The aim of the study is to determine the histological, biochemical, and biomechanical efficacy of fibrin clot and vitamin C in the healing of Achilles tendon ruptures (ATR) in a rat model.52 adult Wistar Albino rats (300–450 g) were used in the study. 12 groups were divided into four groups as Monitor (Group I), Control (Group II), Fibrin Clot (Group III), Fibrin Clot with vitamin C (Group IV). Four rats were used to obtain fibrin clots. Fibroblast Growth Factor (FGF) and Vascular Endothelial Growth Factor (VEGF) were measured in the blood of tail vein (1 cc) on the 3rd, 7th, 14th, and 21st day. Four rats were sacrificed on the 21st day from each group for histological evaluation. The rest of the rats were sacrificed at 42nd day, half for biomechanical and a half for histological evaluation. The 42nd-day HSS scores in group III and group IV were significantly lower than those of group I and group II (p =0.036 and 0.019; respectively). The 42nd-day HSS score of group IV was significantly lower than group III (p =0.036). The Maximum force N value of group III and group IV was significantly higher than those of group I and group II (p <0.05). Group IV showed a significantly higher Maximum force N value than group III (p =0.025). The blood FGF and VEGF levels of group III and group IV on the 3rd, 7th, 14th, and 21st days were higher than those of group I and group II (p <0.05). In the experimentally formed ATR model, fibrin clot and vitamin C produced a stronger tendon structure in terms of biomechanics while providing histological and biochemically better quality tendon healing in the surgical treatment of ATR. We believe that this model can be used to accelerate high-quality tendon healing after ATR

Complex regional pain syndrome type 1 (CRPS-I) is a devastating complication that can occur after limb extremity injuries. The effectiveness of vitamin C in preventing CRPS-I incidence is debatable. Therefore, we conducted a systematic review and meta-analysis to assess the role of vitamin C in CRPS-I prevention and its effect on pain score, functional outcomes and complications rate after wrist, ankle, and foot fractures. We searched Medline, Embase, the Cochrane Library, . Clinicaltrial.gov. , and Google Scholar from infinity to May 2021 for relevant studies comparing the incidence of CRPS-I with administration of perioperative vitamin C versus placebo after wrist, ankle, and foot fractures. Continuous data such as functional outcomes and pain scores were pooled as mean differences (MD), whist dichotomous variables such as the incidence of CRPS-I and complications were pooled as odds ratios (OR), with 95% confidence interval (CI). Data analyses was done using R software (meta package, version 4.9-0) for Windows. Eight studies, including two quasi-experimental studies, were included. The timeframe for vitamin C administration ranged from 42 to 50 days post-injury and/or surgical fixation and the dosage was either 500 mg or 1000 mg. The results showed that vitamin C was associated with a lower rate of CRPS-I relative to a placebo (OR 0.33, 95% CI [0.17, 0.63]). No significant difference was found between vitamin C and placebo in terms of complications (OR 1.90, 95% CI [0.99, 3.65]), functional outcomes (MD 6.37, 95% CI [-1.40, 14.15]), and pain scores (MD -0.14, 95% CI [-1.07, 0.79]). The findings demonstrate that when compared to placebo, at least 42 days of vitamin C prophylaxis is associated with prevention of CRPS-I following wrist, ankle, and foot fractures, irrespective of vitamin C dosage or fracture type. No significant differences were found with secondary outcomes

Introduction and purpose: Vitamin C is essential to the synthesis of the bone’s organic matrix and a subclinical vitamin shortage has been observed in the elderly population of developed countries. The purpose of this paper is to determine whether the intake of vitamin C supplements by the elderly after sustaining a fracture improves healing. Materials and methods: 40 1-year-old ODS rats were subjected to a usual dose of 1 gr/l of vitamin c in water for 2 weeks. Another 40 were placed on a 0.5 gr/l diet (subclinical deficit). A closed femur fracture was provoked. After the fracture, the rats were divided into two groups: the first was kept on the same diet and for the other the diet was supplemented by multiplying the vitamin C dose by two. After 5 weeks, a mechanical (torque) test was performed on the femur, and the vitamin C serum level was determined. Results: Mechanical resistance to callus was significantly higher in the supplemented groups vis-à-vis the non-supplemented ones (p≤0.05). It was also higher in the groups with no previous deficit vis-à-vis those which had a previous deficit (p≤0.05). There was a linear correlation (p≤0.05, R=0.52) between the vitamin C levels at the time of being put down and the mechanical resistance to callus. Conclusions and clinical relevance: In old rats, consolidation depends on the amount of vitamin C ingested during fracture consolidation. If these results were similar in elderly humans, the addition of vitamin C supplements to the diet should be indicated during consolidation

