title: Establishment of age- and sex-adjusted reference data for hand bone mass and investigation of hand bone loss in patients with rheumatoid arthritis treated in clinical practice: an observational study from the DANBIO registry and the Copenhagen Osteoarthritis Study.
abstract: BACKGROUND
  Rheumatoid arthritis is characterised by progressive joint destruction and loss of periarticular bone mass. Hand bone loss (HBL) has therefore been proposed as an outcome measure for treatment efficacy. A definition of increased HBL adjusted for age- and sex-related bone loss is lacking. In this study, we aimed to: 1) establish reference values for normal hand bone mass (bone mineral density measured by digital x-ray radiogrammetry (DXR-BMD)); and 2) examine whether HBL is normalised in rheumatoid arthritis patients during treatment with tumour necrosis factor alpha inhibitors (TNFI).
  
  
  METHODS
  DXR-BMD was measured from hand x-rays in a reference cohort (1485 men/2541 women) without arthritis randomly selected from an urban Danish population. Sex- and age-related HBL/year was estimated. DXR-BMD was measured in rheumatoid arthritis patients (n = 350: at start of TNFI, and ~2 years after TNFI start), of which 135 patients had three x-rays (~2 years prior to TNFI, at start of TNFI, and ~2 years after TNFI start). Individual HBL/year prior to and during TNFI was calculated and compared to reference values.
  
  
  RESULTS
  Estimated HBL/year varied strongly with age and sex. Compared to the reference values, 75 % of 135 patients had increased HBL prior to TNFI treatment and 59 % had increased HBL during TNFI treatment (p = 0.17, Chi-squared). In 38 % (38/101) of patients with increased HBL, HBL was normalised during TNFI treatment, whereas 47 % (16/34) of patients with normal HBL prior to TNFI had increased HBL during TNFI treatment. In the 350 patients, increased HBL during TNFI was associated with time-averaged 28-joint disease activity score (odds ratio 1.69 (95 % Confidence Interval 1.34-2.15)/unit increase, p < 0.001), and patients in time-averaged remission had lower HBL than patients without remission (0.0032 vs. 0.0058 g/cm(2)/year; p < 0.001, Mann-Whitney).
  
