Aluminum deposition at the osteoid-bone interface. An epiphenomenon of the osteomalacic state in vitamin D-deficient dogs.
Aluminum deposition at the osteoid-bone interface. An epiphenomenon of the osteomalacic state in vitamin D-deficient dogs.
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类骨质-骨界面处的铝沉积。
DOI：
10.1172/jci111846
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发表时间：
1985
期刊：
影响因子：
--
通讯作者：
Drezner,MK
中科院分区：
文献类型：
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作者：
Quarles,LD;Dennis,VW;Gitelman,HJ;Harrelson,JM;Drezner,MK
虽然铝过量是透析治疗的慢性肾衰竭患者骨软化的明显致病因素，但铝损害骨矿化的机制尚不清楚。然而，在受影响患者的骨活检中，观察到铝存在于骨-骨界面，这表明它存在于钙化前沿，扰乱了正常矿化的细胞和/或物理化学过程。另外，骨-骨界面处的铝可能反映了先前存在的骨软化骨的沉积，而对矿化过程没有直接影响。我们研究了铝是否优先在骨软化骨中积累，如果是这样，铝的沉积是否发生在钙化前沿并特异性地抑制矿化。5只正常犬和5只缺乏维生素d的骨质疏松犬每周静脉注射氯化铝（1 mg/kg） 3次，持续3周。在给予铝之前，维生素d缺乏的狗有骨软化的生化和骨活检证据。骨软化犬的骨铝含量（15.1 +/- 2.2微克/g）和血浆铝浓度（10.4 +/- 2.1微克/升）与正常犬（10.5 +/- 3.5微克/g和11.9 +/- 1.2微克/升）无显著差异。给铝3周后，正常和维生素D缺乏犬的血浆磷、甲状旁腺激素和25-羟基维生素D浓度没有变化。同样，两组骨组织学均未发生改变。相比之下，缺乏维生素d的狗的骨铝含量（390.3 +/- 24.3微克/克）比正常狗（73.6 +/- 10.6微克/克）增加得更大。此外，在维生素d缺乏的狗中，铝定位于骨软化骨的骨-骨界面，覆盖了42.9 +/- 9.2%的骨-骨表面。此外，尽管继续给予氯化铝（每周一次，每次1毫克/公斤），维生素D缺乏的狗在11周内补充维生素D导致其生物化学正常化。此外，虽然正常犬在持续给铝期间保持正常的骨骼组织学，但维生素D缺乏犬的维生素D补充诱导其骨骼愈合。事实上，愈合骨的水泥线中铝的出现表明矿化发生在先前铝沉积的部位。这些观察结果表明，铝沉积在骨软化骨可能是一个次要事件，不影响骨矿化。因此，尽管铝可能导致慢性肾衰竭的骨软化，但它在矿化前沿的存在可能不是这种紊乱的机制。图片
Although aluminum excess is an apparent pathogenetic factor underlying osteomalacia in dialysis-treated patients with chronic renal failure, the mechanism by which aluminum impairs bone mineralization is unclear. However, the observation that aluminum is present at osteoid-bone interfaces in bone biopsies of affected patients suggests that its presence at calcification fronts disturbs the cellular and/or physiochemical processes underlying normal mineralization. Alternatively, aluminum at osteoid-bone interfaces may reflect deposition in preexistent osteomalacic bone without direct effects on the mineralization process. We investigated whether aluminum accumulates preferentially in osteomalacic bone and, if so, whether deposition of aluminum occurs at calcification fronts and specifically inhibits mineralization. Aluminum chloride (1 mg/kg) was administered intravenously three times per week for 3 wk to five normal and five vitamin D-deficient osteomalacic dogs. Before administration of aluminum the vitamin D-deficient dogs had biochemical and bone biopsy evidence of osteomalacia. Bone aluminum content in the osteomalacic dogs (15.1 +/- 2.2 micrograms/g) and the plasma aluminum concentration (10.4 +/- 2.1 micrograms/liter) were no different than those of normal dogs (10.5 +/- 3.5 micrograms/g and 11.9 +/- 1.2 microgram/liter, respectively). After the 3 wk of aluminum administration the plasma phosphorus, parathyroid hormone, and 25-hydroxyvitamin D concentrations were unchanged in normal and vitamin D-deficient dogs. Similarly, no alteration in bone histology occurred in either group. In contrast, bone aluminum content increased to a greater extent in the vitamin D-deficient dogs (390.3 +/- 24.3 micrograms/g) than in the normal dogs (73.6 +/- 10.6 micrograms/g). Moreover, aluminum localized at the osteoid-bone interfaces of the osteomalacic bone in the vitamin D-deficient dogs, covering 42.9 +/- 9.2% of the osteoid-bone surface. Further, in spite of continued aluminum chloride administration (1 mg/kg two times per week), vitamin D repletion of the vitamin D-deficient dogs for 11 wk resulted in normalization of their biochemistries. In addition, while normal dogs maintained normal bone histology during the period of continued aluminum administration, vitamin D repletion of the vitamin D-deficient dogs induced healing of their bones. Indeed, the appearance of aluminum in the cement lines of the healed bones indicated that mineralization had occurred at sites of prior aluminum deposition. These observations illustrate that aluminum deposition in osteomalacic bone may be a secondary event that does not influence bone mineralization. Thus, although aluminum may cause osteomalacia in chronic renal failure, its presence at mineralization fronts may not be the mechanism underlying this derangement.Images