Montmorency tart cherry protects against age-related bone loss in female C57BL/6 mice and demonstrates some anabolic effects



Age-related bone loss is a consequence of endocrine and immune changes that disrupt bone remodeling. Functional foods (e.g., tart cherries) with antioxidant, anti-inflammatory and prebiotic activity can potentially counter this age-related phenomenon. The aim of this study was to determine if Montmorency tart cherry protects against early age-related bone loss and the culpable alterations in bone metabolism.


Female, 5-month-old, C57BL/6 mice were assigned to baseline or treatment groups: AIN-93M diet supplemented with 0, 1, 5, or 10% tart cherry for 90 days. Bone mineral density (BMD) and trabecular and cortical bone microarchitecture were assessed. Treatment effects on bone metabolism and regulators of bone formation, resorption and mineralization were determined.


Mice consuming the 5% and 10% doses had higher vertebral and tibial BMD (p < 0.05) compared to controls. The age-related decrease in trabecular bone volume (BV/TV) of the distal femur was prevented with these doses. Vertebral trabecular BV/TV and cortical bone thickness of the femur mid-diaphysis were greater (p < 0.05) in the groups receiving the 5% and 10% cherry than the control diet. Notably, these improvements were significantly greater than the baseline controls, consistent with an anabolic response. Although no differences in systemic biomarkers of bone formation or resorption were detected at 90 days, local increases in Phex and decreases in Ppar-γ suggest a bone environment that supports increased mineralization.


These findings demonstrate that cherry supplementation (5% and 10%) improves BMD and some indices of trabecular and cortical bone microarchitecture; these effects are likely attributed to increased bone mineralization.

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  1. 1.

    Woolf AD, Pfleger B (2003) Burden of major musculoskeletal conditions. Bull World Health Organ 81:646–656

    PubMed  PubMed Central  Google Scholar 

  2. 2.

    Khosla S, Riggs BL (2005) Pathophysiology of age-related bone loss and osteoporosis. Endocrinol Metab Clin North Am 34:1015–1030

    CAS  PubMed  Google Scholar 

  3. 3.

    Johnell O, Kanis JA (2006) An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 17:1726–1733

    CAS  PubMed  Google Scholar 

  4. 4.

    Ginaldi L, Di Benedetto MC, De Martinis M (2005) Osteoporosis, inflammation and ageing. Immun Ageing 2:14

    PubMed  PubMed Central  Google Scholar 

  5. 5.

    Manolagas SC (2010) From estrogen-centric to aging and oxidative stress: a revised perspective of the pathogenesis of osteoporosis. Endocr Rev 31:266–300

    CAS  PubMed  PubMed Central  Google Scholar 

  6. 6.

    Khosla S, Melton LJ, Riggs III BL (2011) The unitary model for estrogen deficiency and the pathogenesis of osteoporosis: is a revision needed? J Bone Miner Res 26:441–451

    CAS  PubMed  Google Scholar 

  7. 7.

    Riggs BL, Khosla S, Melton LJ III (2002) Sex steroids and the construction and conservation of the adult skeleton. Endocr Rev 23:279–302

    CAS  PubMed  Google Scholar 

  8. 8.

    Callaway DA, Jiang JX (2015) Reactive oxygen species and oxidative stress in osteoclastogenesis, skeletal aging and bone diseases. J Bone Miner Metab 33:359–370

    CAS  PubMed  Google Scholar 

  9. 9.

    Almeida M, Han L, Martin-Millan M, Plotkin LI, Stewart SA, Roberson PK, Kousteni S, O’Brien CA, Bellido T, Parfitt AM, Weinstein RS, Jilka RL, Manolagas SC (2007) Skeletal involution by age-associated oxidative stress and its acceleration by loss of sex steroids. J Biol Chem 282:27285–27297

    CAS  PubMed  PubMed Central  Google Scholar 

  10. 10.

    Grassi F, Tell G, Robbie-Ryan M, Gao Y, Terauchi M, Yang X, Romanello M, Jones DP, Weitzmann MN, Pacifici R (2007) Oxidative stress causes bone loss in estrogen-deficient mice through enhanced bone marrow dendritic cell activation. Proc Natl Acad Sci USA 104:15087–15092

    CAS  PubMed  Google Scholar 

  11. 11.

