Ketogenic diet delays spinal fusion and decreases bone mass in posterolateral lumbar spinal fusion: an in vivo rat model
- 116 Downloads
Ketogenic diet (KD), a low-carbohydrate-and-high-fat diet, causes a metabolic state of ketogenesis and has been used to treat drug-resistance epilepsy. Our recent studies showed KD neuroprotective after spinal cord injury and causing bone loss. Effects of KD on spinal fusion were still unknown. This study was aimed to evaluate effects of KD on spinal fusion in rats.
Thirty-two Sprague-Dawley rats were randomly divided into KD and standard diet (SD) groups. The KD group was fed with food of 1:4 carbohydrates to fat. All rats were subjected to L4/5 posterolateral lumbar spinal fusion. The blood ketone, and serum calcium, phosphorus, and insulin-like growth factor-1 (IGF-1) were measured, as well as the fusion rates, bone mass (BV), and bone mineral contents (BMC) of fusion sites were estimated at 4 and 8 weeks.
There was no significant difference in serum calcium or phosphorus levels between groups at 4 or 8 weeks. However, there was a significant increase of blood ketone (1.02 mmol/L vs 0.38 mmol/L at 4 weeks; 0.83 mmol/L vs 0.32 mmol/L, at 8 weeks) and decrease of serum IGF-1 (339.4 ng/mL vs 630.6 ng/mL at 4 weeks; 418.8 ng/mL vs 628.6 ng/mL, at 8 weeks) in the KD group compared with the SD group. The spinal fusion occurred less in the KD group (1/16 vs 6/16 at 4 weeks; 7/16 vs 10/16, at 8 weeks), particularly at 4 weeks after surgery. The BV and BMC were lower in the KD group than that in the SD group at 4 weeks, but not different between groups at 8 weeks.
This study demonstrated that KD delayed spinal fusion and decreased bone mass in posterolateral lumbar spinal fusion in rats.
KeywordsBone fusion Bone volume Ketogenic diet Posterolateral spinal fusion Rats
QZ, QL, and XW designed the experiments. QL, XW, ZH, and JH conducted the animal experiments. QL wrote the manuscript. XW and GK completed the data analysis, and QZ revised the manuscript.
This study was supported by the National Natural Science Foundation of China (No. 81472084) and Natural Science Foundation of Guangdong (No. 2014A030313336).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflicts of interest.
All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.
- 6.Bourassa-Moreau E, Mac-Thiong JM, Li A, Ehrmann Feldman D, Gagnon DH, Thompson C, Parent S (2016) Do patients with complete spinal cord injury benefit from early surgical decompression? Analysis of neurological improvement in a prospective cohort study. J Neurotrauma 33:301–306CrossRefPubMedGoogle Scholar
- 7.Brown ML, Yukata K, Farnsworth CW, Chen DG, Awad H, Hilton MJ, O'Keefe RJ, Xing L, Mooney RA, Zuscik MJ (2014) Delayed fracture healing and increased callus adiposity in a C57BL/6J murine model of obesity-associated type 2 diabetes mellitus. PLoS One 9:e99656CrossRefPubMedPubMedCentralGoogle Scholar
- 13.Fehlings MG, Vaccaro A, Wilson JR, Singh A, Cadotte D, Harrop JS, Aarabi B, Shaffrey C, Dvorak M, Fisher C, Arnold P, Massicotte EM, Lewis S, Rampersaud R (2012) Early versus delayed decompression for traumatic cervical spinal cord injury: results of the surgical timing in acute spinal cord injury study (STASCIS). PLoS One 7:e32037CrossRefPubMedPubMedCentralGoogle Scholar
- 15.Ghogawala Z, Whitmore RG, Watters WC 3rd, Sharan A, Mummaneni PV, Dailey AT, Choudhri TF, Eck JC, Groff MW, Wang JC, Resnick DK, Dhall SS, Kaiser MG (2014) Guideline update for the performance of fusion procedures for degenerative disease of the lumbar spine. Part 3: assessment of economic outcome. J Neurosurg Spine 21:14–22CrossRefPubMedGoogle Scholar
- 30.Qin W, Yang T, Ho L, Zhao Z, Wang J, Chen L, Zhao W, Thiyagarajan M, MacGrogan D, Rodgers JT, Puigserver P, Sadoshima J, Deng H, Pedrini S, Gandy S, Sauve AA, Pasinetti GM (2006) Neuronal SIRT1 activation as a novel mechanism underlying the prevention of Alzheimer disease amyloid neuropathology by calorie restriction. J Biol Chem 281:21745–21754CrossRefPubMedGoogle Scholar
- 37.Sroga GE, Wu PC, Vashishth D (2015) Insulin-like growth factor 1, glycation and bone fragility: implications for fracture resistance of bone. PLoS One 10:e117046Google Scholar
- 38.Streijger F, Lee JH, Duncan GJ, Ng MT, Assinck P, Bhatnagar T, Plunet WT, Tetzlaff W, Kwon BK (2014) Combinatorial treatment of acute spinal cord injury with ghrelin, ibuprofen, C16, and ketogenic diet does not result in improved histologic or functional outcome. J Neurosci Res 92:870–883CrossRefPubMedGoogle Scholar
- 41.Tian L, Yu X (2017) Fat, sugar, and bone health: a complex relationship. Nutrients 9Google Scholar
- 46.Yamanaka JS, Yanagihara GR, Carlos BL, Ramos J, Brancaleon BB, Macedo AP, Issa JPM, Shimano AC (2017) A high-fat diet can affect bone healing in growing rats. J Bone Miner MetabGoogle Scholar