TY - JOUR
T1 - Bisphosphonate-induced osteopetrosis
T2 - Novel bone modeling defects, metaphyseal osteopenia, and osteosclerosis fractures after drug exposure ceases
AU - Whyte, Michael P.
AU - McAlister, William H.
AU - Novack, Deborah V.
AU - Clements, Karen L.
AU - Schoenecker, Perry L.
AU - Wenkert, Deborah
N1 - Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.
PY - 2008/10
Y1 - 2008/10
N2 - In 2003, we reported on a 12-yr-old boy who had developed osteopetrosis (OFT) 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 L4 spondylolysis, and previous L5 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.
AB - In 2003, we reported on a 12-yr-old boy who had developed osteopetrosis (OFT) 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 L4 spondylolysis, and previous L5 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.
KW - Alkaline phosphatase
KW - Bone remodeling
KW - Creatine kinase
KW - Endochondral bone
KW - Fracture
KW - Hyperphosphatasemia
KW - Orthodonture
KW - Osteoclast
KW - Osteoclastogenesis
KW - Osteodensitometry
KW - Osteosclerosis
KW - Pamidronate
KW - Skeletogenesis
KW - Spondylolisthesis
UR - http://www.scopus.com/inward/record.url?scp=52949116400&partnerID=8YFLogxK
U2 - 10.1359/jbmr.080511
DO - 10.1359/jbmr.080511
M3 - Article
C2 - 18505375
AN - SCOPUS:52949116400
SN - 0884-0431
VL - 23
SP - 1698
EP - 1707
JO - Journal of Bone and Mineral Research
JF - Journal of Bone and Mineral Research
IS - 10
ER -