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Bone Health

Dietary Dried Plum Increases Bone Mass, Suppresses Proinflammatory Cytokines and Promotes Attainment of Peak Bone Mass in Male Mice

Journal of Nutritional Biochemistry. 32 (2016)73-82. Shahnazari M, Turner RT, Iwaniec UT, Wronski TJ, Li M, Ferruzzi MG, Nissenson RA, Halloran BP.

Building on previous work in which diets with dried plum (DP) were shown to increase bone volume and strength, the investigators studied DP in skeletally mature (6-month) and growing (1 and 2- month-old) C57Bl/6 male mice. In adult mice, DP rapidly increased bone volume (+32%) and trabecular thickness (+24%) within 2 weeks. These changes were associated with decreased osteoclast surface (OcS/BS) and decreased serum CTX, a marker of bone resorption. Osteoblast surface (Ob.S/BS) and bone formation rate were also decreased suggesting that bone gain in adult mice is related to diminished bone resorption and formation, with resorption being reduced more than formation. There was also a decline in interleukins, TNF and MCP-1, suggesting that dried plums’ effect on bone is in part through the immune system to suppress inflammatory activity and reduce the size of osteoclast precursor pool. Feeding dried plum resulted in an increase in plasma phenolics, some of which have been shown to stimulate bone accrual. At levels as low as 5% of the diet (w/w), DP increased bone volume in growing and young adult mice. At 25% of the diet, bone volume was increased as much as 94%. The investigators state that these data demonstrate that DP dramatically increases bone mass during growth

The Effect of Dried Plum on Serum Levels of Receptor Activator of NF-kB Ligand, Osteoprotegerin and Sclerostin in Osteopenic Postmenopausal Women: A Randomised Controlled Trial

British Journal of Nutrition, April 2014. doi:10.1017/S0007114514000671.Shirin Hooshmand, Jayme R. Y. Brisco and Bahram H. Arjmandi

The mechanisms by which dried plums impart bone-protective properties remain unclear. Recent research has shown that osteocytes may control bone formation via the production of sclerostin and bone resorption via the receptor activator of NF-kB ligand (RANKL) and its inhibitor osteoprotegerin (OPG). In this study, the researchers measured serum levels of RANKL, OPG and sclerostin in osteopenic postmenopausal women (n 160) to investigate the mechanism of action of dried plum in reversing bone loss.

Participants were randomly assigned to the treatment group of either 100 g dried plum/d or 75 g dried apple/d (comparative control) for 1 year (Previously reported in “Comparative Effects of Dried Plum and Dried Apple on Bone in Postmenopausal Women”). All participants received 500mg Ca plus 400 IU (10 mg) vitamin D daily. Bone mineral densities (BMD) of the lumbar spine, forearm, hip and whole body were assessed at baseline and at the end of the study using dual-energy X-ray absorptiometry. Blood samples were collected at baseline and after 12 months to assess bone biomarkers. Dried plum significantly increased the BMD of the ulna and spine in comparison with the control group. In comparison with corresponding baseline values, dried plum increased the RANKL levels by only +1.99 v. +18.33% and increased the OPG levels by +4.87 v.-2.15% in the control group. Serum sclerostin levels were reduced by -1.12% in the dried plum group v. +3.78% in the control group. Although percentage changes did not reach statistical significance (P <0•05), these preliminary data may indicate that the positive effects of dried plum on bone are in part due to the suppression of RANKL production, the promotion of OPG and the inhibition of sclerostin.

Dried Plum Diet Protects from Bone Loss Caused by Ionizing Radiation

Scientific Reports 6, Article number 21343 (2016). Access the article at Schreurs A-S, Shirazi-Fard Y, Shahnazari M, Alwood JS, Truong TA, Tahimic CGT, Limoli CL, Turner ND, Halloran B 
and Globus R.

