Combination denosumab and high dose teriparatide for postmenopausal osteoporosis (DATA-HD): a randomised, controlled phase 4 trial

Tsai, Jui‐Hsiu; Lee, Hang; David, Natalie L.; Eastell, Richard; Leder, Benjamin Z.

doi:10.1016/s2213-8587(19)30255-4

Cited by 53 publications

(46 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This had a cost, in which we were unable to determine teriparatide's efficacy as a combination therapy coupled with other anti-resorptive or anabolic agents. A variety of evidence demonstrates teriparatide combined with other therapeutic agents increases total hip and lumbar spine BMD more than either agent alone, or other forms of combination therapy ( Tsai et al, 2019 ; Tsubouchi et al, 2019 ; Lou et al, 2018 ; Lou et al, 2017 ). Based on variable existing evidence coupled with our results ( Lou et al, 2017 ), we observe a variable dose-dependent effect relationship yet questions of optimal evidence-based interval and dosing remain unanswered.…”

Section: Discussionmentioning

confidence: 99%

The efficacy of teriparatide on lumbar spine bone mineral density, vertebral fracture incidence and pain in post-menopausal osteoporotic patients: A systematic review and meta-analysis

et al. 2020

View full text Add to dashboard Cite

Objective Teriparatide has been increasingly utilized in the management of osteoporosis. The efficacy of low and high dose teriparatide on lumbar spine bone mineral density, vertebral fracture incidence and pain is unknown. We sought to determine the efficacy of teriparatide on these patient-important outcomes using a systematic review and meta-analysis. Methods A systematic search of electronic databases (MEDLINE, EMBASE, CENTRAL, CINAHL) was performed to identify randomized controlled trials (RCTs) that evaluate teriparatide to any comparator for the treatment of osteoporosis in postmenopausal women. The Grades of Recommendation Assessment, Development and Evaluation (GRADE) criteria were used by two independent reviewers to assess the strength and quality of evidence. Results A total of 20 studies (n = 6024) were included in this review, with 2855 patients receiving teriparatide and 3169 patients receiving placebo or control treatment. A teriparatide dose of 20 μg/day increased lumbar spine bone mineral density (BMD) (standardized mean difference (SMD) 0.34 standard deviation (SD) units higher (95% CI 0.19–0.48 SDs higher) in comparison to placebo. Relative to anti-resorptive agents, 20 μg/day of teriparatide had a range from 0.14 SD units to 0.96 SD units higher (95% CI, 0.08 SDs lower to 0.36 SDs higher, CI, 0.33–1.59 SDs higher, respectively). 20 μg/day teriparatide had a significant effect on pain severity to placebo or control (SMD 0.80, 95% CI, 1.16–0.43 SDs lower) and also decreased the incidence of vertebral fractures compared to placebo (relative risk 0.31, 95% CI 0.21 to 0.46). Arthralgia and extremity pain incidence were also calculated; there were 15 and 8 fewer events per 1000 patients with the use of 20 μg/day of teriparatide compared to placebo or control, respectively. Conclusion High quality evidence supports the utilization of teriparatide 20 μg/day dose to significantly improve lumbar spine BMD and decrease incidence of vertebral fractures and pain severity relative to all comparators. 40 μg/day dose of teriparatide demonstrated significantly better results with prolonged treatment. This data is valuable for clinicians involved in the care of this growing demographic of patients. Further investigation on the safety and efficacy of teriparatide in higher doses for the long-term treatment of osteoporosis in postmenopausal women should be conducted through high-quality clinical trials.

show abstract

Section: Discussionmentioning

confidence: 99%

The efficacy of teriparatide on lumbar spine bone mineral density, vertebral fracture incidence and pain in post-menopausal osteoporotic patients: A systematic review and meta-analysis

et al. 2020

View full text Add to dashboard Cite

show abstract

“…4 Mean aBMD at the femoral neck and total hip had also increased to a significantly greater extent in the 40 μg group (6•8% [4•1] increase at the neck, 6•1% [3•4] increase at the hip) than the 20 μg group (4•3% [3•7] increase at the neck and 3•9% [2•9] increase at the hip) at 15 months. 4 DATA-HD is important because the increases in BMD and estimated bone strength using high dose teriparatide and denosumab seem to be greater across multiple skeletal sites than any single drug regimen (including the recently approved sclerostin antibody, romosozumab), or any previous combination treatment. Additionally, the high dose teriparatide and denosumab combination was just as well tolerated as the conventional dose teriparatide and denosumab combination.…”

