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Ketogenic diet delays spinal fusion and decreases bone mass in posterolateral lumbar spinal fusion: an in vivo rat model

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Abstract

Background

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.

Methods

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.

Results

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.

Conclusions

This study demonstrated that KD delayed spinal fusion and decreased bone mass in posterolateral lumbar spinal fusion in rats.

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Acknowledgements

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.

Funding

This study was supported by the National Natural Science Foundation of China (No. 81472084) and Natural Science Foundation of Guangdong (No. 2014A030313336).

Author information

Authors and Affiliations

  1. Department of Spinal Surgery, Nanfang Hospital, Southern Medical University, 1838 North Guangzhou Avenue, Guangzhou, 510515, China

    Qi Liu, Zucheng Huang, Junhao Liu, Jianyang Ding, Xiaolin Xu, Ganggang Kong, Xiuhua Wu, Zhou Yang & Qingan Zhu

  2. Department of Spinal Surgery, Longyan Frist Hospital, 105 North Jiuyi Road, Longyan, Fujian, China

    Xiaomeng Wang

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  1. Qi Liu
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Correspondence to Qingan Zhu.

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Comments

After reporting a neuroprotective effect for spinal cord injury and concomitant bone loss with ketogenic diet (KD), the Authors now publish a study concerning the effects of KD on spinal fusion still unknown. 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. There was no significant difference in serum calcium or phosphorus levels between groups at 4 or 8 weeks. However, there was a significantly increase of blood ketone and decrease of serum IGF-1 in KD group compared with SD group. The spinal fusion occurred less in KD group, particularly at 4 weeks after surgery. The BV and BMC were lower in KD group than that in SD group at 4 weeks, but not different between groups at 8 weeks. This study demonstrates that KD delays spinal fusion and decreased bone mass in posterolateral lumbar spinal fusion. As well known a KD, (a low-carbohydrate-and-high-fat diet), causes a metabolic state of ketogenesis and has been used to treat drug-resistance epilepsy. The problem of bone fusion is a very old one and it has been tried to overcome in the past by investigating on harvesting technical reports (2) and special instrumentation and fusion surgical steps in order to optimize fusion (6). Moreover such an observation seems to be very important since many cases of pseudoartrosis are associated with metabolic syndromes like Down’ s an Mucopolisaccaridosys (i.e., Morquio) where it is possible to face with such a complication and to deal with complex metabolic disturbances also concerning the fat and glicoids metabolism ( 1, 3, 4, 5). The topic of pseudoartrosis and non-union in spine surgery in clinical practice both for high and lower spine is still challenging and evergreen, although many papers dealing with stand-alone implants without bone graft both for cervical and lumbar spinal instrumentation procedures is rising up in the worldwide scenario claiming for a better investigation.

Visocchi M

Rome, Italy.

1) Visocchi M, Di Rocco F, Meglio M (2003) Craniocervical junction instability: instrumentation and fusion with titanium rods and sublaminar wires. Effectiveness and failures in personal experience. Acta Neurochir (Wien Austria) 145:265 – 272.

2) Spallone A, Izzo C, Galassi S, Visocchi M (2013) Is “mini-invasive” technique for iliac crest harvesting an alternative to cervical cage implant? An overview of a large personal experience. Surg Neurol Int. 17;4:157. https://doi.org/10.4103/2152-7806.123202. eCollection 2013.

3) Visocchi M, Mattogno PP, Signorelli F, Zhong J, Iacopino G, Barbagallo G. (2017)

Complications in craniovertebral junction instrumentation: hardware removal can be associated with long-lasting stability. Personal experience. ActaNeurochir Suppl. 124:187-194. https://doi.org/10.1007/978-3-319-39546-3_29.

Visocchi M, Sturiale C, G Esposito: (2012) Occipitocervical instrumentation failure after radio–chemio therapy for solitary axis plasmocytoma: a case–based update. Eur J Orthop Surg Traumatol 22 (suppl): S45 – S51.s

Sganzerla EP, Giussani C, Grimaldi M, Parini R, Ingelmo P, Trezza A, Visocchi M (2014) Craniovertebral junction pathological features and their management in the mucopolysaccharidoses. Adv Tech Stand Neurosurg. 40:313-31. https://doi.org/10.1007/978-3-319-01065-6_11.

Visocchi M, Pietrini D, Tufo T, Fernandez E, Di Rocco C(2009) Preoperative irreducible C1- C2 dislocations: intraoperative reduction and posterior fixation. The always posterior strategy Acta Neurochir 151(5):551-9.

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Liu, Q., Wang, X., Huang, Z. et al. Ketogenic diet delays spinal fusion and decreases bone mass in posterolateral lumbar spinal fusion: an in vivo rat model. Acta Neurochir 160, 1909–1916 (2018). https://doi.org/10.1007/s00701-018-3616-7

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