Clin Genet. 2025 Aug 5. doi: 10.1111/cge.70038. Online ahead of print.
ABSTRACT
Avascular necrosis (AVN) and minimal trauma fractures (MTF) cause significant morbidity in patients with telomere biology disorders (TBDs). TBDs are associated with very high risks of bone marrow failure, pulmonary fibrosis, cancer, and many other complications due to pathogenic germline variants in genes essential for telomere function and maintenance. To understand the extent to which AVN and MTF occur in TBDs and identify areas requiring more research in the role of telomeres in bone biology. We assessed the occurrence of AVN and MTF in 233 patients with TBDs. An age, gender, and gene-matched TBD patient control group was used to assess associations between AVN/MTF and clinical characteristics. Forty-two (18%) patients with TBD developed at least one AVN and/or MTF event with 19 patients experiencing their first event in childhood. AVN and MTF were most common in patients with autosomal or X-linked recessive, or heterozygous TINF2 disease (19/36 AVN and 17/19 MTF). Androgen and corticosteroid use were more common in patients with AVN compared with matched patient controls (41.2% vs. 16.3%, p < 0.05 and 41.2% vs. 14%, p < 0.01, respectively); however, 57.1% of patients experienced AVN and/or MTF events in the absence of androgen or corticosteroid use. Severe bone marrow failure and hematopoietic cell transplantation history were significantly more common in MTF patients than in controls (44.2% and 30.2% respectively, p < 0.05). There were no statistically significant associations between low bone mineral density or vitamin D deficiency and AVN or MTF. AVN and MTFs are common, debilitating complications in TBDs and frequently occur independently of androgen or corticosteroid use. Our results underscore the need for disease-specific translational studies as well as improved prevention and therapeutic options for patients with TBDs. Trial Registration: ClinicalTrials.gov identifier: NCT00027274.
PMID:40762130 | DOI:10.1111/cge.70038
