Dried Plums Prevent Inflammation And Improve Bone Health in Osteopenic Men
Condition: Osteoporosis, Osteopenia
MeSH terms: Osteoporosis; Bone Diseases, Metabolic; Inflammation
Study type: Interventional

Summary: 
      The goals of this study are 1) to investigate the extent to which dried plum improves bone
      health by measuring bone density (a measure of bone strength) of whole body, hip, and
      forearm, indicators of bone formation and bone breakdown, and 2) to determine the
      anti-inflammatory effects of dried plum by assessing biomarkers of inflammation.
      Additionally, relevant medical history and lifestyle variables will be recorded.
    

Detailed description: 
      Osteoporosis in men is an important yet an understudied debilitating disease. To date, most
      therapies are directed towards postmenopausal osteoporosis, and the efficacy of these
      therapies is not established for male osteoporosis. Therefore, due to concerns regarding the
      increasing prevalence of male osteoporosis and minimal treatment options available, it is
      imperative to further investigate the role of readily available preventative therapies such
      as functional foods on improving bone health in men.

      In general, consumption of fruits and vegetables has health-protective effects, in part,
      through the prevention of inflammation and its related conditions, including bone loss. These
      protective effects have been primarily attributed to their bioactive components, including
      polyphenols. Dried plums (Prunus domestica L.) have been ranked as having one of the highest
      oxygen radical absorbance capacities among the commonly consumed fruits and vegetables,
      likely due to the fact that they are a rich source of polyphenolic compounds, including
      chlorogenic acid and neochlorogenic acid, which are potent antioxidants. For these reasons,
      dried plums have been investigated to determine if they would have beneficial effects on bone
      health, and their bone-protective effects have been well-established in animal models and to
      some degree in humans by our laboratory as well as others.

      The long-term goal of this proposed research is to develop new approaches to prevent chronic
      inflammation and subsequently to prevent and/or reverse bone loss in osteopenic men, thereby
      reducing the risk of osteoporotic fractures. The rationale for conducting this study is to
      test the extent to which dried plum prevents inflammation and improves bone health in
      osteopenic men. Based on the promising findings of our previous research studies and those of
      others, we hypothesize that chronic consumption of dried plum will prevent inflammation
      thereby preventing and/or reversing further bone loss at the lumbar spine in osteopenic men.
      Healthy men between the ages of 55 and 80 years old with a baseline lumbar spine bone mineral
      density (BMD) t-score between 1 and 2 standard deviations (SD) below the mean, characterizing
      mild to moderate bone loss, will be recruited. The study participants must not have been on
      drug therapy for osteoporosis and must not have begun a new exercise regimen known to affect
      bone metabolism for at least six months prior to the start of the study. Evaluation will be
      based on quantitative assessments of serum and urinary markers of bone formation and bone
      resorption and bone density measurements. Nutrition indices that are known to influence
      skeletal mass such as dietary intakes of calcium, protein, fiber, and magnesium will also be
      assessed as well as relevant medical history and lifestyle variables.

      The rationale for selecting osteopenic men rather than those with normal bone is to test our
      hypothesis that dried plum reverses bone loss similar to male rats. However, no further loss
      of BMD should also be considered a positive finding. Men with a t-score < -2 SD will be
      excluded because they are close to being osteoporotic. Changes in BMD and bone mineral
      content (BMC) of the lumbar spine are the primary outcome variables. Secondary outcome
      variables are the changes in BMD and BMC of whole body, hip, and forearm; and biomarkers of
      inflammation and bone turnover. The rationale for choosing the lumbar spine as our primary
      outcome variable site, is due to the high rates of bone loss that typically occur first in
      the lumbar spine and other areas of high trabecular bone content where there are many
      metabolically active surfaces. To test our hypothesis, two specific aims are proposed as
      follows:

      Aim 1: To investigate the extent to which dried plum improves bone health by measuring:

      Aim 2: To determine the anti-inflammatory effects of dried plum by assessing:

