Context: Several studies have reported increased risk of fragility fractures in patients with mild autonomous cortisol secretion (MACS), discordant to the degree of bone density deterioration.
Objective: To evaluate the effect of MACS on bone metabolism in patients with adrenal adenomas.
Design: Cross-sectional study with prospective enrollment, 2014-2019.
Setting: Referral center.
Patients: 213 patients with adrenal adenomas: 22 Cushing syndrome (CS), 92 MACS and 99 nonfunctioning adrenal tumors (NFAT).
Main outcome measures: Osteocalcin, procollagen I intact N-terminal (PINP), C-terminal telopeptide (CTX), sclerostin.
Results: Patients with CS demonstrated lower markers of bone formation compared with patients with MACS and NFAT (CS vs MACS vs NFAT: mean osteocalcin 14.8 vs 20.1 vs 21.3 ng/mL [P < 0.0001]; mean PINP 34.8 vs 48.7 vs 48.5 µg/L [P = 0.003]). Severity of cortisol excess was inversely associated with sclerostin (CS vs MACS vs NFAT: mean sclerostin 419 vs 538 vs 624 ng/L, [P < 0.0001]). In a multivariable model of age, sex, body mass index, cortisol, and bone turnover markers, sclerostin was a significant predictor of low bone mass in patients with MACS (OR 0.63 [CI 95%, 0.40-0.98] for each 100 ng/L of sclerostin increase).After adrenalectomy, osteocalcin, CTX, and sclerostin increased by a mean difference of 6.3 ng/mL, 0.12 ng/mL, and 171 pg/mL (P = 0.02 for all), respectively.
Conclusions: Lower sclerostin level in patients with MACS reflects a reduction in osteocyte function or number associated with exposure to chronic cortisol excess. Increase in bone turnover markers after adrenalectomy suggests restoration of favorable bone metabolism.
Keywords: Cushing syndrome; MACS; bone turnover markers; nonfunctioning adrenal tumors; osteopenia; osteoporosis; sclerostin.
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