    Smith BJ, Bu SY, Wang Y, Rendina E, Lim YF, Marlow D, Clarke SL, Cullen DM, Lucas EA (2014) A comparative study of the bone metabolic response to dried plum supplementation and PTH treatment in adult, osteopenic ovariectomized rat. Bone 58:151–159

    CAS  PubMed  Google Scholar 

  12. 12.

    Shen CL, Cao JJ, Dagda RY, Tenner TE Jr, Chyu MC, Yeh JK (2011) Supplementation with green tea polyphenols improves bone microstructure and quality in aged, orchidectomized rats. Calcif Tissue Int 88:455–463

    CAS  PubMed  Google Scholar 

  13. 13.

    Hooshmand S, Chai SC, Saadat RL, Payton ME, Brummel-Smith K, Arjmandi BH (2011) Comparative effects of dried plum and dried apple on bone in postmenopausal women. Br J Nutr 106:923–930

    CAS  PubMed  Google Scholar 

  14. 14.

    Chiang SS, Liao JW, Pan TM (2012) Effect of bioactive compounds in lactobacilli-fermented soy skim milk on femoral bone microstructure of aging mice. J Sci Food Agric 92:328–335

    CAS  PubMed  Google Scholar 

  15. 15.

    Halloran BP, Wronski TJ, VonHerzen DC, Chu V, Xia X, Pingel JE, Williams AA, Smith BJ (2010) Dietary dried plum increases bone mass in adult and aged male mice. J Nutr 140:1781–1787

    CAS  PubMed  Google Scholar 

  16. 16.

    Zhang J, Lazarenko OP, Blackburn ML, Shankar K, Badger TM, Ronis MJ, Chen JR (2011) Feeding blueberry diets in early life prevent senescence of osteoblasts and bone loss in ovariectomized adult female rats. PLOS One 6:e24486

    CAS  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Tahiri M, Tressol JC, Arnaud J, Bornet FR, Bouteloup-Demange C, Feillet-Coudray C, Brandolini M, Ducros V, Pepin D, Brouns F, Roussel AM, Rayssiguier Y, Coudray C (2003) Effect of short-chain fructooligosaccharides on intestinal calcium absorption and calcium status in postmenopausal women: a stable-isotope study. Am J Clin Nutr 77:449–457

    CAS  PubMed  Google Scholar 

  18. 18.

    Weaver CM, Martin BR, Nakatsu CH, Armstrong AP, Clavijo A, McCabe LD, McCabe GP, Duignan S, Schoterman MH, van den Heuvel EG (2011) Galactooligosaccharides improve mineral absorption and bone properties in growing rats through gut fermentation. J Agric Food Chem 59:6501–6510

    CAS  PubMed  Google Scholar 

  19. 19.

    Zafar TA, Weaver CM, Zhao Y, Martin BR, Wastney ME (2004) Nondigestible oligosaccharides increase calcium absorption and suppress bone resorption in ovariectomized rats. J Nutr 134:399–402

    CAS  PubMed  Google Scholar 

  20. 20.

    Bu SY, Hunt TS, Smith BJ (2009) Dried plum polyphenols attenuate the detrimental effects of TNF-alpha on osteoblast function coincident with up-regulation of Runx2, Osterix and IGF-I. J Nutr Biochem 20:35–44

    CAS  PubMed  Google Scholar 

  21. 21.

    Bu SY, Lerner M, Stoecker BJ, Boldrin E, Brackett DJ, Lucas EA, Smith BJ (2008) Dried plum polyphenols inhibit osteoclastogenesis by downregulating NFATc1 and inflammatory mediators. Calcif Tissue Int 82:475–488

    CAS  PubMed  Google Scholar 

  22. 22.

    Zhang J, Lazarenko OP, Kang J, Blackburn ML, Ronis MJ, Badger TM, Chen JR (2013) Feeding blueberry diets to young rats dose-dependently inhibits bone resorption through suppression of RANKL in stromal cells. Plos One 8:e70438

    CAS  PubMed  PubMed Central  Google Scholar 

  23. 23.

