Lack of an acute effect of ghrelin on markers of bone turnover in healthy controls and post-gastrectomy subjects ☆ M.S.B. Huda a , B.H. Durham d , S.P. Wong a , T.M. Dovey c , P. McCulloch b , D. Kerrigan b , J.H. Pinkney a , W.D. Fraser d , J.P.H. Wilding a, ⁎ a Clinical Sciences Centre, University of Liverpool Diabetes and Endocrinology Research Group, University Hospital Aintree, Longmoor lane, Liverpool L9 7AL, UK b Department of Surgery, University Hospital Aintree, Liverpool L9 7AL, UK c School of Psychology, University of Liverpool, UK d Department of Clinical Chemistry, Royal Liverpool University Hospital, Prescott Street, Liverpool, UK Received 3 March 2007; revised 9 May 2007; accepted 16 May 2007 Available online 31 May 2007 Abstract Background: Ghrelin is a gut-brain peptide that powerfully stimulates appetite and growth hormone secretion and is also known to directly regulate osteoblast cell function in vitro and in animal models. Little is known about the effects of ghrelin on bone turnover in humans. As the stomach is the main site of ghrelin synthesis, gastrectomy patients are deficient in ghrelin; they are also prone to osteopenia and osteomalacia. Hypothesis: Ghrelin may play a role in bone regulation in humans; ghrelin deficiency following gastrectomy is associated with the disrupted regulation of bone turnover seen in these subjects. Subjects and methods: In a randomised, double-blind, placebo-controlled study 8 healthy controls and 8 post-gastrectomy subjects were infused with intravenous ghrelin (5 pmol/kg/min) or saline over 240 min on different days. Subjects were given a fixed energy meal during the infusion. Ghrelin, GH, type-1 collagen β C-telopeptide (βCTX), a marker of bone resorption, and procollagen type-1 amino-terminal propeptide (P1NP), a marker of bone formation, were measured. Results: Fasting ghrelin was significantly lower in the gastrectomy group during the saline infusion (226.1 ± 62.0 vs. 762 ± 71.1 ng/l p b 0.001). Growth hormone was significantly higher at 90 min after the ghrelin infusion, compared to saline in both healthy controls (61.1 ± 8.8 vs. 1.4 ± 0.6 mIU/l p b 0.001) and gastrectomy subjects (61.1 ± 11.8 vs. 0.9 ± 0.2 mIU/l p b 0.001) confirming the ghrelin was bioactive. Gastrectomy subjects were significantly older and had significantly higher plasma βCTX than healthy controls at all time points (ANOVA p = 0.009). After adjustment for age and BMI ghrelin was found to be a significant predictor of baseline plasma βCTX and was inversely correlated with baseline plasma βCTX (β = - 0.54 p = 0.03 R 2 = 26%). However, there was no significant effect of the ghrelin infusion on plasma βCTX or P1NP in either subject group. Conclusions: Ghrelin infusion has no acute effect on markers of bone turnover in healthy controls and post-gastrectomy subjects, but is inversely correlated with bone resorption. © 2007 Elsevier Inc. All rights reserved. Keywords: Ghrelin; Bone resorption; Bone formation Introduction Ghrelin is a unique gut-brain peptide that stimulates appetite and GH release [1] and circulating concentrations of ghrelin increase progressively in the pre-prandial period and decrease to a nadir within 1 h of eating. [2] Ghrelin was discovered as the natural ligand for the growth hormone secretagogue receptor GHS-R1a [3,4] which has subsequently been identified in several different human tissues including the stomach, heart, lung, pancreas, intestine, gonads, adrenal glands, adipose tissue, bone, T cells, pituitary and hypothalamus [5]. In addition to effects on appetite and GH secretion, ghrelin has been found in a recent study to influence bone turnover [6]. GHS-R1a receptors were found in rat osteoblast cells and in vitro, ghrelin stimulated osteoblast proliferation—this effect Bone 41 (2007) 406 – 413 www.elsevier.com/locate/bone ☆ This work was supported by an International Endocrine Research Prize from Pharmacia awarded to JHP and JPHW. ⁎ Corresponding author. Fax: +44 151 529 5888. E-mail address: j.p.h.wilding@liv.ac.uk (J.P.H. Wilding). 8756-3282/$ - see front matter © 2007 Elsevier Inc. All rights reserved. doi:10.1016/j.bone.2007.05.006