Bone Mineral Density Improvement After Resolution of Endogenous Cushing Syndrome: A Systematic Review and Meta-Analysis

Objective: We aimed to identify all evidence to evaluate bone mineral density (BMD) improvement after resolution of endogenous Cushing syndrome (eCS). Methods: Potentially eligible studies were identified from the EMBASE and PubMed databases from inception to February 2024, utilizing a search strategy incorporating terms related to “Bone mineral density” and "Cushing syndrome". Eligible studies must include patients diagnosed with eCS. These studies must present lumbar spine (LS) or femoral neck (FN) BMD measurements before and after resolution of eCS. Point estimates with standard errors were extracted from each study and combined using the generic inverse variance method. Meta-regression analysis was utilized to explore factors influencing BMD improvement. Results: After systematic review, 5085 records were identified. After systematic review, 12 studies (302 patients, mean age of 13-44 years, % female patients 57%-92%, follow-up time 16-60 months) were eligible. The meta-analysis demonstrated that resolution of eCS resulted in improvements in LS BMD (pooled mean difference T-score: +0.86, I² 80.4%; 95%CI 0.51-1.21; Z-score: +0.86, 95%CI 0.57-1.16, I² 75.9%) and FN BMD (pooled mean difference: T-score: +0.38, 95%CI 0.26-0.51, I² 0.0%; Z-score: +0.44, 95%CI 0.31-0.57, I² 20.3%). The meta-regression analysis identified factors potentially influencing LS BMD increases, including longer follow-up time, higher %female patients and lower mean baseline 24-hour UFC, while none of these factors were significantly associated with FN BMD changes. Conclusion: Our study presents the degree and influencing factors of BMD improvement following eCS resolution. These findings offer guidance for management of eCS-associated osteoporosis.