Energy Metabolism and Ketogenic Diets: What about the Skeletal Health? A Narrative Review and a Prospective Vision for Planning Clinical Trials on this Issue

Abstract

The existence of a common mesenchymal cell progenitor shared by bone, skeletal muscle, and adipocytes cell progenitors, makes the role of the skeleton in energy metabolism no longer surprising. Thus, bone fragility could also be seen as a consequence of a “poor” quality in nutrition. Ketogenic diet was originally proven to be effective in epilepsy, and long-term follow-up studies on epileptic children undergoing a ketogenic diet reported an increased incidence of bone fractures and decreased bone mineral density. However, the causes of such negative impacts on bone health have to be better defined. In these subjects, the concomitant use of antiepileptic drugs and the reduced mobilization may partly explain the negative effects on bone health, but little is known about the effects of diet itself, and/or generic alterations in vitamin D and/or impaired growth factor production. Despite these remarks, clinical studies were adequately designed to investigate bone health are scarce and bone health related aspects are not included among the various metabolic pathologies positively influenced by ketogenic diets. Here, we provide not only a narrative review on this issue, but also practical advice to design and implement clinical studies on ketogenic nutritional regimens and bone health outcomes. Perspectives on ketogenic regimens, microbiota, microRNAs, and bone health are also included.

Incidence and Characteristics of Kidney Stones in Patients on Ketogenic Diet: A Systematic Review and Meta-Analysis

“…In addition, changing dietary patterns, including the ketogenic diet, could possibly be an important environmental trigger in the association, as well [88]. Bone health should be monitored closely in patients on the ketogenic diet and more clinical trials are needed to further define the negative impacts on bone health [89]. Although prophylactic calcium and vitamin D is recommended in all people on the ketogenic diet for bone health [23,24], athletes with dermal calcium loss during exercise/sweating and obese subjects restricting dairy are at further risk of worsening bone health if not on adequate calcium supplements [7,89].…”

“…Bone health should be monitored closely in patients on the ketogenic diet and more clinical trials are needed to further define the negative impacts on bone health [89]. Although prophylactic calcium and vitamin D is recommended in all people on the ketogenic diet for bone health [23,24], athletes with dermal calcium loss during exercise/sweating and obese subjects restricting dairy are at further risk of worsening bone health if not on adequate calcium supplements [7,89]. However, given the reported risk of nephrolithiasis from hypercalciuria, supplementation remains a challenge [20,25].…”

Neuroprotection by the Ketogenic Diet: Evidence and Controversies

“…The effect of the KD on growth and skeletal health was reviewed by Merlotti et al ( 72 ). Multiple studies in rats on the KD and modified KD combined with other treatments indicated reduced biomechanical function, reduced bone mineral density and increased osteoporosis.…”

“…Multiple studies in rats on the KD and modified KD combined with other treatments indicated reduced biomechanical function, reduced bone mineral density and increased osteoporosis. In contrast, most studies with patients on the KD showed no or minimal negative effects on growth, bone mass or molecular markers of bone health over 24 months ( 72 ). In a long-term retrospective study of pediatric patients on the diet for 8 years, a low but significant frequency of individuals with reduced bone mineral density was observed ( 73 ).…”

“…In a long-term retrospective study of pediatric patients on the diet for 8 years, a low but significant frequency of individuals with reduced bone mineral density was observed ( 73 ). This observation may be explained by a potential relationship between the genetic cause of epilepsy and skeletal damage, for example GLUT1 gene mutations ( 72 ). Additionally, in a study on children who had followed the KD for a median of 6 years and then discontinued the diet at least 6 months prior to the study, no long-term effects were observed on physical growth, lipid levels and other measurements ( 74 ).…”