Long-term aerobic exercise and omega-3 supplementation modulate osteoporosis through inflammatory mechanisms in post-menopausal women: a randomized, repeated measures study

Journal Title (Medline/Pubmed accepted abbreviation): Nutr Metab (Lond)
Year: 2011
Volume: 8
Page Numbers: 71 (open access)
doi (if applicable):10.1186/1743-7075-8-71

Summary of background and research design:

Background:Osteoporosis primarily affects older postmenopausal women, decreasing quality of life and increasing societal cost. The decline in bone health in older postmenopausal women parallels estrogen depletion and increased inflammatory activity. Previous studies suggest that polyunsaturated fatty acids (PUFA) supplementation and exercise may suppress inflammation and bone resorption.  

Hypothesis/Purpose: Exercise combined with PUFA supplementation may inhibit inflammation and bone resorption, thereby preserving bone mineral density (BMD).

Subjects: Seventy-nine women ≥ 8 years past menopause with a body mass index ranging from 25.1 to 28.5 kg/m2 and 58 to 78 years of age were enrolled. All women were in good health and were not taking any medications. Analysis was based on 70 women who completed the study.

Experimental design: Randomized, independent groups. Details regarding placebo and blinding procedures were not provided. 

Treatments and protocol:
Women were randomized to 1 of 4 study arms: exercise + supplement (E+S), exercise (E), supplement (S), or control (C). The E+S and S groups received a total of 1,000 mg/day N-3 PUFA. In the first 12 weeks, subjects in E+S and E groups exercised 25 to 30 minutes/day, 3 to 4 days/week, at 45% to 55% of previously determined maximal heart rate (HRmax). In the second 12-week period, exercise was increased to 40 to 45 minutes/day, 4 to 6 days/week, at an intensity of 55% to 65% of HRmax. Blood samples for serum tumor necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), prostaglandin E2 (PGE2), estrogen, osteocalcin, 1,25-vitamin D, carboxy-terminal collagen crosslinks (CTX), parathyroid hormone (PTH), calcitonin (CT), calcium, phosphorus, and fatty acid composition of neutrophil extracts were collected at baseline and at 12 and 24 hours after the last exercise. BMD was assessed at the lumbar spine (LS; L2-L4) and femoral neck (FN) at baseline and at 12 and 24 weeks.

Summary of research findings:
  • At 24 weeks, LS BMD was significantly increased from baseline in the E+S group (+0.17 g/cm2) compared with other groups (P < .05).
    • Similar results were obtained with FN BMD; however, changes were first observed at 12 weeks.
  • TNF-α levels were significantly decreased from baseline at Weeks 12 and 24 in the E+S and S groups compared with the other groups (P < .05).
    • Mixed model regression showed that decrease in TNF-α correlated with increase in BMD.
  • IL-6 levels were significantly decreased from baseline at 24 weeks in the E+S group compared with other groups (P < .05); differences between E and S groups vs control group were also observed.
  • PGE2 levels significantly declined from baseline at 12 weeks in the E+S group (P < .05), but there were no changes in the other groups until 24 weeks.
    • Mixed model regression showed that decrease in PGE2 correlated with increase in BMD.
  • Levels of estrogen, CT, osteocalcin, and vitamin D increased and PTH decreased from baseline at Weeks 12 and 24 in the E+S group compared with the other groups (P < .05 for all).
  • Fatty acid composition of neutrophils increased from baseline for eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) and decreased from baseline for linoleic acid and arachidonic acid in the E+S and the S groups.

Interpretation of findings/Key practice applications:

In sedentary postmenopausal women, exercise and PUFA supplementation may help maintain skeletal health. Although the individual interventions of exercise and PUFA supplementation appear to have beneficial effects, a synergistic benefit is derived when both are combined. The significant gains in BMD at LS and FN as a result of E+S intervention are consistent with the observed effects of these interventions on estrogen, calciotropic hormones, and inflammatory cytokines. PUFA supplementation appears to augment the benefit of exercise by increasing estrogen levels and decreasing calcium resorption from bone.


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