Bone callus formation is highly disrupted by dietary restriction in growing rats sustaining a femoral fracture

Iara Inácio Botega,Yara Terezinha Corrêa Silva Sousa,José Batista Volpon,Ariane Zamarioli,Raquel Assed Bezerra Da Silva,Mariana Maloste Butezloff,João Paulo Mardegan Issa,João Paulo Bianchi Ximenez,Patrícia Madalena San Gregório Guedes

doi:10.1590/s0102-865020190010000002

Iara Inácio Botega, Yara Terezinha Corrêa Silva Sousa + Show 7 more

Open Access

https://doi.org/10.1590/s0102-865020190010000002

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Abstract

Purpose To evaluate the effects of food restriction on fracture healing in growing rats. Methods Sixty-eight male Wistar rats were assigned to two groups: (1) Control and (2) Dietary restriction. After weaning the dietary restricted animals were fed ad libitum for 42 days with 50% of the standard chow ingested by the control group. Subsequently, the animals underwent bone fracture at the diaphysis of the right femur, followed by surgical stabilization of bone fragments. On days 14 and 28 post-fracture, the rats were euthanized, and the fractured femurs were dissected, the callus was analyzed by dual-energy X-ray absorptiometry, micro-computed tomography, histomorphometry, mechanical tests, and gene expression. Results Dietary restriction decreased body mass gain and resulted in several phenotypic changes at the bone callus (a delay in cell proliferation and differentiation, lower rate of newly formed bone and collagen deposition, reductions in bone callus density and size, decrease in tridimensional callus volume, deterioration in microstructure, and reduction in bone callus strength), together with the downregulated expression of osteoblast-related genes. Conclusion Dietary restriction had detrimental effects on osseous healing, with a healing delay and a lower quality of bone callus formation.

Highlights

Several factors are known to play a central role in maximizing skeletal acquisition, which is of great importance as this increases both bone mass and quality, and reduces the risk of fractures and incidence of osteoporosis later in life[1]
Several pathways have been proposed to explain the delayed endochondral bone formation observed in animals restricted to specific nutrients, including poor cellular proliferation with the callus containing a preponderance of undifferentiated tissue and much less cartilage and bone, probably due to reduced levels of growth factors[11,15]
Considering that the peak bone mass achieved during skeletal growth is perhaps one of the most important risk factors for bone osteoporosis later in life[22], any condition leading to a reduction in peak bone mass during the growth period should be considered for its potential long-term effects

Summary

Introduction

Several factors are known to play a central role in maximizing skeletal acquisition, which is of great importance as this increases both bone mass and quality, and reduces the risk of fractures and incidence of osteoporosis later in life[1]. Specific micronutrientrelated malnutrition refers to the lack of nutrients, while the term undernutrition means a general reduction in nutrient intake. Previous authors have documented a disruption in fracture healing in rats submitted to dietary restriction of specific nutrients such as vitamin D or proteins[9,10,11,12,13,14]. Clinical undernutrition exhibited by many patients may be caused by a reduction in total food intake instead of the depletion of specific nutrients[8]. Several pathways have been proposed to explain the delayed endochondral bone formation observed in animals restricted to specific nutrients, including poor cellular proliferation with the callus containing a preponderance of undifferentiated tissue and much less cartilage and bone, probably due to reduced levels of growth factors (i.e., insulin growth factor [IGF])[11,15]

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