Bone structure and function in male C57BL/6 mice: Effects of a high-fat Western-style diet with or without trace minerals
Muhammad Nadeem Aslam, Karl J Jepsen, Basma Khoury, Kristin H Graf, James Varani, Muhammad Nadeem Aslam, Karl J Jepsen, Basma Khoury, Kristin H Graf, James Varani
Abstract
Purpose: Osteoporosis occurs in both women and men, but most of what we know about the condition comes from studies in females. The present study examined bone structure and function over an 18-month period in male C57BL/6 mice maintained on either a rodent chow diet (AIN76A) or a high-fat, Western-style diet (HFWD). Effects of mineral supplementation were assessed in both diets.
Methods: Trabecular and cortical bone structure in femora and vertebrae were assessed by micro-CT analysis. Following this, bone stiffness and strength measurements were made. Finally, bone levels of several cationic trace elements were quantified, and serum biomarkers of bone metabolism evaluated.
Results: Bone loss occurred over time in both diets but was more rapid and extensive in mice on the HFWD. Dietary mineral supplementation reduced bone loss in both diets and increased bone stiffness in the femora and bone stiffness and strength in the vertebrae. Bone content of strontium was increased in response to mineral supplementation in both diets.
Conclusions: Bone loss was more severe in mice on the HFWD and mineral supplementation mitigated the effects of the HFWD. In comparison to previous findings with female C57BL/6 mice, the present studies indicate that males are more sensitive to diet and benefited from a healthy diet (AIN76A), while females lost as much bone on the healthy diet as on the HFWD. Male mice benefited from mineral supplementation, just as females did in the previous study.
Keywords: Bone; calcium; cationic minerals; male mice; osteoporosis; strontium.
Figures
![Fig. 1](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4926831/bin/gr1.jpg)
Fig. 2
Femoral bone: Structural features of…
Fig. 2
Femoral bone: Structural features of cortical bone. Structural features were assessed in the…
Fig. 3
Femoral bone: Biomechanical properties. Femoral…
Fig. 3
Femoral bone: Biomechanical properties. Femoral stiffness and strength were assessed in the 4-point…
Fig. 4
Vertebral bone structure and function.…
Fig. 4
Vertebral bone structure and function. A: Structural features of trabecular bone. B: Structural…
- A mineral-rich extract from the red marine algae Lithothamnion calcareum preserves bone structure and function in female mice on a Western-style diet.Aslam MN, Kreider JM, Paruchuri T, Bhagavathula N, DaSilva M, Zernicke RF, Goldstein SA, Varani J. Aslam MN, et al. Calcif Tissue Int. 2010 Apr;86(4):313-24. doi: 10.1007/s00223-010-9340-9. Epub 2010 Feb 24. Calcif Tissue Int. 2010. PMID: 20180099 Free PMC article.
- Preservation of bone structure and function by Lithothamnion sp. derived minerals.Aslam MN, Bergin I, Jepsen K, Kreider JM, Graf KH, Naik M, Goldstein SA, Varani J. Aslam MN, et al. Biol Trace Elem Res. 2013 Dec;156(1-3):210-20. doi: 10.1007/s12011-013-9820-7. Epub 2013 Oct 6. Biol Trace Elem Res. 2013. PMID: 24096551 Free PMC article.
- A mineral-rich red algae extract inhibits polyp formation and inflammation in the gastrointestinal tract of mice on a high-fat diet.Aslam MN, Paruchuri T, Bhagavathula N, Varani J. Aslam MN, et al. Integr Cancer Ther. 2010 Mar;9(1):93-9. doi: 10.1177/1534735409360360. Epub 2010 Feb 11. Integr Cancer Ther. 2010. PMID: 20150219 Free PMC article.
- Osteoporosis and the role of diet.Eaton-Evans J. Eaton-Evans J. Br J Biomed Sci. 1994 Dec;51(4):358-70. Br J Biomed Sci. 1994. PMID: 7756943 Review.
