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. 2017 Apr 19;9(4):401. doi: 10.3390/nu9040401

Table 4.

Animal studies.

Reference Location Animal Model Plum Product Methods Markers Measured Duration Results
Arjmandi et al. 2010 [15] USA Sprague-Dawley rats Dried plum (P. domestica), DP puree, DP juice, DP pulp/skin, DPP After surgery to establish bone loss, rats placed on various diets supplemented with 13 different combinations of fructooligosaccharides and DP vs. a control diet. BMD and BMC (whole body, right femur, 4th lumbar vertebrae), calcium loss (4th lumbar), TbS, serum OC, serum IGF-1, calcium, phosphorus, and magnesium. 60 days Compared to the other treatments, diets supplemented with 5% FOS and 7.5% DP was most effective in reversing both right femur and fourth lumbar BMD and fourth lumbar calcium loss while significantly decreasing TbS. No significant effects of treatment on serum or urine measures of bone turnover.
Bu et al. 2007 [16] USA Male Sprague-Dawley rats Dried plum (P. domestica) vs. parathyroid hormone Diet supplementation of 6-month old male rats with 25% DP vs. a control diet. BMA, BMC, BMD (whole body, femur, vertebrae), trabecular architecture, cortical bone, serum ALP, serum protein, BV/TV, TbN, TbSp, femur and vertebral (connectivity density, SMI, linear attenuation), total force, stiffness, physiological force. 90 days DPs induced a significant increase in vertebra and femoral BMD compared to controls. DPs induced a significant increase in femur BMC compared to controls. The DP group had significantly:

  • Higher femur and vertebra BV/TV, TbN.

  • Higher femur connectivity density, femur and vertebral linear attenuation.

  • Higher cortical thickness and cortical area.

  • Lower TbSp and femur SMI,

  • Higher total force, stiffness, and physiological force.

  • Lower average von Mises stresses.
Deyhim et al. 2005 [17] USA Sprague-Dawley rats Dried plum (P. domestica) Dietary supplementation of adult osteopenic rats with 5%, 15% or 25% DP vs. a control diet. Serum ALP, TRAP activities, calcium, magnesium, IGF-I, BMD (femur, tibia, vertebra), trabecular microarchitecture, urinary DPD, L4 BMD, BV/TV, connectivity density, TbSp, and TbTh. 60 days Compared to OVX controls:

  • All DP groups had significantly higher femur BMD, tibia BMD, as well as lower TbSp.

  • 25% DP groups had significantly higher L4 BMD, BV/TV, and connectivity density.

  • 15% and 25% DP groups had significantly higher TbN and lower TbTh.
Franklin et al. 2006 [18] USA Male Sprague–Dawley rats Dried plum (P. domestica) Dietary supplementation of male rats with 5%, 15% or 25% DP vs. a control diet. Whole body BMC, BMA, BMD), BMC (femur, L4 vertebra), trabecular bone microarchitecture markers (BV/TV, TbN, TbSp), serum ALP, osteocalcin, IGF-I, RANKL, OPG, cortical strength, cortical area, medullary area, cortical porosity, distal femur and L4 vertebral (SMI, connectivity density, LinAtt), IGF, DPD, OPG, RANKL. 90 days 15% and 25% DP groups significantly prevented a reduction in whole body BMD, as well as femur and L4 vertebra BMC. 15% and 25% DP groups protected against the decrease in mechanical strength required to break the femur bone. Compared to controls:

  • 5% and 25% DP groups had significantly higher distal femur BV/TV.

  • 25% DP group had significantly higher L4 vertebra BV/TV, TbN and significantly lower L4 vertebra TbSp.

  • All DP groups had significantly higher distal femur TbN and lower distal femur TbSp, DPD, RANKL.

  • 15% and 25% DP groups had significantly higher cortical strength and lower vertebral SMI and OPG.

