Context: Two adipokines highly expressed in fat mass, adiponectin with antiinflammatory and anti-atherogenic properties and visfatin with an insulin-mimetic effect, are potential contributors to bone metabolism. In acromegaly, data on adiponectin are contradictory, and there are no data on visfatin. Objectives: The aim of the study was to evaluate adiponectin and visfatin in acromegaly, compared to control subjects, and to analyze their relationship with body composition and bone markers. Methods: Bone markers [osteocalcin, total amino-terminal propeptide of type 1 procollagen (total P1NP), carboxy-terminal telopeptide (β-Crosslaps)], body composition (by dual-energy x-ray absorptiometry), adiponectin (by ELISA), and visfatin (by immunoanalysis)] were evaluated in 60 acromegalic patients (24 males and 36 females) and in 105 age- and gender-matched healthy controls (33 males and 72 females). Acromegalic patients were classified as controlled, with normal IGF-I and nadir GH no greater than 1 μg/liter (n = 41), or active (n = 19). Results: Acromegalic patients had lower adiponectin (P < 0.01), more lean body mass (P < 0.01), more total body mass (P < 0.01), higher bone formation markers (osteocalcin and total P1NP, P < 0.05 and P < 0.01, respectively), but less bone resorption markers (β-Crosslaps, P < 0.001) than controls. No differences in visfatin and BMD were found between patients and controls. Adiponectin correlated negatively with BMD (r=-0.374; P<0.05) and lean mass (r=-0.301; P<0.05) and positively with age (r = 0.341; P < 0.001) in acromegaly. Visfatin correlated negatively with BMD (r = -0.359; P < 0.05). BMD was the predictor for adiponectin and visfatin. Conclusions: Acromegalic patients present hypoadiponectinemia and a favorable bone marker profile. Adiponectin and visfatin could be a link between fat mass and bone in acromegaly. Copyright © 2009 by The Endocrine Society.