 In the abstract, the authors state that bone loss caused by ionizing radiation is a potential health concern for radiotherapy patients, radiation workers and astronauts. In animal studies, exposure to ionizing radiation increases oxidative damage in skeletal tissues, and results in an imbalance in bone remodeling initiated by increased bone-resorbing osteoclasts. The researchers evaluated various candidate interventions with antioxidant or anti-inflammatory activities (antioxidant cocktail, dihydrolipoic acid, ibuprofen, dried plum) both for their ability to blunt the expression of resorption-related genes in marrow cells after irradiation with either gamma rays (photons, 2 Gy) or simulated space radiation (protons and heavy ions, 1 Gy) and to prevent bone loss. Dried plum was most effective in reducing the expression of genes related to bone resorption (Nfe2l2, Rankl, Mcp1, Opg, TNF-α) and also preventing later cancellous bone decrements caused by irradiation with either photons or heavy ions. Thus, according to the authors, dietary supplementation with DP may prevent the skeletal effects of radiation exposures either in space or on Earth.

Evidence for Anti-inflammatory and Antioxidative Properties of Dried Plum Polyphenols in Macrophage RAW 264.7 Cells

Food and Function (Food Funct). 2015,6:1719. Hooshmand S, Kumar A, Zhang JY, Johnson SA, Chaid SC and Arjmandi BH.

According to the abstract, the researchers investigated the anti-inflammatory and antioxidative properties of dried plum (Prunus domestica L.) polyphenols in macrophage RAW 264.7 cells. They hypothesized that dried plum polyphenols have strong anti-inflammatory and antioxidant properties against lipopolysaccharide (LPS)-induced production of the pro-inflammatory markers, nitric oxide (NO) and cyclooxygenase-2 (COX-2), and the lipid peroxidation product, malondialdehyde, in activated macrophage RAW 264.7 cells. Macrophage RAW 264.7 cells were stimulated with either 1 μg ml−1 (for measurement of NO production) or 1 ng ml−1 (for measurement of COX-2 expression) of LPS to induce inflammation and were treated with different doses of dried plum polyphenols (0.0, 0.1, 1, 10, 100 and 1000 μg ml−1). Dried plum polyphenols at a dose of 1000 μg ml−1 was able to significantly (P < 0.05) reduce NO production by 43%. Additionally, LPS-induced expression of COX-2 was significantly (P < 0.05) reduced by 100 and 1000 μg ml−1 dried plum polyphenols. To investigate the antioxidant activity of dried plum polyphenols, macrophage RAW 264.7 cells were stimulated with 100 μg ml−1 of FeSO4 + 1 mM ml−1 of H2O2 to induce lipid peroxidation. Dried plum polyphenols at a dose of 1000 μg ml−1 showed a 32% reduction in malondialdehyde production. These findings indicate that dried plum polyphenols are potent anti-inflammatory and antioxidative agents in vitro. The investigators state that these cell culture findings cannot be directly extrapolated to in vivo conditions and that additional studies are needed to explore the bioactivity, metabolism, and tissue distribution and excretion mechanisms of dried plum polyphenols using an animal model of inflammation to confirm the findings.

Effects of low dose of dried plum (50 g) on bone mineral density and bone biomarkers in older postmenopausal women

Dina Metti, Pouneh Shamloufard, Amanda Cravinho, Paulina Delgado, Mark Kern, Bahram H. Arjmandi, Shirin Hooshmand

