Τίτλος:
The effect of pharmacological cessation and restoration of menstrual cycle on bone metabolism in premenopausal women with endometriosis
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
Introduction: GnRH-analogs induce bone loss. We aimed to investigate the effects of goserelin-induced menstrual cessation (MC) and subsequent menstrual restoration (MR) on bone metabolism (BM). Methods: In this prospective cohort study, premenopausal women (PMW) with histologically verified endometriosis (n = 21) received goserelin monthly for 6 months (6 m) resulting in MC and were followed up for another 6 m after MR (12 m). Age- and BMI-matched healthy PMW (n = 20) served as controls for bone mineral density (BMD) measurements. The primary endpoint was changes in lumbar spine (LS)-BMD at 6 m and 12 m; Secondary endpoints were changes in femoral neck (FN)-BMD, bone turnover markers (P1NP and CΤx), sclerostin, and expression of bone-related circulating microRNAs (miRNAs) at 6 m and 12 m. Results: Goserelin-induced MC reduced LS- and FN-BMD at 6 m (both p < 0.001). From 6 m to 12 m, LS-BMD increased (p < 0.001) but remained below baseline values (p = 0.012), whereas FN-BMD remained stable (p = 1.000). CTx and P1NP levels increased at 6 m (both p < 0.001) and decreased at 12 m (p < 0.001 and p = 0.013, respectively), while CTx (p = 1.000) alone and not P1NP (p = 0.020) returned to baseline. Sclerostin levels did not change. Relative expression of miRNAs targeting RUNX 2 and beta-catenin was significantly downregulated at 6 m compared to baseline (p < 0.001), while the expression of miRNAs targeting osteoblast and osteoclast function at both directions demonstrated a robust increase (up to 400fold) at 12 m (p < 0.001). Conclusions: Six months of goserelin-induced MC lead to significant bone loss associated with increased bone turnover and changes in the expression of bone-related miRNAs, changes that are only partially reversed at 6 m after MR. © 2022 Elsevier Inc.
Συγγραφείς:
Anastasilakis, A.D.
Papachatzopoulos, S.
Makras, P.
Gkiomisi, A.
Nikolakopoulos, P.
Polyzos, S.A.
Ntenti, C.
Ballaouri, I.
Gerou, S.
Tsachouridou, O.
Papatheodorou, A.
Aliazis, K.
Fermanoglou, S.
Bisbinas, I.
Yavropoulou, M.P.
Εκδότης:
W B SAUNDERS CO-ELSEVIER INC
Λέξεις-κλειδιά:
beta catenin; carboxy terminal telopeptide; circulating microRNA; gonadorelin derivative; goserelin; procollagen; procollagen type 1 n terminal propeptide; sclerostin; transcription factor RUNX2; unclassified drug, adult; Article; body mass; bone density; bone metabolism; bone turnover; cell differentiation; cell function; clinical article; cohort analysis; controlled clinical trial; controlled study; correlation analysis; down regulation; drug induced mentrual cessation; endometriosis; female; femoral neck; follow up; gene expression; histology; human; lumbar spine; menstrual cycle; metabolic bone disease; molecular mechanics; osteoblast; osteoclast; osteolysis; premenopause; prospective study; protein blood level; protein expression
DOI:
10.1016/j.bone.2022.116354