  • 25% DP group had significantly lower femur SMI and higher femur and vertebral connectivity density, vertebral LinnAtt, and IGF.

  • 5% and 25% DP groups had significantly higher LinAtt.

No significant differences on other markers measured.
Halloran et al. 2010 [19] USA Harlan Sprague Dawley mice Dried plum (P. domestica) Dietary supplementation of adult and old male mice with 15%, 25% DP vs. a control diet. BV/TV, TbN, TbSp, P1NP, SMI, connective density, degree of anisotropy, ObS, OcS, BFR, cortical thickness, bone area, cortical area, Medullary area, BMD and PYD. 6 months Within both adult and old mice, increasing DP supplementation was associated with greater BV. Mice fed 25% DP had significantly greater BV compared to controls. Mice fed 25% DP had significantly greater BV compared to those fed 15%. The differences in magnitude of the percent changes between control mice and those fed 25% DP were significantly greater in adult vs. old mice. Compared to controls:

  • Adult mice fed 25%DP had higher BV/TV, TbN, connective density, and lower SMI.

  • Old mice fed 25% DP had higher degree of anisotropy and cortical thickness, and lower medullary area and PYD.

  • Old mice fed 15% DP had higher cortical area.

No significant differences on other markers measured.
Johnson et al. 2011 [20] USA Sprague-Dawley rats Dried plum (P. domestica) Female ovarian hormone deficient rats a fed control, soy, soy + FOS, soy + 7.5% DP, and soy + 7.5% DP + FOS diet vs. a control diet. BMD, BMC (Whole body, right femur, 4th lumbar vertebrae), serum ALP, urinary creatinine, urinary DPD, femur strength, TbN, BV/TV, TbTh, and TbSp. 60 days Whole body and 4th lumbar BMD were significantly higher in diets with DP + FOS compared to the control and soy diets. No significant differences on other markers measured.
Leotoing et al. 2016 [21] France Wistar rats High and low chlorogenic acid dried plum (P. domestica) and DP juice concentrate (15%) Female rats High and low chlorogenic acid dried plum (P. domestica) and DP juice concentrate (15%) diets vs. a control diet. Urinary DPD, OC, CPII, CTX-II, BMD (Total femoral, metaphyseal), BMC, urine calcium, primary pre-osteoblasts (proliferation, ALP), bone remodeling index, and cartilage remodeling index. 90 days (in vivo), 7 days (ex vivo) 10 and 50 μmol/L concentrations of neochlorogenic, chlorogenic, or caffeic acid significantly decreased pre-osteoblast ALP activity and increased pre-osteoblast proliferation. The low chlorogenic acid DP juice and DP juice concentrate groups showed significantly higher trabecular distal BMD, significantly increased cortical BMD, and increased total BMC compared to control. High chlorogenic acid DP juice group had significantly higher trabecular distal BMD compared to controls. High chlorogenic acid DP juice, low chlorogenic acid DP juice + fiber and low chlorogenic acid DP juice concentrate significantly prevented increase in OC. Low chlorogenic acid DP juice + fiber and low chlorogenic acid DP juice concentrate significantly prevented increase in DPD. Both high and low chlorogenic acid DP juice and DP juice concentrate lead to higher urinary calcium excretion compared to controls. Only high chlorogenic acid DP juice significantly counteracted the decrease in CPII. Only the high chlorogenic acid DP juice group had significantly higher CRI.
Monsefi et al. 2013 [22] Iran Pregnant mice Dried plum (P. domestica) extract (8 mL/kg) and DP hydroalcoholic extracts (1.6 g/kg) Pregnant mice were fed DP extracts vs. a control diet and outcomes measured on their fetuses. Serum calcium, magnesium, ALP, bone calcium, and phosphorus. 30 days Non-pregnant mice fed DP extract had significantly higher bone calcium compared to non-pregnant controls. Non-pregnant mice fed DP hydroalcoholic extracts had significantly higher bone phosphorus compared to non-pregnant controls. Non-pregnant mice fed both DP extract and DP hydroalcoholic extract had significantly higher bone calcium compared to non-pregnant controls.
