Effects of Omega-3 Fatty Acids on Bone and Frailty

The purpose of this study is to examine the effects of essential fatty acid (EFA) supplementation on bone metabolism and frailty in postmenopausal women. The overall hypothesis is that EFA supplementation, via its immunoregulatory and anti-inflammatory activity, will decrease bone turnover, decrease prostaglandins and cytokines associated with bone metabolism and frailty, and change physical outcome measures associated with frailty in postmenopausal women with low bone mass and frailty.

Study Overview

• Status: Unknown
• Conditions: Frailty; Osteoporosis
• Intervention / Treatment: Dietary supplement: DHA/EPA; Dietary supplement: Calcium with vitamin D; Dietary supplement: Placebo capsule

Detailed Description

Osteoporosis is a bone thinning disease that results in fractures that occur with minimal trauma. The direct health care costs related to osteoporosis are estimated to be $14 billion per year, comparable to costs in heart failure and asthma. Frailty, or poor physiologic reserve to deal with stressors, is estimated to be 7% in the general population over age 65. The frailty syndrome is characterized by sarcopenia or muscle loss, inflammation, low estrogen, growth hormone and testosterone levels, poor nutrition and disability, and is associated with an increased risk of falls and fracture. Omega-3 fatty acids found in fish oil (eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA)) have been shown to decrease markers of inflammation (cytokines) and decrease death due to heart disease. A number of studies in animals suggest that fish oil (EPA and DHA) supplementation inhibits bone break down, increases calcium absorbed from the diet and enhances calcium in bone. Few studies have assessed the role of n-6 and n-3 fatty acids in the diet in bone disease in humans. As far as we know, no study has evaluated the role of n-3 fatty acids in the frailty syndrome.

• Study Type: Interventional
• Enrollment (Anticipated): 150
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Connecticut
    • Farmington, Connecticut, United States, 06030
      • University of Connecticut Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 61 years and older (Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Postmenopausal women over 65 years old
• Spine or hip bone density T score less than -1
• Hand grip strength 2 standard deviations below weight adjusted norms
• Able to travel to the clinical sites for follow-up visits

Exclusion Criteria:

• Any disease that may affect bone metabolism, (i.e Paget's disease, primary hyperparathyroidism)
• Cancer of any kind (except basal or squamous cell of skin) in past 5 years.
• Use of calcitonin, calcitriol, heparin, phenytoin, phenobarbital, and estrogen in the past 6 months
• Use of bisphosphonates, long-term corticosteroids (more than 6 months), methotrexate, or fluoride at any time
• Current use of any medication or herbs with anticoagulant or antiplatelet activity, tetracycline, and magnesium or zinc supplementation
• Estimated creatinine clearance less than 50 ml/min
• History of chronic liver disease or evidence of liver disease on screening
• History of hip fracture or known vertebral fracture within the past year
• Untreated hypertension or a history of clotting disorders
• History of allergy to fish or fish oil

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: 1	Dietary supplement: DHA/EPA; 1.2 gram capsule daily for 6 months; Dietary supplement: Calcium with vitamin D; 1000 mg of calcium with 1000 IU vitamin D daily for 6 months
Placebo Comparator: 2	Dietary supplement: Calcium with vitamin D; 1000 mg of calcium with 1000 IU vitamin D daily for 6 months; Dietary supplement: Placebo capsule; daily for 6 months

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Bone turnover markers	baseline, 3 and 6 months

Secondary Outcome Measures

Outcome Measure	Time Frame
Bone Mineral Density	baseline, 3 and 6 months
Physical performance measures	baseline, 3 and 6 months
Blood pressure and lab work, including lipids, cytokines, prostaglandins, lymphocyte characterization, and EPA/DHA in blood and plasma	baseline, 3 and 6 months
Cognitive status, mood and depression	baseline, 3 and 6 months

Collaborators and Investigators

• Sponsor: Donaghue Medical Research Foundation
• Collaborators: University of Connecticut
• Investigators: Principal Investigator: Anne Kenny, MD, University of Connecticut Center on Aging

Publications and helpful links

General Publications

• Arlt W, Callies F, van Vlijmen JC, Koehler I, Reincke M, Bidlingmaier M, Huebler D, Oettel M, Ernst M, Schulte HM, Allolio B. Dehydroepiandrosterone replacement in women with adrenal insufficiency. N Engl J Med. 1999 Sep 30;341(14):1013-20. doi: 10.1056/NEJM199909303411401.
• Callies F, Fassnacht M, van Vlijmen JC, Koehler I, Huebler D, Seibel MJ, Arlt W, Allolio B. Dehydroepiandrosterone replacement in women with adrenal insufficiency: effects on body composition, serum leptin, bone turnover, and exercise capacity. J Clin Endocrinol Metab. 2001 May;86(5):1968-72. doi: 10.1210/jcem.86.5.7483.
• Morales AJ, Haubrich RH, Hwang JY, Asakura H, Yen SS. The effect of six months treatment with a 100 mg daily dose of dehydroepiandrosterone (DHEA) on circulating sex steroids, body composition and muscle strength in age-advanced men and women. Clin Endocrinol (Oxf). 1998 Oct;49(4):421-32. doi: 10.1046/j.1365-2265.1998.00507.x.

Study record dates

Study Major Dates

• Study Start: January 1, 2007
• Primary Completion (Anticipated): June 1, 2009
• Study Completion (Anticipated): June 1, 2009

Study Registration Dates

• First Submitted: March 11, 2008
• First Submitted That Met QC Criteria: March 11, 2008
• First Posted (Estimate): March 13, 2008

Study Record Updates

• Last Update Posted (Estimate): February 2, 2009
• Last Update Submitted That Met QC Criteria: January 29, 2009
• Last Verified: January 1, 2009

More Information

Terms related to this study

• Keywords: Omega-3 fatty acids; immune response
• Additional Relevant MeSH Terms: Pathologic Processes; Metabolic Diseases; Musculoskeletal Diseases; Bone Diseases; Bone Diseases, Metabolic; Frailty; Osteoporosis; Physiological Effects of Drugs; Micronutrients; Vitamins; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Vitamin D; Calcium
• Other Study ID Numbers: AG0096