Endocrine Abstracts

Background

Endogenous Cushing’s syndrome (CS) is detrimental to bone. The skeletal complications are characterized by decreased bone formation and increased bone resorption, resulting in decreased bone mineral density (BMD) and an increased risk of fractures at time of diagnosis. After remission of the disease, BMD improves towards normal values but fracture rate remains elevated. Therefore, components of bone quality other than BMD, such as bone material properties, must be affected in CS, even after remission. Bone material properties can be assessed by Impact Microindentation (IMI) in a minimally-invasive way.

Aim

To evaluate bone material properties using IMI in patients with CS in remission.

Methods

In this cross-sectional study, 57 consecutive patients (45 women), 16 with prevalent fragility fractures, and 57 controls matched for age, sex, and BMD (45 women), 25 with fragility fractures, were included. Bone material strength index (BMSi) was measured by IMI using the OsteoProbe device at the midshaft of the tibia after applying local anesthetic. In addition, laboratory investigation, BMD, and vertebral fracture assessment were performed. Remission was defined according to the Endocrine Society Clinical Practice guidelines.

Results

Mean age of the patients was 54.5 ± 12.5 years and 55.2 ± 12.4 years in controls, (P = 0.70). The main origin of hypercortisolism was pituitary in 47 patients, followed by adrenal (n = 8) and ectopic origin (n = 2). Median time of remission was 6 years (IQR 3 to 15 years). BMD was comparable in patients and controls at the lumbar spine (0.98 ± 0.16 g/cm² vs 0.95 ± 0.11 g/cm², P = 0.49) and the femoral neck (0.75 ± 0.12 g/cm² vs 0.74 ± 0.12 g/cm², P = 0.73). However, BMSi was significantly lower in patients compared to controls (76.5 ± 6.9 vs 81.4 ± 5.1, P < 0.001). In patients, BMSi was negatively correlated with BMI (r = -0.51, P < 0.001), but not related to the presence of fragility fractures, dependence, duration and dosage of hydrocortisone suppletion, or other pituitary failure. In controls, BMSi was not related to BMI, but significantly lower in those with fragility fractures compared to those without fragility fractures (78.1 ± 4.5 vs 84.0 ± 4.1, P < 0.001).

Conclusion

BMSi was significantly lower in CS patients in remission than in matched controls, independently of BMD. Our findings indicate that bone material properties are permanently altered in patients with endogenous Cushing’s syndrome even after long-term remission, which may contribute for their persisting increased fracture risk. The IMI technique might be a valuable additional tool in the evaluation of bone fragility in these patients.