Vitamin E and the Healing of Bone Fracture: The Current State of Evidence
Table 2
Results of past animal studies on the effect of vitamin E on healing of bone fracture.
Study
Reported results
Model proposed for mechanism of action of vitamin E in study
Conclusion of effect of vitamin E based on the phase of fracture healing examined in study
Reported descriptive values of main outcome measure(s)
Reported inferential statistical analysis
Reported conclusion
(A) Radiological-based grade of bone formation [16]
(1) Day 20 Control group (): , Treatment group (): ,
Mann-Whitney test:
The radiological-based bone formation grade of the treatment group was significantly higher than the control group on day 30 and day 40. There was no significant difference on day 20
(2) Day 30 Control group: mean () = 3.46, s.d. = 0.83 Treatment group: mean () = 4.60, s.d. = 0.91
Mann-Whitney test:
(3) Day 40 Control group: mean () = 5.46, s.d. = 0.83 Treatment group: mean () = 7.73, s.d. = 1.09
Mann-Whitney test:
The positive effect of antioxidant property of -tocopherol (measured based on Total Antioxidant Capacity level) on secondary bone healing (intramembranous ossification) in normal bone
Favourable effect seen during ischemic phase (day 30), but not inflammatory phase of healing (day 5) in rabbits The mechanism model was reported to be supported by the results in the study
(B) Ratio of osteoblastic activity (distracted/normal)
(1) Day 5 Control group: mean () = 0.97, s.d. = 0.18 Treatment group: mean () = 1.06, s.d. = 0.20
Mann-Whitney test:
The osteoblastic activity of the treatment group was significantly higher than the control group on day 20. There was no significant difference on day 5
(2) Day 20 Control group: mean () = 1.65, s.d. = 0.54 Treatment group: mean () = 3.63, s.d. = 1.06
Mann-Whitney test:
(C) Histological-based grade of bone formation [17]
The histological-based bone formation grade of the treatment group was significantly higher than the control group and showed mature bone formation
(1) Day 40 Control group: mean () = 8.00, s.d. = 0.92 Treatment group: mean () = 9.86, s.d. = 0.35
Mann-Whitney test:
(A) Callous volume
(1) Day 14 sham group (): mean = ±0.15, variability = ? (graph form only) Ovariectomized control group (): mean = ±0.17, variability = ? (graph form only) Ovariectomized treatment group (): mean = ±0.20, variability = ? (graph form only)
(however, it is not known whether ANOVA or Kruskal-Wallis tests was used)
There was no significant difference in the callous volume between the three groups
(B) Radiological-based score of callous staging [19]
The boosting-up effect of -tocopherol on antioxidant enzymes activities (measured based on Bone Superoxide Dismutase and Bone Glutathione Peroxidase levels) on secondary bone healing in osteoporotic bone
Favourable effect seen during early phase of healing (day 14) in rats The mechanism model was reported to be supported by the results in the study (only for bone superoxide dismutase)
(1) Day 14 Sham group (): Score 1 (), Score 2 (), Score 3 () Ovariectomized control group (): Score 2 (), Score 3 (), Score 4 () Ovariectomized treatment group (): Score 2 (), Score 3 (), Score 4 ()
Pearson chi-square test:
There was no significant difference of callous staging grades between the three groups
(C) Radiological-based score of fracture healing staging [20]
Ovariectomized control group has significantly more Score 2 and less Score 3 of the fracture healing grade than both sham-operated and ovariectomized treatment group The fracture healing score of the ovariectomized treatment group was similar with the sham-operated group
(1) Day 14 Sham-operated group (): Score 2 (), Score 3 () Ovariectomized control group (): Score 2 (), Score 3 () Ovariectomized treatment group (): Score 2 (), Score 3 ()
Pearson chi-square test: (difference between ovariectomized control group against sham-operated and ovariectomized treatment groups in terms of score)
(A) Radiological-based evaluation of callous formation staging (unspecified)
It was stated that callous formation stage is better in the treatment group compared to the control one
(1) Day 1, week 2, month 1, month 2, month 3, and month 4 Control group (): no descriptive value reported Treatment group (): no descriptive value reported
No statistical analysis was reported
The boosting-up effect of -tocopherol on antioxidant enzymes activities (measured based on Serum Catalase level) on primary bone healing in normal bone
Favourable effect of -tocopherol given for 30 days postosteotomy seen from week 1 to the end of the third month of the study (i.e., from early to the late phase of healing) in dogs The mechanism model was reported to be supported by the results in the study
(B) Radiological-based evaluation of bone remodelling staging (unspecified)
It was stated that bone remodeling stage is better in the treatment group compared to the control
