Dataset Information

Effects of denosumab versus teriparatide in glucocorticoid-induced osteoporosis patients with prior bisphosphonate treatment.

ABSTRACT:

Introduction

Osteoporosis is one of the serious adverse effects associated with glucocorticoid therapy. Although bisphosphonates have been used for glucocorticoid-induced osteoporosis (GIO), some patients have shown an inadequate response. In such cases, denosumab or teriparatide are used. However, there is no consensus on which of these two drugs is superior. We prospectively compared denosumab's and teriparatide's effects on the bone mineral density (BMD) in GIO patients with prior bisphosphonate treatment.

Materials and methods

After receiving oral bisphosphonates for ≥2 years, GIO patients with low T-score BMD (<-2.5) were switched from bisphosphonates to denosumab (n = 20) or daily teriparatide (n = 21). We measured the BMD (lumbar spine, femoral neck, and total hip) in both groups every 6 months for 24 months.

Results

At 24 months of treatment, the lumbar spine BMD increased significantly from baseline in both the denosumab and teriparatide groups (baseline vs. denosumab and teriparatide; 5.9 ± 5.6%, P < 0.001 and 7.9 ± 5.4%, P < 0.001). A significant increase in femoral neck BMD from baseline occurred only in the teriparatide group (6.6 ± 10.8%, P < 0.05); denosumab (1.5 ± 5.0%). No significant changes occurred in the total hip BMD from baseline in either group (-0.1 ± 5.6% and 3.3 ± 7.5%, respectively). There was no significant difference between the denosumab and teriparatide groups at 24 months in lumbar spine and femoral neck BMD, but was significantly higher in the teriparatide group at 12 months (P < 0.01 and P < 0.05 in the lumbar spine and femoral neck, respectively).

Conclusion

Teriparatide might have some advantages over denosumab and be a good alternative for treating GIO patients with prior bisphosphonate treatment.

SUBMITTER: Hirooka Y

PROVIDER: S-EPMC7352055 | biostudies-literature | 2020 Dec

REPOSITORIES: biostudies-literature

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Publications

Effects of denosumab versus teriparatide in glucocorticoid-induced osteoporosis patients with prior bisphosphonate treatment.

Hirooka Yasuaki Y Nozaki Yuji Y Inoue Asuka A Li Jinhai J Shiga Toshihiko T Kishimoto Kazuya K Sugiyama Masafumi M Kinoshita Koji K Funauchi Masanori M Matsumura Itaru I

Bone reports 20200704

<h4>Introduction</h4>Osteoporosis is one of the serious adverse effects associated with glucocorticoid therapy. Although bisphosphonates have been used for glucocorticoid-induced osteoporosis (GIO), some patients have shown an inadequate response. In such cases, denosumab or teriparatide are used. However, there is no consensus on which of these two drugs is superior. We prospectively compared denosumab's and teriparatide's effects on the bone mineral density (BMD) in GIO patients with prior bis ...[more]

