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

Abstract

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

Keywords: HIGH‐RESOLUTION PERIPHERAL QUANTITATIVE COMPUTED TOMOGRAPHY (HR‐pQCT); OSTEOPETROSIS; TCIRG1; TRANSPLANTATION.

Fig. 1

Chest radiographs before and after transplantation in adult with osteopetrosis. Chest radiographs are shown for patient 2, (A) before transplantation and (B) after transplantation, demonstrating generalized increased bone density of all bones, and a rugger Jersey spine appearance.

Fig. 2

High‐resolution peripheral quantitative computed tomography images of the patient's distal tibia. 2D and 3D tomographic views and frontal cut‐away view show near complete obliteration of the trabecular compartment and extensive cortical porosity in patient 2, 11 years posttransplant (left images). For comparison, an adult male with autosomal dominant osteopetrosis due to CLCN7 mutation (middle images) and a healthy control adult male (right images) are shown.