Pawlowski et al. 2014 [23] USA Sprague-Dawley rats Dried plum powder extract (0.20% and 0.45% w/w total dietary polyphenols) Randomized, crossover intervention trial to evaluate 12 different polyphenolics containing diets on bone turnover. Urine calcium (total and 45Ca), NTx and ALP. 10 days Bone calcium retention was significantly improved due to dietary intervention with 0.45% DP extract compared to baseline. 0.45% DP extract improved bone calcium retention compared with the 0.20% DP extract. No significant effect on other outcomes.
Rendina et al. 2012 [24] USA Adult female C57BL/6J mice Dried plum (Prunus domestica) Adult female mice placed on 5%, 15% or 25% DP intervention vs. a control diet. BMA, BMC and BMD of the 4th to 5th lumbar vertebrae (L4–L5), TbN, BV/TV, TbTh, TbSp, connectivity density, SMI, PINP IGF-I, NFATc, Runx2, biomechanical properties of trabecular bone, OC, IL-6, and TNF-α. 4 weeks Mean BMC and BMA were significantly higher in the 25% DP group compared to the control. 15% DP group had a significantly higher plasma IGF-1 compared to the control. 15% and 25% DP groups significantly increased BV/TV compared to the control. 15% and 25% DP groups significantly decreased TbSp beyond that of the control group. 15% and 25% DP groups experienced a significant increase in vertebra TbTh compared to the control. 15% and 25% DP groups had significantly lower Von Mises stress distribution compared to the control. 15% and 25% DP groups had significantly higher vertebral connective density and tibia apparent mean/density, and lower vertebral SMI and OC expression and TNF-α. 25% DP group had significantly higher apparent mean/density and tibia connective density, and significantly lower tibia SMI. 25% DP group significantly increased TbN compared to the control. All doses of DP groups had significantly lower plasma PINP, NFATc and Runx2 compared to the control.
Rendina et al. 2013 [25] USA Adult osteopenic ovariectomized C57BL/6 mice Dried plum (Prunus domestica), 25% This study was designed to compare the efficacy of DP, apple, apricot, grape, and mango vs. a control in the restoration of bone in an osteopenic mouse model. Whole body and L4–5 (BMA, BMC, BMD), TbN, BV/TV, TbTh, TbSp, SMI, biomechanical testing of vertebra and tibia, connective density, NFATc1, ALP, Col1a1, OC, Bak1, Casp3, and Casp9. 8 weeks Compared to the control the DP group had significantly higher whole body and spine BMA, BMD and BMC. DP group had significantly higher vertebral BV/TV, TbN, TbTh, connective density, SMI, and trabecular density compared to the control group. DP group had significantly higher proximal tibia BV/TV compared to the control group. DP group had significantly higher vertebral total force, stiffness, size independent stiffness compared to the control group. DP group had significantly lower NFATc1 compared to the control group. DP group had significantly higher Bak1 and lower Casp3 and compared to the control group. No significant differences on other markers.
Schreurs et al. 2016 [26] USA Male C57BL/6J mice Dried plum (Prunus domestica), 25% This study randomized mice to 25% DP intervention vs. a control to protect from bone loss and then later exposed them to ionizing radiation. Nfe2l2, RANL, MCP-1, OPG, TNF-α, TbN, BV/TV, TbTh, TbSp, 7–21 days Compared to the irradiated controls, levels of Nfe2l2, RANKL, MCP-1, OPG, and TNF-α in the DP group were not statistically different. After exposure to radiation, DP mice did not have any significant decrease in TbN, BV/TV, TbTh or TbSp indicating a radio-protective effects against cancellous bone loss compared to irradiated controls. DP fed mice had significantly higher BV/TV, TbTh and TbN after being exposed to simulated space radiation compared to control diet.
Shahnazari et al. 2016 [27] USA C57Bl/6 mice Dried plum (Prunus domestica) Skeletally mature (6-month-old) and growing (1- and 2-month-old) male mice were placed on a 5%, 15% or 25% DP intervention vs. a control diet. BV/TV, TbTh, TbN, SMI, OcS, ObS, MAR, MS/BS, BFR/BS, Ctsk, OPG, RANKL, CTX, and P1NP. 1–4 weeks BV/TV and TbTh significantly increased and SMI significantly decreased after 2 and 4 weeks of DP. TbN significantly increased after 4 weeks of DP. After 2 and 4 weeks of DP:

