New insights into the metabolic-bone crosstalk in active acromegaly

Introduction: Body composition (BC) and adipokines share bone active properties and display an altered profile in acromegaly. The fibroblast growth factor 23 (FGF23)/alpha-Klotho system, also involved in bone metabolism, is upregulated in growth hormone (GH) excess states. Hence, we aimed to investigate their impact on bone in active acromegaly, compared to controls. Material and methods: BC, bone mineral density (BMD) (via dual X-ray absorptiometry), serum adipokines (leptin, adiponectin, resistin), parathyroid hormone (PTH), FGF23, alpha-Klotho, and osteocalcin were assessed in a cross-sectional study enrolling 35 patients with active acromegaly (Acro), compared to 35 sex, age, and body mass index (BMI) one-to-one matched healthy controls (CTL). Results: The Acro group had higher bone density scores (p< 0.05), lower visceral fat depots (p = 0.011), and lower serum leptin (p < 0.001) but elevated adiponectin (p < 0.001) and resistin (p = 0.001) concentrations when compared to the CTL group. alpha-Klotho was not related to the GH/IGF1 axis in the Acro group. Resistin was higher in both diabetic and non-diabetic Acro compared to CTL (p < 0.05). Age and BC were the main independent BMD predictors in regression analysis in both groups, while IGF1 was a positive predictor of osteocalcin levels in the Acro (beta= 0.48, p = 0.006). The correlations between adipokines, the FGF23/alpha-Klotho system, and bone parameters, respectively, were lost after adjusting for age and BC. Conclusions: Age and BC were the main independent BMD predictors in the acromegalic patients with active disease, while IGF1 was independently associated with serum osteocalcin concentrations. The role of alpha-Klotho in evaluating acromegaly and the associated osteopathy in the long-term appears to be limited. Our study is among the first to report significant serum resistin changes in patients with active acromegaly, opening new insights in the GH-mediated insulin resistance. The GH-resistin relationship merits further investigations.