(1) Day 1, week 2, month 1, month 2, month 3, and month 4 Control group (): no descriptive value reported Treatment group (): no descriptive value reported
No statistical analysis was reported
(A) Radiological-based grade of bone formation [16]
The radiological-based bone formation grade was significantly superior in the treatment group compared to the control group
(1) Day 60: Control group (): Grade 3 (), Grade 4 () Treatment group () = Grade 3 (), Grade 4 ()
Pearson chi-square test: (difference between control group and treatment group in terms of Grade 3 and Grade 4)
The positive effect of antioxidant property of -tocopherol (measured based on Erythrocyte Malondialdehyde level) on secondary bone healing in normal bone
Favourable effect seen during early phase (day 15) up to late phase (day 60) of healing in rats The mechanism model was reported to be supported by the results in the study
(B) Histological-based grade of fracture healing [22]
The histological-based bone formation grade was significantly superior in the treatment group compared to the control group
(1) Day 60: Control group (): Grade 2 (), Grade 3 (), Grade 4 () Treatment group () = Grade 3 (), Grade 4 ()
Pearson chi-square test: (difference between control group and treatment group in terms of Grade 3 and Grade 4)
(A) Histological-based grade of fracture healing [22]
The histological-based bone formation grade of the treatment group was significantly higher than the control group
No specific mechanism model was tested for the effect of -tocopherol on secondary bone healing in normal bone
Favourable effect of -tocopherol given for 5 days postfracture seen up to day 21 of study in rabbits (actual healing phase not stated)
(1) Day 21 (16 days after the last treatment): Control group (): Grade 2 (), Grade 3 () [mean = 2.4, s.d. = 0.5] Treatment group () = Grade 2 (), Grade 3 (), Grade 4 () [mean = 1.46, s.d. = 0.51]
Mann-Whitney test:
(A) Callous index
(1) Day 14 Control group (): mean = 1.64, variability = not reported Vit. E only treatment group (): mean = 1.49, variability = not reported Vit. C only treatment group (): mean = 2.17, variability = not reported Vit. E and C combination treatment group (): mean = 1.88, variability = not reported
Kruskal-Wallis test:
Post-hoc test using Mann-Whitney test: (a) for comparison between Vit. C only group and combination group
On day 14, the mean callous index for the vitamin C only group was significantly higher than the combination group, whereas the vitamin E only group was the lowest and was similar to the control group On day 21, the mean callous index for the vitamin C only group was significantly higher than all groups, whereas the vitamin E only group was higher (although not significant) than the combination and control groups
(2) Day 21 Control group (): mean = 1.90, variability = not reported Vit. E only treatment group (): mean = 2.37, variability = not reported Vit. C only treatment group (): mean = 2.54, variability = not reported Vit. E and C combination treatment group (): mean = 1.93, variability = not reported
Kruskal-Wallis test:
Posthoc test using Mann-Whitney test: (a) —Vit. C only group versus control group (b) —Vit. C only group vs. Vit. E only group (c) —Vit. C only group versus combination group
(B) Histological-based grade of fracture healing [22]
No specific mechanism model was tested for the effect of -tocopherol on secondary bone healing in normal bone
No favourable effect seen during the early phase (day 14) of healing in rats
(1) Day 14 Control group (): mean = 1.67, variability = not reported Vit. E only treatment group (): mean = 1.50, variability = not reported Vit. C only treatment group (): mean = 2.67, variability = not reported Vit. E and C combination treatment group (): mean = 2.16, variability = not reported
Kruskal-Wallis test:
Posthoc test using Mann-Whitney test: (a) —Vit. C only group versus control group. (b) —Vit. C only group versus Vit. E only group. (c) —Combination group versus control group. (d) —Combination group versus Vit. E only group
The mean grade for the vitamin C only group and combination group was significantly higher than the vitamin E only group and control group on day 14 and day 21. On day 14, the mean grade for the vitamin E only group was lower (although not significant) than the control group, whereas, on day 21, the mean grade for the vitamin E only group was higher (although not significant) than the control group
(2) Day 21 Control group (): mean = 2.00, variability = not reported Vit. E only treatment group (): mean = 2.33, variability = not reported Vit. C only treatment group (): mean = 3.17, variability = not reported Vit. E and C combination treatment group (): mean = 3.00, variability = not reported
Kruskal-Wallis test:
Posthoc test using Mann-Whitney test: (a) —Vit. C only group versus control group. (b) —Vit. C only group versus Vit. E only group (c) —Combination group versus control group (d) —Combination group versus Vit. E only group