mentioning

confidence: 93%

“…In the context of combination therapy, the study by Joy Tsai and colleagues 4 in The Lancet Diabetes & Endocrinology is of particular interest. In their previous Denosumab and Teriparatide Administration (DATA) study, 5 the investigators showed that the combination of the bone formation-stimulating drug, teriparatide (used at the standard US Food and Drug Administration approved dose of 20 μg daily), with the potent anti-resorptive drug, denosumab, increased bone mineral density (BMD) to a greater extent than either drug alone.…”

mentioning

confidence: 99%

“…The DATA study was of particular importance because it was the first combination treatment found to unequivocally improve BMD outcomes compared with either drug alone, and thus it offered a new approach for the treatment of patients with osteoporosis at high risk of fracture. In the DATA-HD study, 4 the investigators combined a higher dose of teriparatide (40 μg daily) with denosumab and showed that this combination is substantially better at improving BMD at multiple sites than the standard dose combination (teriparatide 20 μg daily). 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]).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Personalising osteoporosis treatment for patients at high risk of fracture

Khosla

2019

The Lancet Diabetes & Endocrinology

View full text Add to dashboard Cite

Although a number of effective drugs are available for the treatment of osteoporosis, 1 the therapeutic strategy for fracture prevention has generally been rather simplistic-ie, a onesize-fits-all approach. Thus, most patients who meet criteria for pharmacological treatment 2 are offered bisphosphonates at standardised doses as first-line therapy. According to patient or physician preference, some patients might be offered alternatives, including denosumab, or if fracture risk is deemed particularly high, one of the bone formation-stimulating drugs (teriparatide, abaloparatide, or romosozumab) might be used. 1 However, to date, little effort has been made to systematically personalise the pharmacological approach for patients with osteoporosis on the basis of refined risk stratification.

show abstract

“…These drugs usually cause adverse effects, and consequently result in decreased adherence. In the case of teriparatide, research has shown that 77% of participants taking 20 µg and 78% of participants taking 40 µg experienced an adverse side effect, including joint pain, muscle cramp, and fatigue (Tsai et al, 2019). Estrogen therapy has known side effects on the breasts and uterus particularly with longterm use.…”

Section: Introductionmentioning

confidence: 99%

Exosomes as a Novel Approach to Reverse Osteoporosis: A Review of the Literature

Xie

Xiong

et al. 2020

Front. Bioeng. Biotechnol.

View full text Add to dashboard Cite

Osteoporosis is a chronic disease requiring long-term, sometimes lifelong, management. With the aging population, the prevalence of osteoporosis is increasing, and with it so is the risk of hip fracture and subsequent poor quality of life and higher mortality. Current therapies for osteoporosis have various significant side effects limiting patient compliance and use. Recent evidence has demonstrated the significant role of exosomes in osteoporosis both in vivo and in vitro. In this review, we summarize the pathogenesis of senile osteoporosis, highlight the properties and advantages of exosomes, and explore the recent literature on the use of exosomes in osteogenesis regulation. This is a very helpful review as several exosomes-based therapeutics have recently entered clinical trials for non-skeletal applications, such as pancreatic cancer, renal transplantation, and therefore it is urgent for bone researchers to explore whether exosomes can become the next class of orthobiologics for the treatment of osteoporosis.

show abstract

Combination denosumab and high dose teriparatide for postmenopausal osteoporosis (DATA-HD): a randomised, controlled phase 4 trial

Cited by 53 publications

References 40 publications

The efficacy of teriparatide on lumbar spine bone mineral density, vertebral fracture incidence and pain in post-menopausal osteoporotic patients: A systematic review and meta-analysis

The efficacy of teriparatide on lumbar spine bone mineral density, vertebral fracture incidence and pain in post-menopausal osteoporotic patients: A systematic review and meta-analysis

Personalising osteoporosis treatment for patients at high risk of fracture

Exosomes as a Novel Approach to Reverse Osteoporosis: A Review of the Literature

Contact Info

Product

Resources

About