Bisphosphonate Vs. Placebo Prior to Parathyroidectomy in Primary Hyperparathyroidisme: a Randomized, Double-blinded Placebo-controlled Trial
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 140
- 试验地点
- 1
- 主要终点
- Effects of ZOL vs. placebo at time of parathyroidectomy based on change in aBMD at lumbar spine meased at baseline compared to one year after PTX.
研究概览
简要总结
This study is a randomized, double-blinded, placebo-controlled trial investigating the effects of zoledronic acid (ZOL) versus placebo in patients with primary hyperparathyroidism (PHPT) undergoing parathyroidectomy (PTX). PHPT is a common endocrine disorder associated with hypercalcemia, reduced bone mineral density (BMD), increased fracture risk, renal calcifications, and cardiovascular complications. While PTX remains the definitive treatment, the potential role of bisphosphonates in optimizing post-surgical outcomes remains unclear.
This trial aims to evaluate whether a single infusion of ZOL prior to PTX impacts bone health, cardiovascular parameters, and renal function one year post-surgery. The primary endpoint is the change in areal bone mineral density (aBMD) at the lumbar spine one year after PTX. Secondary endpoints include changes in aBMD at other skeletal sites, volumetric BMD, bone microarchitecture, bone turnover markers, coronary artery calcium score, arterial stiffness, and renal calcifications.
A total of 140 postmenopausal women and men over 50 years with PHPT and low BMD will be enrolled and randomized to receive either ZOL or placebo 2-4 weeks before PTX. Participants will undergo extensive imaging, biochemical analysis, and cardiovascular assessments at baseline and one year post-surgery.
This study seeks to clarify whether ZOL improves post-surgical bone recovery or interferes with the natural bone remodeling process following PTX. Additionally, it will provide insight into the cardiovascular and renal effects of bisphosphonate therapy in PHPT patients. Findings may help guide treatment strategies for optimizing long-term skeletal and systemic health in this patient population.
详细描述
Aim The overall aim of this study is a physiological investigation of the effect of bisphosphonate treatment versus placebo at time of parathyroidectomy (PTX) in patients with primary hyperparathyroidism (PHPT) on bone, kidney and the cardiovascular system one-year post-surgery.
Hypothesis:
In patients with PHPT and low areal bone mineral density (aBMD), treatment at time of PTX with zoledronic acid (ZOL) compared to placebo:
- does not improve aBMD
- does not improve bone microarchitecture
- does not improve volumetric bone mineral density (vBMD)
- does not influence changes in BTM
- does not improve coronary artery calcium score (CACS)
- does not improve arterial stiffness (pulse wave velocity [PWV])
- does not improve degree of renal calcifications or urinary parameters
Background:
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Postmenopausal females or males > 50 years
- •A diagnosis of hyperparathyroid hypercalcemia due to sporadic PHPT referred to PTX
- •aBMD T-score ≤ -1 at total hip, femoral neck, or lumbar spine
- •25-hydroxyvitamin D ≥ 50 nmol/l prior to randomization
- •Willingness to undergo PTX
排除标准
- •Known or suspected familial ethology (e.g., MEN1 or 2)
- •Estimated glomerular filtration rate < 35 ml/min
- •Known allergy to bisphosphonates
- •Planned or recent (within the last 3 months) major dental procedures (e.g., jaw surgery or tooth extraction)
- •Chronic or acute disorders (e.g., rheumatoid arthritis, inflammatory bowel disease, cancer) or prior medications (e.g., lithium, glucocorticoids within the last year, antiresorptive or bone anabolic treatment within the last 3 years) known to affect bone metabolism.
研究组 & 干预措施
Zoledronic acid
Patients referred to Aarhus University Hospital (AUH) for PTX due to PHPT will be included prospectively. We aim to include 140 patients with PHPT - 70 patients in each group. Patients will be enrolled consecutively until the required number of participants have been achieved. Enrolled participants will be randomized to intervention (active medicine) or placebo group and receive either zoledronate or placebo (saline water) 2-4 weeks prior to PTX.
干预措施: Zoledronic acid 4 mg (Drug)
Placebo
Patients referred to Aarhus University Hospital (AUH) for PTX due to PHPT will be included prospectively. We aim to include 140 patients with PHPT - 70 patients in each group. Patients will be enrolled consecutively until the required number of participants have been achieved. Enrolled participants will be randomized to intervention (active medicine) or placebo group and receive either zoledronate or placebo (saline water) 2-4 weeks prior to PTX.
干预措施: Natriumklorid 9 mg/ml, Fresenius Kabi (Drug)
结局指标
主要结局
Effects of ZOL vs. placebo at time of parathyroidectomy based on change in aBMD at lumbar spine meased at baseline compared to one year after PTX.
时间窗: 12 months (one year)
aBMD (g/cm\^3) will be measured by DXA-scans at baseline and one year after PTX.
次要结局
- Effects of ZOL at aBMD at distal forearm(12 months (one year))
- Effects of ZOL at aBMD at femoral neck(12 months (one year))
- Effects of ZOL at aBMD at total hip(12 months (one year))
- Effects on microarchitecture measured by high-resolution peripheral computed tomography (HRpQCT).(12 months)
- Effects on biochemical bone turnover markers (BTM).(12 months)
- Effects on vBMD at the hip(12 months)
- Effects on vBMD at the lumbar spine.(12 months)
- Effects on coronary artery calcium score (CACS)(12 months)
- Effects on pulse wave velocity (PWV)(12 months)
- Effects of ZOL on renal calcifications(12 months)
- Effects of ZOL on urinary analytes(12 months)