Abstract
Ketogenic diet (KD) compromised the microstructure of cancellous bone and the mechanical property in the appendicular bone of mice, while the effects of KD on the axial bone have not been reported. This study aimed to compare the changes in the microstructure and mechanical properties of the forth lumbar (L4) vertebra in KD and ovariectomized (OVX) mice. Forty eight-week-old female C57BL/6J mice were assigned into four groups: SD (standard diet) + Sham, SD + OVX, KD + Sham, and KD + OVX groups. L4 vertebra was scanned by micro-CT to examine the microstructure of cancellous bone, after which simulative compression tests were performed using finite element (FE) analysis. Vertebral compressive test and histological staining of the L4 and L5 vertebrae were performed to observe the biomechanical and histomorphologic changes. The KD + Sham and SD + OVX exhibited a remarkable declination in the parameters of cancellous bone compared with the SD + Sham group, while KD + OVX demonstrated the most serious bone loss in the four groups. The stiffness was significantly higher in the SD + Sham group than the other three groups, but no difference was found between the remaining groups. The trabecular parameters were significantly correlated with the stiffness. Meanwhile, the OVX + Sham and KD + OVX groups showed a significant decrease in the failure load of compressive test, while there was no difference between the KD + Sham and SD + Sham groups. These findings suggest that KD may compromise the vertebral microstructure and compressive stiffness to a similar level as OVX did, indicating adverse effects of KD on the axial bone of the mice.
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Kose E, Guzel O, Demir K, Arslan N (2017) Changes of thyroid hormonal status in patients receiving ketogenic diet due to intractable epilepsy. J Pediatr Endocrinol Metab 30:411–416
McArtney R, Bailey A, Champion H (2016) What is a ketogenic diet and how does it affect the use of medicines? Arch Dis Child Educ Pract Ed 102:194–199
Branco AF, Ferreira A, Simoes RF, Magalhaes-Novais S, Zehowski C, Cope E, Silva AM, Pereira D, Sardao VA, Cunha-Oliveira T (2016) Ketogenic diets: from cancer to mitochondrial diseases and beyond. Eur J Clin Invest 46:285–298
Winesett SP, Bessone SK, Kossoff EH (2015) The ketogenic diet in pharmacoresistant childhood epilepsy. Expert Rev Neurother 15:621–628
Van der Auwera I, Wera S, Van Leuven F, Henderson ST (2005) A ketogenic diet reduces amyloid beta 40 and 42 in a mouse model of Alzheimer’s disease. Nutr Metab (Lond) 2:28
Prins ML, Fujima LS, Hovda DA (2005) Age-dependent reduction of cortical contusion volume by ketones after traumatic brain injury. J Neurosci Res 82:413–420
Tai KK, Nguyen N, Pham L, Truong DD (2008) Ketogenic diet prevents cardiac arrest-induced cerebral ischemic neurodegeneration. J Neural Transm (Vienna) 115:1011–1017
Tai KK, Truong DD (2007) Ketogenic diet prevents seizure and reduces myoclonic jerks in rats with cardiac arrest-induced cerebral hypoxia. Neurosci Lett 425:34–38
Puchowicz MA, Zechel JL, Valerio J, Emancipator DS, Xu K, Pundik S, LaManna JC, Lust WD (2008) Neuroprotection in diet-induced ketotic rat brain after focal ischemia. J Cereb Blood Flow Metab 28:1907–1916
Hahn TJ, Halstead LR, DeVivo DC (1979) Disordered mineral metabolism produced by ketogenic diet therapy. Calcif Tissue Int 28:17–22
Bergqvist AG, Schall JI, Stallings VA (2007) Vitamin D status in children with intractable epilepsy, and impact of the ketogenic diet. EPILEPSIA 48:66–71
Bergqvist AC, Schall JI, Stallings VA, Zemel BS (2008) Progressive bone mineral content loss in children with intractable epilepsy treated with the ketogenic diet. Am J Clin Nutr 88:1678–1684
Chen B, Li Y, Yang X, Xie D (2012) Femoral metaphysis bending test of rat: introduction and validation of a novel biomechanical testing protocol for osteoporosis. J Orthop SCI 17:70–76
Rachner TD, Khosla S, Hofbauer LC (2011) Osteoporosis: now and the future. Lancet 377:1276–1287
Lane NE (2006) Epidemiology, etiology, and diagnosis of osteoporosis. Am J Obstet Gynecol 194:S3–S11
Verhulp E, van Rietbergen B, Muller R, Huiskes R (2008) Indirect determination of trabecular bone effective tissue failure properties using micro-finite element simulations. J Biomech 41:1479–1485
Johnell O, Kanis JA (2006) An estimate of the worldwide prevalence and disability associated with osteoporotic fractures. Osteoporos Int 17:1726–1733
Wu X, Huang Z, Wang X, Fu Z, Liu J, Huang Z, Kong G, Xu X, Ding J, Zhu Q (2017) Ketogenic diet compromises both cancellous and cortical bone mass in mice. Calcif Tissue Int 101:412–421