Following ischaemia-reperfusion (I-R) tissues undergo a neutrophil mediated oxidant injury. Vitamin C is a water-soluble endogenous anti-oxidant, which has been shown in previous studies to abrogate neutrophil mediated endothelial injury. Our aim was to evaluate Vitamin C supplementation in the prevention of I-R induced acute muscle injury. Sprague-Dawley rats (n-6/group) were randomised into control, I-R and I-R pretreated with Vitamin C (3.3g over 5 days). Cremasteric muscle was isolated on its neuro-vascular pedicle and I-R injury induced by clamping the pedicle for 3 hours, the tissue was subsequently reperfused for 60 minutes. Following reperfusion muscle function was assessed by electrical field stimulation: peak twitch (PTV), maximum tetanus (MTV) and fatigability values were recorded. Tissue neutrophil infiltration was assessed by tissue myeloperoxidase (MPO) activity and tissue oedema by wet:dry ratio (WDR). Ischaemia-reperfusion (I-R) resulted in a significant decrease in muscle function (PTV< MTV) there was no difference in fatigability values between groups. I-R also resulted in a significant increase in neutrophil infiltration (MPO) and tissue oedema (WDR). Pre-treatment with Vitamin C attenuated I-R injury as assessed by these parameters. This data suggests that oral Vitamin C reduce I-R induced acute muscle injury, possibly by attenuating neutrophil mediated tissue injury

Purpose of the study: The pathophysiology of reflex dystrophy or type I complex regional pain syndrome remains poorly understood, but the cost is considerable in terms of public health expenditures both for programmed and emergency orthopedic surgery. We present a historical cohort assessed to evaluate the usefulness of vitamin C for the prevention of reflex dystrophy in programmed foot and ankle surgery. Material and methods: The study included two groups of patients treated in two successive periods: July 2002 to June 2003 and July 2003 to June 2004. All patients underwent foot and ankle surgery performed by the same senior surgeon. Diabetic feet were excluded. The first group (185 feet, 177 patients) was not given any particular preventive treatment. The second group (235 feet, 215 patients) was given one gram vitamin C for 45 days. The diagnosis of reflex dystrophy was retained on the basis of clinical and radiological arguments noted at follow-up visits with the operator. Several factors were studied: gender, age, type of disease condition, history of reflex dystrophy, psychological context, duration of tourniquet, cast immobilization. Results: Reflex dystrophy occurred in 18 feet in group. 1 (9.6%) and in 4 (1.7%) in group 2. The difference was significant. Presence of a history of dystrophy was significantly associated with development of dystrophy (RR=10.4). A psychological context appeared to increase the risk of dystrophy (RR 2.6) but did not reach significance. There was no statistical relationship with age, gender, duration of tourniquet, type of disease condition, or surgical procedure performed. Discussion: Vitamin C has been found to be effective in the prevention of reflex dystrophy after wrist fractures. Data in the literature is scarce on dystrophy of the foot and ankle. Our study provided objective evidence of the usefulness of vitamin C for the prevention of reflex dystrophy in foot and ankle surgery patients, a complication frequently observed in our control group (9.6%). The psychological context and history of dystrophy increase the risk of dystrophy. Conclusion: Vitamin C is associated with a lower risk of reflex dystrophy in the postoperative period after foot and ankle surgery. We advocate preventive treatment with vitamin C

