Denosumab and teriparatide transitions in postmenopausal osteoporosis (the DATA-Switch study): extension of a randomised controlled trial.
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ABSTRACT:
SUBMITTER: Leder BZ
PROVIDER: S-EPMC4620731 | biostudies-literature | 2015 Sep
REPOSITORIES: biostudies-literature
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Denosumab and teriparatide transitions in postmenopausal osteoporosis (the DATA-Switch study): extension of a randomised controlled trial.
Leder Benjamin Z BZ Tsai Joy N JN Uihlein Alexander V AV Wallace Paul M PM Lee Hang H Neer Robert M RM Burnett-Bowie Sherri-Ann M SA
Lancet (London, England) 20150702 9999
<h4>Background</h4>Unlike most chronic diseases, osteoporosis treatments are generally limited to a single drug at a fixed dose and frequency. Nonetheless, no approved therapy is able to restore skeletal integrity in most osteoporotic patients and the long-term use of osteoporosis drugs is controversial. Thus, many patients are treated with the sequential use of two or more therapies. The DATA study showed that combined teriparatide and denosumab increased bone mineral density more than either d ...[more]
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Project description:BackgroundIn the Denosumab and Teriparatide Administration (DATA) study, we showed that denosumab fully inhibits teriparatide-induced bone resorption while allowing for continued teriparatide-induced bone formation, resulting in larger increases in hip and spine bone mineral density (BMD) than with either drug alone. We aimed to assess whether administration of denosumab with high dose teriparatide would stimulate larger increases in bone mass than those observed in the DATA study.MethodsDATA-HD was an open-label, randomised, controlled phase 4 trial done at Massachusetts General Hospital. Eligible women were postmenopausal women (at least 36 months since last menses or since hysterectomy with a follicle-stimulating hormone concentration of ≥40 U/L) with osteoporosis. Participants were randomly assigned (1:1) to receive teriparatide 20 μg (standard dose) or 40 μg (high dose) daily via subcutaneous injection for 9 months. At 3 months, both groups were started on denosumab 60 mg every 6 months via subcutaneous injection for 12 months. Areal BMD (aBMD) was measured at 0, 3, 9, and 15 months. Treatment was given open label, but outcome assessors were masked. The primary endpoint was percentage change from baseline in spine areal BMD (aBMD) at 15 months. Women who completed at least one study visit after baseline were included in the modified intention-to-treat analysis. Safety was assessed in all randomly assigned participants. This study is registered with ClinicalTrials.gov, number NCT02176382.FindingsBetween Oct 15, 2014, and June 10, 2016, 269 women were assessed for eligibility. 76 participants were randomly assigned to 20 μg teriparatide (n=39) or 40 μg teriparatide (n=37), of whom 69 completed at least one post-baseline visit. At 15 months, mean spine aBMD had increased to a significantly greater extent in the 40 μg group (17·5% [SD 6·0] increase) than the 20 μg group (9·5% [3·2]; difference 8·1%, 95% CI 5·5 to 10·6, p<0·0001). Mean femoral neck aBMD had also increased to a greater extent in the 40 μg group (6·8% [SD 4·1] increase) than the 20 μg group (4·3% [3·7]; difference 2·5%, 0·5 to 4·5, p=0·04), as did mean total hip aBMD (40 μg group, 6·1% [3·4] increase; 20 μg group, 3·9% [2·9] increase; difference 2·2%, 0·6 to 3·8, p<0·0001). 30 (77%) of 39 participants in the 20 μg group and 29 (78%) of 37 participants in the 40 μg group had an adverse event, and seven (18%) and two (5%) patients had serious adverse events. The most frequent adverse events were joint pain (15 [38%]), muscle cramp (15 [38%]), and fatigue (12 [31%]) in the 20 μg group group and fatigue (14 [38%]), nausea (16 [43%]), and joint pain (17 [46%]) in the 40 μg group. No deaths were reported.InterpretationCombined treatment with teriparatide 40 μg and denosumab increases spine and hip BMD more than standard combination therapy. This large and rapid increase in bone mass suggest that this high dose regimen might provide a method of restoring skeletal integrity in patients with osteoporosis.FundingNational Institutes of Health and the Dart Foundation.