April 2015 The FASEB Journal vol. 29 no. 1 Supplement 738.12

Our previous findings in osteopenic postmenopausal women indicated that daily consumption of 100 g dried plum for one year is highly effective in increasing bone mineral density (BMD), as well as improving indices of bone turnover. The objective of our current study was to examine whether 50 g dried plum would be as effective as 100 g dried plum in reversing bone loss in osteopenic older postmenopausal women. Forty Eight osteopenic women (65-79 years old) were randomly assigned into one of three treatment groups: 1) 50 g dried plum; 2) 100 g dried plum; and 3) control (0 g dried plum) with forty two subjects completing the study. All groups received 500 mg calcium and 400 IU vitamin D as a daily supplement. Blood samples were collected at baseline, three and six months to assess biomarkers of bone turnover. Physical activity recall and three-day food records were obtained at baseline, three and six months to examine physical activity and dietary confounders as potential covariates. Both doses of dried plum were able to prevent the loss of BMD of the total body compared with that of the control group. Tartrate resistant acid phosphatase-5b (TRAP-5b, a marker of bone resorption) decreased at three months and six months in both dried plum groups. These results confirm the ability of dried plum in improving BMD in older postmenopausal women and suggest that lower doses of dried plum (i.e. 50 g) may be as effective as 100 g dried plum in preventing bone loss in older, osteopenic postmenopausal women. Hence, our findings suggest that the consumption of a reasonable amount of dried plum is beneficial for older, osteopenic women.

Comparative Effects of Dried Plum and Dried Apple on Bone in Postmenopausal Women

British Journal of Nutrition 2011;106:923:-930. Hooshmand S, Chai SC, Saadat RL, Payton ME, Brummel-Smith K and Arjmandi BH.

This study examined the extent to which dried plum reverses bone loss in osteopenic postmenopausal women. Participants were 1-10 years postmenopausal and not on hormone replacement therapy or other prescribed medication known to influence bone metabolism. Qualified participants (n 160) were randomly assigned to one of two treatment groups: dried plum (100g/d) or dried apple (comparative control). Participants also received 500 mg calcium and 400 IU vitamin D daily. Bone mineral density (BMD) of lumbar spine, forearm, hip and whole body was assessed at baseline and at the end of the study using dual-energy X-ray absorptiometry. Blood samples collected at baseline, 3,6, and 12 months assessed bone biomarkers. Physical activity recall and 1-week-food frequency questionnaires were obtained at baseline, 3,6, and 12 months to examine physical activity and dietary confounders as potential covariates.

Dried plum significantly increased BMD of ulna and spine compared to dried apple. Compared to corresponding baseline values, only dried plum significantly decreased serum levels of bone turnover markers including bone-specific alkaline phosphatase and tartrate-resistant acid phosphatase-5b. The authors maintain that the findings confirmed the ability of dried plum to imporve BMD in postmenopausal women in part due to suppressing the rate of bone turnover.


Dried Plum’s Unique Capacity to Reverse Bone Loss and Alter Bone Metabolism in Postmenopausal Osteoporosis Model.

PLoS ONE 2013; 8(3): e60569.Rendina E, Hembree KD, Davis MR, Marlow D, Clarke SL, Halloran BR, Lucas EA and Smith BJ.

This study compared the effects of dried plum on bone to other dried fruits (apple, apricot, grape or mango) and further explored the potential mechanisms of action by which dried plum may exert its osteoprotective effects. Adult osteopenic ovariectomized (OVX) mice were fed a control diet or diet supplemented with 25% (w/w) dried fruit for 8 weeks. Whole body and spine bone mineral density improved in mice fed the dried plum, apricot and grape diets compared to the OVX control; but only dried plum had an anabolic effect on trabecular bone in the vertebra and prevented bone loss in the tibia. Restoration of biomechanical properties occurred along with the changes in trabecular bone in the spine. According to the researchers, compared to other dried fruits in this study, dried plum was unique in its ability to down-regulate osteoclast differentiation while up-regulating osteoblast and glutathione activities. These alternations in bone metabolism and antioxidant status compared to other dried fruits provide some insight into dried plum’s unique effects on bone.