  
  CONCLUSIONS
  We established age- and sex-specific reference values for DXR-BMD in a large cohort without arthritis. HBL was increased in the majority of rheumatoid arthritis patients initiating TNFI in clinical practice, and only normalised in a minority during TNFI.
authors.affiliation: DANBIO registry and Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Centre of Head and Orthopedics, Ndr. Ringvej 57, DK-2600, Glostrup, Denmark. lykke@oernbjerg.dk.|Rigshospitalet, Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. lykke@oernbjerg.dk.
authors.forename: Lykke Midtbøll
authors.initials: LM
authors.lastname: Ørnbjerg
authors.affiliation: DANBIO registry and Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Centre of Head and Orthopedics, Ndr. Ringvej 57, DK-2600, Glostrup, Denmark. mo@dadlnet.dk.|Rigshospitalet, Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. mo@dadlnet.dk.
authors.forename: Mikkel
authors.initials: M
authors.lastname: Østergaard
authors.affiliation: Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark. twj@dadlnet.dk.
authors.forename: Trine
authors.initials: T
authors.lastname: Jensen
authors.affiliation: Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark. hyld@dadlnet.dk.
authors.forename: Lars
authors.initials: L
authors.lastname: Hyldstrup
authors.affiliation: Department of Endocrinology, Hvidovre Hospital, Hvidovre, Denmark. pb-m@dadlnet.dk.
authors.forename: Pernille
authors.initials: P
authors.lastname: Bach-Mortensen
authors.affiliation: Department of Rheumatology, Diakonhjemmet Hospital, Oslo, Norway. pernilleboyesen@gmail.com.
authors.forename: Pernille
authors.initials: P
authors.lastname: Bøyesen
authors.affiliation: DANBIO registry and Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Centre of Head and Orthopedics, Ndr. Ringvej 57, DK-2600, Glostrup, Denmark. anjathormann@hotmail.com.
authors.forename: Anja
authors.initials: A
authors.lastname: Thormann
authors.affiliation: Department of Rheumatology, Aarhus University Hospital, Aarhus, Denmark. ulritarp@rm.dk.
authors.forename: Ulrik
authors.initials: U
authors.lastname: Tarp
authors.affiliation: Department of Medicine, Hospital of South West Jutland, Esbjerg, Denmark. wolfgang.peter.boehme@rsyd.dk.
authors.forename: Wolfgang Peter
authors.initials: WP
authors.lastname: Bøhme
authors.affiliation: Department of Rheumatology, Odense University Hospital, Odense, Denmark. hanne.lindegaard@rsyd.dk.
authors.forename: Hanne
authors.initials: H
authors.lastname: Lindegaard
authors.affiliation: Rheumatism Hospital, University of Southern Denmark, Gråsten, Denmark. upoulsen@gigtforeningen.dk.
authors.forename: Uta Engling
authors.initials: UE
authors.lastname: Poulsen
authors.affiliation: Department of Rheumatology, Aalborg University Hospital, Aalborg, Denmark. a.schlemmer@rn.dk.
authors.forename: Anette
authors.initials: A
authors.lastname: Schlemmer
authors.affiliation: Department of Infectious Diseases and Rheumatology, Copenhagen University Hospital Rigshospitalet Blegdamsvej, Copenhagen, Denmark. niels.graudal@regionh.dk.
authors.forename: Niels
authors.initials: N
authors.lastname: Graudal
authors.affiliation: Center for Rheumatology and Spine Diseases, Rigshospitalet Glostrup, Glostrup, Denmark. anne.roedgaard@regionh.dk.
authors.forename: Anne
authors.initials: A
authors.lastname: Rødgaard
authors.affiliation: Department of Internal Medicine, Lillebælt Hospital, Vejle, Denmark. jakob.espesen@rsyd.dk.
authors.forename: Jakob
authors.initials: J
authors.lastname: Espesen
authors.affiliation: Department of Rheumatology, Copenhagen University Hospital Bispebjerg and Frederiksberg, Copenhagen, Denmark. gina.birgitte.kollerup@regionh.dk.
authors.forename: Gina Birgitte
authors.initials: GB
authors.lastname: Kollerup
authors.affiliation: Department of Internal Medicine, Holbæk Hospital, Holbæk, Denmark. glintborg@dadlnet.dk.
authors.forename: Bente
authors.initials: B
authors.lastname: Glintborg
authors.affiliation: Department of Medicine and Rheumatology, Copenhagen University Hospital Gentofte, Gentofte, Denmark. ole.rintek.madsen@regionh.dk.
authors.forename: Ole Rintek
authors.initials: OR
authors.lastname: Madsen
authors.affiliation: Department of Rheumatology, Nordsjællands Hospital, Hillerød, Denmark. dorte.vendelbo.jensen.02@dadlnet.dk.
authors.forename: Dorte Vendelbo
authors.initials: DV
authors.lastname: Jensen
authors.affiliation: DANBIO registry and Copenhagen Center for Arthritis Research, Center for Rheumatology and Spine Diseases, Centre of Head and Orthopedics, Ndr. Ringvej 57, DK-2600, Glostrup, Denmark. merete.hetland@dadlnet.dk.|Rigshospitalet, Department of Clinical Medicine, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark. merete.hetland@dadlnet.dk.
authors.forename: Merete Lund
authors.initials: ML
authors.lastname: Hetland
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018501:Antirheumatic Agents / Q000627:therapeutic use; D001172:Arthritis, Rheumatoid / Q000000981:diagnostic imaging* / Q000188:drug therapy / Q000473:pathology; D015519:Bone Density; D003718:Denmark; D005260:Female; D050276:Hand Bones / Q000000981:diagnostic imaging*; D006801:Humans; D008297:Male; D008875:Middle Aged; D012016:Reference Values; D012042:Registries; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors; D055815:Young Adult
chemical_list: D018501:Antirheumatic Agents; D014409:Tumor Necrosis Factor-alpha