PMID: 32676524

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Project description:MicroRNAs regulate bone homeostasis, and circulating microRNAs have been proposed as novel bone biomarkers. The effect of anti-osteoporotic treatment on circulating microRNAs has not been described in detail. Therefore, we performed a comprehensive analysis of microRNA serum levels in ovariectomized (OVX) and sham-operated (SHAM) rats over 12 weeks of antiresorptive or osteoanabolic treatment. Forty-two Sprague Dawley rats underwent SHAM surgery (n = 10) or ovariectomy (n = 32). After 8 weeks, OVX rats were randomized to antiresorptive treatment with zoledronate (n = 11), osteoanabolic treatment with teriparatide (n = 11), or vehicle treatment (n = 10). Serum samples were collected at weeks 8, 12, 16, and 20 after surgery. A total of 91 microRNAs were analyzed by RT-qPCR in serum samples collected at week 20. Based on the results, 29 microRNAs were selected for longitudinal analysis at all four study time points. Changes in bone mineral density and microstructure were followed up by in vivo micro-CT and ex vivo nano-CT. Ovariectomy resulted in the loss of trabecular bone, which was reversed by osteoanabolic and antiresorptive treatment. Differential expression analysis identified 11 circulating miRNAs that were significantly regulated after treatment. For example, miR-107 and miR-31-5p increased in vehicle-treated OVX animals, whereas they decreased during teriparatide treatment. Additional miRNAs were identified that showed significant correlations to bone microstructure or bone miRNA expression, including miR-203a-3p, which exhibited a significant negative correlation to vertebral and tibial trabecular bone volume fraction (%). Longitudinal analysis confirmed eight microRNAs with significant changes in serum over time that were prevented by teriparatide and zoledronate treatment (miR-34a-5p, miR-31-5p, miR-30d-3p, miR-378a-5p) or teriparatide treatment only (miR-375-3p, miR-183-5p, miR-203a-3p, miR-203b-3p). Gene target network analysis identified WNT and Notch signaling as the main signaling pathways controlled by these miRNAs. Thus, ovariectomy results in time-dependent deregulation of circulating miRNAs compared with SHAM animals. Anti-osteoporotic treatments can rescue this effect, showing that bone-related miRNAs might act as novel biomarkers for treatment monitoring. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Project description:BackgroundThis paper presents the model and results to evaluate the use of teriparatide as a first-line treatment of severe postmenopausal osteoporosis (PMO) and glucocorticoid-induced osteoporosis (GIOP). The study's objective was to determine if teriparatide is cost effective against oral bisphosphonates for two large and high risk cohorts.MethodsA computer simulation model was created to model treatment, osteoporosis related fractures, and the remaining life of PMO and GIOP patients. Natural mortality and additional mortality from osteoporosis related fractures were included in the model. Costs for treatment with both teriparatide and oral bisphosphonates were included. Drug efficacy was modeled as a reduction to the relative fracture risk for subsequent osteoporosis related fractures. Patient health utilities associated with age, gender, and osteoporosis related fractures were included in the model. Patient costs and utilities were summarized and incremental cost-effectiveness ratios (ICERs) for teriparatide versus oral bisphosphonates and teriparatide versus no treatment were estimated.For each of the PMO and GIOP populations, two cohorts differentiated by fracture history were simulated. The first contained patients with both a historical vertebral fracture and an incident vertebral fracture. The second contained patients with only an incident vertebral fracture. The PMO cohorts simulated had an initial Bone Mineral Density (BMD) T-Score of -3.0. The GIOP cohorts simulated had an initial BMD T-Score of -2.5.ResultsThe ICERs for teriparatide versus bisphosphonate use for the one and two fracture PMO cohorts were €36,995 per QALY and €19,371 per QALY. The ICERs for teriparatide versus bisphosphonate use for the one and two fracture GIOP cohorts were €20,826 per QALY and €15,155 per QALY, respectively.ConclusionsThe selection of teriparatide versus oral bisphosphonates as a first-line treatment for the high risk PMO and GIOP cohorts evaluated is justified at a cost per QALY threshold of €50,000.

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Project description:OBJECTIVE:Clinical trial results have shown that, in glucocorticoid-treated patients, treatment with denosumab 60 mg subcutaneously once every 6 months (Q6M) increased spine and hip bone mineral density (BMD) at month 12 significantly more than treatment with risedronate 5 mg orally once daily (QD). The present analysis was performed to compare efficacy and characterize safety through month 24. METHODS:This phase III study enrolled men and women ≥18 years old who had received ≥7.5 mg daily prednisone or equivalent for <3 months (glucocorticoid-initiating) or for ≥3 months (glucocorticoid-continuing) before screening. All patients <50 years old had a history of osteoporotic fracture. Glucocorticoid-continuing patients ≥50 years old had T scores of -2.0 or less (or -1.0 or less with fracture history). Patients were randomized (1:1) to receive denosumab 60 mg subcutaneously Q6M or risedronate 5 mg orally QD for 24 months, with daily calcium and vitamin D. RESULTS:Of 795 patients, 590 (74.2%) completed the study (in the glucocorticoid-initiating group, 109 of 145 patients treated with denosumab and 117 of 145 patients treated with risedronate; in the glucocorticoid-continuing group, 186 of 253 patients treated with denosumab and 178 of 252 patients treated with risedronate). Denosumab was superior to risedronate in increasing lumbar spine and total hip BMD at all time points assessed, among glucocorticoid-initiating patients (24-month lumbar spine: BMD increase of 6.2% versus 1.7%, respectively [P < 0.001]; 24-month total hip: BMD increase of 3.1% versus 0.0% [P < 0.001]) and among glucocorticoid-continuing patients (24-month lumbar spine: BMD increase of 6.4% versus 3.2% [P < 0.001]; 24-month total hip: BMD increase of 2.9% versus 0.5% [P < 0.001]). Adverse events, serious adverse events (including infections), and fractures were similar between treatment groups. CONCLUSION:Denosumab was superior to risedronate in terms of increases in spine and hip BMD through month 24, and the safety profile was similar between treatment groups. Denosumab may offer a new osteoporosis treatment option for glucocorticoid-treated patients.

Dataset Information

Effects of denosumab versus teriparatide in glucocorticoid-induced osteoporosis patients with prior bisphosphonate treatment.

Introduction

Materials and methods

Results

Conclusion

Publications

Effects of denosumab versus teriparatide in glucocorticoid-induced osteoporosis patients with prior bisphosphonate treatment.

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