  • OcS, ObS, MAR, MS/BS, BFR/BS decreased significantly.

  • Osteoclasts significantly decreased.

DP fed mice had significantly lower:

  • Ctsk gene expression.

  • Immune-related cytokines (IL-1a, IL-1b, IL-10, IL-12, IL-13, IL-17, TNF-α, and MCP-1).

  • CTX

BV/TV increased significantly in mice fed 5%, 15% or 25% DP. TbTh increased significantly among mice fed 25% DP. TbN increased significantly in mice fed 5%, 15% or 25% DP. SMI decreased significantly for mice fed 15% and 25% DP. Among 2-month-old mice, ObS increased significantly among mice fed 5%, 15% or 25% DP. Among 3-month-old mice, ObS increased significantly among mice fed 5% DP. No significant differences on other markers.
Smith et al. 2014b [28] USA Female Sprague-Dawley rats Dried plum (Prunus domestica) Osteopenic rats were placed on 5%, 15% or 25% DP intervention vs. a control diet. BMD (whole body, femur and vertebra), BV/TV, TbN, TbSp, connective density, TbTh (proximal tibia, vertebra), Cortical thickness, cortical area, medullary area, cortical porosity, DPD, P1NP, cancellous BFR and MS/BS, MAR, MS/bone area, BFR/BV, Periosteal (BFR, MS, MAR), endocortical (BFR, MS, MAR), Bmp2, Bmp4, Coll1a, IGF-1, Nfatc1, and RANKL. 6 weeks Compared to controls:

  • Vertebral BMD increased significantly in 15% and 25% DP groups

  • Femur BMD increased significantly in 5%, 15%, and 25% DP groups

  • Whole body BMD increased significantly in 5%, 15%, and 25% DP groups

Within the vertebra and when compared to controls:

  • BV/TV, TbN, TbSp, connective density increased significantly in 5%, 15% and 25% DP groups.

  • TbTh increased significantly in 15% and 25% DP groups.

Within the proximal tibia and when compared to controls: TbSp decreased significantly in 15% and 25% DP groups. When compared to controls: cortical thickness increased significantly in 5%, 15%, and 25% DP groups. 25% of DP significantly suppressed increase in urinary DPD excretion. 5%, 15%, and 25% DP groups significantly suppressed serum P1NP.Compared to controls:

  • 15% and 25% DP groups significantly suppressed increase in cancellous BFR and MS/BS.

  • 15% and 25% DP groups significantly suppressed increase in cancellous BFR and MS/BS.

  • 15% DP groups significantly suppressed increase in MAR

  • MS/bone area, BFR/BV, Periosteal BFR levels were significantly decreased in 5%, 15%, and 25% DP groups.

  • All groups of DP increased significantly Bmp4 expression.

  • 25% group significantly increased IGF-1 expression.

  • Relative abundance of NFATc1 mRNA was significantly lower in all DP groups.

