Whyte Michael P, McAlister William H, Novack Deborah V, Clements Karen L, Schoenecker Perry L, Wenkert Deborah
Center for Metabolic Bone Disease and Molecular Research, Shriners Hospitals for Children, St Louis, Missouri 63131-3597, USA.
J Bone Miner Res. 2008 Oct;23(10):1698-707. doi: 10.1359/jbmr.080511.
In 2003, we reported on a 12-yr-old boy who had developed osteopetrosis (OPT) while receiving pamidronate (PMD) for idiopathic bone pain and enigmatic elevation in circulating bone alkaline phosphatase. Now 17 yr of age, he was re-evaluated 6.5 yr after PMD exposure stopped. Our patient described less bone pain but further limb fractures. His growth plates were fused, yet hyperphosphatasemia persisted. Radiographs documented interval fractures of a metacarpal, an osteosclerotic distal radius, and a dense diaphyseal segment of an ulna where a "chalkstick" break remained incompletely healed after 2 yr. There was new L(4) spondylolysis, and previous L(5) spondylolysis had caused spondylolisthesis. Modeling disturbances of OPT persisted, but partial recovery was shown by metaphyseal surfaces with a unique concave shape. Metaphyseal osteosclerosis had remodeled imperfectly to become focal areas of dense, diaphyseal bone. Newer metaphyseal bone was unexpectedly osteopenic, especially in his distal femurs where cortices were thin and a paucity of trabeculae was documented by CT. Femoral necks had become short and wide with an abnormal contour. A "bone-within-bone" configuration was now present throughout his skeleton. In vertebrae, endplates were thin, and trabecular osteopenia was present central and peripheral to the bands of osteosclerosis. BMD Z-scores assessed by DXA had decreased into the normal range in his spine, hip, and whole body. Iliac crest biopsy showed active bone formation, with much less accumulated primary spongiosa than during the PMD infusions. Osteoclasts that had been dysmorphic, round cells without polarization and off of bone surfaces were now unremarkable in number, location, and appearance. In conclusion, bisphosphonate toxicity during childhood can impair skeletal modeling and remodeling with structural changes that evolve and carry into adult life.
2003年，我们报道了一名12岁男孩，他在接受帕米膦酸盐（PMD）治疗特发性骨痛和循环骨碱性磷酸酶神秘升高时患上了骨硬化症（OPT）。现在他17岁了，在停止接触PMD 6.5年后接受了重新评估。我们的患者称骨痛减轻，但仍有肢体骨折。他的生长板已经融合，但高磷酸酶血症仍然存在。X线片记录了掌骨、骨硬化的桡骨远端和尺骨骨干致密段的间歇性骨折，其中一处“粉笔样”骨折在2年后仍未完全愈合。出现了新的L4椎体峡部裂，之前的L5椎体峡部裂导致了椎体滑脱。OPT的塑形障碍持续存在，但干骺端表面呈现独特的凹形，显示出部分恢复。干骺端骨硬化未完全重塑，形成骨干致密骨的局灶性区域。较新的干骺端骨出人意料地骨质减少，尤其是在他的股骨远端，皮质薄，CT显示小梁稀少。股骨颈变得短而宽，轮廓异常。他的整个骨骼现在都出现了“骨中骨”结构。在椎体中，终板变薄，在骨硬化带的中央和周边出现小梁骨减少。通过双能X线吸收法（DXA）评估的骨密度Z值在他的脊柱、髋部和全身已降至正常范围。髂嵴活检显示有活跃的骨形成，与PMD输注期间相比，积累的初级海绵骨要少得多。曾经形态异常、呈圆形、无极化且远离骨表面的破骨细胞，现在在数量、位置和外观上都不明显了。总之，儿童期双膦酸盐毒性可损害骨骼塑形和重塑，其结构变化会持续发展并延续至成年期。
