title: Changes in bone mineral density and bone turnover in patients on 'drug holiday' following bisphosphonate therapy: real-life clinic setting.
abstract: OBJECTIVE
  Treatment discontinuation after long-term bisphosphonate (BP), termed a 'drug holiday', has been proposed to reduce the risk of BP-associated complications. The duration of treatment cessation remains unclear. Changes in bone mineral density (BMD), bone turnover markers (BTMs) and their relationship with FRAX were assessed to help determine the optimum length of a 'drug holiday'.
  
  
  METHODS
  A retrospective analysis of 134 patients (13M, 121F) aged [mean (SD)] 68·4 (8·2) years who discontinued BPs after treatment for 5·9 (3·0) years for osteoporosis was undertaken. BMD at the lumbar spine (LS), total hip (TH), and femoral neck (FN) and biochemical parameters including serum 25 (OH) vitamin D, bone turnover markers (plasma CTX, P1NP) and FRAX scores were determined at discontinuation, 12-18 months and 24-30 months off treatment.
  
  
  RESULTS
  BMD decreased significantly at the LS [% change mean (SD): -0·94 (3·6), P = 0·008], TH [-1·4 (2·4), P < 0·001] and FN [-1·8 (4·4), P < 0·001] after treatment discontinuation for 12-18 months. In the subgroup who remained off treatment for 24-30 months, a progressive decline in BMD was seen at the TH and FN with total % decrease of -2·52 (3·5) and -2·7 (4·76), P < 0·001, respectively. CTX and P1NP increased significantly at 12-18 months after discontinuation [% change CTX: 95 (88), P < 0·001, P1NP: 88 (73), P < 0·001]. FRAX scores were significant predictors of % change in BMD at the FN (P < 0·05), independently of bone turnover and vitamin D status. In summary, our data show that following a 'drug holiday', the use of DEXA scans, BTMs and FRAX may help guide when to resume treatment.
authors.affiliation: Department of Chemical Pathology and Metabolic Medicine, St Thomas' Hospital, London, UK.|Metabolic Bone Clinic, Department of Rheumatology, Guy's Hospital, London, UK.
authors.forename: J
authors.initials: J
authors.lastname: Roberts
authors.affiliation: Department of Chemical Pathology and Metabolic Medicine, St Thomas' Hospital, London, UK.|Metabolic Bone Clinic, Department of Rheumatology, Guy's Hospital, London, UK.
authors.forename: C
authors.initials: C
authors.lastname: Castro
authors.affiliation: Osteoporosis Unit, Division of Imaging Sciences (Kings College London), Guy's Hospital, London, UK.
authors.forename: A E B
authors.initials: AE
authors.lastname: Moore
authors.affiliation: Metabolic Bone Clinic, Department of Rheumatology, Guy's Hospital, London, UK.|Osteoporosis Unit, Division of Imaging Sciences (Kings College London), Guy's Hospital, London, UK.
authors.forename: I
authors.initials: I
authors.lastname: Fogelman
authors.affiliation: Department of Chemical Pathology and Metabolic Medicine, St Thomas' Hospital, London, UK.|Metabolic Bone Clinic, Department of Rheumatology, Guy's Hospital, London, UK.
authors.forename: G
authors.initials: G
authors.lastname: Hampson
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000627:therapeutic use; D016723:Bone Remodeling / Q000187:drug effects*; D004164:Diphosphonates / Q000008:administration & dosage / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000188:drug therapy* / Q000503:physiopathology; D017063:Outcome Assessment, Health Care / Q000379:methods; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D012189:Retrospective Studies; D013997:Time Factors; D014807:Vitamin D / Q000031:analogs & derivatives / Q000097:blood; D028761:Withholding Treatment
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D010446:Peptide Fragments; D011347:Procollagen; C047202:procollagen Type I N-terminal peptide; D014807:Vitamin D; C104450:25-hydroxyvitamin D