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

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.

Advances and Promises of Nutritional Influences on Natural Bone Repair

“…This was highlighted in a pre-clinical model in which Wistar rats fed a restricted diet experienced impaired femoral fracture healing. 48 Beyond general caloric needs, adequate dietary protein appears to be vital for JOURNAL OF ORTHOPAEDIC RESEARCH ® APRIL 2020 Orthopaedic patients often present with malnutrition, particularly nutrient deficiencies. Malnutrition can also arise from increased metabolism, decreased food consumption and nutrient absorption.…”

“…). This was highlighted in a pre‐clinical model in which Wistar rats fed a restricted diet experienced impaired femoral fracture healing . Beyond general caloric needs, adequate dietary protein appears to be vital for natural fracture healing, as pre‐clinical studies in rats have consistently demonstrated that protein restriction, that mimics protein malnutrition, impairs fracture healing .…”

Advances in bone regeneration with growth factors for spinal fusion: A literature review

“…2 ). The bone regeneration process (e.g., fracture healing) involves the following stages: the inflammatory stage, endochondral bone formation stages (cartilage formation and mineralization), and remodeling stage [ 1 , 25 ]. Several cytokines play an integral role in each process, and BMPs in particular are strongly involved in all the processes.…”

Advances in Growth Factor Delivery for Bone Tissue Engineering

“…For instance, BMPs have been shown to elicit new bone formation both at the bone defect site and at heterotopic sites in a large number of species. The process of bone regeneration encompasses the initial inflammatory phase, soft callus formation, mineralization, and bone remodeling [ 32 ]. The different phases of bone regeneration engage multiple GFs in specific spatiotemporal patterns ( Figure 1 ).…”