Dried Plum Restores Bone in Aging Mice

J. Nutr. October 1, 2010 vol. 140 no. 10 1781-1787.Halloran BP et al.

Therapies to prevent or restore bone progessively lost with advancing age are limited.  The only effective proanabolic regimen presently available to restore bone is intermittent treatment with teriparatide (parathyroid hormone 1–34). Previous studies suggest that dietary supplementation with dried plum (DP) can prevent bone loss due to estrogen deficiency. This study was undertaken to investigate whether dietary DP supplementation can prevent the loss of bone with aging and whether bone that has already been lost can be restored in an animal model. Adult (6 mo) and old (18 mo) male mice were fed a normal diet or isoenergetic, isonitrogenous diets supplemented with DP (0, 15, and 25% DP by weight) for 6 mo. MicroCT analysis and bone histomorphometry assessed bone volume, structure, and metabolic activity before, during, and after dietary supplementation. The researchers report that mice fed the 0% DP diet (control diet) lost bone, whereas both adult and old mice fed the 25% DP-supplemented diet gained bone. Adult but not old mice fed the 15% diet also gained bone. Cancellous bone volume in mice receiving 25% DP exceeded baseline levels by 40–50%. Trabecular structure varied with diet and age and responses in old mice were generally blunted. Trabecular, but not cortical, mineral density varied with age and measures of bone anabolic activity were lower in aged mice. Findings suggest that DP contains proanabolic factors that can dramatically increase bone volume and restore bone that has already been lost due to aging. In turn, DP may provide effective prophylactic and therapeutic agents for the treatment of osteoporosis.

Dried Plum Polyphenols Attenuate Detrimental Effects on Osteoblast Function

Journal of Nutritional Biochemistry DOI:10.1016/j.jnutbio.2007.11.012 Published online ahead of print May 20, 2008.     Bu, S.Y., Hunt, T.S., and Smith, B.J.

This cell culture study investigated how dried plum polyphenols and different concentrations ((0, 2.5, 5, 10 and 20 μg/ml) might influence osteoblast activity and mineralized nodule formation under normal and inflammatory conditions. Polyphenol doses of 5, 10 and 20 μg/ml enhanced the production of compounds linked to bone formation and countered the detrimental effects of TNF-a addition.

Dried Plum Polyphenols Inhibit Osteoclastogenesis

Calcified Tissue International(DOI 10.1007/s00223-008-9139-0).  Bu SY, Lerner M, Stoecker BJ, Boldrin E, Brackett DJ, Lucas EA and Smith BJ.

This study investigated dried plum polyphenols' effect on osteoclast differentiation and activity in cell cultures.  Results of this study, combined with results of the authors' previous reports, suggest that the antiresorptive properties of dried plums observed in animal studies are in part mediated by polyphenols suppression of osteoclast differentiation and activity under normal, oxidative stress, and inflammatory conditions.

Dried Plum Prevents Bone Loss in a Male Osteoporosis Model via IGF-I and the RANK Pathway

BONE 39, no. 6 (2006): 1331–1342 Franklin, M., Bu, S.Y., Lerner, M.R., Lancaster, E.A., Bellmer, D., Marlow, D., Lightfoot, S. A., Arjmandi, B.H., Brackett, D.J., Lucas, E.A. and Smith, B.J.

The study was designed to determine the extent to which dried plum prevents skeletal deterioration in gonadal hormone deficient male animals and to begin to understand the mechanism. Sham operated on orchidectomized male rats fed dried plum diets at 5, 15 and 25 percent (w/w) levels. The 15 and 25 percent dried plum diets prevented the ORX-induced decrease in whole body, femur and lumbar vertebrae bone mineral density. Results of other biomechanical testing are discussed. The authors conclude that dried plum prevents osteopenia in androgen deficient male rats and that the benefits may be attributed in part to a decrease in osteoclastogenesis via down-regulation of the RANKl and stimulation of bone formation mediated by IGF-I.

DP Prevents Bone Loss in an Osteopenic Rat Model of Osteoporosis

Menopause (2005)12:755-762.Deyhim F, Stoecker BJ, Brusewitz GH, Devareddy L, and Arjmandi BH.

This study evaluated whether dried plum was able to restore bone mass in osteopenic ovariectomized rats.  Dried plum at 5% of the diet was effective in restoring femoral and tibial bone density and increased lumbar bone density.  The increase in femoral bone density in rats fed dried plum diets resulted in improved bone quality as indicated by 6.9% and 6.0% improvement in overall yield and ultimate force respectively.  The improvement in biomechanical properties of long bones due to dried plum, in part, may be due to the favorable microstructural changes as evident by enhanced tibial bone volume and connectivity.