No significant differences on other markers.
Smith et al. 2014a [29] USA Male C57BL/6 mice Dried plum (Prunus domestica) Osteopenic rats were placed on 25% DP intervention vs. a control diet. Whole-body and vertebral (BMD, BMC, BMA) lumbar vertebra, distal femur, femur mid-diaphysis (BV/TV, TbN, TbTh, TbS, connective density, SMI), P1NP, PYD, glutathione peroxidase activity, OcS, ObS, MS, BFR, MAR, Pparc, Osx, Bmp2, Bmp4, ALP, Col1a1, OC, RANKL, OPG, NFATc1, and Ctsk. 4 or 12 weeks At 4weeks:

  • Whole body BMD, vertebra (BMD, BMC) were significantly higher in the DP group.

  • Lumbar BV/TV, connective density, femur cortical thickness, were significantly higher in the DP group.

  • SMI was significantly lower in the DP group. At 12 weeks:

  • Whole body BMA, BMC and BMD, as well as vertebra BMD and BMC were significantly higher in the DP group.

  • BV/TV (lumbar and distal femur), trabecular number (lumbar and distal femur), connectivity density (lumbar and distal femur), and femur cortical thickness, were significantly higher in the DP group.

  • Trabecular separation (lumbar and distal femur), SMI (lumbar and distal femur) were significantly lower in the DP group. At 4 and 12 weeks, serum P1NP of DP group were significantly reduced compared to controls. At 12 weeks, serum PYD was significantly lower in the DP group. The DP group had significantly higher glutathione peroxidase activity than the control at 12 weeks. At 4 weeks, the DP group had significantly lower OcS, ObS, MS, and BMR. At 4 weeks, the DP group had significantly higher Pparc; lower Osx, Bmp4, ALP, Col1a1, Bglap2, RANKL, and NFATc1.
Arjmandi et al. 2001 [30] USA Female Sprague-Dawley rats (Prunus domestica) Female rats were either ovariectomized or sham operated. The ovariectomized groups were then fed either a 5% or 25% DP supplemented diet vs. a control diet. Trabecular (total area, bone area, % bone area). Cortical (total area, bone area, marrow space, endosteal perimeter, and periosteal perimeter. 45 days Compared to the controls the 25% DP group had significantly higher trabecular BA. Unreported results (data not shown):

  • DP diets dose-dependently enhanced IGF-1.

ALP = alkaline phosphatase; BAK1 = BRI1-associated kinase 1; BFR = bone formation rate; BMA = bone mineral area; BMC = bone mineral content; BMD = bone mineral density; BMP2 = bone morphogenetic protein-2; BMP4 = bone morphogenetic protein-4; BS = bone surface; BS = bone surface; BV = bone volume; Casp3 = caspase-3; Casp9 = caspase-9; Col1a1 = collagen type 1a1; Coll1a = collagen type 1; CPII = C-propeptide of type II collagen; Ctsk = cathepsin K; CTX = C-terminal telopeptide of type II collagen; DP = dried plum; DPD = deoxypyridinoline; DPP = dried plum polyphenols; FOS = fructooligosaccharides; IGF = insulin-like growth factor; IGF-1 = Insulin-like growth factor-1; IL-6 = Interlukin-6; LinAtt = Linear X-ray attenuation coefficient; MAR = Mineral absorption rate; MCP-1 = Monocyte chemoattractant 1; MS = Mineralizing surface; NFATc = Nuclear factor of activated T cells; NFATc1 = Nuclear factor of activated T cells-1; Nfe212 = Nuclear factor erythroid derived 212; NTx = N-telopeptides of type-1 collagen; ObS = Osteoblast surface; OC = osteocalcin; OcS = Osteoclast surface; OPG = osteoprotegerin; Osx = osterix; PINP = procollagen type I N-terminal propeptide; Pparc = proliferator-activated receptor gamma; PYD = pyridinoline; RANKL = receptor activator of nuclear factor kappa-B ligand; Runx2 = Runt-related protein 2; SMI = structural model indexTbN = trabecular bone number; TbSp = trabecular bone separation; TbTh = trabecular thickness; TNF-a = tumor necrosis factor-alpha; TRAP = tartrate-resistant acid phosphatase; TV = trabecular volume.