No Improvement in Bone Mineral Density With TNFi Therapy in RA With Osteoporosis

A retrospective study was performed to investigate the effects of TNFi on bone mineral density in patients with RA who received bisphosphonate.

Among patients with rheumatoid arthritis (RA) and newly diagnosed osteoporosis receiving bisphosphonate, treatment with tumor necrosis factor inhibitors (TNFi) does not increase bone mineral density (BMD), according to research results published in Rheumatology International.

Investigators performed a retrospective, longitudinal study investigating the effects of TNFi therapy on BMD in patients with RA who received bisphosphonate. Medical records of 199 South Korean patients with RA and newly diagnosed osteoporosis, between January 2005 and March 2017, were retrospectively reviewed.

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Patients with RA receiving bisphosphonates were divided into 2 groups: 1 group receiving TNFi therapy, and the other group not receiving TNFi therapy. A majority of patients in both groups were women; there were no significant differences between groups in terms of age, body mass index, Disease Activity Score in 28 Joints (DAS28), the proportion of positivity of rheumatoid factor, or anticyclic citrullinated peptide antibodies. However, RA duration was significantly longer in patients receiving TNFi therapy.

Bisphosphonates included for treatment were alendronate (43.7%), risedronate (39.1%), ibandronate (16.6%), and zoledronate (0.05%). The types of bisphosphonate were similar between groups. A total of 8 patients (27.6%) were treated with TNFi before bisphosphonate exposure, with a mean duration of 13±8.6 months. The TNFi treatments included etanercept (62.1%), adalimumab (27.6%), infliximab (20.7%), and golimumab (17.2%).

The 1-year median percentage change in BMD from baseline to follow-up in the lumbar spine was 3.82%±6.28% in patients receiving TNFi therapy and 4.82%±6.10% in patients not receiving TNFi therapy. Median percentage change in femur neck BMD was 1.79% (range, -14.92% to 8.07%) and 0.84% (range, -15.10% to 76.33%) in patients with and without TNFi, respectively. A significant improvement in lumbar spine BMD (≥3%) was noted in 55.2% (n=16) and 60.6% (n=103) of patients in the TNFi and non-TNFi groups, respectively. In the femur neck, 31% (n=9) and 28.8% (n=49) of patients with and without TNFi showed significant improvement, respectively.

Multivariate analysis of the lumbar spine showed that DAS28 and vitamin D supplementation were associated with significant improvement in BMD, however, cumulative steroid dose was seen to have a negative effect on BMD improvement in the femur neck. Overall, both univariate and multivariate analyses showed no relationship in TNFi use improvement in BMD in either the lumbar spine or the femur neck.

Limitations included the retrospective, single-center nature of the study, and thus, the inability to exclude selection bias. There were also baseline characteristics that could be considered confounding factors, including RA disease duration. In addition, the patient population that received TNFi was relatively small, the treatment duration was short, bone metabolism markers were not examined, and the effects of reduced risk for fractures were not considered.

“Our findings suggest that TNF blockade cannot be considered to be a preferred therapeutic option in terms of bone health for [patients with] RA with osteoporosis receiving bisphosphonate,” the researchers concluded.


Lee JS, Lim D-H, Oh JS, et al. Effect of TNF inhibitors on bone mineral density in rheumatoid arthritis patients receiving bisphosphonate: a retrospective cohort study [published online August 14, 2019]. Rheumatol Int. doi:10.1007/s00296-019-04418-1