Rapid CommunicationEffects of prior osteoporosis treatment on early treatment response of romosozumab in patients with postmenopausal osteoporosis
Introduction
With the advent of various novel anti-osteoporosis agents, goal-directed treatment for osteoporosis has been recommended to reduce imminent fracture risk [1]. One novel anabolic agent is romosozumab (ROMO), a monoclonal anti-sclerostin antibody that promotes bone formation and inhibits bone resorption [2]. Because of this unique dual effect, the anabolic window (i.e., the difference between bone formation and bone resorption), which determines the effects of osteoporosis treatment, is assumed to be larger in ROMO than other osteoporosis treatments [3]. Indeed, in postmenopausal women, ROMO has shown superior effects in increasing lumbar spine (LS) bone mineral density (BMD) than alendronate or teriparatide (TPTD) [2]. In addition, the increase in the bone formation markers and decrease in the bone resorption markers become largest within a month after treatment induction [2], suggesting that this early bone turnover response may be beneficial in predicting early treatment response to ROMO.
The effects of prior treatment on bone anabolic agents have been reported. Prior antiresorptive treatment such as bisphosphonates (BP) blunted the hip BMD response to TPTD [4,5], and switching from denosumab (DMAb) to TPTD led to a transient increase in the bone resorption markers and a consequent decrease in BMD [6]. On the other hand, only a few studies have demonstrated the effects of subsequent treatment of ROMO after administration of other osteoporosis agents, such as alendronate [7] or DMAb [8]. We recently reported a case in which ROMO was not effective in preventing multiple spontaneous clinical vertebral fractures after DMAb discontinuation [9]. However, patients transitioned from oral BP to ROMO showed gains in hip BMD that were not observed with TPTD, suggesting the difference of sequential effects between these two agents [10].
Taken together, we hypothesized that prior antiresorptive treatment (such as BP or DMAb) may diminish the effects of ROMO, although may differ from that of TPTD. However, there has been no direct comparison between prior treatment-naïve cases or prior treatment by TPTD cases.
Japan was the first country to approve ROMO on March 2019, and its clinical data based on real-world settings is of great interest. This study aims to clarify the effects of prior treatment and determine predictors for early treatment response of ROMO in patients with postmenopausal osteoporosis.
Section snippets
Study design and subjects
This prospective, observational, nonrandomized study was conducted in six centers in accordance with the Japanese Guidelines for Prevention and Treatment of Osteoporosis 2011 [11]. A total of 130 postmenopausal patients with osteoporosis who were treatment naïve (Naïve; n = 37) or previously treated by BP (n = 33), DMAb (n = 45), or TPTD (n = 15) were switched to ROMO based on the decision of the patients' physicians (mainly judged by insufficient increase of BMD associated with prior
Results
Table 1 shows patient clinical backgrounds at ROMO induction. Among the groups, no significant difference was observed in baseline age, body mass index, prior vertebral and nonvertebral fracture incidence ratio, combined vitamin D and calcium dose or usage or serum calcium, estimated glomerular filtration rate, and 25(OH)D levels, whereas there was a significant difference in the duration of prior treatment (P < .001), LS BMD (g/cm2; P = .04), TH BMD (g/cm2; P = .03), FN BMD (g/cm2; P = .006),
Discussion
To the best of our knowledge, this is the first study to demonstrate the effects of prior treatment and predictors of ROMO in patients with postmenopausal osteoporosis. It has been reported that in addition to the apoptosis of osteoclasts by BP uptake, osteoblasts also uptake BP, and animal studies have demonstrated that BP suppress bone formation by the lining cells (i.e., bone modeling) [17]. Indeed, the BP group showed smaller percent decrease of TRACP-5b compared to the Naïve group.
Availability of data and material
The dataset used or analyzed in the current study are available from the corresponding author on reasonable request.
Consent for publication
Not applicable.
Funding
None.
CRediT authorship contribution statement
Kosuke Ebina:Conceptualization, Data curation, Methodology, Validation, Visualization, Formal analysis, Investigation, Resources, Project administration, Funding acquisition, Writing - original draft, Writing - review & editing.Makoto Hirao:Conceptualization, Project administration, Supervision.Hideki Tsuboi:Data curation, Project administration, Supervision.Yoshio Nagayama:Data curation, Project administration, Conceptualization.Masafumi Kashii:Data curation, Conceptualization, Methodology,
Declaration of competing interest
KE is affiliated with the Department of Musculoskeletal Regenerative Medicine, Osaka University, Graduate School of Medicine, which is supported by Taisho. KE and MH have received research grants from Asahi-Kasei, Astellas, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, and Ono. KE has received payments for lectures from Asahi-Kasei, Astellas, Chugai, Daiichi Sankyo, Eisai, Eli Lilly, and Ono. HT has received a research grant from Chugai, and has received payments for lectures from Asahi-Kasei,
Acknowledgments
The authors thank Yasunori Tsukamoto, Yasushi Kato, Hideki Yoshikawa, and all of the medical staff for their excellent cooperation in conducting the study.
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