Musculoskeletal Assessment in Patients with Adrenal Incidentalomas: Should We Integrate the Trabecular Bone Score and/or Circulating Irisin?

<b>Background/Objectives</b>: Current musculoskeletal health assessment expanded beyond bone mineral density (BMD) at central DXA to include, for instance, trabecular bone score (TBS) and emergent biomarkers, such as adipokines and myokines (e.g., irisin) assays. A current gap in their application is reflected in limited research regarding adrenal tumors, especially non-functional adrenal tumors/mild autonomous cortisol secretion (NFATs/MACS). To assess this current gap, we aimed to explore beyond BMD, specifically, TBS and circulating irisin, in relation to the adrenal status in NFATs/MACS. <b>Methods</b>: This is a prospective, cross-sectional, single-center, exploratory study, conducted between October 2024 and December 2025. <b>Results</b>: A total of 81 menopausal women were included (mean age of 63.26 ± 8.82 years, 15.86 ± 9.5 years since menopause, average BMI of 30.69 ± 5.76 kg/sqcm. Out of them, 33.33% had NFATs/MCAS (group AI) and 66.67% were controls (group C), with similar age, years since menopause, and BMI. The prevalence of type 2 diabetes was 66.67% versus 68.52% (<i>p</i> = 0.865). TBS correlated with lumbar BMD/T-score (<i>N</i> = 33), while age and lumbar BMD were independent TBS predictors (<i>N</i> = 81), but not type 2 diabetes nor NFAs/MCAS. TBS correlated with the five-year age groups (r = -0.273, <i>p</i> = 0.003). Irisin correlated with osteocalcin (r = -0.252, <i>p</i> = 0.007), P1NP (r = -0.187, <i>p</i> = 0.049) and CrossLaps (r = -0.209, <i>p</i> = 0.026) in tumor-free controls. In the AI group, a higher irisin was associated with a higher second-day cortisol after 1 mg DST (r = 0.11, <i>p</i> = 0.584) and a lower ACTH (r = -0.716, <i>p</i> < 0.001). The rate of low TBS (based on 1.350 cutoffs) was 48.15% versus 38.89% in group AI versus C. In the AI group, patients with low TBS had lower osteocalcin, P1NP, and CrossLaps than those with normal TBS, with a similar rate of type 2 diabetes (which might reduce the bone turnover markers) and MACS-positive prevalence (between 25 and 28%). <b>Conclusions</b>: The median glycated hemoglobin A1c (5.78% versus 5.93%, <i>p</i> = 0.94) and median HOMA-IR (1.53 versus 1.42, <i>p</i> = 0.948) suggest a certain level of glucose control, which might not be reflected in severely damaged bone microarchitecture, as shown by TBS. Irisin may be one of the additional factors in these tumors reflecting the hormonal burden. Irisin was statistically significantly elevated with the increase in BMI groups. To our best awareness, this is the first synchronous analysis of TBS and irisin levels in this type of tumor to address the bone status in relation to the glucose profile and adrenal panel. Noting this is an exploratory, hypothesis-generating study, further research will highlight the true value of TBS and irisin for practitioners in the adrenal field, including multi-layered models of bone status prediction.