| S-EPMC6980341 | biostudies-literature
Project description:ContextCurrent osteoporosis medications increase bone mineral density (BMD) modestly and reduce, but do not eliminate, fracture risk. Attempts to improve efficacy by administering anabolic agents and bisphosphonates concomitantly have been unsuccessful. Conversely, 12 months of concomitant denosumab and teriparatide therapy increases BMD more than either drug alone.ObjectiveThe purpose of this study was to determine whether 24 months of combined denosumab and teriparatide will increase hip and spine BMD more than either individual agent.DesignPreplanned continuation of the Denosumab and Teriparatide Administration (DATA) randomized controlled trial in which postmenopausal osteoporotic women received teriparatide (20 μg daily), denosumab (60 mg every 6 months), or both medications for 24 months.ParticipantsParticipants were 94 postmenopausal women with osteoporosis.Outcome measuresLumbar spine, femoral neck, total hip, and distal radius BMD and serum markers of bone turnover were measured.ResultsAt 24 months, lumbar spine BMD increased more in the combination group (12.9 ± 5.0%) than in either the teriparatide (9.5 ± 5.9%, P = .01) or denosumab (8.3 ± 3.4%, P = .008) groups. Femoral neck BMD also increased more in the combination group (6.8 ± 3.6%) than in either the teriparatide (2.8 ± 3.9%, P = .003) or denosumab (4.1 ± 3.8%, P = .008) groups. Similarly, total hip BMD increased more in the combination group (6.3 ± 2.6%) than in the teriparatide (2.0 ± 3.0%) or denosumab (3.2 ± 2.5%) groups (P < .001 for both). Although spine and hip BMD continued to increase in the second year in all groups, these year 2 increases did not differ among groups. Serum C-telopeptide and N-terminal propeptide of type 1 procollagen were equally suppressed in the denosumab and combination groups, whereas osteocalcin decreased more in the denosumab group than in the combination group, a difference that persisted, but lessened, in the second year of therapy.ConclusionsTwo years of concomitant teriparatide and denosumab therapy increases BMD more than therapy with either medication alone and more than has been reported with any current therapy. The combination of these agents may prove to be an important treatment option in patients at high risk of fracture.
| S-EPMC4010689 | biostudies-literature
Project description:BackgroundOsteoporosis medications increase bone-mineral density (BMD) and lower but do not eliminate fracture risk. The combining of anabolic agents with bisphosphonates has not improved efficacy. We compared combined teriparatide and denosumab with both agents alone.MethodsFrom September, 2009, to January, 2011, we enrolled postmenopausal women with osteoporosis into this randomised, controlled trial. Patients were assigned in a 1:1:1 ratio to receive 20 μg teriparatide daily, 60 mg denosumab every 6 months, or both. BMD was measured at 0, 3, 6, and 12 months. Women who completed at least one study visit after baseline were assessed in a modified intention-to-treat analysis. This trial is registered with ClinicalTrials.gov, number NCT00926380.Findings94 (94%) of 100 eligible women completed at least one study visit after baseline. At 12 months, posterior-anterior lumbar spine BMD increased more in the combination group (9·1%, [SD 3·9]) than in the teriparatide (6·2% [4·6], p=0·0139) or denosumab (5·5% [3·3], p=0·0005) groups. Femoral-neck BMD also increased more in the combination group (4·2% [3·0]) than in the teriparatide (0·8% [4·1], p=0·0007) and denosumab (2·1% [3·8], p=0·0238) groups, as did total-hip BMD (combination, 4·9% [2·9]; teriparatide, 0·7% [2·7], p<0·0001; denosumab 2·5% [2·6], p=0·0011).InterpretationCombined teriparatide and denosumab increased BMD more than either agent alone and more than has been reported with approved therapies. Combination treatment might, therefore, be useful to treat patients at high risk of fracture.FundingAmgen, Eli Lilly, National Center for Research Resources.
