Dried Plums and Bone Health in Postmenopausal Women

Given the current high incidence of osteoporosis, reducing the risk of osteoporosis
development is essential. Recent estimates, based on the 2010 US Census, indicate that
approximately 10.3 million people age 50 and older have osteoporosis. By 2030 the prevalence
of osteoporosis for women 50 years and older is projected to reach 13.6 million.
Postmenopausal osteoporosis is characterized not only by hypoestrogenism, but also by
increased production of reactive oxygen species, oxidative stress, and inflammatory response.
Current first line strategies are treatment of osteoporosis with pharmacologic approaches.
Complementary recommendations include the maintenance of calcium (Ca2+) and vitamin D (VitD)
intake to meet the current recommendations. Although the anti-resorptive therapies are
effective they are also associated with an array of negative side effects, which reduce
patient compliance to use of the therapy.

Non-pharmacologic options to reducing the risk of bone loss are becoming more attractive to
many postmenopausal women. The phenolics and bioavailable conjugated metabolites found in
dried plums are proposed to modulate the inflammatory signaling pathways and have the
potential to influence bone formation and bone resorption, thus modulating the risk of bone
loss. The investigators are conducting a 52 week dose ranging randomized controlled trial
that builds upon previous rodent and human work and addresses the experimental design
limitations of the previous work, to assess bone outcomes with clinical (BMD) and mechanistic
(bone geometry, bone metabolism markers, and inflammation markers) techniques. Additionally,
this study will include a detailed assessment of the phenolics in the dried plums to explore
the relationship between these compounds and bone outcomes.

Participants will participate in a 1-2 week screening period followed by a 1-2 week baseline
period. At the end of baseline randomization to 1 of 3 groups will occur (Ca2+ and VitD only;
50g Dried Plums/day and Ca2+ and VitD; 100g Dried Plums/day and Ca2+ and VitD). Dried plums
and Calcium/Vitamin D supplements will be provided to participants for the duration of the
intervention. At the beginning of the 52 week intervention participants will begin
consumption of dried plums and will be given a run in period where the number of dried plums
consumed per day increases slowly to minimize the side effects felt by the participants. The
dried plums will be consumed as snacks in the morning, midday, and in the evening.
Participants will visit the laboratory for testing every 4 weeks during the 52 week
intervention, with more testing occurring during weeks 12, 24, 36, and 52 than the other
testing periods.

At testing period visits participants will be asked to complete some or all of the following:
body weight measurement; blood sampling; 24-hour urine collection; stool sample collection;
DXA scan; peripheral quantitative computed tomography (pQCT) scan; completion of health,
physical activity, and nutrition questionnaires; completion of supplement/symptom, diet, and
physical activity logs.

A total of 300 participants will be enrolled and screed with an expected randomization of 79
participants per group. The investigators anticipate a 20% drop-out rate between baseline and
week 52, thus will anticipate having a final sample size of 63 participants per group
complete the study. This sample size provides over 80% power to detect differences with the
primary BMD, bone geometry, and bone strength variables.

Inclusion Criteria:

- Postmenopausal women

- not severely obese (BMI < 40 kg/m2);

- healthy (determined by a screening questionnaire, complete metabolic panel);

- willing to include dried plums in their daily diet;

- not taking any natural dietary supplement containing phenolics, blueberries or apples
for at least 2 months prior to study entry; can stop for 2 months to meet entry
criteria

- non-smoking; ambulatory;

- low BMD as measured by dual energy X-ray absorptiometry (DXA). Eligible BMD values
(T-scores) for DXA measures of the lumbar spine, total hip and/or femoral neck will
correspond to T-scores between 0 and -3.0.

Exclusion Criteria:

- Women who regularly consume dried plums, dried apples, prune juice, or heavy consumers
of blueberries (1 cup or more/day). Potential volunteers who will refrain from
consumption of the afore mentioned foods for the duration of the study will become
eligible after a 2 month washout period;

- vitamin D deficiency (<20 ng/mL);

- history of vertebral fracture or fragility fracture of the wrist, humerus, hip or
pelvis after age 50 yr);

- untreated hyper- or hypothyroidism;

- current hyper- or hypoparathyroidism;

- significantly impaired renal function; high potassium

- current hypo- or hypercalcemia;

- history of spinal stenosis;

- history of heart attack, stroke, thromboembolism, kidney disease, malabsorption
syndrome, seizure disorders;

- positive for HIV, Hep-C or Hep-B surface antigen and malignancy.

- Use of the following agents affecting bone metabolism:

- intravenous bisphosphonates at any time;

- fluoride (for osteoporosis) within the past 24 months;

- denosumab at any time;

- bisphosphonates, parathyroid hormone or strontium within the past 12 months;

- calcitonin or selective estrogen receptor modulators within the past 12 months;

- systemic oral or transdermal estrogen within the past 3 months;

- systemic glucocorticosteroids (≥ 5 mg prednisone equivalent per day for more than
10 days); or

- tibolone within the past 3 months.

- Participants who will not consume study therapy or will not stop taking natural
product supplements of their own selection.