The Effect of LRP5 Polymorphisms on Bone Mineral Density Is Apparent in Childhood

Paget’s disease of bone (PDB) can adversely affect quality of life, but relatively little is known about the clinical predictors of reduced quality of life in patients with the disease. Here, we studied quality of life and its determinants in a large cohort of PDB patients who had been enrolled into the PRISM study, a randomized comparative trial of intensive versus symptomatic treatment for PDB. Health-related quality of life was assessed using the Short-Form 36 (SF36) questionnaire and other validated assessment instruments in 1,324 subjects with PDB. Clinical predictors of quality of life were identified by multivariate regression analysis. The physical summary (mean ± standard deviation) score of the SF36 was substantially reduced in PDB to 36.3 ± 11.3 compared with the expected population norm of 50 (P < 0.001). The mental summary score was only slightly reduced, to 48.7 ± 11.8, in PDB; but this was statistically significant (P < 0.001). Bone pain due to PDB, previous bisphosphonate therapy, and increasing age were identified as negative predictors of the SF36 physical summary score (P < 0.001); but serum levels of total alkaline phosphatase (ALP) did not predict physical summary score. We conclude that PDB has a substantial negative impact on health-related quality of life, which mainly affects physical functioning. The lack of correlation between ALP and quality of life observed in this study emphasizes the importance of addressing quality-of-life issues when treating PDB and not just focussing on response of ALP levels. The PRISM Trial Group. Writing Group: Marion K. Campbell, William D. Fraser, Anne L. Langston, Graeme MacLennan, Stuart H. Ralston, Peter L. Selby. Independent Trial Steering Committee: Maarten Boers (chair), Juliet Compston (member), Philip Hannaford (observer, host institution representative), Marilyn McCallum (member), Graham Russell (member). Data Monitoring Committee: Ade Adebajo, Nigel Arden, Howard Bird, Margaret Byron, Alison Carr, Ernest Choy (chair 2001–06), Peter Croft, Vern Farewell, Ian Harvey, Sarah Hewlett, Shabbar Jaffar, Martyn Lewis, Gary MacFarlane (chair 2006), Chris Roberts, Lee Shepstone, Deborah Symmons. Trial Office Team: Gary Adams (data manager), Daniel Barnett (trial programmer), Marie Cameron (research assistant), Janice Cruden (data manager), Magnus McGee (trial statistician), Donna Patterson (data manager), Clare Robertson (research assistant), Allan Walker (trial programmer), Euan Wiseman (trial programmer). Local Trial Investigators (the following people were responsible for the local coordination of the study at the collaborating hospital sites, *lead consultant): Aberdeen Royal Infirmary, UK, Vera Herd, Stuart H. Ralston*; University Hospital Aintree, UK, Rose McIver, Mashood Siddiqi*; Royal National Hospital for Rheumatic Disease, Bath, UK, Ashok Bhalla,* Diana Cochran, Sharon Grieve, Sara Mills; Musgrave Park Hospital, Belfast, UK, Katrina Hughes, Richard Wallace*; Queen Elizabeth Hospital, Birmingham, UK, Neil Gittoes,* Liz McGregor; Royal Bolton Hospital, UK, Keatley R. H. Adams,* Mary Adams; Ninewells Hospital, Dundee, UK, Vera Herd, Graham Leese,* Ellen Malcolm; University Hospital of North Durham, UK, Sarah Hailwood*; Medway Maritime Hospital, Gillingham, UK, Paul Ryan,* Gwen Worcester; Western Infirmary, Glasgow, UK, Alastair McLellan,* Debby Nelson; Huddersfield Royal Infirmary, UK, Allan Fairclough, Richard Reece*; Raigmore Hospital, Inverness, UK, Fiona McGhie, Malcolm Steven*; Airedale Hospital, Keighley, UK, Annie Cooper,* Stuart H. Ralston*; Leicester Royal Infirmary and Leicester General Hospital, UK, Margaret Coe, S. Javed Iqbal,* Geraldine McHugh; Royal Liverpool University Hospital, UK, William D. Fraser,* Ya-Wen Jessica Huang, Margaret Little, Vinita Mishra, Nicola Wherly; Llandudno General Hospital, UK, Merle Maddison, Lyn Vaterlaws*; Guy’s Hospital, London, UK, Ignac Fogelman,* Nina Prescod; King’s College Hospital, London, UK, Rama Chandra, Tina Mangion, Caje Moniz*; Manchester Royal Infirmary, UK, Susan Harrison, Peter L. Selby*; James Cook University Hospital, Middlesbrough, UK, John N. Fordham,* Val Lunn, Dawn Youll; Freeman Hospital, Newcastle, UK, Roger Francis*; Norfolk & Norwich University Hospital, UK, Jane Leeder, David G. I. Scott*; City Hospital, Nottingham, UK, David Hosking,* Pat San; Robert Jones & Agnes Hunt Orthopaedic Hospital, Oswestry, UK, Michael Davie,* Teresa Jones, Dawn Pugh; Nuffield Orthopaedic Centre, Oxford, UK, Matthew Brown, Vicky Toghill, John Wass,* Jo Young; Llandough Hospital, Penarth, UK, Roz Broadbent, Mike Stone,* Jane Turton; Derriford Hospital, Plymouth, UK, Charles Hutton,* Maggie Jolly; Poole Hospital, UK, Julia Taylor, Paul Thompson*; Harold Wood Hospital, Romford, UK, Kuntal Chakravarty*; Oldchurch Hospital, Romford, UK, Christine Heron, Christopher Kelsey*; Hope Hospital, Salford, UK, Sylvia Mercer, Terence W. O’Neill*; Northern General Hospital, Sheffield, UK, Jenny Cliffe, Linda Kersh, Eugene McCloskey*; Southampton General Hospital, UK, Trish Byng, Janet Cushnaghan, Cyrus Cooper,* Nick Harvey, Karen Walker-Bone; Royal National Orthopaedic Hospital, Stanmore, UK, Richard Keen,* Maggie Partridge; Great Western Hospital, Swindon, UK, Lynne Kerton, Elizabeth Price*; Queen Elizabeth II Hospital, Welwyn Garden City, UK, Jill Lomas, Peter Winocour*; Arrowe Park Hospital, Wirral, UK, E. George, T. D. Kennedy,* Anthony Lake; Yeovil District Hospital, UK, Nita Beacham, Clare Buckley, Jenny Knight, Lisa Martin, T. G. Palferman.*