Introduction

Glucocorticoids (GCs) are used to treat various conditions, including rheumatic diseases, and they improve treatment outcomes. However, one of their side effects is GC-induced osteoporosis (GIOP), which is the most common form of secondary osteoporosis.1 Glucocorticoids cause bone loss and fragility by promoting bone resorption and suppressing bone formation. Approximately 6%**-12% of BMD is lost within the first year of GC therapy, followed by a further decline of around 3% per yr.2 Fracture rates increase by 50% with oral prednisolone (PSL) doses of 5 mg/d or higher for 3 mo or longer, with fractures occurring in 30%-**50% of long-term users.3 Furthermore, GC exposure primarily causes trabecular bone loss, increasing the risk of vertebral fractures. Previous epidemiological studies report a 2.59-fold higher risk with PSL doses of 2.5 mg/d or more, but less than 7.5 mg/d, compared to the non-exposed group.4

The Wnt signaling pathway is considered to be one of the mechanisms underlying GIOP and promotes bone formation while inhibiting bone resorption. This pathway is inactivated by negative regulators of Wnt signaling, including sclerostin and Dickkopf-1 (Dkk-1). We previously demonstrated that GC therapy increases serum sclerostin and decreases Wnt3a, a ligand for the Wnt signaling pathway.5,6 These findings suggest that inhibiting sclerostin could be an effective treatment for GIOP.

Romosozumab (ROMO), a humanized anti-sclerostin monoclonal antibody, has been shown to promote bone formation and inhibit bone resorption. Large randomized controlled trials (RCTs) in patients with PMO demonstrated that, compared to placebo or bisphosphonates (BP), ROMO significantly increased the BMD of the LS, FN and TH after 12 mo, and reduced the incidence of both vertebral and non-vertebral fractures.7,8

The first-line treatment for GIOP, as stated in the prior Japanese Society for Bone and Mineral Research’s Guidelines for the Management and Treatment of GIOP (2014 Revised Edition),9 is BP, an antiresorptive agent. Consequently, BPs are administered to many patients with GIOP. However, in our daily clinical practice of treating patients with rheumatic diseases, we frequently encounter patients with GIOP who experience new or multiple vertebral fractures despite receiving BP therapy.

We recently reported that ROMO increases BMD of the LS, FN and TH to a greater extent than BP do in patients newly initiating moderate to high dose GC therapy.10 However, there is little information on the efficacy and safety of using ROMO sequentially in patients with GIOP following long-term BP exposure, which is an issue that requires urgent resolution. Therefore, this study was conducted to clarify the efficacy and safety of ROMO as sequential therapy following BP in patients with GIOP, compared with continued BP administration.