Inflammation and Remodeling Research Unit, Pfizer Discovery Research, Cambridge, MA 02140, USA.
J Bone Joint Surg Am. 2013 Jan 2;95(1):36-47. doi: 10.2106/JBJS.K.00668.
Osteoporosis results in a decrease in bone density, bone quality, and strength throughout the skeleton. Despite systemic therapies, the morbidity and mortality that are associated with hip fractures remain a major consequence of osteoporosis.
We used fourteen chronic ovariectomized female cynomolgus monkeys in this study. Six animals received an intraosseous injection of 0.5 mL of 1.5 mg/mL recombinant human bone morphogenetic protein-2/calcium phosphate matrix (rhBMP-2/CPM) into the femoral neck of one femur, and six animals received an intraosseous injection of 0.5 mL of CPM alone into the femoral neck of one femur. The contralateral femur of each of the animals was left untreated. The proximal aspect of each femur was evaluated monthly with use of radiography and at six months with use of peripheral quantitative computed tomography, microcomputed tomography, histological analysis, and mechanical testing. Two additional animals received an intraosseous injection of 0.5 mL of 1.5 mg/mL rhBMP-2/CPM into the femoral neck of one femur. The contralateral femur of each animal was left untreated. Bone formation in the intact specimens from these animals was histologically analyzed at one month in one animal and at three months in the other.
Radiographic evaluation over the six-month study period demonstrated an increase in cortical thickness and density in the rhBMP-2/CPM-treated femora as compared to the findings in the untreated contralateral femora or the femora that had been treated with CPM alone. At six months, the rhBMP-2/CPM-treated femora had decreased cortical density and increased cross-sectional area, cortical thickness, trabecular density, and trabecular volume fraction as compared with the contralateral untreated femora and the femora that had received CPM treatment alone, but the differences between the femora that had been treated with CPM alone and the contralateral untreated femora did not reach significance. Increases in bone structure resulted in a 13.7% ± 7.6% (p = 0.032) increase in the maximum bending force at the femoral neck as compared with that at the femoral neck of the contralateral untreated femora. The maximum bending force at the femoral neck was similar between the femora that had been treated with CPM alone and the contralateral untreated femora. De novo and appositional bone formation was present at one month after treatment in the rhBMP-2/CPM-treated femora.
This study demonstrates an increase in bone structure and mechanical properties at six months following a single injection of rhBMP-2/CPM into the femoral neck of chronic ovariectomized nonhuman primates.
骨质疏松症导致整个骨骼的骨密度、骨质量和强度下降。尽管有系统治疗，但与髋部骨折相关的发病率和死亡率仍然是骨质疏松症的主要后果。
本研究使用了 14 只慢性卵巢切除的食蟹猴。6 只动物的一侧股骨颈内注射 0.5ml 浓度为 1.5mg/ml 的重组人骨形态发生蛋白-2/磷酸钙基质（rhBMP-2/CPM），6 只动物的一侧股骨颈内注射 0.5mlCPM。每个动物的对侧股骨均未进行处理。每月使用 X 线摄影术评估每只股骨的近端，每 6 个月使用外周定量计算机断层扫描、微计算机断层扫描、组织学分析和机械测试进行评估。另外 2 只动物的一侧股骨颈内注射 0.5ml 浓度为 1.5mg/ml 的 rhBMP-2/CPM。每个动物的对侧股骨均未进行处理。这 2 只动物的完整标本在注射后 1 个月和 3 个月进行了组织学分析。
在为期 6 个月的研究期间，放射学评估显示 rhBMP-2/CPM 治疗组的股骨皮质厚度和密度增加，与未治疗的对侧股骨或单独接受 CPM 治疗的股骨相比。6 个月时，rhBMP-2/CPM 治疗组的股骨皮质密度降低，横截面积、皮质厚度、骨小梁密度和骨小梁体积分数增加，与未治疗的对侧股骨和单独接受 CPM 治疗的股骨相比，但单独接受 CPM 治疗的股骨与未治疗的对侧股骨之间的差异无统计学意义。骨结构的增加导致股骨颈的最大弯曲力比未治疗的对侧股骨增加了 13.7%±7.6%（p=0.032）。单独接受 CPM 治疗的股骨和未治疗的对侧股骨的股骨颈最大弯曲力相似。rhBMP-2/CPM 治疗组在治疗后 1 个月出现新骨和成骨。
本研究在慢性卵巢切除的非人类灵长类动物的股骨颈单次注射 rhBMP-2/CPM 后 6 个月，证明了骨结构和机械性能的增加。