Rotator cuff repair is performed to treat shoulder pain and disability. Failure of the tendon repair site is common; one strategy to improve healing is to enforce a period of post-operative immobilisation. Immobilisation may have unintended effects on tendon healing. Tenocytes under uniaxial strain form more organised collagen and up regulate expression of proliferative genes. Vitamin C (ascorbic acid), an anti-oxidant that is a co-factor for collagen synthesis, has also been reported to enhance collagen deposition and organisation. The purpose of this study was to compare human tenocyte cultures exposed to uniaxial cyclical strain with or without slow-release ascorbic acid (ascorbyl-2 phosphate) to determine their individual and combined effects on tissue remodelling and expression of tissue repair genes. Rotator cuff tissues were collected from degenerative supraspinatus tears from eight patients. Tenocytes were incorporated into 3D type I collagen culture matrices. Cultures were divided into four groups: 1) ascorbic acid (0.6mMol/L) + strain (1%–20% uniaxial cyclic strain at 0.1 Hz), 2) ascorbic acid unstrained, 3) strain + vehicle 4) unstrained + vehicle. Samples were fixed in paraffin, stained with picrosirius red and analysed with circular polarising light. A second set of cultures were divided into three groups: 1) 0.5mM ascorbic acid, 2) 1mM ascorbic acid, 3) vehicle cultured for 24, 72, 120 and 168 hours. Cell-free collagen matrix was used as a control. Tenocyte proliferation was assessed using the water soluble tetrazolium-1 (WST1) assay and f tissue repair gene expression (TGFB1, COL1A1, FN1, COLIII, IGF2, MMP1, and MMP13), were analysed by qPCR. The data were analysed using a Split model ANOVA with contrast and bonferroni correction and a one-way ANOVAs and Tukey's test (p<0.05 was significant). Our results indicated that unstrained cultures with or without exposure to slow release ascorbic acid exhibited greater picrosirius red birifringency and an increase in collagen fiber deposition in a longitudinal orientation compared to strained tenocytes. We found that slow release ascorbic acid promoted significant dose and culture-time dependent increases in tenocyte proliferation (p<0.05) but no obvious enhancement in collagen deposition was evident over cultures without ascorbic acid supplementation. Based on these data, applying strain to tenocytes may result in less organised formation of collagen fibers, suggestive of fibrotic tissue, rather than tendon remodelling. This may indicate that a short period of immobilisation post-rotator cuff repair is beneficial for the healing of tendons. Exposure to slow release ascorbic acid enhanced tenocyte proliferation, suggesting that supplementation with Vitamin C may improve tendon repair post-injury or repair. Future studies will assess levels of tissue repair-associated proteins as well as comparing traumatic and degenerative rotator cuff tears to healthy uninjured rotator cuff tissue

Osteoarthritis of the trapeziometacarpal joint can be treated by different surgical procedures. These are known to lead to complications, complex regional pain syndrome (CRPS) type I being one of them. We investigated prospectively our clinical results after total joint arthroplasty under vitamin C prophylaxis. Patients with trapeziometacarpal joint arthritis stage II or III (according to Dell) underwent joint arthroplasty. Visual analogue scale (VAS) scores for pain, activities of daily living (ADL), satisfaction and first web opening were taken pre- and postoperatively. Vitamin C 500 mg daily was started two days prior to surgery during 50 days as prophylaxis for CRPS. Postoperative treatment consisted of a bandage with collar and cuff for 5 days. Follow-up was at 2 and 6 weeks, 6 months and 12 months (with check radiographs). We performed 34 arthroplasties in 29 patients (23 females and 6 males) with a mean follow-up of 39 months. Mean age was 61 years. The degree of osteoarthritis according to Dell was stage II in 13 cases, stage III 20 times and in one case there was a traumatic trapeziometacarpal dislocation. Operation was performed in day care under general or regional anesthesia. We implanted a hydroxy-apatite coated, semi-constrained prosthesis, type Roseland (total trapeziometacarpal joint prosthesis; Depuy International Ltd, Leeds, England). First web opening increased with 18 degrees and there was a significant improvement for pain, ADL and satisfaction as well (p = 0.000). There were no signs of loosening of the prosthesis, no infections and no cases of CRPS. In this study the postoperative treatment was completely functional. The semi-constrained design of the Roseland prosthesis doesn’t require immobilisation. Torrededia reported 5 patients with CRPS after 38 operations with this same implant (13%). The positive trend in preventing CRPS gives us enough arguments to further investigate this in the form of a RCT

Aim: There were no reports of epiphyseal separation in cerebral palsy/spastic conditions, though cases of displaced metaphyseal & diaphyseal fractures have been reported. Materials and Methods: There were 9 cases of epiphyseal separation involving the distal femur and proximal humerus in 4 severely handicapped children with spastic cerebral palsy. In these 9 cases there was significant epiphyseal slip with periosteal stripping with extensive subperiosteal ossification obvious on the X-rays. The X-rays also showed the following radiological signs: Frankel’s line and a scurvy line. Clinically the area was swollen and painful. Results: The X-ray appearances confirmed the cause to be that of scurvy. Treatment was with Vitamin C, Vitamin D, nutritional support and splintage which resulted in rapid healing with excellent re-modelling. Lack of Vitamin C results in suppression of osteoblasts and interferes with collagen synthesis. Conclusion: Scurvy should be considered as a potential cause of an epiphyseal slip in a child suffering from severe cerebral palsy. Routine Vitamin C dietary supplementation in this group of potentially mal-nourished, non-ambulant children should be considered. The cause of the slip is thought to be lack of Vitamin C in combination with weakness of the bone, spastic muscle acting on long, fragile bones and in some cases, anti-convulsant treatment

