The Impact of Long-Term Biologics/Target Therapy on Bone Mineral Density in Rheumatoid Arthritis

A Propensity Score-Matched Analysis

Jia-Feng Chen; Chung-Yuan Hsu; Shan-Fu Yu; Chi-Hua, Ko; Wen-Chan Chiu; Han-Ming Lai; Ying-Chou Chen; Yu-Jih Su; Tien-Tsai Cheng


Rheumatology. 2020;59(9):2471-2480. 

In This Article

Abstract and Introduction


Objectives: To investigate changes in BMD in RA patients receiving 3-year biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD) or conventional synthetic DMARD (csDMARD).

Methods: Patients with RA were recruited from September 2014 until March 2019. Clinical characteristics, BMD and evidence of fragility fractures at enrolment were documented. Participants were treated according to the National Institute for Health and Care Excellence (NICE) guidelines over a 3-year observation period. Repeated BMD was measured at the end of the study period. Participants were grouped into those receiving b/tsDMARD or csDMARD and by propensity score matching (1:2).

Results: A total of 388 participants completed the 3-year follow-up. After propensity score matching, 92 and 184 participants were allocated to the b/tsDMARD (Group I) and csDMARD (Group II), respectively. After 3 years, BMD remained stable at the femoral neck (FN), hip (total) (TH) and lumbar vertebra (L1–4) (P =0.09, 0.15, 0.87) in Group I. However, BMD decreased significantly in Group II (P=0.045, <0.001, 0.004) at corresponding sites. Participants receiving combined b/tsDMARD and anti-osteoporosis therapy experienced a greater BMD preserving effect than other subgroups.

Conclusion: Long-term b/tsDMARDs therapy had protective effects on bone loss for patients with RA. Patients receiving concomitant anti-osteoporosis therapy and b/tsDMARDs therapy experienced the greatest BMD preserving effect.


RA, an autoimmune disease primarily affecting peripheral joints, also leads to deteriorated skeletal microarchitecture and bone strength. This deterioration is due to the release of proinflammatory cytokines such as TNF-α, IL-6 and IL-17, which interferes with the balance between bone formation by osteoblasts and resorption by osteoclasts. The chronic inflammation in RA not only results in peripheral bony erosion but in generalized bone loss. It has been demonstrated that the annual bone loss rate in patients with active RA ranges between 5.5% and 10%.[1] Compared with the general population, the prevalence of osteoporosis is approximately two-fold greater in patients with RA,[2] ranging from 7% to 26% in the hip and 11% to 32% in the spine.[2–5] In addition, the risk of developing clinical or hip/vertebral fractures in patients with RA has been reported to be 2.25 or 2–6 fold, respectively, and was higher than that of controls.[6]

In recent decades, several cytokines inhibitors, in particular biological/targeted synthetic disease-modifying antirheumatic drugs (b/tsDMARD) have been developed. The b/tsDMARD therapy directly targets pathological cytokines and halts the inflammatory cascade and has demonstrated anti-inflammatory effects for patients with RA. Since the advent of b/tsDMARDs, the regimens have demonstrated marked clinical symptom alleviation, improved quality of life, and decelerated joint damage in patients with RA. In addition, the notion of treat-to-target strategy accelerated the optimisation of patient management and outcomes.[7]

In previous studies,[8–13] b/tsDMARDs had demonstrated a potentially beneficial effect on bone loss. However, these studies either focused on changes in bone turnover markers,[10–13] had a short-term observation period,[8,14–17] or lacked an adequate control group.[8,9] Therefore, the long-term effect of b/tsDMARDs on generalized bone loss in patients with RA remained unknown. Medications for the treatment of postmenopausal osteoporosis including denosumab, bisphosphonates and parathyroid hormone (hPTH 1–34) have been assessed in terms of preventing bone loss in patients with RA. They have demonstrated efficacy in the prevention of systemic bone loss or in reducing localized bone erosions.[18–20]

In the current study, we aimed to investigate the impact of long-term b/tsDMARDs therapy on BMD changes in patients with RA via a 3-year real-world, prospective, cohort and observational study. In addition, we explored the synergistic effect of a 3-year treatment with b/tsDMARDs and with or without anti-osteoporosis therapy (AOT) on BMD changes in patients with RA.