| S-EPMC4083737 | biostudies-literature
Project description:In postmenopausal women, 2 yr of combined teriparatide and denosumab increases bone mineral density more than either drug alone, and switching from either combination or teriparatide to denosumab for an additional 2 yr further increases bone mineral density. Conversely, switching from denosumab to teriparatide results in transient bone loss. The effects of these interventions on spine microarchitecture are unknown. In the DATA and DATA-Switch studies, 94 postmenopausal osteoporotic women were randomized to receive 24 mo of teriparatide (20 µg daily), denosumab (60 mg every 6 mo), or both. Then, women originally assigned to 24 mo of teriparatide received 24 mo of denosumab, whereas subjects originally randomized to 24 mo of denosumab received 24 mo of teriparatide. Subjects who received both drugs received an additional 24 mo of denosumab alone. Spine trabecular bone score (TBS, a gray-level textural assessment of bone microarchitecture) was measured blinded from treatment groups using images from 2-dimensional dual-energy X-ray absorptiometry spine scans at 0, 12, 24, 30, 36, and 48 mo in 65 women who had posterior-anterior spine dual-energy X-ray absorptiometry images suitable for TBS analysis. After 24 mo, TBS increased by 2.7 ± 4.7% in the teriparatide group (p = 0.009 vs baseline), by 1.8 ± 5.0% in the denosumab group (p = 0.118 vs baseline), and by 4.5 ± 6.7% in the combination group (p = 0.017 vs baseline), with no significant between-group differences. In the 6 mo after the treatments were switched (months 24-30), TBS continued to increase in the combination-to-denosumab and teriparatide-to-denosumab groups but decreased by -1.1 ± 4.0% in the denosumab-to-teriparatide group (p < 0.05 vs other groups). After 48 mo, compared to month 0, TBS increased by 5.1 ± 5.8% in the teriparatide-to-denosumab group, by 3.6 ± 4.2% in the denosumab-to-teriparatide group, and by 6.1 ± 4.7% in the combination-to-denosumab group (p < 0.001 vs baseline for all groups, p = not significant for between-group differences). Switching from teriparatide to denosumab also increased spine TBS. Conversely, switching from denosumab to teriparatide transiently degraded spine trabecular microarchitecture, the clinical consequences of which require further study.
| S-EPMC5673584 | biostudies-literature
Project description:Aim: Evidence on the efficacy of combination treatment of teriparatide and denosumab for osteoporosis remains controversial. We aim to compare the efficacy between the combination treatment and monotherapy among patients with postmenopausal osteoporosis. Methods and results: We systematically searched PubMed, EMBASE, the Cochrane Library, and Web of Science up to 26 January 2022, for relevant studies. This meta-analysis reviewed all randomized controlled trials (RCTs) that reported on the combination treatment of teriparatide and denosumab in patients with postmenopausal osteoporosis. The articles were examined individually by two reviewers, and the relevant data was extracted. We combined weighted mean difference (WMD) for bone mineral density (BMD) using random- or fixed- effect models and conducted subgroup analyses. Sensitivity analyses were performed, and possible publication bias was also assessed. Overall, combination treatment enhanced the mean percent change of bone mineral density in lumbar spine than monotherapy (WMD = 2.91, 95%CI: 1.983.83; p = 0.00). And, combination treatment has been beneficial for enhancing the mean percent change of BMD in hip (WMD = 3.19, 95%CI: 2.25∼4.13; p = 0.00). There was no significant difference between combination treatment and monotherapy in terms of the adverse events (RR = 0.81, 95%CI: 0.45∼1.45; p = 0.472). Conclusion: The meta-analysis indicates that combination treatment led to greater BMD at the lumbar spine and hip in comparison to monotherapy, without an increased incidence of adverse events. Systematic Review Registration: (https://inplasy.com/), identifier (Inplasy Protocol 2734).