Dried Plums Improve Indices of Bone Formation in Postmenopausal Women

Journal of Women’s Health and Gender-Based Medicine 11, no. 1 (2002): 61–68
Arjmandi, B.H., Khalil, D.A., Lucas, E.A., Georgis, A., Stoecker, B.J., Hardin, C., Payton, M.E. and Wild, R.A.

The study assessed the effect of daily consumption of 100 grams (10–12) of dried plums for three months on markers of bone turnover. Compared to baseline, dried plums significantly increased serum levels of IGF-I and BSAP activity. According to the authors, higher levels are associated with greater rates of bone formation.

Dried Plums Prevent Ovariectomy-Induced Bone Loss in Rats

Journal of the American Nutraceutical Association 4 (2001): 50–56 Arjmandi, B.H., Lucas, E.A., Juma, S., Soliman, A., Stoecker, B.J., Khalil, D.A., Smith, B. J. and Wang, C.

In an animal model of hormone deficiency, female rats were fed dried plums at 5 percent and 25 percent (w/w) of the diet. Ovariectomy significantly reduced bone mineral density of the 4th lumbar vertebrae and femurs and decreased trabecular bone area of the tibia. The high dose dried plum diet prevented this bone loss and the dried plum diet’s dose dependently enhanced circulating IGF-I, known to stimulate bone formation.

Viewpont: Dried Plum, An Emerging Functional Food that May Effectively Improve Bone Health

Ageing Research Reviews 2009. 8:122-127. Hooshmand S and Arjmandi BH.

This review summarizes findings of studies published to date which examine the beneficial effects of dried plum on bone in both female and male animals models of osteoporosis as well as a published clinical trial. Animal studies indicate that dried plum protects against but more importantly reverses bone loss in two separate models of osteopenia. A 3-month clincial trial indicated that consumption of dried plum daily by postmenopausal women significantly increased serum markers of bone formation, total alkaline phosphatase, bone-specific alkaline phosphatase and insulin-like growth factor-1 by 12, 6, and 17% respectively.

The Effect of Two Doses of Dried Plum on Bone Density and Bone Biomarkers in Osteopenic Postmenopausal Women: A Randomized, Controlled Trial

Osteoporosis International, published online February 22, 2016. Hooshmand S, Kern M, Metti D, Shamloufard P, Chai SC, Johnson SA, Payton ME, and Arjmandi BH.

Building on their previous research that demonstrated the ability of 100 g of dried plums/prunes to help prevent bone loss in older, osteopenic postmenopausal women, the investigators examined the possible dose-dependent effects in 48 osteopenic postmenopausal women (65-79 y). The three treatment groups included a control, 50 g dried plums or 100 g dried plums for 6 months. Total body, hip, and lumbar bone mineral density (BMD) were measured at baseline and 6 months using dual-energy X-ray absorptiometry. Bone biomarkers measured at baseline, 3 and 6 months included bone-specific alkaline phosphatase (BAP), tartrate-resistant acid phosphastase (TRAP-5b, a marker of bone resporption), high-sensitivity C-reactive protein (hs-CRP), insulin-like growth factor-1 (IGF-1), and sclerostin. In addition, osteoprotegerin (OPG)), receptor activator of nuclear factor kappa-B ligand (RANKL), calcium, phosphorous, and vitamin D were measured at baseline and 6 months.
According to the results, both doses of dried plums prevented the loss of total body BMD compared to the control (P<0.05). TRAP-5b decreased at 3 months and was sustained at 6 months for both 50 g and 100 g doses. There were no significant changes in BAP for either dose of dried plum groups, although the BAP/TRAP-5b ratio was significantly (p<0.05) greater at 6 months in both dried plum groups whereas there were no changes in the control group.
The results suggest that a lower dose (50 g) of dried plums may be as effective as 100 g in preventing bone loss in older, osteopenic postmenopausal women. The investigators suggest that this may be due in part to the ability of dried plums to prevent bone resorption.