- Treatment for osteoporosis in people with ß-thalassaemia.Bhardwaj A, Swe KM, Sinha NK, Osunkwo I. Bhardwaj A, et al. Cochrane Database Syst Rev. 2016 Mar 10;3:CD010429. doi: 10.1002/14651858.CD010429.pub2. Cochrane Database Syst Rev. 2016. PMID: 26964506 Review.
- Bone fragility during the COVID-19 pandemic: the role of macro- and micronutrients.Moretti A, Liguori S, Paoletta M, Migliaccio S, Toro G, Gimigliano F, Iolascon G. Moretti A, et al. Ther Adv Musculoskelet Dis. 2023 Mar 14;15:1759720X231158200. doi: 10.1177/1759720X231158200. eCollection 2023. Ther Adv Musculoskelet Dis. 2023. PMID: 36937822 Free PMC article. Review.
- Red Marine Algae Lithothamnion calcareum Supports Dental Enamel Mineralization.R Carrilho M, Bretz W. R Carrilho M, et al. Mar Drugs. 2023 Feb 2;21(2):109. doi: 10.3390/md21020109. Mar Drugs. 2023. PMID: 36827150 Free PMC article.
- Evaluation of an Ionic Calcium Fiber Supplement and Its Impact on Bone Health Preservation in a Dietary Calcium Deficiency Mice Model.Herrera-Rodríguez SE, García-Márquez E, Padilla-Camberos E, Espinosa-Andrews H. Herrera-Rodríguez SE, et al. Nutrients. 2022 Jan 18;14(3):422. doi: 10.3390/nu14030422. Nutrients. 2022. PMID: 35276779 Free PMC article.
- Trabecular Bone Microarchitecture Improvement Is Associated With Skeletal Nerve Increase Following Aerobic Exercise Training in Middle-Aged Mice.Lee S, Shin YA, Cho J, Park DH, Kim C. Lee S, et al. Front Physiol. 2022 Feb 22;12:800301. doi: 10.3389/fphys.2021.800301. eCollection 2021. Front Physiol. 2022. PMID: 35273515 Free PMC article.
- The Use of Mushrooms and Spirulina Algae as Supplements to Prevent Growth Inhibition in a Pre-Clinical Model for an Unbalanced Diet.Sides R, Griess-Fishheimer S, Zaretsky J, Shitrit A, Kalev-Altman R, Rozner R, Beresh O, Dumont M, Penn S, Shahar R, Monsonego-Ornan E. Sides R, et al. Nutrients. 2021 Nov 29;13(12):4316. doi: 10.3390/nu13124316. Nutrients. 2021. PMID: 34959867 Free PMC article.
-
- Ammann P., Shen V., Robin B., Mauras Y., Bonjour J.P., Rizzoli R. Strontium ranelate improves bone resistance by increasing bone mass and improving architecture in intact female rats. J. Bone Miner. Res. 2004;19:2012–2020. - PubMed
-
- Aslam M.N., Kreider J.M., Paruchuri T., Bhagavathula N., DaSilva M., Zernicke R.F., Goldstein S.A., Varani J. A mineral-rich extract from the red marine algae lithothamnion calcareum preserves bone structure and function in female mice on a Western-style diet. Calcif. Tissue Int. 2010;86:313–324. - PMC - PubMed
- Full Text Sources
- Other Literature Sources
- Medical
NCBI Literature Resources
The PubMed wordmark and PubMed logo are registered trademarks of the U.S. Department of Health and Human Services (HHS). Unauthorized use of these marks is strictly prohibited.
