Abstract | UNLABELLED: We report on a case of osteoclast-poor osteopetrosis who received a hematopoietic stem cell graft and, despite hematological engraftment, showed little signs of response in the skeletal defect. Clinical and laboratory studies supported the concept that the bone microenvironment remained abnormal, thus reducing the clinical response to transplantation. INTRODUCTION: MATERIALS AND METHODS: RESULTS: Before transplantation few, small mononuclear osteoclasts formed ( F-actin ring-positive cells, co-localizing with vitronectin receptor [ alphavbeta3 integrin] and TRACP) associated with occasional, small resorption lacunae. Low levels of collagen C-terminal telopeptide (CTx) fragments were released from these cultures as assessed by ELISA ( CrossLaps; patient, 12.85 nM; control, 448.6 nM). In contrast, osteoclasts formed in cultures after transplantation formed to a similar degree to control cultures from healthy individuals: large numbers of osteoclasts containing numerous nuclei were present, and approximately 50% of the surface of bone slices was resorbed, associated with intermediate levels of collagen fragment release (116.48 nM). The culture data reflect the histopathology and radiological findings and also support previous studies showing that neither M-CSF nor RANKL rescues osteoclast-poor osteopetrosis. CONCLUSIONS: This is the first case reported in which a successful hematopoietic engraftment failed to correct an osteopetrotic skeletal defect, and this finding may be credited to the age at which the child was transplanted.
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Authors | Brian M Nicholls, Robbert G M Bredius, Neveen A T Hamdy, Egbert J A Gerritsen, Arjan C Lankester, Pancras C W Hogendoorn, Stephen A Nesbitt, Michael A Horton, Adrienne M Flanagan |
Journal | Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
(J Bone Miner Res)
Vol. 20
Issue 12
Pg. 2264-70
(Dec 2005)
ISSN: 0884-0431 [Print] United States |
PMID | 16294279
(Publication Type: Case Reports, Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)
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Chemical References |
- CD11c Antigen
- CD18 Antigens
- Carrier Proteins
- Collagen Type I
- Glycoproteins
- Integrin alphaVbeta3
- Isoenzymes
- Membrane Glycoproteins
- Osteoprotegerin
- Peptides
- RANK Ligand
- Receptor Activator of Nuclear Factor-kappa B
- Receptors, Cytoplasmic and Nuclear
- Receptors, Tumor Necrosis Factor
- TNFRSF11A protein, human
- TNFRSF11B protein, human
- TNFSF11 protein, human
- collagen type I trimeric cross-linked peptide
- Macrophage Colony-Stimulating Factor
- Collagen
- Acid Phosphatase
- Tartrate-Resistant Acid Phosphatase
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Topics |
- Acid Phosphatase
(analysis)
- Biopsy
- CD11c Antigen
(analysis)
- CD18 Antigens
(analysis)
- Carrier Proteins
(pharmacology)
- Cartilage
(pathology)
- Cell Differentiation
(drug effects)
- Child
- Collagen
(metabolism)
- Collagen Type I
- Cord Blood Stem Cell Transplantation
- DNA Mutational Analysis
- Female
- Femur
(pathology)
- Glycoproteins
(blood)
- Hematologic Diseases
(etiology)
- Humans
- Humerus
(pathology)
- Integrin alphaVbeta3
(analysis)
- Isoenzymes
(analysis)
- Leukocytes, Mononuclear
(drug effects, pathology)
- Macrophage Colony-Stimulating Factor
(pharmacology)
- Membrane Glycoproteins
(pharmacology)
- Osteoclasts
(chemistry, metabolism, pathology)
- Osteopetrosis
(complications, pathology, therapy)
- Osteoprotegerin
- Peptides
(metabolism)
- RANK Ligand
- Receptor Activator of Nuclear Factor-kappa B
- Receptors, Cytoplasmic and Nuclear
(blood)
- Receptors, Tumor Necrosis Factor
(blood)
- Tartrate-Resistant Acid Phosphatase
- Transplantation, Homologous
- Treatment Outcome
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