Step-down Therapy After Long-term Osteoporosis Treatment: A Randomized Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 44
- 试验地点
- 1
- 主要终点
- Change in Lumbar Spine BMD Over 2 Years
研究概览
简要总结
Maintaining bone mineral density (BMD) after discontinuing denosumab (Prolia) is a major clinical challenge, as rapid bone loss commonly occurs when treatment is stopped, especially after more than three years of use. Standard sequential therapy with bisphosphonates such as zoledronic acid (Aclasta) often fails to fully prevent BMD decline, and most bone loss occurs within the first year, making effective suppression of the rebound effect essential.
This study investigates whether a de-escalation strategy-using half-dose denosumab (30 mg every six months) combined with sequential zoledronic acid-can better preserve lumbar spine BMD after long-term denosumab therapy. Eligible participants include postmenopausal women and men ≥50 years old with osteoporosis or osteopenia-related fractures who have received ≥3 years of denosumab.
The open-label trial applies stratified randomization based on denosumab duration (<4 years vs. ≥4 years), assigning 22 participants to each group.
Control group: standard therapy with one zoledronic acid infusion at the end of denosumab's effect and a second infusion one year later.
Intervention group: half-dose denosumab plus zoledronic acid at study entry, a second half-dose denosumab injection at six months, and a second zoledronic acid infusion at twelve months.
The study aims to determine whether this combined tapering-plus-bisphosphonate approach more effectively prevents lumbar spine BMD loss compared with conventional sequential therapy.
详细描述
Effective maintenance of bone mineral density (BMD) after discontinuing denosumab (Prolia) remains a major clinical challenge. Although denosumab is highly effective in increasing BMD, patients frequently discontinue therapy due to issues such as adherence, comorbidities, or personal circumstances. This interruption can lead to rapid and profound bone loss, substantially increasing fracture risk. Current clinical consensus recommends follow-on bisphosphonate therapy-most commonly alendronate (Fosamax) or zoledronic acid (Aclasta)-after the pharmacologic effect of denosumab wears off. However, evidence indicates that in patients treated with denosumab for more than three years, conventional bisphosphonate transition alone is often insufficient to fully prevent post-discontinuation BMD decline. Importantly, most bone loss occurs within the first year after stopping denosumab, highlighting the urgent need for strategies that can suppress the rebound increase in bone turnover during this critical period.
This study aims to investigate whether a dose-reduction (de-escalation) strategy-administering half-dose denosumab (30 mg every six months) combined with sequential zoledronic acid therapy-can better preserve lumbar spine BMD after long-term denosumab treatment. The target population includes (1) postmenopausal women with osteoporosis or osteopenia-associated fractures who have received at least three years of denosumab treatment, and (2) men aged ≥50 years with osteoporosis or osteopenia-associated fractures and ≥3 years of denosumab therapy.
The study uses an open-label, stratified randomized trial design. After enrollment, participants are stratified according to total duration of prior denosumab use: <4 years or ≥4 years. Within each stratum, participants are randomized into two groups, with 22 participants per group.
Control Group (Standard Sequential Therapy):
Participants receive conventional post-denosumab management. A single infusion of zoledronic acid is administered at the expected end of denosumab's pharmacologic effect, followed by a second zoledronic acid infusion one year later (±1 week).
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Postmenopausal women aged ≥50 and ≤85 years with osteoporosis- or osteopenia-related fractures who have received denosumab (Prolia) continuously for at least 3 years, with no dosing interval exceeding 9 months; and men aged ≥50 and ≤85 years with osteoporosis- or osteopenia-related fractures who have received continuous denosumab (Prolia) therapy for at least 3 years, with dosing intervals not exceeding 9 months.
排除标准
- •Secondary osteoporosis Metabolic bone diseases Active or prior malignancy Ongoing systemic glucocorticoid therapy Current use of hormone replacement therapy Use of any medications that affect bone metabolism Estimated glomerular filtration rate (eGFR) < 50 mL/min/1.73 m² Known hypersensitivity to zoledronic acid Hypocalcemia Any other contraindications to zoledronic acid use
研究组 & 干预措施
Control
Zoledronate is given 6 months after the final denosumab injection, with a second zoledronate infusion administered 18 months after the last denosumab dose.
干预措施: zoledronate (Drug)
Denosumab De-escalation + Zoledronate
Half-dose denosumab plus zoledronic acid at 6 months after the last denosumab dose, followed by a second half-dose denosumab injection at 12 months and a second zoledronic acid infusion at 18 months after the final denosumab dose.
干预措施: zoledronate (Drug)
Denosumab De-escalation + Zoledronate
Half-dose denosumab plus zoledronic acid at 6 months after the last denosumab dose, followed by a second half-dose denosumab injection at 12 months and a second zoledronic acid infusion at 18 months after the final denosumab dose.
干预措施: Denosumab De-escalation (Drug)
结局指标
主要结局
Change in Lumbar Spine BMD Over 2 Years
时间窗: 2 Years
Change in Lumbar Spine BMD Over 2 Years
次要结局
- Incidence of clinical osteoporotic fracture(2 years)
- Change in Total hip BMD Over 2 Years(2 Years)
- Change in Femoral Neck BMD Over 2 Years(2 Years)
- Change in C-terminal telopeptide Over 2 Years(2 Years)
- Change in Procollagen Type I N-Propeptide Over 2 Years(2 Years)