National Library of Medicine
8600 Rockville Pike
Bethesda, MD 20894
![Fig. 2](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4926831/bin/gr2.jpg)
Fig. 3
Femoral bone: Biomechanical properties. Femoral…
Fig. 3
Femoral bone: Biomechanical properties. Femoral stiffness and strength were assessed in the 4-point…
Fig. 4
Vertebral bone structure and function.…
Fig. 4
Vertebral bone structure and function. A: Structural features of trabecular bone. B: Structural…
- A mineral-rich extract from the red marine algae Lithothamnion calcareum preserves bone structure and function in female mice on a Western-style diet.Aslam MN, Kreider JM, Paruchuri T, Bhagavathula N, DaSilva M, Zernicke RF, Goldstein SA, Varani J. Aslam MN, et al. Calcif Tissue Int. 2010 Apr;86(4):313-24. doi: 10.1007/s00223-010-9340-9. Epub 2010 Feb 24. Calcif Tissue Int. 2010. PMID: 20180099 Free PMC article.
- Preservation of bone structure and function by Lithothamnion sp. derived minerals.Aslam MN, Bergin I, Jepsen K, Kreider JM, Graf KH, Naik M, Goldstein SA, Varani J. Aslam MN, et al. Biol Trace Elem Res. 2013 Dec;156(1-3):210-20. doi: 10.1007/s12011-013-9820-7. Epub 2013 Oct 6. Biol Trace Elem Res. 2013. PMID: 24096551 Free PMC article.
- A mineral-rich red algae extract inhibits polyp formation and inflammation in the gastrointestinal tract of mice on a high-fat diet.Aslam MN, Paruchuri T, Bhagavathula N, Varani J. Aslam MN, et al. Integr Cancer Ther. 2010 Mar;9(1):93-9. doi: 10.1177/1534735409360360. Epub 2010 Feb 11. Integr Cancer Ther. 2010. PMID: 20150219 Free PMC article.
- Osteoporosis and the role of diet.Eaton-Evans J. Eaton-Evans J. Br J Biomed Sci. 1994 Dec;51(4):358-70. Br J Biomed Sci. 1994. PMID: 7756943 Review.
- Treatment for osteoporosis in people with ß-thalassaemia.Bhardwaj A, Swe KM, Sinha NK, Osunkwo I. Bhardwaj A, et al. Cochrane Database Syst Rev. 2016 Mar 10;3:CD010429. doi: 10.1002/14651858.CD010429.pub2. Cochrane Database Syst Rev. 2016. PMID: 26964506 Review.
- Bone fragility during the COVID-19 pandemic: the role of macro- and micronutrients.Moretti A, Liguori S, Paoletta M, Migliaccio S, Toro G, Gimigliano F, Iolascon G. Moretti A, et al. Ther Adv Musculoskelet Dis. 2023 Mar 14;15:1759720X231158200. doi: 10.1177/1759720X231158200. eCollection 2023. Ther Adv Musculoskelet Dis. 2023. PMID: 36937822 Free PMC article. Review.
- Red Marine Algae Lithothamnion calcareum Supports Dental Enamel Mineralization.R Carrilho M, Bretz W. R Carrilho M, et al. Mar Drugs. 2023 Feb 2;21(2):109. doi: 10.3390/md21020109. Mar Drugs. 2023. PMID: 36827150 Free PMC article.
- Evaluation of an Ionic Calcium Fiber Supplement and Its Impact on Bone Health Preservation in a Dietary Calcium Deficiency Mice Model.Herrera-Rodríguez SE, García-Márquez E, Padilla-Camberos E, Espinosa-Andrews H. Herrera-Rodríguez SE, et al. Nutrients. 2022 Jan 18;14(3):422. doi: 10.3390/nu14030422. Nutrients. 2022. PMID: 35276779 Free PMC article.
- Trabecular Bone Microarchitecture Improvement Is Associated With Skeletal Nerve Increase Following Aerobic Exercise Training in Middle-Aged Mice.Lee S, Shin YA, Cho J, Park DH, Kim C. Lee S, et al. Front Physiol. 2022 Feb 22;12:800301. doi: 10.3389/fphys.2021.800301. eCollection 2021. Front Physiol. 2022. PMID: 35273515 Free PMC article.