    Franklin M, Bu SY, Lerner MR, Lancaster EA, Bellmer D, Marlow D, Lightfoot SA, Arjmandi BH, Brackett DJ, Lucas EA, Smith BJ (2006) Dried plum prevents bone loss in a male osteoporosis model via IGF-I and the RANK pathway. Bone 39:1331–1342

    CAS  PubMed  Google Scholar 

  24. 24.

    He X, Andersson G, Lindgren U, Li Y (2010) Resveratrol prevents RANKL-induced osteoclast differentiation of murine osteoclast progenitor RAW 264.7 cells through inhibition of ROS production. Biochem Biophys Res Commun 401:356–362

    CAS  PubMed  Google Scholar 

  25. 25.

    Graef JL, Rendina-Ruedy E, Crockett EK, Ouyang P, King JB, Cichewicz RH, Lucas EA, Smith BJ (2017) Select phenolic fractions from dried plum enhance osteoblast activity through BMP-2 signaling. J Nutr Biochem 55:59–67

    PubMed  PubMed Central  Google Scholar 

  26. 26.

    USDA Nation (2014) Nutrient database for standard reference, release 27

  27. 27.

    Jovanovic-Malinovska R, Kuzmanova S, Winkelhausen E (2014) Oligosaccharide profile in furits and vegetables as sources of prebiotics and functional foods. Int J Food Prop 17:949–965

    CAS  Google Scholar 

  28. 28.

    Bell PG, Walshe IH, Davison GW, Stevenson E, Howatson G (2014) Montmorency cherries reduce the oxidative stress and inflammatory responses to repeated days high-intensity stochastic cycling. Nutrients 6:829–843

    PubMed  PubMed Central  Google Scholar 

  29. 29.

    Seymour EM, Lewis SK, Urcuyo-Llanes DE, Tanone II, Kirakosyan A, Kaufman PB, Bolling SF (2009) Regular tart cherry intake alters abdominal adiposity, adipose gene transcription, and inflammation in obesity-prone rats fed a high fat diet. J Med Food 12:935–942

    CAS  PubMed  Google Scholar 

  30. 30.

    Mulabagal V, Lang GA, DeWitt DL, Dalavoy SS, Nair MG (2009) Anthocyanin content, lipid peroxidation and cyclooxygenase enzyme inhibitory activities of sweet and sour cherries. J Agric Food Chem 57:1239–1246

    CAS  PubMed  Google Scholar 

  31. 31.

    Seeram NP, Bourquin LD, Nair MG (2001) Degradation products of cyanidin glycosides from tart cherries and their bioactivities. J Agric Food Chem 49:4924–4929

    CAS  PubMed  Google Scholar 

  32. 32.

    Seymour EM, Singer AA, Kirakosyan A, Urcuyo-Llanes DE, Kaufman PB, Bolling SF (2008) Altered hyperlipidemia, hepatic steatosis, and hepatic peroxisome proliferator-activated receptors in rats with intake of tart cherry. J Med Food 11:252–259

    CAS  PubMed  Google Scholar 

  33. 33.

    Kang SY, Seeram NP, Nair MG, Bourquin LD (2003) Tart cherry anthocyanins inhibit tumor development in Apc(Min) mice and reduce proliferation of human colon cancer cells. Cancer Lett 194:13–19

    CAS  PubMed  Google Scholar 

  34. 34.

    Glatt V, Canalis E, Stadmeyer L, Bouxsein ML (2007) Age-related changes in trabecular architecture differ in female and male C57BL/6J mice. J Bone Miner Res 22:1197–1207

    PubMed  Google Scholar 

  35. 35.

    Rendina E, Hembree KD, Davis MR, Marlow D, Clarke SL, Halloran BP, Lucas EA, Smith BJ (2013) Dried plum’s unique capacity to reverse bone loss and alter bone metabolism in postmenopausal osteoporosis model. Plos One 8:e60569

    CAS  PubMed  PubMed Central  Google Scholar 

  36. 36.

