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

描述（由申请人提供）：骨质疏松症是一种“沉默的”进行性和衰弱性疾病，其特征是骨质流失、皮质骨变薄和骨小梁紊乱，导致骨脆性和骨折。当骨形成和骨吸收的过程不耦合，骨吸收的速度远远大于骨形成的速度时，骨质疏松症就产生了。fda批准的药物干预具有抗吸收特性。有些药物有严重的副作用。氟化物(F)疗法如氟化钠是唯一一种能持续增加骨量的疗法，但也有报道称会增加骨折风险。提出的研究目标是在钙（Ca）磷酸体系（Mg/Zn/F- bcp）中开发含有镁（Mg），锌（Zn）， F离子的新型材料。另外，这些离子与骨形成、生物矿化和骨质疏松症治疗有关。具体目标是：(1)制备和表征一系列Mg/Zn/F-BCP材料的晶体学、形态学和化学性质；(2)测定Aim 1中制备的材料的Ca、Mg、Zn、P、F离子的短期和长期初始溶出速率和释放量；(3)利用人成骨细胞样细胞和大鼠破骨细胞样细胞测定骨形成（成骨细胞）和骨吸收（破骨细胞）细胞对不同成分Mg/Zn/ f - bcp的体外反应；(4)测定口服各种Mg/Zn/ f - bcp对成年和老年雌性和雄性大鼠骨性能（机械强度、密度、质量、组成和组织形态学参数）和骨矿物质（结晶度、组成和溶出度）的影响；(b)成年大鼠骨质疏松症（饮食不足所致）的发生；(5)通过生物力学、组织形态学测量、骨化学分析和血浆分析，确定各种注射Mg/Zn/ f - bcp对去卵巢大鼠的治疗效果。假设：在磷酸钙基质中含有锌、镁和氟离子的生物材料（用作膳食补充剂和释放离子的可注射“植入物”）将改善骨骼健康。

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.