- The Use of Mushrooms and Spirulina Algae as Supplements to Prevent Growth Inhibition in a Pre-Clinical Model for an Unbalanced Diet.Sides R, Griess-Fishheimer S, Zaretsky J, Shitrit A, Kalev-Altman R, Rozner R, Beresh O, Dumont M, Penn S, Shahar R, Monsonego-Ornan E. Sides R, et al. Nutrients. 2021 Nov 29;13(12):4316. doi: 10.3390/nu13124316. Nutrients. 2021. PMID: 34959867 Free PMC article.
-
- Ammann P., Shen V., Robin B., Mauras Y., Bonjour J.P., Rizzoli R. Strontium ranelate improves bone resistance by increasing bone mass and improving architecture in intact female rats. J. Bone Miner. Res. 2004;19:2012–2020. - PubMed
-
- Aslam M.N., Kreider J.M., Paruchuri T., Bhagavathula N., DaSilva M., Zernicke R.F., Goldstein S.A., Varani J. A mineral-rich extract from the red marine algae lithothamnion calcareum preserves bone structure and function in female mice on a Western-style diet. Calcif. Tissue Int. 2010;86:313–324. - PMC - PubMed
- Full Text Sources
- Other Literature Sources
- Medical
![Fig. 3](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4926831/bin/gr3.jpg)
Fig. 4
Vertebral bone structure and function.…
Fig. 4
Vertebral bone structure and function. A: Structural features of trabecular bone. B: Structural…
![Fig. 4](https://www.ncbi.nlm.nih.gov/pmc/articles/instance/4926831/bin/gr4.jpg)
References
- Adler R.A. Osteoporosis in men: a review. Bone Res. 2014;2:14001.
- Ammann P., Shen V., Robin B., Mauras Y., Bonjour J.P., Rizzoli R. Strontium ranelate improves bone resistance by increasing bone mass and improving architecture in intact female rats. J. Bone Miner. Res. 2004;19:2012–2020.
- Aslam M.N., Kreider J.M., Paruchuri T., Bhagavathula N., DaSilva M., Zernicke R.F., Goldstein S.A., Varani J. A mineral-rich extract from the red marine algae lithothamnion calcareum preserves bone structure and function in female mice on a Western-style diet. Calcif. Tissue Int. 2010;86:313–324.
- Aslam M.N., Paruchuri T., Bhagavathula N., Varani J. A mineral-rich red algae extract inhibits polyp formation and inflammation in the gastrointestinal tract of mice on a high-fat diet. Integr Cancer Res. 2010;9:93–99.
- Aslam M.N., Bergin I., Naik M., Hampton A., Allen R., Kunkel S.L., Rush H., Varani J. A multi-mineral natural product inhibits liver tumor formation in C57BL/6 mice. Biol. Trace Elem. Res. 2012;147:267–274.
- Aslam M.N., Bergin I., Naik M., Paruchuri T., Hampton A., Rehman M., Dame M.K., Rush H., Varani J. A multimineral natural product from red marine algae reduces colon polyp formation in C57BL/6 mice. Nutr. Cancer. 2012;64:1020–1028.
- Aslam M.N., Bergin I., Jepsen K., Kreider J.M., Graf K.H., Naik M., Goldstein S.A., Varani J. Preservation of bone structure and function by Lithothamnion sp. derived minerals. Biol. Trace Elem. Res. 2013;156:210–220.
- Bastie C.C., Gaffney-Stomberg E., Lee T.W.A., Dhima E., Pessin J.E., Augenlicht L.H. Dietary cholecalciferol and calcium levels in a Western-style diet alter energy metabolism and inflammatory responses in mice. J. Nutr. 2012;142:859–865.
- Boskey A.L., Coleman R. Aging and bone (Crit. Rev Oral Biol Med) J. Dent. Res. 2010;89:1333–1348.
