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

描述（由申请人提供）：骨质疏松症是一种“无声的”进行性衰弱性疾病，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。当骨形成和骨吸收过程脱节并且骨吸收速度远大于骨形成速度时，就会导致骨质疏松症。 FDA 批准的药物干预措施具有抗骨吸收特性。其中一些药物有严重的副作用。氟化物 (F) 疗法，因为氟化钠是唯一一种能够持续增加骨量的疗法，但也有报道称会增加骨折风险。拟议研究的目标是开发在磷酸钙 (Ca) 体系中加入镁 (Mg)、锌 (Zn)、F 离子的新型材料 (Mg/Zn/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。具体目标是：（1）制备一系列Mg/Zn/F-BCP材料并表征其晶体学、形貌和化学性质； (2)测定目标1中制备的材料的短期和长期初始溶解速率以及Ca、Mg、Zn、P和F离子的释放； (3)使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)细胞对各种成分的Mg/Zn/F-BCP的体外反应； (4) 确定口服各种 Mg/Zn/F-BCP 对成年和老年雌性和雄性大鼠的 (a) 骨特性（机械强度、密度、质量、成分和组织形态参数以及骨矿物质（结晶度、成分和溶解）；和 (b) 对成年大鼠骨质疏松症（缺乏饮食诱导的）发展的影响；以及 (5) 确定各种注射 Mg/Zn/F-BCP 对骨质疏松症的治疗效果使用生物力学、组织形态测量和骨化学分析以及血浆分析对卵巢切除的大鼠进行假设：磷酸钙基质中含有 Zn、Mg 和 F 离子的生物材料（用作膳食补充剂和离子释放注射“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.