Bone phenotype of patients with telomere biology disorders

Telomere biology disorders (TBD) are a group of diseases that interfere with normal maintenance of telomeres, the ends of chromosomes that protect them from DNA damage. The most common manifestations are bone marrow failure, pulmonary and liver fibrosis. Systematic data on bone health in patients with TBD are scarce. Our aim was to elucidate the bone phenotype of these patients. The cohort comprises 36 adult patients (20 women and 16 men), with genetically confirmed TBD. Demographic, clinical and genetic characteristics, dual-energy X-ray absorptiometry (DXA) scans, spine X-rays and treatment details were reviewed. Median age of patients was 53.5 (43.0, 64.2) years. (Likely) pathogenic variants of the TERT gene were present in most patients. Osteopenia was diagnosed in 38.9% and osteoporosis in 25.0% of patients, 25.0% had a clinical fracture within the past 5 years, and 40.0% had at least one prevalent vertebral fracture (grade 1-3). T-score at the lumbar spine (-0.98 ± 1.48SD) was lower than at the femoral neck (-0.60 ± 1.09SD). Mean trabecular bone score (TBS) T-score was -1.32 ± 1.29SD. Bone-active therapy was used by 44.4% of the population, mostly oral bisphosphonates (85.7%). To conclude, we reported a high prevalence of osteopenia, osteoporosis, recent fractures and prevalent vertebral fractures, in patients with TBD. These results highlight the necessity of addressing the risk of osteoporosis and fractures in these patients during medical assessments. Most importantly, additionally to a DXA scan, a vertebral fracture assessment (VFA) or spine X-ray, is recommended to evaluate vertebral fractures.