Biomaterials (Mg/Zn/F-BCPs)for osteoporosis therapy

用于骨质疏松症治疗的生物材料（Mg/Zn/F-BCP）

• 批准号: 6737692
• 负责人: Racquel Zapanta LeGeros
• 金额: $ 48.91万
• 依托单位: NEW YORK UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2003
• 资助国家: 美国
• 起止时间: 2003-09-30 至 2007-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6737692
• 关键词: biomaterial development /preparation; biotechnology; calcium phosphate; carbonates; clinical research; dietary supplements; fluorine; implant; laboratory rat; magnesium; musculoskeletal disorder therapy; osteoblasts; osteoclasts; osteoporosis; zinc

DESCRIPTION (provided by applicant): Osteoporosis is a 'silent' progressive and debilitating disease characterized by bone loss, thinning cortical bone and disorganized trabecular bone leading to bone fragility and fracture. Osteoporosis results when the processes of bone formation and bone resorption become uncoupled and the rate of bone resorption becomes much greater than that of bone formation. FDA-approved pharmaceutical interventions have antiresorptiive properties. Some of these drugs have serious side effects. Fluoride (F) therapy as sodium fluoride is the only one shown to consistently increase bone mass, but was also reported to increase fracture risk. The goal of the proposed research is to develop novel materials incorporating magnesium (Mg), zinc (Zn), F ions in a calcium (Ca) phosphate system (Mg/Zn/F-BCP). Separately, these ions have been associated with bone formation, biomineralization and osteoporosis therapy. Specific aims are to: (1) prepare and characterize the crystallographic, morphologic, and chemical properties of a series of Mg/Zn/F-BCP materials; (2) determine the short and long term initial dissolution rates and release of Ca, Mg, Zn, P and F ions of the materials prepared in Aim 1; (3) determine in vitro response of bone forming (osteoblasts) and bone resorbing (osteoclasts) cells to Mg/Zn/F-BCPs of various compositions using human osteoblast-like cells and rat osteoclast-like cells; (4) determine the effect of orally administered various Mg/Zn/F-BCPs on (a) bone properties (mechanical strength, density, quality, composition, and histomorphometric parameters and bone mineral (crystallinity, composition and dissolution) of adult and aged female and male rats; and (b) on the development of osteoporosis (deficient-diet induced) in adult rats; and (5) determine therapeutic effect of various injected Mg/Zn/F-BCPs on ovariectomized rats using biomechanical, histomorphometric measurements and chemical analyses on bone and plasma analyses. Hypothesis: Biomaterials with Zn, Mg and F ions in a calcium phosphate matrix (used as dietary supplement and ion releasing injectible 'implants') will improve bone health.

描述(申请人提供)：骨质疏松症是一种“沉默的”进行性和衰弱的疾病，其特征是骨质丢失，皮质变薄，松质骨紊乱，导致骨骼脆弱和骨折。当骨形成和骨吸收的过程变得分离，骨吸收的速度远远大于骨形成的速度时，就会产生骨质疏松症。FDA批准的药物干预具有抗吸收特性。其中一些药物有严重的副作用。作为氟化钠的氟化物(F)疗法是唯一一种被证明持续增加骨量的疗法，但据报道也会增加骨折的风险。本研究的目标是开发在钙(Ca)磷酸盐体系中加入镁、锌、氟离子的新型材料(镁/锌/F-BCP)。另外，这些离子与骨形成、生物矿化和骨质疏松症治疗有关。具体目的是：(1)制备和表征一系列镁/锌/氟-BCP材料的晶体、形态和化学性质；(2)测定目标1中制备的材料的短期和长期的初始溶出速率和钙、镁、锌、磷、氟离子的释放；(3)测定成骨细胞(成骨细胞)和骨吸收(破骨细胞)细胞对不同组成的镁/锌/氟-BCP的体外反应；(4)通过对成年和老年雌雄大鼠的骨性能(力学强度、密度、质量、成分、组织形态计量学参数)和骨矿物质(结晶度、成分和溶解度)的测定，以及(B)对成年大鼠骨质疏松(饮食缺乏所致)形成的影响；(5)通过对去卵巢大鼠的生物力学、组织形态计量学和骨和血浆化学分析，确定不同剂量的镁/锌/氟-BCPs对去卵巢大鼠的治疗作用。假设：在磷酸钙基质中含有锌、镁和氟离子的生物材料(用作膳食补充剂和离子释放注射型“植入物”)将改善骨骼健康。