title: Suppression of bone turnover by B-cell depletion in patients with rheumatoid arthritis.
abstract: The role of B cells in inflammatory bone formation and resorption is controversial. We investigated this in patients with rheumatoid arthritis (RA) treated with rituximab, a B-cell depleting antibody. We found a significant suppression in bone turnover, possibly a direct effect or as a consequence of a reduction in inflammation and disease activity.
  
  
  BACKGROUND
  RA is the most prevalent inflammatory joint disease, in which B cells play an important role. However, the role of B cells in bone turnover is controversial and RA subjects treated with rituximab, a B-cell depleting monoclonal antibody, provide an ideal model for determining the role of B cells in inflammatory bone resorption.
  
  
  METHODS
  Serum from 46 RA patients, collected pre- and post-rituximab therapy, was analysed for biomarkers of bone turnover (procollagen type I amino-terminal propeptide [P1NP], osteocalcin, β-isomerised carboxy-terminal telopeptide of type 1 collagen [βCTX] and osteoprotegerin [OPG]).
  
  
  RESULTS
  A significant decrease in bone resorption was observed 6 months after rituximab (median change βCTX -50 ng/L, 95%CI -136, -8 p < 0.001, this equates to -37%; 95%CI -6, -49), mirrored by a reduction in disease activity. Similarly, there was a significant increase in P1NP, a marker of bone formation (median change P1NP 5.0 μg/L, 95%CI -1.0, 11.2, p = 0.02; 13%; 95%CI -3, 39), but no significant change in osteocalcin or OPG levels. The percentage change from baseline of βCTX in a subgroup of patients (not on prednisolone or bisphosphonate) was significantly correlated with the percentage reduction in DAS28 score (r (s) = 0.570, p = 0.014).
  
  
  CONCLUSIONS
  In conclusion, we have found that B-cell depletion increases bone formation and decreases bone resorption in RA patients; this may be a direct effect on osteoblasts and osteoclasts, respectively, and be at least partially explained by the decreased inflammation and disease activity.
authors.affiliation: Department of Biochemistry, The James Cook University Hospital, Middlesbrough, TS4 3BW, UK. gill.wheater@stees.nhs.uk
authors.forename: G
authors.initials: G
authors.lastname: Wheater
authors.forename: V E
authors.initials: VE
authors.lastname: Hogan
authors.forename: Y K O
authors.initials: YK
authors.lastname: Teng
authors.forename: J
authors.initials: J
authors.lastname: Tekstra
authors.forename: F P
authors.initials: FP
authors.lastname: Lafeber
authors.forename: T W J
authors.initials: TW
authors.lastname: Huizinga
authors.forename: J W J
authors.initials: JW
authors.lastname: Bijlsma
authors.forename: R M
authors.initials: RM
authors.lastname: Francis
authors.forename: S P
authors.initials: SP
authors.lastname: Tuck
authors.forename: H K
authors.initials: HK
authors.lastname: Datta
authors.forename: J M
authors.initials: JM
authors.lastname: van Laar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D058846:Antibodies, Monoclonal, Murine-Derived / Q000009:adverse effects*; D018501:Antirheumatic Agents / Q000009:adverse effects*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy*; D001402:B-Lymphocytes / Q000378:metabolism*; D001861:Bone Regeneration / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects*; D024042:Collagen Type I / Q000097:blood; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D053244:Osteoprotegerin / Q000097:blood; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D011347:Procollagen / Q000097:blood; D000069283:Rituximab
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018501:Antirheumatic Agents; D024042:Collagen Type I; D053244:Osteoprotegerin; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D000069283:Rituximab