Predictors of low bone density and fracture risk in Loeys-Dietz syndrome.

PURPOSE: Loeys-Dietz syndrome (LDS) is a connective tissue disorder affecting multiple organ systems, including bone.

METHODS

We defined the bone phenotype and clinical predictors of low bone density and fracture risk in 77 patients with LDS type 1 to type 5.

RESULTS

Patients with LDS had dual-energy x-ray absorptiometry (DXA) Z-scores significantly < 0, and 50% of children and 9% of adults had Z-scores < -2. Sixty percent of patients had ≥1 fracture, and 24% of patients with spinal x-rays scans showed spinal compression fractures. Lower body mass index, asthma, male sex and eosinophilic gastrointestinal disease were correlated with lower DXA Z-scores. The count of 5 LDS-associated skeletal features (scoliosis, pes planus, arachnodactyly, spondylolisthesis, and camptodactyly) in patients with LDS was correlated with DXA Z-score. Adults with ≥1 skeletal features had DXA Z-scores significantly < 0, and children with >2 features had DXA Z-score significantly < -2. Bone turnover markers suggest accelerated bone resorption. Data from 5 patients treated with bisphosphonates suggest a beneficial effect.

CONCLUSION

All LDS types are associated with reduced bone density and increased risk of fracture, which may be due to increased bone resorption. Clinical features can predict a subgroup of patients at highest risk of low bone density and fracture risk.