Quarles L D, Drezner M K
Department of Medicine, Duke University Medical Center, Durham, North Carolina 27710.
Endocrinology. 1992 Jul;131(1):122-6. doi: 10.1210/endo.131.1.1611990.
The mechanism by which aluminum chloride stimulates de novo bone formation is unknown. To evaluate the role of bone remodeling and mature osteoblastic function in aluminum-induced neoosteogenesis, we compared the osteogenic effects of aluminum in normal beagles to those in animals with low turnover osteomalacia induced by treatment with etidronate [1-hydroxyethane-1,1-diphosphoric acid (HEBP)]. As assessed by quantitative bone histomorphology, beagles treated with HEBP developed low turnover osteomalacia characterized by a 78% reduction in osteoblast number, a 5.5-fold increase in osteoid volume, complete absence of active mineralization, and diminished resorption surfaces compared to untreated controls. The iv administration of aluminum chloride to normal dogs generated new trabecular structures in the marrow cavity consistent with induction of de novo bone formation. This response consisted of increased trabecular bone volume and number, accumulation of woven osteoid, and increased number of bone-forming cells. The concomitant administration of HEBP failed to prevent induction of de novo bone formation by aluminum. Instead, the neoosteogenic process was superimposed on low turnover osteomalacia in HEBP-treated dogs. Serum aluminum concentrations were increased 2-fold, whereas bone aluminum accumulation was reduced by 58% in HEBP- and aluminum-treated dogs compared to that in aluminum-treated controls. These findings indicate that aluminum stimulation of neoosteogenesis in beagles is independent of mature osteoblast function, normal bone remodeling, and total bone aluminum accumulation. Rather, aluminum-induced de novo bone formation appears to result from stimulation of mesenchymal precursors to form a primitive type of bone which is distinct from coupled bone formation.
氯化铝刺激骨新生的机制尚不清楚。为了评估骨重塑和成熟成骨细胞功能在铝诱导的新骨形成中的作用，我们比较了正常比格犬与用依替膦酸[1-羟基乙烷-1,1-二膦酸（HEBP）]治疗诱导的低转换骨软化症动物中铝的成骨作用。通过定量骨组织形态计量学评估，与未治疗的对照组相比，用HEBP治疗的比格犬出现了低转换骨软化症，其特征为成骨细胞数量减少78%，类骨质体积增加5.5倍，完全没有活跃矿化，吸收表面减少。向正常犬静脉注射氯化铝在骨髓腔中产生了新的小梁结构，这与骨新生的诱导一致。这种反应包括小梁骨体积和数量增加、编织状类骨质积累以及成骨细胞数量增加。同时给予HEBP未能阻止铝诱导的骨新生。相反，在HEBP治疗的犬中，新骨形成过程叠加在低转换骨软化症之上。与铝治疗的对照组相比，HEBP和铝治疗的犬血清铝浓度增加了2倍，而骨铝积累减少了58%。这些发现表明，铝对比格犬新骨形成的刺激独立于成熟成骨细胞功能、正常骨重塑和总骨铝积累。相反，铝诱导的骨新生似乎是由于间充质前体细胞受到刺激而形成一种与耦联骨形成不同的原始类型的骨。
