Oral Presentation 29th Australian and New Zealand Bone and Mineral Society Annual Scientific Meeting 2019

PYY is a negative regulator of bone mass and strength (#37)

Victoria D Leitch 1 2 , Mary Jane Brassill 1 , Sofia Rahman 3 , Natalie C Butterfield 1 , Pattara Ma 1 , John G Logan 1 , Alan Boyde 4 , Holly Evans 5 , Peter I Croucher 6 , Rachel L Batterham 7 , Graham R Williams 1 , JH Duncan Bassett 1
  1. Department of Medicine, Imperial College London, London, UK
  2. RMIT Centre for Additive Manufacturing, RMIT, Melbourne, VIC, Australia
  3. Centre for Obesity Research, University College London, London, UK
  4. Oral BioEngineering, Queen Mary University of London, London, UK
  5. Sheffield Myeloma Research Team, University of Sheffield, Sheffield, UK
  6. Bone Biology Laboratory, Garvan Institute of Medical Research, Sydney, NSW, Australia
  7. National Institute of Health Research, University College London, London, UK

Bone loss in anorexia nervosa and following bariatric surgery is associated with an elevated circulating concentration of the gastrointestinal, anorexigenic hormone, peptide YY (PYY). Selective deletion of the PYY receptor Y1R in osteoblasts or Y2R in the hypothalamus results in high bone mass, but deletion of PYY in mice has resulted in conflicting skeletal phenotypes leading to uncertainty regarding its role in the regulation of bone mass. As PYY analogs are under development for treatment of obesity, we aimed to clarify the relationship between PYY and bone mass. The skeletal phenotype of Pyy knockout (KO) mice was investigated during growth (postnatal day P14) and adulthood (P70 and P186) using X-ray microradiography, micro-CT, back-scattered electron scanning electron microscopy (BSE-SEM), histomorphometry and biomechanical testing. Bones from juvenile and Pyy KO mice were longer (P<0.001), with decreased bone mineral content (P<0.001). Whereas, bones from adult Pyy KO mice had increased bone mineral content (P<0.05) with increased mineralisation of both cortical (P<0.001) and trabecular (P<0.001) compartments. Long bones from adult Pyy KO mice were stronger (maximum load P<0.001), with increased stiffness (P<0.01) and toughness (P<0.05) compared to wild-type (WT) control mice despite increased cortical vascularity and porosity (P<0.001). The increased bone mass and strength in Pyy KO mice resulted from increases in trabecular (P<0.01) and cortical bone formation (P<0.05). These findings demonstrate that PYY acts as a negative regulator of osteoblastic bone formation, implicating increased PYY levels in the pathogenesis of bone loss during anorexia or following bariatric surgery.