Osteocalcin in Bone Metabolism and Aging: Effect of Vitamin K Supplementation on Circulating Levels of Osteocalcin, on Glucose and Energy Metabolism and on Muscle Mass and Function
试验速览
- 阶段
- 不适用
- 状态
- 终止
- 入组人数
- 99
- 试验地点
- 1
- 主要终点
- Circulating levels of GluOC
研究概览
简要总结
This is an interventional study on nutraceuticals. It is a randomized controlled, open-label, prospective, single-center study that involves the enrollment of 82 patients with osteoporosis and 41 subjects without osteoporosis.
The hypothesis the decarboxylated form of Osteocalcin (OC), called GluOC, represents a clinically useful marker for monitoring the effects of supplementation with vitamin K in association with anabolic treatment with teriparatide will be analyzed not only on bone but also on skeletal muscle and energy metabolism in patients with severe osteoporosis.
详细描述
Background:
OC, also known as bone-Gla-protein (BGP), is the main non-collagen protein of the extracellular matrix in mineralized tissues. It is synthesized by osteoblasts, odontoblasts, and hypertrophic chondrocytes and, through its negative charges, binds calcium and regulates the formation of hydroxyapatite crystals.
In humans, circulating OC levels negatively correlate with fasting blood glucose and insulin, Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), body mass index (BMI), hyperlipidemia, and circulating concentrations of leptin. Weight loss (resulting from diet and / or physical activity) improves metabolic profile and muscle strength and increases OC levels.
It's interesting to note that high plasma levels of vitamin K or dietary supplementation (MK-7, the natural derivative of vitamin K2), correlate with a reduction in the loss of bone mass and quality. In addition, short-term (1 week) and long-term (3 years) vitamin K supplementation improves insulin resistance in both young and old males and high vitamin K consumption is associated with reduced insulin resistance and reduced risk of developing type 2 mellitus diabetes.
Recently, it has been reported in mice that the combination of teriparatide (TPT) and vitamin K is more effective than ionotherapy in improving bone formation, bone density and strength, and in inhibiting bone resorption.
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
- None
入排标准
- 年龄范围
- 65 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Exclusion criteria for the group of "Patients with osteoporosis":
- •causes of secondary osteoporosis: current glucocorticoid therapy, active and uncontrolled rheumatic diseases, endogenous hypercortisolism, uncontrolled hyperthyroidism or hypothyroidism (except known hypothyroidism well compensated with L-thyroxine), chronic renal failure (IRC) with glomerular filtration rate (GFR) <30 ml / min, multiple myeloma, liver failure (chronic liver disease of CHILD class B and C), heart failure (New York Heart Association, also said NHYA) NHYA> 2, active neoplasms, type 1 and type 2 diabetes mellitus
- •ongoing therapies: glucocorticoids, antiepileptics, aromatase inhibitors and similar gonadotropin-releasing hormone (GnRH, contraindicated for teriparatide).
- •Exclusion criteria for the group "subjects without osteoporosis":
- •ongoing therapies: glucocorticoids, antiepileptics, diphosphonates, teriparatide, denosumab, statins, oral or injective hypoglycemic agents, aromatase inhibitors, similar GnRH or other oncological therapies
- •diagnosis of osteoporosis (according to World Health Organization, WHO) T-score <-2.5 standard deviation (SD), at any site evaluated with ''Dual-Energy X-ray Absorptiometry'' (DXA)
- •diagnosis of sarcopenia (according to ''Appendicular Skeletal Muscle Mass'', ASMMI) ASMMI <7.59 kg / m2 for males and 5.47 kg / m2 for females evaluated with DXA
- •diagnosis of IRC with estimated GFR <30 ml / minute, liver failure (chronic liver disease of CHILD class B and C), heart failure with NHYA> 2 , active neoplasms, endocrinopathies (except known hypothyroidism well compensated with L-thyroxine ), type 1 and type 2 diabetes mellitus.
研究组 & 干预措施
Patients with osteoporosis treated with teriparatide + Vitamin K
Patients will have to take teriparatide (standard of care) + Vitamin K (MK7) at the dosage of 375 microg / day
干预措施: Vitamin K (MK7) (Dietary Supplement)
Patients with osteoporosis treated with teriparatide + Vitamin K
Patients will have to take teriparatide (standard of care) + Vitamin K (MK7) at the dosage of 375 microg / day
干预措施: Teriparatide (Drug)
Patients with osteoporosis treated with teriparatide
Patients will have to take teriparatide (standard of care)
干预措施: Teriparatide (Drug)
结局指标
主要结局
Circulating levels of GluOC
时间窗: 18 months
Circulating levels of GluOC measured after 18 months of treatment with vitamin K
次要结局
- Circulating levels of OC isoforms(18 months)