Elsevier

Bone

Volume 140, November 2020, 115574
Bone

Rapid Communication
Effects of prior osteoporosis treatment on early treatment response of romosozumab in patients with postmenopausal osteoporosis

https://doi.org/10.1016/j.bone.2020.115574Get rights and content

Highlights

  • Treatment response to romosozumab was evaluated by the change of bone mineral density and bone turnover markers.

  • Prior bone-resorption inhibitors' treatment attenuates early treatment response to romosozumab.

  • Early treatment response to romosozumab was highest in treatment-naïve cases.

  • Early treatment response to romosozumab was predicted by the early change of bone turnover markers.

Abstract

Purpose

To investigate the effects of prior treatment and the predictors of early treatment response to romosozumab (ROMO) in patients with postmenopausal osteoporosis.

Methods

In this prospective, observational, multicenter study, 130 treatment-naïve patients (Naïve; n = 37) or patients previously treated with bisphosphonates (BP; n = 33), denosumab (DMAb; n = 45), or teriparatide (TPTD; n = 15) (age, 75.0 years; T-scores of the lumbar spine [LS] −3.2 and femoral neck [FN] −2.9) were switched to ROMO based on their physician's decision. Bone mineral density (BMD) and serum bone turnover markers were evaluated for six months.

Results

At six months, LS BMD changes were 13.6%, 7.5%, 3.6%, and 8.7% (P < .001 between groups) and FN BMD changes were 4.2%, 0.4%, 1.6%, and 1.5% (P = .16 between groups) for Naïve, BP, DMAb, and TPTD groups, respectively. Changes in N-terminal type I procollagen propeptide (PINP; μg/L) levels from baseline → one month were 72.7 → 139.0, 33.5 → 85.4, 30.4 → 54.3, and 98.4 → 107.4, and those of isoform 5b of tartrate-resistant acid phosphatase (TRACP-5b) (mU/dL) were 474.7 → 270.2, 277.3 → 203.7, 220.3 → 242.0, and 454.1 → 313.0 for Naïve, BP, DMAb, and TPTD groups, respectively. Multivariate regression analysis revealed that significant predictors of LS BMD change at six months were prior treatment difference (r = −3.1, P = .0027) and TRACP-5b percentage change (r = −2.8, P = .0071) and PINP value at one month (r = 3.2, P = .0021).

Conclusion

Early effects of ROMO on the increase in LS BMD are significantly affected by the difference of prior treatment and are predicted by the early change in bone turnover markers.

Mini abstract

Early effects of ROMO on the increase in LS BMD at six months is significantly affected by the difference of prior treatment and also predicted by the early change of bone turnover markers 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.

References (20)

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