Goodman W G
J Lab Clin Med. 1984 May;103(5):749-57.
Aluminum may be a pathogenic factor in dialysis-associated osteomalacia. To study the early effects of AI on bone, cortical bone growth was measured in pair-fed rats given Al and control rats over two consecutive intervals of 28 (period I) and 16 (period II) days, respectively, using tetracycline labeling of bone. Al (2 mg elemental Al per rat) was administered intraperitoneally for 5 days each week, except for the first week of study, when an incremental dose of Al was given. Control rats received saline vehicle only. For the entire 44-day study, bone and matrix formation were reduced from control values in rats given Al. Although bone and matrix formation remained at control levels during period I in rats given Al, both measurements decreased from control values during period II. During Al exposure, bone and matrix apposition at the periosteum were reduced from control levels in period II, but not in period I. Neither osteoid width nor mineralization front width increased from control values in rats given Al. These findings indicate that Al reduces bone and matrix formation early in the course of Al exposure and prior to the development of histologic osteomalacia. Rather than acting as an inhibitor of mineralization, the early effect of Al on bone is the suppression of matrix synthesis. Our results suggest that the state of low bone formation seen in dialysis-associated osteomalacia may be the consequence of a direct toxic effect of Al on the cellular activity of osteoblasts.
铝可能是透析相关性骨软化症的致病因素。为研究铝对骨骼的早期影响，分别在连续两个时间段（第I阶段为28天，第II阶段为16天）对成对喂养的给予铝的大鼠和对照大鼠进行皮质骨生长测量，采用四环素标记骨骼的方法。除研究的第一周给予递增剂量的铝外，每周5天腹腔注射铝（每只大鼠2毫克元素铝）。对照大鼠仅接受生理盐水载体。在整个44天的研究中，给予铝的大鼠的骨和基质形成均低于对照值。虽然在第I阶段给予铝的大鼠的骨和基质形成保持在对照水平，但在第II阶段这两项测量值均低于对照值。在铝暴露期间，第II阶段骨膜处的骨和基质附着低于对照水平，但在第I阶段并非如此。给予铝的大鼠的类骨质宽度和矿化前沿宽度均未高于对照值。这些发现表明，铝在暴露过程早期且在组织学骨软化症发生之前就会减少骨和基质形成。铝对骨骼的早期作用不是作为矿化抑制剂，而是抑制基质合成。我们的结果表明，透析相关性骨软化症中所见的低骨形成状态可能是铝对成骨细胞的细胞活性产生直接毒性作用的结果。