      Study Overview Two hundred men whose lumbar spine BMD t-score is between 1 and 2 SD below the
      mean will be recruited from primary care and specialty clinics and by advertisement at large.
      After an initial telephone screening, all participants will be requested to report to the
      study site for their first visit. On the first visit (screening), the Study Coordinator will
      provide the potential subjects with verbal and written explanation of the project and will
      answer any questions regarding the study. Then the individual will be asked to sign an
      informed consent form, followed by a DXA scan to confirm osteopenia. Baseline assessments
      will be performed for medical history, medications use, dietary intake, and physical
      activity. If volunteers meet the study criteria, they will be scheduled for their second
      visit two weeks later (actual baseline data collection) and randomly assigned to their
      treatment group: 50 g dried plum, 100 g dried plum, or control for one year. In order to
      provide some protection against further bone loss, all study participants will receive 500 mg
      elemental calcium and 400 IU vitamin D3 daily. They will be given a three-day food record to
      take home and bring back on the second visit. Additionally, subjects will be asked to collect
      a 24-hour urine sample the day prior to their next visit and bring this with them to the
      clinical research facility and they will repeat this the day prior to each subsequent visit.
      During each visit (baseline, 3, 6, and 12 months) between the hours of 6-10 A.M., venous
      blood will be drawn from the antecubital vein. Subjects' anthropometrics including height,
      weight, and waist and hip circumferences will be measured. Participants will be asked to
      complete a Physical Activity Questionnaire. Participants will undergo a DXA scan for bone
      density measurements (lumbar spine, whole body, hip, and forearm BMD and BMC) at screening
      (considered baseline for BMD and BMC values), 6 months, and 12 months.

      Data Analyses - Descriptive statistics will be calculated for all variables and will include
      means, standard deviations, medians, minima and maxima. Distributions of outcome variables
      will be examined graphically for symmetry and for outliers. If a lack of symmetry is noted,
      the variable will be transformed before analysis, most probably by a logarithmic
      transformation. Extreme outliers will be investigated for technical or clerical errors. If
      the size of the measurement cannot be attributed to such an error, it will be included in the
      analysis and the effect of deleting the observation will also be reported. Baseline
      characteristics for the study groups will be compared and if differences occur in variables
      that could influence bone mass, subsequent analyses will adjust for the effects of these
      variables. The data will be analyzed using PC SAS version 9.3 and SAS PROC MIXED. The overall
      effect of treatments will be inspected. The primary outcomes of interest will be the changes
      observed in lumbar spine BMD and BMC from baseline. The secondary outcome variables will be
      change in hip, forearm, and total body BMD and BMC, and biochemical markers of bone formation
      and bone resorption. Some covariates such as initial bone mass and baseline characteristics
      identified in the preliminary analysis will be included. Other factors that might affect the
      results, such as physical activity, dietary intakes and ethnicity, will also be examined.

      For statistical purposes, the study may be considered a factorial design (3 treatments)*(2
      times) for density measurements and (3 treatments)*(4 times) for serum and urine analyses. It
      is a repeated measures on the time factor (2 levels for DXA and 4 levels for blood and urine
      analyses). Analysis of variance techniques appropriate for this design will provide the
      primary statistical hypothesis testing procedures. To directly address primary research
      questions, planned comparisons will be made between the changes from baseline in the control
      group with changes in the dried plum groups. These comparisons will be made using actual
      differences as response variable, with current values, values adjusted by covariance for
      baseline, and with change as % of baseline as response variable. Clearly these tests are not
      independent, but results may offer different insights. It is anticipated that some subjects
      may leave the study and dropout rates between the three groups; hence, Kaplan Myer time to
      event analysis will be used to examine for possible differences in time to dropout patterns.
      The comparison of changes will first be made using only data for subjects who finish the
      study. A second examination will be made as intent to treat analysis using the MIXED
      procedure to adjust for missing data.

      The relationship between bone mass and biochemical markers of bone turnover will be
      investigated through linear correlation coefficients. The lumbar spine will be the primary
      site of interest although bone mass, i.e. BMD and BMC, at other sites will also be evaluated.
      Hip, forearm, and total body BMD and BMC, as well as serum and urinary biochemical indices of
      bone formation and resorption will comprise the secondary independent variables to be
      considered. Preliminary models will examine the effect of each biochemical index
      individually, and then stepwise methods of variable selection will be employed through the
      use of multiple regression models to determine which combination of indices is strongly
      associated with BMD.
    

Intervention name(s): Dried Plum; 800 IU vitamin D and 450mg elemental calcium
Intervention type(s): Dietary Supplement; Dietary Supplement
Intervention description(s): Dried plum fruit, 100g or 50g depending on treatment group randomized to; Supplemental vitamin D and calcium to protect against further bone loss
Intervention MeSH terms: Vitamin D; Calcium
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Primary purpose: Prevention
Keywords: prune; dried plum; osteoporosis; osteopenia; men