Introduction and Aim: While displaced metaphyseal and diaphyseal fractures in children with severe spastic cerebral palsy have been reported in literature, there is no reference to epiphyseal separations in this group. Physeo-epiphyseal injuries have been reported in meningomyelocoele patients, but these injuries differ significantly in their etiology and natural history. Method and Results: We report nine epiphyseal separations involving the distal femur and proximal humerus in four severely handicapped children with spastic cerebral palsy, and find scurvy to be the major cause of such epiphyseal slips. These epiphyseal slips have a good prognosis unlike those reported in MMC children. Treatment with vitamin C and splintage, without any attempt at reduction, resulted in rapid healing with excellent remodelling. Scurvy should be considered a potential cause for an epiphyseal slip in a child suffering from severe cerebral palsy. Conclusion: We recommend routine vitamin C dietary supplementation in this group of malnourished, non-ambulant children

Introduction. Recently, oxidative stress has been implicated in the development of osteonecrosis. Here we focused on vitamins with marked antioxidant potency to see whether their use might prevent the development of osteonecrosis associated with corticosteroid administration. Methods. Fifteen male Japanese white rabbits weighing about 3.5 kg were injected once into the right gluteal muscle with methylprednisolone (MPSL) 40 mg/kg (S Group). Ten other rabbits, in addition, received consecutive daily intravenous injections of vitamin E 50 mg/kg starting from the day of MPSL administration (E Group), and 10 other animals similarly received consecutive daily intravenous injections of vitamin C 30 mg/kg (C Group). All animals were euthanized 2 weeks after MPSL administration, and femurs were extracted, and stained with hematoxylin-eosin. Blood levels of glutathione (GSH) were also measured. Results. In S Group, the osteonecrosis development rate was 93%, in contrast to 60% in C Group, and none in E Group (P<0.05). Also, GSH levels in both S and C Groups abruptly decreased from the 1st day after MPSL administration, whereas, in E Group, the decline in GSH levels was significantly suppressed on days 1 and 3 after MPSL administration (P<0.05). Conclusion. Vitamin E significantly inhibited the decrease in blood GSH levels noted in the groups not receiving it. Since GSH reflects oxidative stress in vivo, vitamin E administration may be preventative in the setting of this kind of corticosteroid-induced osteonecrosis rabbit model

Introduction: Oxidative stress occurs when reactive oxygen species (ROS) are produced faster than they can be removed by cellular defence mechanisms contributing to ageing, many chronic diseases, such as atherosclerosis, RA, Parkinson and Alzheimer’s disease and skeletal pathologies. Here we address the impact of ROS on the viability of early osteogenic precursors in the bone marrow and study the influence of estrogen on this interaction. Cells have a number of mechanisms to protect themselves from ROS, which are constantly being formed in the cell through normal metabolic pathways, such as Vitamin E, C and estrogen. Estrogen has been shown to prevent intracellular accumulation of peroxide and to attenuate oxidant-induced death of neuronal and endothelial cells. In addition, it contributes significantly to bone turnover and relieves postmenopausal symptoms. This study has focused on the potential anti-oxidant properties of estrogen against oxidative on bone marrow stromal cells. stress induced by H. 2. O. 2. Methods: Primary bone marrow stromal cells were pre-treated with several different doses between 10. −6. M – 10. −8. M of estrogen prior to H. 2. O. 2. administration at 0.08–0.4 mM 30% (v/v) for 2–24h. The cellular production of ROS was determined by using the free radical indicator DCFH-DA. Apoptosis was determined by morphological criteria. Results: H. 2. O. 2. induced an increase in apoptosis of osteoprogenitor cells (p< 0.05). Determination of apoptosis and cell number by nuclear staining, indicated that pre-treatment of bone marrow stromal cells with 17-beta estradiol reduced the apoptotic response induced by H. 2. O. 2. (p< 0.05) and restored cell number to control levels. In order to test the anti-oxidant activity of estrogen, the dye DCFH-DA was introduced in a cell free system in the presence or absence of 17-beta estradiol and H. 2. O. 2. The same experiment was repeated in the presence of bone marrow stromal cells. H. 2. O. 2. increased both intracellularly and extracellularly oxidant activity and estradiol has the capacity of modifying this activity both inside and outside the cell. Discussion: These data demonstrate the ability of estrogen, used at physiological doses, to block oxidant-induced apoptosis of osteoprogenitor cells. Estrogen appears to reduce the generation of ROS in these cells. These data could have important implications on the maintenance of osteogenic stem cells during fractures, ageing and disease