- Bouxsein M.L., Boyd S.K., Christiansen B.A., Guldberg R.E., Jepsen K.J., Müller R. Guidelines for assessment of bone microstructure in rodents using micro–computed tomography. J. Bone Miner. Res. 2010;25:1468–1486.
- Cashman K., Flynn A. Trace elements and bone metabolism. In: Sandstrom B., Walter P., editors. Role of Trace Elements for Health Promotion and Disease Prevention. Bibl Nutr Dieta. Vol. 54. Karger; Basel: 1998. pp. 150–164.
- Center J.R., Nguyen T.V., Schneider D., Sambrook P.N., Eisman J.A. Mortality after all major types of osteoporotic fractures in men and women: an observational study. Lancet. 1999;353:878–882.
- De Laet C.E., Van Hout B.A., Burger H., Weel A.E., Hofman A., Pols H.A. Hip fracture prediction in elderly men and women: validation in the Rotterdam study. J. Bone Miner. Res. 1998;13:1587–1593.
- Gielen E., Vanderschueren D., Callewaert F., Boonen S. Osteoporosis in men. Best Pract. Res. Clin. Endocrinol. Metab. 2011;25:321–335.
- Glatt V., Canalis E., Stadmeyer L., Bouxsein M.L. Age-related changes in trabecular architecture differ in female and male C57BL/6J mice. J. Bone Miner. Res. 2007;22:1197–1207.
- Guggenbuhl P. Osteoporosis in males and females: is there really a difference. Joint Bone Spine. 2009;76:595–601.
- Hannon R.A., Clowes J.A., Eagleton A.C., Al Hadari A., Eastell R., Blumsohn A. Clinical performance of immunoreactive tartrate resistant acid phosphatase isoform 5b as a marker of bone resorption. Bone. 2004;34:187–194.
- Heaney R.P., Weaver C.M. Newer perspectives on calcium nutrition and bone quality. J. Am. Coll. Nutr. 2005;24:574S–581S.
- Johnell O., Kanis J.A. An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos. Int. 2006;17:1726–1733.
- Jugdaohsingh R. Silicon and bone health. J. Nutr. Health Aging. 2007;11:99–110.
- Lowe N.M., Lowe N.M., Fraser W.D., Jackson M.J. Is there potential therapeutic value of copper and zinc for osteoporosis? Proc. Nutr. Soc. 2002;61:181–185.
- Marie P.J., Ammann P., Boivin G., Rey C. Mechanisms of action and therapeutic potential of strontium in bone. Calcif. Tissue Int. 2001;69:121–129.
- Meganck J.A., Kozloff K.M., Thornton M.M., Broski S.M., Goldstein S.A. Beam hardening artifacts in micro-computed tomography scanning can be reduced by X-ray beam filtration and the resulting images can be used to accurately measure BMD. Bone. 2009;45:1104–1106.
- Meunier P.J., Roux C., Seeman E., Ortolani S., Badurski J.E., Spector T.D., Cannata J., Balogh A., Lemmel E.M., Pors-Nielsen S., Rizzoli R., Genant H.K., Reginster J.Y. The effects of strontium ranelate on the risk of vertebral fracture in women with postmenopausal osteoporosis. N. Engl. J. Med. 2004;350:459–468.
- Newmark H.L., Yang K., Kurihara N., Fan K., Augenlicht L.H., Lipkin M. Western style diet-induced colonic tumors and their modulation by calcium and vitamin D in C57BI/6 mice: a preclinical model for human sporadic colon cancer. Carcinogenesis. 2009;30:88–92.
- Odabasi E., Turan M., Aydin A., Akay C., Kutlu M. Magnesium, zinc, copper, manganese and selenium levels in postmenopausal women with osteoporosis: can magnesium play a key role in osteoporosis? Ann. Acad. Med. Singap. 2008;37:564–567.