Wu J, Moverare-Skrtic S, Borjesson AE, Lagerquist MK, Sjogren K, Windahl SH, Koskela A, Grahnemo L, Islander U, Wilhelmson AS, Tivesten A, Tuukkanen J, Ohlsson C (2016) Enzalutamide reduces the bone mass in the axial but not the appendicular skeleton in male mice. Endocrinology 157:969–977
Muller R, Ruegsegger P (1995) Three-dimensional finite element modelling of non-invasively assessed trabecular bone structures. Med Eng Phys 17:126–133
Ruyssen-Witrand A, Gossec L, Kolta S, Dougados M, Roux C (2007) Vertebral dimensions as risk factor of vertebral fracture in osteoporotic patients: a systematic literature review. Osteoporos Int 18:1271–1278
Zhao F, Kirby M, Roy A, Hu Y, Guo XE, Wang X (2018) Commonality in the microarchitecture of trabecular bone: a preliminary study. Bone 111:59–70
Chen H, Kubo KY (2014) Bone three-dimensional microstructural features of the common osteoporotic fracture sites. World J Orthop 5:486–495
Boyd SK, Davison P, Muller R, Gasser JA (2006) Monitoring individual morphological changes over time in ovariectomized rats by in vivo micro-computed tomography. Bone 39:854–862
Genant HK, Baylink DJ, Gallagher JC (1989) Estrogens in the prevention of osteoporosis in postmenopausal women. Am J Obstet Gynecol 161:1842–1846
Li L, Chen X, Lv S, Dong M, Zhang L, Tu J, Yang J, Zhang L, Song Y, Xu L, Zou J (2014) Influence of exercise on bone remodeling-related hormones and cytokines in ovariectomized rats: a model of postmenopausal osteoporosis. PLoS One 9:e112845
Zaid SS, Sulaiman SA, Sirajudeen KN, Othman NH (2010) The effects of Tualang honey on female reproductive organs, tibia bone and hormonal profile in ovariectomised rats–animal model for menopause. BMC Complement Altern Med 10:82
Campbell GM, Buie HR, Boyd SK (2008) Signs of irreversible architectural changes occur early in the development of experimental osteoporosis as assessed by in vivo micro-CT. Osteoporos Int 19:1409–1419
Hsu PY, Tsai MT, Wang SP, Chen YJ, Wu J, Hsu JT (2016) Cortical bone morphological and trabecular bone microarchitectural changes in the mandible and femoral neck of ovariectomized rats. PLoS One 11:e154367
Lei T, Liang Z, Li F, Tang C, Xie K, Wang P, Dong X, Shan S, Jiang M, Xu Q, Luo E, Shen G (2018) Pulsed electromagnetic fields (PEMF) attenuate changes in vertebral bone mass, architecture and strength in ovariectomized mice. Bone 108:10–19
Sornay-Rendu E, Munoz F, Garnero P, Duboeuf F, Delmas PD (2005) Identification of osteopenic women at high risk of fracture: the OFELY study. J Bone Miner Res 20:1813–1819
Bevill G, Keaveny TM (2009) Trabecular bone strength predictions using finite element analysis of micro-scale images at limited spatial resolution. Bone 44:579–584
Ladd AJ, Kinney JH, Haupt DL, Goldstein SA (1998) Finite-element modeling of trabecular bone: comparison with mechanical testing and determination of tissue modulus. J Orthop Res 16:622–628
Kabel J, van Rietbergen B, Dalstra M, Odgaard A, Huiskes R (1999) The role of an effective isotropic tissue modulus in the elastic properties of cancellous bone. J Biomech 32:673–680
Tsafnat N, Wroe S (2011) An experimentally validated micromechanical model of a rat vertebra under compressive loading. J Anat 218:40–46
Arias-Moreno AJ, Ito K, van Rietbergen B (2016) Micro-Finite Element analysis will overestimate the compressive stiffness of fractured cancellous bone. J Biomech 49:2613–2618
Torcasio A, Zhang X, Duyck J, van Lenthe GH (2012) 3D characterization of bone strains in the rat tibia loading model. Biomech Model Mechanobiol 11:403–410
Gibson LJ (1985) The mechanical behaviour of cancellous bone. J Biomech 18:317–328
Ito M, Nishida A, Koga A, Ikeda S, Shiraishi A, Uetani M, Hayashi K, Nakamura T (2002) Contribution of trabecular and cortical components to the mechanical properties of bone and their regulating parameters. Bone 31:351–358
Liu Q, Xu X, Yang Z, Liu Y, Wu X, Huang Z, Liu J, Huang Z, Kong G, Ding J, Li R, Lin J, Zhu Q (2019) Metformin alleviates the bone loss induced by ketogenic diet: an in vivo study in mice. Calcif Tissue Int 104:59–69
Bielohuby M, Matsuura M, Herbach N, Kienzle E, Slawik M, Hoeflich A, Bidlingmaier M (2010) Short-term exposure to low-carbohydrate, high-fat diets induces low bone mineral density and reduces bone formation in rats. J Bone Miner Res 25:275–284
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Wu, X., Ding, J., Xu, X. et al. Ketogenic diet compromises vertebral microstructure and biomechanical characteristics in mice. J Bone Miner Metab 37, 957–966 (2019). https://doi.org/10.1007/s00774-019-01002-2
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DOI: https://doi.org/10.1007/s00774-019-01002-2