Bone resorption during therapy with denosumab in patients with rheumatoid arthritis, positive for the main immunological markers

Abstract

Objective. Inflammation in rheumatoid arthritis (RA) leads to the development of local and generalized bone loss. Rheumatoid factor (RF) and anti-cyclic citrullinated peptide antibodies (ACCP) are believed to play a negative role in the radiological progression of RA. The use of such antiresorptive therapy as denosumab – monoclonal antibodies to RANKL (receptor activator of nuclear factor kappa-B ligand), reduces the activity of osteoclasts, increases bone mineral density (BMD), and also potentially affects the erosive process at RA. The aim of the study is to evaluate the effect of denosumab therapy on BMD and erosion count in patients with RA and osteoporosis (OP) in consideration of the positivity in the RF and ACCP in serum and the baseline RA activity. Materials and methods. The 12-month prospective study of the efficacy of denosumab therapy (60 mg subcutaneously every 6 months) in patients with RA and OP included 66 postmenopausal women; age – 59.4±7.5 years, duration of RA – 17.8±10.6 years, RF-positive – 47 (72%) patients, ACCP-positive – 48 (74%) patients. At baseline and after 12 months, dual-energy X-ray absorptiometry was performed with an assessment of BMD in the lumbar spine (L1– L4), proximal femur (hip neck and total hip), distal forearm; X-ray of the hands and distal parts of the feet in direct projection, followed by assessment of erosive-destructive changes according to the Sharp/van der Heijde method. Results. A significant increase in BMD was established in all studied sites of the skeleton despite the positivity of the RF and ACCP (for the hip neck p=0.05), while a significant increase in BMD in the RF- and ACCP-negative group was detected only in L1–L4 site. The progression of the increase in erosion count was noted in the RF- and ACCP-positive group while in the RF- and ACCP-negative group this indicator did not change. Regardless of the baseline activity of RA (by DAS28 (Disease Activity Score 28)) the BMD of most parts of the skeleton were stabilized. In patients with moderate RA activity, BMD increased significantly in L1–L4 in both groups: RF- and ACCP-positive and -negative , as well as in the total hip – in RF- and ACCP-positive group. The dynamics of the erosion count in RA patients did not depend on the baseline degree of DAS28 activity, no significant changes were detected in the analyzed groups. Conclusions. RF and ACCP positivity in serum in patients with RA and OP treated with denosumab did not have a negative effect on the dynamics of BMD, while the number of erosions increased. The baseline RA activity level did not affect the dynamics of the erosion count and the dynamics of BMD in most subgroups – BMD levels have been increased or stabilized.