Clinical trial NCT02822378: Dried Plums and Bone Health in Postmenopausal Women
Official title: Randomized Control Trial of Dietary Supplementation With Dried Plums on Bone Density, Geometry and Estimated Bone Strength in Postmenopausal Women
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: NA
Conditions: Postmenopausal Osteoporosis
Keywords: Postmenopausal Osteoporosis
Human
Female
Non-pharmacologic therapy
Lead sponsor: Penn State University
Sponsor class: OTHER
Collaborators: name: California Dried Plum Board
First posted: 2016-07-04
Enrollment: 322
Sex: FEMALE
Minimum age (years): 55
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Postmenopausal women often seek non-pharmacologic interventions for the protection of bone health. Previous research in humans and rodents has indicated that dietary dried plum consumption may be beneficial for bone health, especially in postmenopausal women. However, it is unknown in what quantity dried plums need to be consumed to be of benefit and through what mechanisms dried plums act to impact bone health. Therefore, the purpose of this study is to evaluate the impact of 52 weeks of dried plums consumption in varying quantities on bone mineral density (BMD), bone geometry, and estimated bone strength in postmenopausal women. The investigators also seek to evaluate the mechanisms underlying the effects of dried plums as a dietary supplement by assessing polyphenols and the bioavailable conjugated metabolites in the urine of postmenopausal women taking different doses of dietary dried plums. The investigators aim to further investigate the mechanisms of dried plum action on bone by measuring markers of bone metabolism in response to dried plum consumption.

Detailed description: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percent change from baseline in areal bone mineral density (via DXA) of the lumbar spine, total hip, and femoral neck
timeFrame: at screening, week 24, and week 52
Secondary outcomes:
measure: Percent change from baseline in DXA hip structural analysis
timeFrame: at screening, week 24, and week 52
measure: Percent change from baseline in DXA spine trabecular bone score
timeFrame: at screening, week 24, and week 52
measure: Percent change from baseline in pQCT volumetric BMD of the tibia and radius
timeFrame: at baseline, week 24, and week 52
measure: Percent change from baseline in pQCT geometry measurements of the tibia and radius
timeFrame: at baseline, week 24, and week 52
measure: Percent change from baseline in pQCT strength measurements of the tibia and radius
timeFrame: at baseline, week 24, and week 52
measure: Change from baseline in bone turnover markers
timeFrame: at baseline, week 12, week 24, week 36, and week 52
Other outcomes:
measure: Change from baseline in cellular bone metabolism
timeFrame: at baseline, week 12, week 24, week 36, and week 52
measure: Change from baseline in urine phenolic concentrations
timeFrame: at baseline and every 4 weeks during the intervention
measure: Change from baseline in serum phenolic concentrations
timeFrame: at baseline, week 12, week 24, week 36, and week 52
measure: Change from baseline in expression of inflammatory markers
timeFrame: at baseline, week 12, week 24, week 36, and week 52
measure: Change from baseline in gut microbiome
timeFrame: at baseline, week 24, and week 52
Locations:
city: University Park
country: United States
facility: Women's Health and Exercise Laboratories, The Pennsylvania State University
state: Pennsylvania
Study officials:
affiliation: The Pennsylvania State University
name: Mary Jane De Souza, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: De Souza MJ, Strock NCA, Williams NI, Lee H, Koltun KJ, Rogers C, Ferruzzi MG, Nakatsu CH, Weaver C. Prunes preserve hip bone mineral density in a 12-month randomized controlled trial in postmenopausal women: the Prune Study. Am J Clin Nutr. 2022 Oct 6;116(4):897-910. doi: 10.1093/ajcn/nqac189.