ABSTRACT
Rheumatoid arthritis (RA) is associated with a high risk of osteoporosis and fracture. Interleukin (IL)-6 inhibitors may suppress osteoclast activation. Anticitrullinated protein antibody (ACPA) titers are inversely associated with bone mineral density (BMD). However, the differential effect of ACPA on bone turnover marker (BTM) and BMD changes after IL-6 inhibition remains unclear. This prospective study recruited patients with active RA with inadequate response to methotrexate or biologics. BMD was measured before and after 2-year tocilizumab (TCZ) treatment. Serum osteocalcin, N-terminal propeptide of type I collagen (P1NP), and C-terminal cross-linking telopeptide of type I collagen (CTX) levels were assessed at the baseline and after treatment. We enrolled 76 patients with RA (89.5% women, age: 57.2 ± 13.3 years) receiving TCZ. The 28-joint disease activity score was negatively correlated with BMD and T-scores of the lumbar spine and bilateral femoral neck. ACPA-positive patients had lower lumbar spine and femoral neck T-scores. After 2-year TCZ treatment, CTX levels significantly decreased (0.32 ± 0.21 vs. 0.26 ± 0.17, p = 0.038). Femoral neck BMD increased significantly (0.71 ± 0.22 vs. 0.69 ± 0.55, p = 0.008). Decreased CTX levels and improved BMD were observed only in ACPA-positive patients. After treatment, femoral neck BMD significantly increased only in patients receiving a glucocorticoid dose of ≥5 mg/day. Two-year TCZ treatment reduced bone resorption and increased femoral BMD in ACPA-positive patients. The net effects of glucocorticoids and IL-6 inhibition on BMD imply that strict inflammation control might affect bone metabolism.
Subject(s)
Anti-Citrullinated Protein Antibodies/blood , Antibodies, Monoclonal, Humanized/therapeutic use , Antirheumatic Agents/therapeutic use , Arthritis, Rheumatoid/drug therapy , Bone Density/drug effects , Adult , Aged , Arthritis, Rheumatoid/genetics , Arthritis, Rheumatoid/immunology , Arthritis, Rheumatoid/pathology , Collagen Type I/genetics , Collagen Type I/immunology , Drug Therapy, Combination , Female , Femur Neck/drug effects , Femur Neck/immunology , Femur Neck/pathology , Gene Expression Regulation , Glucocorticoids/therapeutic use , Humans , Interleukin-6/antagonists & inhibitors , Interleukin-6/genetics , Interleukin-6/immunology , Lumbar Vertebrae/drug effects , Lumbar Vertebrae/immunology , Lumbar Vertebrae/pathology , Male , Methotrexate/therapeutic use , Middle Aged , Osteocalcin/genetics , Osteocalcin/immunology , Peptide Fragments/genetics , Peptide Fragments/immunology , Peptides/genetics , Peptides/immunology , Procollagen/genetics , Procollagen/immunology , Prospective StudiesABSTRACT
To identify a possible role of lymphocytic infiltrates in failure mechanism of the metal-on-metal hip resurfacing arthroplasty, the extent of lymphocytic infiltration was compared with reasons for prosthesis failure in a series of retrieval specimens. One hundred eighty-one femoral head and neck remnants were subjected to thorough analysis of histological findings and clinical data. Lymphocytic infiltrates were considered weak to moderate in 52 (28.7%) and excessive in ten (5.5%) cases. Six cases with excessive lymphocytic infiltrates belonged to the group of 33 (18.2%) revisions without obvious cause (periprosthetic fracture, component loosening, and infection) for prosthesis failure. Excessive lymphocytic infiltrates were strongly linked to the presence of proliferative desquamative synovitis (p < 0.0001). Both the excessive lymphocytic infiltrates and proliferative desquamative synovitis were associated with female gender (p < 0.05). We hypothesize that a specific cause of groin pain might be related to excessive intraosseous lymphocytic infiltrates and explained possibly by the hypersensitivity reaction of the delayed type after the hip resurfacing arthroplasty. Proliferative desquamative synovitis might constitute another morphologic feature associated with the delayed type hypersensitivity reaction.