| S-EPMC9170942 | biostudies-literature
Project description:PurposeThe efficacy and safety of denosumab was compared with placebo in Korean postmenopausal women with osteoporosis in this phase III study.Materials and methodsWomen aged 60 to 90 years with a T-score of <-2.5 and ≥-4.0 at the lumbar spine or total hip were randomized to a single 60 mg subcutaneous dose of denosumab or placebo for the 6-month double-blind phase. Eligible subjects entered the 6-month open-label extension phase and received a single dose of denosumab 60 mg.ResultsBaseline demographics were similar in the 62 denosumab- and 64 placebo-treated subjects who completed the double-blind phase. Treatment favored denosumab over placebo for the primary endpoint {mean percent change from baseline in lumbar spine bone mineral density (BMD) at Month 6 [3.2% (95% confidence interval 2.1%, 4.4%; p<0.0001)]}; and secondary endpoints (mean percent change from baseline in lumbar spine BMD at Month 1, total hip, femoral neck, and trochanter BMD at Months 1 and 6, and median percent change from baseline in bone turnover markers at Months 1, 3, and 6). Endpoint improvements were sustained over 12 months in the open-label extension (n=119). There were no new or unexpected safety signals.ConclusionDenosumab was well tolerated and effective in increasing BMD and decreasing bone turnover markers over a 12-month period in Korean postmenopausal women. The findings of this study demonstrate that denosumab has beneficial effects on the measures of osteoporosis in Korean postmenopausal women.
| S-EPMC4951467 | biostudies-literature
Project description:This case-control study investigated the impact of switching from bisphosphonates to denosumab, teriparatide, or romosozumab in postmenopausal osteoporosis. Romosozumab demonstrated the most significant improvements in bone mineral density, particularly in the lumbar spine and total hip, by reducing bone resorption and increasing bone formation markers.PurposeTo investigate the impact of switching from bisphosphonates (BP) to denosumab (DMAb), teriparatide (TPTD), or romosozumab (ROMO) in postmenopausal osteoporosis.MethodsThis retrospective, case-controlled, multicenter study included 389 patients who switched from BP to DMAb, TPTD, or ROMO due to treatment inefficacy. Propensity score matching was used to align patient backgrounds, resulting in 45 patients per group. Baseline characteristics included a mean age of 73.8 years, prior BP treatment duration of 37.1 months, and bone mineral density (BMD) T-scores of -2.8 in the lumbar spine (LS), -2.5 in the total hip (TH), and -2.7 in femoral neck (FN). BMD and bone turnover markers were assessed over 12 months.ResultsFollowing the switch from BP, the ROMO group demonstrated a dual effect of decreased bone resorption and increased bone formation markers. The TPTD group exhibited the highest increases in both markers, while the DMAb group suppressed both. After 12 months, the ROMO group demonstrated significantly greater BMD increases in the LS (11.4%) compared to the DMAb (6.3%; p < 0.001) and TPTD (5.9%; p < 0.001) groups. Additionally, the ROMO group showed greater increases in the TH (3.3%) than TPTD group (0.8%; p < 0.01). Only the ROMO group showed a significant BMD increase in the FN (2.0%; p < 0.01 from baseline).ConclusionSignificant BMD increases were observed in the LS for all groups, in the TH for the ROMO and DMAb groups, and in the FN for the ROMO group. ROMO showed the most substantial BMD improvements following BP therapy.
| S-EPMC11882683 | biostudies-literature
Project description:Study designA systematic review and Meta-analysis.ObjectiveTo compare the efficacy and safety of denosumab and teriparatide versus oral bisphosphonates to treat postmenopausal osteoporosis.Summary of background dataWhile bisphosphonates have historically been the cornerstone of pharmacological management for bone protection in patients, emerging evidence suggests that teriparatide and denosumab warrant further investigation as potential first-line treatments. The optimal choice among denosumab, teriparatide, and oral bisphosphonates for the treatment of postmenopausal osteoporosis remains a subject of ongoing debate and controversy within the scientific community.MethodsThis systematic review adhered meticulously to the rigorous standards outlined by the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analysis) guidelines as well as the Cochrane Collaboration recommendations. Additionally, it employed the AMSTAR (Assessing the methodological quality of systematic reviews) criteria to ensure methodological robustness and enhance the credibility of the findings. A systematic electronic search was conducted across Web of Science, PubMed, and the Cochrane Library databases from their inception dates up to February 2024.ResultsIn this meta-analysis of studies, our findings suggest that compared to bisphosphonates, both teriparatide and denosumab demonstrated notable increases in percentage changes in lumbar spine bone mineral density (BMD) among postmenopausal osteoporosis patients. Furthermore, denosumab exhibited superiority over teriparatide and oral bisphosphonates in enhancing percentage changes in both femoral neck and total hip BMD, indicating its potential as a more efficacious option. Regarding safety outcomes, no significant differences were observed in the incidence of serious adverse events among patients treated with teriparatide, denosumab, and bisphosphonates. However, teriparatide showed superiority over oral bisphosphonates in terms of a lower risk of general adverse events, suggesting a favorable safety profile.ConclusionIn conclusion, our study suggests that teriparatide and denosumab demonstrate comparable or potentially superior efficacy and safety profiles compared to oral bisphosphonates for the treatment of postmenopausal osteoporosis.Systematic review registrationPROSPERO, identifier CRD42024508382.