- Parhaml F., Tintut Y., Beamer W.G., Gharavi N., Goodman W., Demer L.L. Atherogenic high-fat diet reduces bone mineralization in mice. J. Bone Miner. Res. 2001;16:182–188.
- Peacock M., Liu G., Carey M., McClintock R., Ambrosius W., Hui S., Johnston C.C. Effect of a calcium or 25OHD vitamin D3 dietary supplementation on bone loss at the hip in men and women over the age of 60. J. Clin. Endocrinol. Metab. 2000;85:3011–3019.
- Pelton K., Krieder J., Joiner D., Freeman M.R., Goldstein S.A., Solomon K.R. Hypercholesterolemia promotes an osteoporotic phenotype. Am. J. Pathol. 2012;181:928–936.
- Peterlik M., Cross H.S. Vitamin D and calcium deficits predispose for multiple chronic diseases. Eur. J. Clin. Investig. 2005;35:290–304.
- Peterlik H., Roschger P., Klauhofer K., Fratzl P. From brittle to ductile fracture of bone. Nat. Mater. 2006;5:52–55.
- Pilvi T.K., Korpela R., Huttunen M., Vapaatalo H., Mervaala E.M. High-calcium diet with whey protein attenuates body-weight gain in high-fat-fed C57BL/6J mice. Br. J. Nutr. 2007;98:900–907.
- Prentice A. Diet, nutrition and the prevention of osteoporosis. Public Health Nutr. 2004;7(1A):227–243.
- Risteli J., Risteli L. Products of bone collagen metabolism. In: Seibel M.J., Robins S.P., Bilezikian J.P.G., editors. Dynamics of Bone and Cartilage Metabolism: Principles and Clinical Applications. second ed. Academic Press; London: 2006. pp. 391–405.
- Rosen C.J., Klibanski A. Bone, fat, and body composition: Evolving concepts in the pathogenesis of osteoporosis. Am. J. Med. 2009;122:409–414.
- Saidak Z., Marie P.J. Strontium signaling: molecular mechanisms and therapeutic implications in osteoporosis. Pharmacol. Ther. 2012;136:216–226.
- Salem G.J., Zernicke R.F., Martinez D.A., Vailas A.C. Adaptations of immature trabecular bone to moderate exercise: geometrical, biochemical, and biomechanical correlates. Bone. 1993;14:647–654.
- Strause L., Saltman P., Smith K.T., Bracker M., Andon M.B. Spinal bone loss in post-menopausal women supplemented with calcium and trace metals. J. Nutr. 1994;124:1060–1064.
- Tommasini S.M., Wearne S.L., Hof P.R., Jepsen K.J. Percolation theory relates corticocancellaous architecture to mechanical function in vertebrae of inbred mouse strains. Bone. 2008;42:743–750.
- Turner C.H. Bone strength: current concepts. Ann. N. Y. Acad. Sci. 2006;1068:429–446.
- US Department of Agriculture . 8th. ed. 2015. 2015–2020 Dietary Guidelines for Americans. Washington DC.
- von Muhlen D., Safii S., Jassal S.K., Svartberg J., Barrett-Connor E. Associations between the metabolic syndrome and bone health in older men and women: the Rancho Bernardo Study. Osteoporos. Int. 2007;18:1337–1344.
- Ward W.E., Kim S., Bruce W.R. A western-style diet reduces bone mass and biomechanical bone strength to a greater degree in male compared with female rats during development. Br. J. Nutr. 2003;90:589–595.
- Yamaguchi M. Role of zinc in bone formation and bone resorption. J. Trace Elem. Exp. Med. 1998;11:119–135.
- Zernicke R.F., Salem G.J., Barnard R.J., Schramm E. Long-term high-fat sucrose diet alters rat femoral neck and vertebral morphology, bone mineral content and mechanical properties. Bone. 1995;16:25–31.
Source: PubMed