Reduced Bone Material Strength Index in Cushing's Syndrome Patients Post-Remission
Overview
Patients with endogenous Cushing's syndrome (CS) in long-term remission exhibit significantly reduced bone material strength index (BMSi) compared to matched controls, despite similar bone mineral density (BMD). This persistent alteration in bone material properties may contribute to the sustained elevated fracture risk observed in this population.
Background
Cushing's syndrome is characterized by endogenous glucocorticoid excess leading to decreased bone formation, increased resorption, and consequent osteoporosis and fragility fractures. Although BMD improves after remission, fracture risk remains elevated, indicating that BMD alone does not fully capture bone fragility in CS. Bone quality encompasses architecture and tissue material properties, the latter measurable in vivo by impact microindentation (IMI) as bone material strength index (BMSi). Prior studies have shown altered bone microarchitecture and decreased BMSi in glucocorticoid-treated patients, but data on endogenous CS patients post-remission were lacking.
Data Highlights
Parameter
CS Patients (n=60)
Controls (n=60)
P Value
Median Age (years)
56.5
56.5
—
Women (n)
48
48
—
BMD (Lumbar Spine & Femoral Neck)
Comparable
Comparable
—
Fragility Fractures (n)
21
27
0.22
Median Remission Duration (years)
6 (range 1-41)
—
—
BMSi (mean ± SD)
76.2 ± 6.7
80.5 ± 4.9
<0.001
Key Findings
Bone material strength index (BMSi) was significantly lower in CS patients in remission compared to age-, sex-, and BMD-matched controls (76.2 ± 6.7 vs 80.5 ± 4.9; P < .001).
BMSi negatively correlated with body mass index (BMI) in CS patients (r = −0.354, P = .01).
BMSi was not associated with fracture presence, hydrocortisone replacement therapy, other pituitary insufficiencies, or time since remission.
Despite normalization of BMD after remission, bone material properties remain impaired in CS patients.
These persistent abnormalities in bone tissue quality may contribute to the sustained increased fracture risk in CS patients post-remission.
Clinical Implications
Assessment of fracture risk in patients with endogenous Cushing's syndrome should consider bone quality parameters beyond BMD, such as bone material strength index measured by impact microindentation. Persistent impairment in bone material properties despite remission highlights the need for ongoing fracture risk monitoring and potentially targeted therapies addressing bone quality. Clinicians should be aware that normal BMD does not exclude increased bone fragility in this population.
Conclusion
Bone material strength remains compromised in patients with endogenous Cushing's syndrome even after long-term remission, which may underlie the persistent elevated fracture risk despite normalized bone mineral density. Incorporating bone quality assessment could improve fracture risk evaluation in this group.
References
Endocrine Society Clinical Practice Guidelines, Pituitary Society Update -- Diagnosis and Treatment of Cushing's Syndrome
Impact Microindentation and Bone Fragility Studies -- OsteoProbe® Device Validation
Studies on Bone Microarchitecture and Material Properties in Glucocorticoid Excess -- Prior Research
by Manuela Schoeb, Paula J C Sintenie, Leontine E H Bakker, Nienke R Biermasz, Femke M van Haalen, Michiel F Nijhoff, Friso de Vries, Elizabeth M Winter, Alberto M Pereira, Natasha M Appelman-Dijkstra
