{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,11]],"date-time":"2026-08-11T16:04:22Z","timestamp":1786464262621,"version":"build-2736575974"},"reference-count":49,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The classic paradigm of somatotropic-gonadal axis synergy in pubertal bone acquisition lacks validation in central precocious puberty (CPP), and the driver of the significant bone turnover marker (BTM) heterogeneity in this population is unknown.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>To investigate the independent and potential synergistic associations of insulin-like growth factor-1 (IGF-1) and peak luteinizing hormone (LH) with BTMs in girls with CPP.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective cohort included 190 treatment-na\u00efve girls with CPP. Participants were stratified into Low, Medium, and High bone turnover groups based on tertiles of a bone age-standardized composite Z-score of bone gla protein (BGP) and \u03b2-C-terminal telopeptide (\u03b2-CTX). We used multiple linear regression adjusted for chronological age, supplemented by E-value analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Marked BTM heterogeneity was confirmed (\n                      <jats:italic>p<\/jats:italic>\n                      for trend &amp;lt; 0.001). IGF-1 and peak LH levels exhibited significant graded increases across groups (\n                      <jats:italic>p<\/jats:italic>\n                      for trend = 0.003 and 0.030). After age-adjustment, IGF-1 independently correlated with both BGP (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u00a0=\u00a00.069,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.005) and \u03b2-CTX (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u00a0=\u00a00.001,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.030), while peak LH associated only with BGP (\n                      <jats:italic>\u03b2<\/jats:italic>\n                      \u00a0=\u00a00.411,\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.026). Critically, the IGF-1 \u00d7 LH peak interaction was non-significant (\n                      <jats:italic>p<\/jats:italic>\n                      \u00a0=\u00a00.655 and 0.791 for BGP and \u03b2-CTX, respectively). In contrast, glucolipid metabolic parameters showed no differences, arguing against their major role and highlighting neuroendocrine specificity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In this cross-sectional study of girls with CPP, heterogeneity in bone turnover was more strongly and consistently associated with the somatotropic axis (IGF-1) than with gonadotropin activity, and no significant synergy was observed. These findings suggest a potential shift toward a somatotropic-dominant mechanism in the context of pathological pubertal acceleration, highlight IGF-1 as a pivotal biomarker for skeletal metabolism assessment, and challenge the classical paradigm of somatotropic-gonadal axis collaboration.\u200b The proposed mechanism requires validation in longitudinal studies.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fendo.2026.1858179","type":"journal-article","created":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T04:41:58Z","timestamp":1784695318000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Somatotropic axis drives bone turnover heterogeneity independently of gonadotropin synergy in girls with central precocious puberty"],"prefix":"10.3389","volume":"17","author":[{"given":"Fuhui","family":"Liu","sequence":"first","affiliation":[{"name":"School of Clinical Medicine, Shandong Second Medicine 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