Oligopin Supplementation and Bone Turnover Markers and Antioxidant Changes in Postmenopausal Osteopenic Women

Study Overview
=================
Brief Summary
-----------------
Osteoporosis fractures impose a significant economic burden on the health system. There is evidence that osteoporosis has a high prevalence in Iran (4.8% for men and 7.7% for women), and the frequency of osteopenia is 36.8% for men and 39.3% for women in Iran Accordingly, the prevention of osteopenia progression towards osteoporosis has been considered as an important issue in medicine. Bone is a dynamic tissue that is constantly being remodeled thus the equilibrium between bone formation and resorption done by simultaneously regulating osteoclasts and osteoblasts is important. Imbalance between bone deposition and resorption contributes to reducing bone mineral density and hence increasing the risk of osteoporosis Recently, new therapies have been focused on use of medicinal herbs, especially phytochemicals. Among phytochemicals, phytonutrients, and especially polyphenols, can act both on osteoblast and on osteoclast. Pine bark extract (oligopin) is a rich source of polyphenols that exerts strong antioxidant and anti-inflammatory activities. It has also beneficial effects on bone turnover based on in vitro studies and animal models. Investigators aimed to investigate the effects of oligopin on bone turnover markers and plasma and peripheral mononuclear cells oxidative stress in postmenopausal women with osteopenia in a double-blind randomized clinical trial. Participants are forty four women with osteopenia divided into two groups randomly (22, having oligopin, 150 mg, once daily, for 12 weeks). The 2nd group (22 women with osteopenia) receives the same amount of the placebo. At the first and the end of the study, blood sample are taken to measure in order to peripheral blood mononuclear cells isolation and plasma separation. The levels of bone alkaline phosphatase and carboxy terminal collagen type I in plasma oxidative stress markers such as total anti-oxidant capacity, malondialdehyde, and protein carbonyl were evaluated. Furthermore, oxidative stress will be evaluated in peripheral blood mononuclear cells by measurement of expression and activity of magnesium superoxide dismutase,catalase and Nuclear factor (erythroid-derived 2)-like 2.

Official Title
-----------------
Valuating the Effects of Oligopin Supplementation on the Turnover of Bone Formation and Antioxidant Changes in Postmenopausal Osteopenic Women: A Randomized Double-blind Clinical Trial With Placebo-concurrent Controls

Conditions
-----------------
Osteopenia

Intervention / Treatment
-----------------
* Drug: Oligopin
* Drug: Placebo


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Inclusion criteria: Postmenopausal women; Aged between 50-65; Diagnosis of osteopenia based on Tscore ( -2.5 SD ≤ Tscore ≤ -1 SD); To have equal physical, pediatric and complementary therapies for at least three months before entrance to study ;Absence of history of Bone Diseases; Absence of the history of chronic diseases including cancer, diabetes, kidney failure, liver disease, systemic inflammatory diseases, degenerative joint diseases and rheumatologic disorders, primary thalassemia, hyperparathyroidism, hyperthyroidism-Cushing's, Hypercalcaemia syndrome, Hyperglycemia ;Absence of gastrointestinal disease including Crohn's disease, ulcerative colitis, celiac disease, and chronic diarrhea and gastric or duodenal ulcers treated or with a history of gastrointestinal bleeding (according to the patient's history); Absence of history of the use of drugs that affect bone metabolism and have been regularly used for at least 6 months in the past two years: such as osteoporosis drugs (bisphosphonates, estrogen receptor selective agonists / selective antagonists, alternative HRTs, PTH), diuretics, thiazides, anticonvulsants (phenytoin, phenobarbital, sodium valproate), glucocorticoids, nonsteroidal anti-inflammatory drugs such as analgesics (nonsteroidal anti-inflammatory drugs such as naproxen, aspirin and ibuprofen), cigarettes; Absence of motor disabilities, skeletal disorders, untreated psychiatric illnesses such as psychosis, Alzheimer's disease, Parkinson's disease; To accept randomization; Absence of morbid Obesity: BMI is above 40 Exclusion Criteria: Fracture report during the study period; Unwillingness of participants to continue the project; The occurrence of any visible side effects of supplemental effects -

Ages Eligible for Study
-----------------
Minimum Age: 50 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: postmenopausal osteopenic women receiveing Oligopin<br>postmenopausal osteopenic women receiving Oligopin ,150 mg ,once daily, 12 week | Drug: Oligopin<br>* Oligopin ,150 mg ,once daily, 12 week<br>|
| Placebo Comparator: postmenopausal osteopenic women receiving placebo<br>postmenopausal osteopenic women receiving placebo, 150 mg,once daily,12 weeks | Drug: Placebo<br>* Placebo,150 mg ,once daily, 12 week<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Plasma Osteocalcin Concentration | Osteocalcin levels in plasma | up to third month after intervention | 
| Plasma Carboxyl terminal collagen type I Concentration | Carboxyl terminal collagen type I in plasma | up to third month after intervention | 
| Osteocalcin/Carboxyl terminal collagen type I ratio | Osteocalcin/Carboxyl terminal collagen type I ratio | up to third month after intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| MnSOD activity in peripheral blood mononuclear cells | MnSOD activity in peripheral blood mononuclear cells | Baseline and third month after intervention | 
| Catalase activity in peripheral blood mononuclear cells | Catalase activity in peripheral blood mono nuclear cells | Baseline and third month after intervention | 
| MnSOD mRNA expression peripheral blood mononuclear cells | MnSOD mRNA expression peripheral blood mononuclear cells | Baseline and third month after intervention | 
| Catalase mRNA expression peripheral blood mononuclear cells | Catalase mRNA expression peripheral blood mononuclear cells | Baseline and third month after intervention | 
| NrF2 mRNA expression peripheral blood mononuclear cells | NrF2 mRNA expression peripheral blood mononuclear cells | Baseline and third month after intervention | 
| Plasma Malondialdehide Concentration | Malondialdehide levels in plasma | Baseline and third month after intervention | 
| total antioxidant capacity | total antioxidant capacity in plasma | Baseline and third month after intervention | 
| protein carbonyl content | protein carbonyl content in plasma | Baseline and third month after intervention | 
| Plasma Total thiol concentration | Total thiol level in plasma | Baseline and third month after intervention | 
| Catalase activity in Plasma | Catalase activity in plasma | Baseline and third month after intervention | 
| MnSOD activity in Plasma | MnSOD activity in plasma | Baseline and third month after intervention | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
osteopenia, oligopin, postmenopause, antioxidant, bone