Research Article: Bone callus formation is highly disrupted by dietary restriction in growing rats sustaining a femoral fracture1

Date Published: February 14, 2019

Publisher: Sociedade Brasileira para o Desenvolvimento da Pesquisa em

Author(s): Iara Inácio Botega, Ariane Zamarioli, Patrícia Madalena San Gregório Guedes, Raquel Assed Bezerra da Silva, João Paulo Mardegan Issa, Mariana Maloste Butezloff, Yara Terezinha Corrêa Silva Sousa, João Paulo Bianchi Ximenez, José Batista Volpon.


To evaluate the effects of food restriction on fracture healing in growing

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.

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

Dietary restriction had detrimental effects on osseous healing, with a
healing delay and a lower quality of bone callus formation.

Partial Text

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 thus,
reduces the risk of fractures and incidence of osteoporosis later in life1. Epidemiologic data indicate that a 10% increase in peak bone mass may
decrease the risk of fracture2. Conversely, low bone mass in young adults represents a substantial risk
factor for postmenopausal osteoporosis3. Thus, genetic inheritance, good health, and adequate nutritional intake are
critical factors in optimizing bone mass accrual during skeletal maturation1,4. Conversely, it has been shown in rats that caloric restriction during rapid
skeletal growth is detrimental to bone mass and architecture1.

Considering that the peak bone mass achieved during skeletal growth is perhaps one
of the most important risk factors for bone osteoporosis later in life22, any condition leading to a reduction in peak bone mass during the growth
period should also be considered for its potential long-term effects. Malnutrition
is one such condition that may occur at any stage of life and impairs bone




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