Unusual Cortical Phenotype After Hematopoietic Stem Cell Transplantation in a Patient With Osteopetrosis

Sonia Afshariyamchlou, Michelle Ng, Asmaa Ferdjallah, Stuart J. Warden, Paul Niziolek, Imranul Alam, Lynda E. Polgreen, Erik A. Imel, Paul Orchard, Michael J. Econs

Research output: Contribution to journalArticlepeer-review


The osteopetroses are a group of rare genetic diseases caused by osteoclast dysfunction or absence. The hallmark of osteopetrosis is generalized increased bone mineral density (BMD). However, the bone is fragile and fractures are common. Autosomal recessive osteopetrosis is usually a severe disorder and often life-threatening in childhood. We present male siblings with autosomal recessive osteopetrosis due to biallelic variants in TCIRG1 who survived childhood and underwent hematopoietic stem cell transplant (HSCT) in adulthood. One sibling died of posttransplant complications. After transplant, the other sibling had improvement of multiple clinical parameters, including some decline in BMD Z-scores by dual-energy X-ray absorptiometry (DXA) and cessation of fractures. However, spine quantitative computed tomography 11 years after transplant demonstrated an anvil pattern of sclerosis with BMD Z-score of +18.3. High-resolution peripheral quantitative computed tomography (HR-pQCT) of the tibia demonstrated near complete obliteration of the marrow space combined with an unusual cortical phenotype, suggesting extensive cortical porosity at the distal tibia. This case highlights that despite successful transplantation and subsequent improvement in clinical parameters, this patient continued to have significantly elevated bone density and decreased marrow space. Transplant-associated increased cortical porosity is multifactorial and occurs in two-thirds of non-osteopetrotic patients undergoing HSCT. This finding after transplant in osteopetrosis may suggest particular sensitivity of the cortical bone to resorptive activity of transplanted osteoclasts. The case also suggests HR-pQCT may be a useful modality for imaging and assessing the therapeutic effects on bone in individuals with osteopetrosis.

Original languageEnglish (US)
Article numbere10616
JournalJBMR Plus
Issue number6
StatePublished - Jun 2022

Bibliographical note

Funding Information:
This study was funded in part by the National Institutes of Health through NIAMS grant P30AR072581 (The Indiana Center for Musculoskeletal Health Clinical Research Cores), NIAMS grant R01AR077869, and by the NCATS award UL1TR002529 (The Indiana Clinical and Translational Sciences Institute). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The authors thank the patient for participating in this study.

Publisher Copyright:
© 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.


  • TCIRG1

PubMed: MeSH publication types

  • Journal Article


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