| S-EPMC11402677 | biostudies-literature
Project description:Background: Several medications have been used for glucocorticoids-induced osteoporosis (GIO). However, the best therapeutic option for GIO is still controversial. A Bayesian network meta-analysis was conducted to compare the efficacy and safety of denosumab, teriparatide and bisphosphonates for patients with GIO. Methods: Relevant randomized controlled trials published in PubMed, Embase, Cochrane Library and ClinicalTrials.gov up to August 2023 were searched. The following efficiency and safety outcomes were extracted for comparison: bone mineral density (BMD) percentage changes in lumbar spine, femur neck and total hip, and incidences of adverse events (AEs), serious adverse events (SAEs), vertebrae and non-vertebrae fracture. Bayesian random effects models were used for multiple treatment comparisons. Results: 11 eligible RCTs involving 2,877 patients were identified. All the six medications including alendronate, risedronate, etidronate, zoledronate, teriparatide, and denosumab and were effective in increasing BMD. Teriparatide and denosumab were more effective in improving lumbar spine and femur neck BMD, and reducing vertebrae fracture. Alendronate and denosumab were more effective in improving total hip BMD. Alendronate and teriparatide had the lowest incidences of AEs and SAEs. Conclusion: Teriparatide denosumab and the bisphosphonates are all effective in improving BMD for GIO patients. Based on this network meta-analysis, teriparatide and denosumab have higher efficiency in improving lumbar spine and femur neck BMD, and reducing vertebrae fracture. Systematic Review Registration: 10.17605/OSF.IO/2G8YA, identifier CRD42023456305.
| S-EPMC10834754 | biostudies-literature
Project description:The combination of denosumab and teriparatide is an effective treatment strategy in postmenopausal osteoporosis, though skeletal gains are promptly lost when these agents are discontinued. In the DATA-HD study, we reported that a single dose of zoledronic acid (ZOL) maintains the increases in areal spine and hip bone mineral density (BMD) achieved with this combination for at least 12 months. The capacity of ZOL to maintain corresponding improvements in peripheral volumetric BMD and microarchitecture, however, has not been reported. In the 15-month DATA-HD study, 76 postmenopausal osteoporotic women were randomized to receive 9 months of teriparatide (20-μg or 40-μg daily) overlapped with denosumab (60 mg at months 3 and 9). In the Extension study, 53 participants received a single dose of ZOL (5 mg intravenously) 24-35 weeks after the last denosumab dose. We measured volumetric BMD and microarchitecture at the distal radius and tibia using high-resolution peripheral quantitative computed tomography at months 27 and 42. Despite ZOL administration, total and cortical BMD gradually decreased over 27 months resulting in values similar to baseline at the radius but still significantly above baseline at the tibia. At both sites, cortical porosity decreased to values below pretreatment baseline at month 27 but then increased from month 27 to 42. There were no significant changes in trabecular parameters throughout the 27-month post-ZOL observation period. Stiffness and failure load, at both sites, decreased progressively from month 15 42 though remained above baseline at the tibia. These findings suggest that in contrast to the largely maintained gains in dual-energy X-ray absorptiometry (DXA)-derived spine and hip BMD, a single dose of ZOL was not as effective in maintaining the gains in volumetric peripheral bone density and microarchitecture produced by 15 months of overlapping treatment with denosumab and teriparatide. Alternative therapeutic approaches that can fully maintain improvements in peripheral bone parameters require further study. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
| S-EPMC10098948 | biostudies-literature