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: 7100250
• 负责人: Racquel Zapanta LeGeros
• 金额: $ 41.3万
• 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 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7100250
• 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（由申请人提供）：骨质疏松症是一种“无症状”进行性和使人衰弱的疾病，其特征是骨丢失、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变得解偶联并且骨吸收的速率变得远大于骨形成的速率时，骨质疏松症就会发生。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）治疗（如氟化钠）是唯一一种能持续增加骨量的治疗方法，但也有报道称会增加骨折风险。本研究的目的是开发一种新型材料，将镁（Mg），锌（Zn），F离子引入磷酸钙（Ca）体系（Mg/Zn/F-BCP）。这些离子分别与骨形成、生物矿化和骨质疏松症治疗有关。具体目标是：（1）制备并表征一系列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）测定骨形成的体外反应（成骨细胞）和骨吸收使用人成骨细胞样细胞和大鼠破骨细胞样细胞，将Mg/Zn/F-BCP与各种组成的Mg/Zn/F-BCP结合;（4）测定口服施用的各种Mg/Zn/F-BCP对（a）骨性质的影响（成年和老年雌性和雄性大鼠的机械强度、密度、质量、组成和组织形态学参数以及骨矿物质（结晶度、组成和溶解度）;和（B）对成年大鼠骨质疏松症（缺乏饮食诱导的）的发展;和（5）使用生物力学、组织形态测量和对骨和血浆分析的化学分析来确定各种注射的Mg/Zn/F-BCP对卵巢切除大鼠的治疗效果。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。

项目成果

Solubility of Mg-containing beta-tricalcium phosphate at 25 degrees C.

• DOI: 10.1016/j.actbio.2008.06.010
• 发表时间: 2009-01
• 期刊: ACTA BIOMATERIALIA
• 影响因子: 9.7
• 作者: Li, Xia;Ito, Atsuo;Sogo, Yu;Wang, Xiupeng;LeGeros, R. Z.
• 通讯作者: LeGeros, R. Z.

Long-term therapeutic effect of novel calcium phosphate-based compounds injected in ovariectomized rats.

• DOI: 10.1002/jbm.b.31277
• 发表时间: 2009-07
• 期刊: Journal of biomedical materials research. Part B, Applied biomaterials
• 作者: Y. Tokudome;M. Otsuka;A. Ito;R. Legeros

The optimum zinc content in set calcium phosphate cement for promoting bone formation in vivo.

• DOI: 10.1016/j.msec.2008.08.021
• 发表时间: 2009-04-30
• 期刊: MATERIALS SCIENCE & ENGINEERING C-MATERIALS FOR BIOLOGICAL APPLICATIONS
• 影响因子: 7.9
• 作者: Li, Xia;Sogo, Yu;Ito, Atsuo;Mutsuzaki, Hirotaka;Ochiai, Naoyuki;Kobayashi, Takayuki;Nakamura, Satoshi;Yamashita, Kimihiro;LeGeros, Racquel Z.
• 通讯作者: LeGeros, Racquel Z.