Bone Material Strength index is low in Patients with Cushing's Syndrome even after long-term remission

Objective: Hypercortisolism in endogenous Cushing's syndrome (CS) results in decreased bone mineral density (BMD) and increased fracture risk. Although after remission BMD improves, fracture rate remains elevated, suggesting that BMD may not adequately reflect fracture risk in this group. The aim was to evaluate bone material properties, another component of bone quality, using Impact Microindentation (IMI) in patients with CS in remission.

Methods: Cross-sectional study in 60 patients and 60 age-, sex-, and BMD-matched controls at a tertiary referral center between 2019 and 2021. Bone material strength index (BMSi) was measured by IMI using the OsteoProbe® device at the tibia. In addition, laboratory investigation, BMD, and vertebral fracture assessment were performed.

Results: By design, patients and controls were comparable for age (median age 56.5 years), sex (48 women), BMD at the lumbar spine and femoral neck. They were also comparable regarding the number of fragility fractures (21 vs. 27, p=0.22). Median time of remission in patients was 6 years (range 1 to 41). Despite comparable BMD, BMSi was significantly lower in patients compared to controls (76.2±6.7 vs 80.5±4.9, p<0.001). In patients, BMSi was negatively correlated with BMI (r= -0.354, p=0.01), but not related to the presence of fracture, physiological hydrocortisone replacement use, other pituitary insufficiencies, or time since remission.

Conclusion: Bone material properties remain altered in patients with endogenous CS, even after long-term remission. These abnormalities, known to be associated with fractures in other populations, may play a role in the persistent bone fragility of steroid excess.