Vitamin E and the Healing of Bone Fracture: The Current State of Evidence

Table 1

Evidence table for past animal studies of the effect of vitamin E on bone fracture healing.

Study	Sample; (size of study groups)	Study design
		Affected bone(s)	Fracture production	Fracture type	Fracture fixation/distraction	Dose of vitamin E analog used in treatment group	Duration of treatment	Intervention in control and other comparison group(s)	Main outcome measure(s)
Kurklu et al. [15]	Adult New Zealand white rabbits; (control = 15; treatment = 15)	Middle third of right tibia; (normal bone model)	Osteotomy	Open fracture	Distraction using circular external fixator	20 mg/kg/day 𝛼-tocopherol (intramuscular)	30 days	Control group did not receive any treatment.	Radiological evaluation of bone formation (based upon the grading system by Lane and Sandhu [16]) on day 20, day 30, and day 40 of study; Scintigraphical assessments to calculate the osteoblastic activity ratio (distracted tibia/contralateral normal tibia) on day 5 and day 20 of study; Histopathological evaluation of bone formation of the distracted tibial segments (based upon the grading system by Huddleston et al. [17]) on day 40 of study
Shuid et al. [18]	Female Sprague-Dawley rats; (sham = 8; control = 8; treatment = 8)	Mid-diaphysis of right femur (osteoporotic bone model)	Three-point bending method using a guillotine device	Closed fracture	Internal fixation using Kirschner wires	60 mg/kg/day of 𝛼-tocopherol (per oral gavage) (ovariectomized treatment group)	14 days	Sham-operated and ovariectomized control groups received vehicle only (oral gavage)	CT-scan measurement of axial callous volume of the dissected femora after day 14 of study; Radiological evaluation of callous staging (based upon the grading system by Shuid et al. [19]) of the dissected femora after day 14 of study; Radiological evaluation of fracture healing (based upon grading system by Warden et al. [20]) of the dissected femora after day 14 of study
Paskalev et al. [8]	Mixed-breed adult male dogs; (control = 6; treatment = 6)	Diaphyses of right tibia and fibula (normal bone model)	Osteotomy	Open fracture	Internal fixation using plates	100 mg/day 𝛼-tocopherol (per oral)	30 days	Control group did not receive any treatment	Radiological evaluation of callous formation and bone remodeling staging of the operated limb on day 1, week 2, month 1, month 2, month 3, and month 4 after the surgery (the grading system was not stated)
Turk et al. [21]	Male Sprague-Dawley rats; (control = 30; treatment = 30)	Right tibia (normal bone model)	Unspecified manual fracture procedure	Closed fracture	Internal fixation using Kirschner wires	20 mg/kg/day 𝛼-tocopherol (intraperitoneal)	60 days	Control groups received saline (intraperitoneal)	Radiological evaluation of the bone formation (based upon the grading system by Lane and Sandhu [16]) of the right tibia on day 60 of study; Histopathological evaluation of the fracture healing (based upon the grading system by Allen et al. [22]) of the dissected right tibia after day 60 of study
Durak et al. [23]	New Zealand male white rabbits; (Control = 10; Treatment = 10)	Right femur (Normal bone model)	Manual stress angulation	Closed fracture	External fixation using cast immobilization.	20 mg/kg 𝛼-tocopherol (intramuscular) 1 hour before and at the time of the procedure.; 20 mg/kg/day 𝛼-tocopherol (intramuscular) after the procedure	5 days	Control group did not receive any treatment.	Histopathological evaluation of the fracture healing (based upon the grading system by Allen et al. [22]) of the dissected right tibia after day 21 of study.
Sarisözen et al. [24]	Adult Sprague-Dawley rats; (control = 12; Vit. E only; treatment = 12; Vit. C only; treatment = 12; Vit. E and Vit. C combination; treatment = 12)	Right femur; (normal bone model)	Manual stress angulation	Closed fracture	Fracture left in situ	40 mg/kg α-tocopherol (intraperitoneal) daily from day 1 to day 3 and three times a week from day 4 onward	14 days; 21 days	Control group did not receive any treatment; Vit. C only group received 200 mg/kg vit. C daily (intraperitoneal) from day 1 to day 3 and three times a week from day 4 onward; Vit. C and Vit. E combination group received 40 mg/kg vit. E and 200 mg/kg Vit. C daily (intraperitoneal) from day 1 to day 3 and three times a week from day 4 onward	Radiological evaluation of fracture healing (based upon the callous index calculation by Oni et al. [25]) of the right tibias from the rats sacrificed on day 14 and 21; Histopathological evaluation of fracture healing (based upon the grading system by Allen et al. [22]) of the dissected right tibias from the rats sacrificed on day 14 and 21