Effects of Age and Osteoclast Inhibition on Bone Formation
试验速览
- 阶段
- 早期 1 期
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 81
- 试验地点
- 1
- 主要终点
- Gene expression changes in bone cells
研究概览
简要总结
This protocol addresses: 1) How gene expression changes in bone cells are affected by aging? 2) Is aging associated with decreased signaling between bone cells? 3) How does treatment with the osteoporosis medication denosumab affect bone cell signaling?
详细描述
This protocol collectively addresses the following goals: 1) What are the changes in gene expression in osteoblasts and osteocytes that lead to impaired bone formation with aging; 2) Since recent work from the investigators' group has demonstrated that osteoclasts produce a number of growth factors and cytokines (coupling factors) that enhance osteoblast proliferation and/or differentiation, is aging associated with reduced osteoclast coupling factor production; and 3) If osteoclasts are markedly reduced using the FDA-approved medication for osteoporosis, denosumab, how does that effect the quantity of coupling factors in the bone microenvironment and the target genes of these coupling factors in osteoblasts?
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Basic Science
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 25 Years 至 80 Years（Adult, Older Adult）
- 性别
- Female
- 接受健康志愿者
- 是
入选标准
- •normal premenopausal women aged 25-40 years
- •normal postmenopausal women aged 60-80 years
- •at least 5 yrs since their last menses
- •follicle stimulating hormone (FSH) > 20 IU/L
排除标准
- •Abnormality in any of the screening laboratory studies
- •Presence of significant liver or renal disease
- •Malignancy (including myeloma)
- •Malabsorption
- •Hypoparathyroidism
- •Hyperparathyroidism
- •Acromegaly
- •Cushing's syndrome
- •Hypopituitarism
- •Severe chronic obstructive pulmonary disease
- •Undergoing treatment with any medications that affect bone turnover, including the following:
- •adrenocorticosteroids (> 3 months at any time or > 10 days within the previous yr)
- •anticonvulsant therapy (within the previous year)
- •pharmacological doses of thyroid hormone (causing decline of thyroid stimulating hormone below normal)
- •calcium supplementation of > 1200 mg/d (within the preceding 3 months)
- •bisphosphonates (within the past 3 yrs)
- •denosumab
- •estrogen (E) therapy within the past year
- •treatment with a selective E receptor modulator within the past year
- •teriparatide within the past yr
- •Clinical history of osteoporotic fracture (vertebral, hip, or distal forearm)
- •Recent (within the past 6 months) fracture
- •Serum 25-hydroxyvitamin D levels of < 20 ng/ml
研究组 & 干预措施
placebo
single subcutaneous injection of placebo (normal saline)
干预措施: placebo (Drug)
Denosumab
single subcutaneous injection of denosumab 60 mg
干预措施: denosumab (Drug)
结局指标
主要结局
Gene expression changes in bone cells
时间窗: 3 months
Ratio of selected genes as expressed between each of the 3 arms (i.e. relative runx2 gene expression levels in each arm).
次要结局
- Osteoclast-osteoblast coupling factor changes(3 months)