Clinical trial NCT00789425: Investigating the Effect of Standardized Olive Extract on Bone Turnover Markers in Postmenopausal Women
Official title: A Randomised, Double Blind, Parallel Group, 12-month Comparison of a Standardized Olive Extract With Placebo in Postmenopausal Women With Decreased Bone Mineral Density
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Osteoporosis
Osteopenia
Keywords: osteoporosis
osteopenia
olive extract
oleuropein
Lead sponsor: BioActor
Sponsor class: INDUSTRY
First posted: 2008-11-11
Enrollment: 64
Sex: FEMALE
Minimum age (years): 50
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The purpose of this study is to determine whether the intake of a daily dosage of standardized olive extract provides any protection against bone loss.

Detailed description: Apart from estrogen deficiency, the early postmenopausal period is also characterised by an increasing inflammatory and oxidant status, which further contributes to the development of osteoporosis/osteopenia. The link between systemic inflammation and osteoporosis has only been established recently as it was found that higher circulating hsCRP levels are associated with lower bone mineral density in both healthy pre- and postmenopausal women. Furthermore, it was already known for a long time that one of the most important cytokines implicated in the pathogenesis of various metabolic bone diseases, including postmenopausal osteoporosis, is interleukin (IL)-6, which is produced by osteoblasts, monocytes and T-cells.

Olive oil is the principle fat source of the traditional Mediterranean diet, a diet that has been associated with a low incidence of some diseases, including coronary heart disease and osteoporosis. In addition to the main ingredient (ie. oleic acid) extra virgin olive oil also contains phenolic compounds, such as oleuropein- and ligstroside-aglycones and their derivatives. They are formed in olives by enzymatic removal of glucose from the polar parent compound oleuropein-glycoside. A Mediterranean diet rich in olive oil supplies 10 - 20 mg of phenols per day.

The main metabolic attribute of oleuropein is that it exerts both antioxidant and anti-inflammatory activity by lowering the levels of proinflammatory cytokines like IL-1, IL-6 or TNF-alpha. By inhibiting osteoclast activity, this may result in lowering the rate of bone resorption and, at least in part, protect against osteoporosis development.

Formulated as a capsule it is expected that the compliance and tolerability will be improved compared to the liquid administration. The present study is designed to investigate the effect of 250 mg of a standardized extract of olive polyphenols per day on bone loss in postmenopausal women with decreased bone mass (osteopenia) .

Eligibility criteria: Inclusion Criteria:

* Signed written informed consent
* Gender female
* Between 50-70 years of age
* At least 2 years post menopause
* Bone mineral density (BMD) \< or equal to -1.5 and \> or equal to -2.5 SD% Young Adult
* Patients with stabilised food habits
* Patients able to understand the nature of the study and able to give signed written informed consent.

Exclusion Criteria:

* Patients with any diseases affecting bone tissue e.g. primary hyperparathyroidism.
* Patients during any therapy affecting bone tissue e.g. HRT, corticosteroids.
* Patients with any associated illness of sufficient severity, or clinically relevant abnormalities in the pre-study screening, which in the opinion of the investigator would make them unsuitable for inclusion in the study, e.g. severe heart failure, severe ischaemic heart disease etc.
* Planned hospitalisation (major surgery) during the study.
* Patients who have any known allergy or intolerance to any compound in the test product.
* Patients who are unwilling or unable to comply with the study protocol for any other reason.

Primary outcomes:
measure: Serum levels of Osteocalcin and CTX will be used as bone turnover markers
timeFrame: 0, 3, 6, and 12 months
Secondary outcomes:
measure: Bone mineral density as measured by DEXA in lumbar spine and total hip
timeFrame: 0 and 12 months
measure: hs-CRP and IL-6 in serum as inflammation markers
timeFrame: 0, 6, and 12 months
measure: ORAC values in serum as oxidative stress marker
timeFrame: 0, 6, and 12 months
measure: Total cholesterol, HDL-C, LDL-C, triglycerides in serum as CVD-risk markers.
timeFrame: 0, 6, and 12 months
Other outcomes:
Locations:
city: Lublin
country: Poland
facility: Osteoporosis Outpatient of the Institute of Agricultural Medicine
Study officials:
affiliation: Institute of Agricultural Medicine
name: Rafal Filip, MD PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Filip R, Possemiers S, Heyerick A, Pinheiro I, Raszewski G, Davicco MJ, Coxam V. Twelve-month consumption of a polyphenol extract from olive (Olea europaea) in a double blind, randomized trial increases serum total osteocalcin levels and improves serum lipid profiles in postmenopausal women with osteopenia. J Nutr Health Aging. 2015 Jan;19(1):77-86. doi: 10.1007/s12603-014-0480-x.