    Rendina E, Lim YF, Marlow D, Wang Y, Clarke SL, Kuvibidila S, Lucas EA, Smith BJ (2012) Dietary supplementation with dried plum prevents ovariectomy-induced bone Loss in C57BL/6 mice and modulates the immune response. J Nutr Biochem 23:60–68

    CAS  PubMed  Google Scholar 

  37. 37.

    Bai XC, Lu D, Bai J, Zheng H, Ke ZY, Li XM, Luo SQ (2004) Oxidative stress inhibits osteoblastic differentiation of bone cells by ERK and NF-kappaB. Biochem Biophys Res Commun 314:197–207

    CAS  PubMed  Google Scholar 

  38. 38.

    Almeida M, Ambrogini E, Han L, Manolagas SC, Jilka RL (2009) Increased lipid oxidation causes oxidative stress, increased peroxisome proliferator-activated receptor-gamma expression, and diminished pro-osteogenic Wnt signaling in the skeleton. J Biol Chem 284:27438–27448

    CAS  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Lee NK, Choi YG, Baik JY, Han SY, Jeong DW, Bae YS, Kim N, Lee SY (2005) A crucial role for reactive oxygen species in RANKL-induced osteoclast differentiation. Blood 106:852–859

    CAS  PubMed  Google Scholar 

  40. 40.

    Zhang Z, Zhang J, Xiao J (2014) Selenoproteins and selenium status in bone physiology and pathology. Biochim Biophys Acta 1840:3246–3256

    CAS  PubMed  Google Scholar 

  41. 41.

    Lean JM, Jagger CJ, Kirstein B, Fuller K, Chambers TJ (2005) Hydrogen peroxide is essential for estrogen-deficiency bone loss and osteoclast formation. Endocrinology 146:728–735

    CAS  PubMed  Google Scholar 

  42. 42.

    Staines KA, Zhu D, Farquharson C, MacRae VE (2014) Identification of novel regulators of osteoblast matrix mineralization by time series transcriptional profiling. J Bone Miner Metab 32:240–251

    CAS  PubMed  Google Scholar 

  43. 43.

    Kirakosyan A, Seymour EM, Wolforth J, McNish R, Kaufman PB, Bolling SF (2015) Tissue bioavailability of anthocyanins from whole tart cherry in healthy rats. Food Chem 171:26–31

    CAS  PubMed  Google Scholar 

  44. 44.

    Ou B, Bosak KN, Brickner PR, Iezzoni DG, Seymour EM (2012) Processed tart cherry products—comparative phytochemical content, in vitro antioxidant capacity and in vitro anti-inflammatory activity. J Food Sci 77:H105–H112

    CAS  PubMed  Google Scholar 

  45. 45.

    Smith BJ, Graef JL, Wronski TJ, Rendina E, Williams AA, Clark KA, Clarke SL, Lucas EA, Halloran BP (2014) Effects of dried plum supplementation on bone metabolism in adult C57BL/6 male mice. Calcif Tissue Int 94:442–453

    CAS  PubMed  Google Scholar 

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The authors would like to express their appreciation to VanDrunen Farms (Momence, IL, USA) for supplying the dried tart cherry powder and to Miss Sandra Peterson for her technical assistance with the animal study.


This research was supported by Cherry Research Committee of the Cherry Marketing Institute.

Author information




BJS and EAL designed the research; BJS, EKC, PC, JLG, ER, SLC and EAL conducted the research; BJS, EKC and PC analyzed the data; and BJS, EKC and PC wrote the paper. BJS and EAL had primary responsibility for the final content. All authors read and approved the final manuscript.

Corresponding author

Correspondence to Brenda J. Smith.

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Conflict of interest

The authors, B. J. Smith, E.K. Crockett, P. Chongwatpol, J. L. Graef, E. Rendina-Ruedy, S. L. Clarke and E. A. Lucas, have no conflicts of interest.

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Smith, B.J., Crockett, E.K., Chongwatpol, P. et al. Montmorency tart cherry protects against age-related bone loss in female C57BL/6 mice and demonstrates some anabolic effects. Eur J Nutr 58, 3035–3046 (2019).

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  • Osteoporosis
  • Aging
  • Antioxidants
  • Bone
  • Polyphenols