectively. After two years of treatment, ALN-treated animals showed no significant difference in μCT or biomechanical parameters when compared to Veh. However, treatment with CatKi-H resulted in a 30% increase in yield and peak loads, and apparent peak and yield stress as compared to Veh (p < 0.05) and gave average mechanical values greater than the Sham sample. Treatment with CatKi-L exhibited a similar trend of increase to CatKi-H (p < 0.08). Intriguingly, these changes were realized despite no significant differences in mean values of trabecular bone morphologic parameters. Together these data suggest matrix-level changes in bone composition that are unique to the CatK inhibition mechanism, resulting in the preservation of bone compressive load with treatment.
- Clinical characteristics and recurrence-related factors of medication-related osteonecrosis of the jaw. [Journal Article]
- JKJ Korean Assoc Oral Maxillofac Surg 2018; 44(5):225-231
- CONCLUSIONS: The identified risk factors in patients taking bone resorption inhibitors can aid dental clinicians in ensuring prevention and proper treatment of MRONJ.
- Open-label study of treatment with alendronate sodium plus vitamin D in men and women with osteoporosis in Thailand. [Journal Article]
- BMBMC Musculoskelet Disord 2018 Nov 06; 19(1):392
- CONCLUSIONS: Oral alendronate sodium 70 mg plus vitamin D3 5600 IU once weekly had an acceptable safety profile in this study, and increased serum 25(OH)D and reduced β-CTx levels in osteoporosis patients. This treatment improved 25(OH)D levels, without causing abnormally high levels, after 26 weeks' treatment.
- Comparison of Treatment Regimens for the Management of Severe Hypercalcemia due to Vitamin D Intoxication in Children. [Journal Article]
- JCJ Clin Res Pediatr Endocrinol 2018 Nov 05
- CONCLUSIONS: In mild cases, prednisolone or bisphosphonate treatments are not needed. Prednisolone is less effective in the treatment of children with severe hypercalcaemia secondary to vitamin D intoxication and timely implementation of other treatment regimens would be considered.
New Search Next
- Odanacatib Restores Trabecular Bone of Skeletally Mature Female Rabbits With Osteopenia but Induces Brittleness of Cortical Bone: A Comparative Study of the Investigational Drug With PTH, Estrogen, and Alendronate. [Published Erratum]
- JBJ Bone Miner Res 2018; 33(11):2084-2085