Introduction

Bone loss is common in patients with RA who are treated with glucocorticoids, which increases the risk of spine and hip fragility fractures 2-fold.  Denosumab, a RANKL inhibitor,  is approved for use in RA patients using glucocorticoids; however, the effects of denosumab discontinuation on bone mineral density (BMD) have not been established.

Study Design

This was a randomized, double-blind, placebo-controlled, phase II study involving 82 RA patients receiving glucocorticoids (mean duration of glucocorticoids = 19.4 of 24-month study duration) who were treated with denosumab (60 ir 180 mg every 6 months) for 12 months.  Bone turnover markers (serum C-terminal telopeptide of type I collagen [CTX] and serum procollagen type I N-terminal propeptide [PINP] and BMD of the lumbar spine and hip were determined 12 months after discontinuation of denosumab treatment.

Results and Conclusions

Twelve months after discontinuing denosumab, the CTX level had returned to baseline within 6 months and did not differ between the placebo or denosumab (60 and 180 mg) groups.  Similarly, the PINP level returned to baseline within 6 months off treatment and was higher than the placebo group by 12 months.  No osteoporotic fractures occurred off treatment; however, the lumbar spine and hip BMD values returned to baseline by 12 months.

Related Research

Consider these findings from similar research studies:

• Intravenous administration of zoledronate 6 months after discontinuing denosumab in postmenopausal women with osteoporosis prevented bone loss for 2 years independent of bone turnover (Anastasilakis AD, Papapoulos SE, Polyzos SA, et al. Zoledronate for the prevention of bone loss in women discontinuing denosumab treatment.  A prospective 2-year clinical trial. J Bone Miner Res 2019;34:2220-8).

• Intravenous administration of zoledronate after discontinuing denosumab in postmenopausal women with osteoporosis resulted in preservation of greater than 50% of the increase in BMD, and unlike patients who discontinued denosumab without bisphosphonate treatment, no vertebral fractures occurred (Everts-Graber J, Reichenbach S, Ziswiler HR, et al. A single infusion of zoledronate in postmenopausal women following denosumab discontinuation results in partial conservation of bone mass gains. J Bone Miner Res 2020;35:1207-15). 

Original Source

Sagg KG, McDermott MT, Adachi J, et al. The effect of discontinuing denosumab in patients with rheumatoid arthritis treated with glucocorticoids. Arthritis Rheum 2022;74:604-11.