The effect of 3 versus 6  years of zoledronic acid treatment in osteoporosis: A randomized extension to the HORIZON-Pivotal Fracture Trial (PFT)

Black, Dennis M.; Reid, Ian R.; Cauley, Jane A.; Boonen, Steven; Cosman, Felicia; Leung, Ping Chung; Lakatos, Péter; Man, Zulema; Cummings, Steve; Hue, Trisha F.; Ruzycky, Mary Ellen; Martinz, R; Su, Guoqin; Bucci‐Rechtweg, Christina; Eastell, Richard

doi:10.1016/j.bone.2011.03.127

Cited by 105 publications

(151 citation statements)

References 15 publications

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“…Changes in BMD at the 1/3 radius have been shown to be limited with many antiresorptives ; however, a statistically significant increase in BMD of the 1/3 radius was observed with denosumab treatment, compared with risedronate treatment, at month 24. The treatment difference for BMD at each skeletal site was larger at month 24 than at month 12, reflecting the progressive increase for most measures of BMD in the denosumab group versus the plateau in the risedronate group beyond 12 months, which has also been shown in other studies .…”

Section: Discussionsupporting

confidence: 79%

“…However, inconvenient dosing regimens and potential side effects of bisphosphonates can lead to low adherence in patients with osteoporosis . Furthermore, the increase in bone mineral density (BMD) with bisphosphonate therapy plateaus after 3–4 years . Teriparatide may also reduce fracture risk in those taking glucocorticoids , but daily injections and restriction to a 2‐year lifetime for treatment limit its use.…”

Section: Introductionmentioning

confidence: 99%

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Denosumab Versus Risedronate in Glucocorticoid‐Induced Osteoporosis: Final Results of a Twenty‐Four–Month Randomized, Double‐Blind, Double‐Dummy Trial

Saag

Pannacciulli

Geusens

et al. 2019

Arthritis & Rheumatology

114

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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.

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Section: Discussionsupporting

confidence: 79%

Section: Introductionmentioning

confidence: 99%

Denosumab Versus Risedronate in Glucocorticoid‐Induced Osteoporosis: Final Results of a Twenty‐Four–Month Randomized, Double‐Blind, Double‐Dummy Trial

Saag

Pannacciulli

Geusens

et al. 2019

Arthritis & Rheumatology

114

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“…The incidence of adverse and serious adverse events was balanced between the denosumab and placebo groups, with no increased risk of cancer, cardiovascular disease, delayed fracture healing or hypocalcemia with denosumab treatment . In contrast to the bisphosphonates, for which BMD increases level off and plateaus after 4–5 years , long‐term treatment with denosumab leads to continuously increasing BMD for up to 10‐years of treatment . In 2343 women from the FREEDOM trial, 10 years of continuous denosumab increased BMD in the spine and total hip by 21.7% and 9.2%, respectively.…”

Section: Currently Used Osteoporosis Medicationmentioning

confidence: 99%

“…Two randomized and placebo‐controlled trials investigated effects on BMD and anti‐fracture efficacy with prolonged bisphosphonates in postmenopausal women. Continued treatment for up to 10 years vs. 5 for alendronate and for 6 years vs. 3 for zoledronic acid resulted maintained BMD levels and reduced the risk of vertebral but not of other fractures . Based on these findings and acceptable benefit‐to‐risk ratio with long‐term treatment, the American Society for Bone and Mineral Research Task Force recommended that treated patients should be evaluated after 3 and 5 years treatment with zoledronic acid and alendronate, respectively.…”

Section: The Treatment Gap and Aspects Of Treatment Durationmentioning

confidence: 99%

Treating osteoporosis to prevent fractures: current concepts and future developments

Lorentzon

2019

J Intern Med

133

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Lorentzon M (University of Gothenburg, Gothenburg and Sahlgrenska University Hospital, M€ olndal; Sweden). Treating osteoporosis to prevent fracturescurrent concepts and future developments (Review). J Intern Med 2019; 285: 381-394.Antiresorptive drugs, such as the bisphosphonates and the RANKL inhibitor denosumab, are currently the most widely used osteoporosis medications. These drugs increase bone mineral density (BMD) and reduce the risk of vertebral (by 40-70%), nonvertebral (by 25-40%) and hip fractures (by 40-53%) in postmenopausal women with osteoporosis. Due to the risk of rare side-effects, the use of bisphosphonates has been limited to up to 10 years with oral bisphosphonates and 6 years with intravenous zoledronic acid. Despite their well-proven efficacy and safety, few women at high risk of fracture are started on treatment. Case finding strategies, such as fracture risk-based screening in primary care using the fracture risk assessment tool (FRAX) and Fracture Liaison Services, have proved effective in increasing treatment rates and reducing fracture rates. Recently, anabolic therapy with teriparatide was demonstrated to be superior to the bisphosphonate risedronate in preventing vertebral and clinical fractures in postmenopausal women with vertebral fracture. Treatment with the sclerostin antibody romosozumab increases BMD more profoundly and rapidly than alendronate and is also superior to alendronate in reducing the risk of vertebral and nonvertebral fracture in postmenopausal women with osteoporosis. For patients with severe osteoporosis and high fracture risk, bisphosphonates alone are unlikely to be able to provide long-term protection against fracture and restore BMD. For those patients, sequential treatment, starting with a bone-building drug (e.g. teriparatide), followed by an antiresorptive, will likely provide better longterm fracture prevention and should be the golden standard of future osteoporosis treatment. a Denotes median AE interquartile range.Treating osteoporosis to prevent fractures / M. Lorentzon

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“…Currently, these issues can best be addressed by focusing on the extension trials for alendronate and zoledronate, and the subsequent analyses these trials spawned. The clinical extension trials designed to address the long‐term safety and efficacy of bisphosphonates are the alendronate 10‐year Fracture Intervention Trial Long‐term Extension (FLEX) and the zoledronate 6‐year Health Outcomes and Reduced Incidence with Zoledronic acid Once Yearly–Pivotal Fracture Trial (HORIZON‐PFT) . The limitations of these include the small number of participants, the inability to generalize the findings across diverse populations, and an insufficient knowledge of the circumstances or timing of fractures in the aging study population.…”

Section: Introductionmentioning

confidence: 99%

Review: Breaking From Bisphosphonates

Seton

2017

Arthritis & Rheumatology

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The effect of 3 versus 6 years of zoledronic acid treatment in osteoporosis: A randomized extension to the HORIZON-Pivotal Fracture Trial (PFT)

Cited by 105 publications

References 15 publications

Denosumab Versus Risedronate in Glucocorticoid‐Induced Osteoporosis: Final Results of a Twenty‐Four–Month Randomized, Double‐Blind, Double‐Dummy Trial

Denosumab Versus Risedronate in Glucocorticoid‐Induced Osteoporosis: Final Results of a Twenty‐Four–Month Randomized, Double‐Blind, Double‐Dummy Trial

Treating osteoporosis to prevent fractures: current concepts and future developments

Review: Breaking From Bisphosphonates

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