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

We studied the effect of vitamin C on fracture healing in the elderly. A total of 80 elderly Osteogenic Disorder Shionogi rats were divided into four groups with different rates of vitamin C intake. A closed bilateral fracture was made in the middle third of the femur of each rat. Five weeks after fracture the femora were analysed by mechanical and histological testing. The groups with the lower vitamin C intake demonstrated a lower mechanical resistance of the healing callus and a lower histological grade. The vitamin C levels in blood during healing correlated with the torque resistance of the callus formed (r = 0.525). Therefore, the supplementary vitamin C improved the mechanical resistance of the fracture callus in elderly rats. If these results are similar in humans, vitamin C supplementation should be recommended during fracture healing in the elderly

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

Ischaemia-reperfusion injury (IRI) is caused by endothelial and subendothelial damage by neutrophil-derived oxidants. Vitamin C is an antioxidant which attenuates endothelial injury after IRI. Our aim was to evaluate the effect of oral vitamin C in the prevention of IRI in skeletal muscle. We used a model of cross-clamping (3 hours) and reperfusion (1 hour) of the cremaster muscle in rats. Muscle function was assessed electrophysiologically by electrical field stimulation. Infiltration by neutrophils was determined by the activity of tissue myeloperoxidase (MPO) and tissue oedema by the wet-to-dry ratio. Neutrophil respiratory burst activity was measured in control animals and groups pretreated with vitamin C. IRI significantly decreased muscle function and increased muscle neutrophil MPO activity and muscle oedema. Pretreatment with vitamin C preserved muscle function and reduced tissue oedema and neutrophil infiltration. Neutrophil respiratory burst activity was reduced in the group treated with vitamin C compared with the control group. We conclude that pretreatment with oral vitamin C protects against acute muscle IRI, possibly by attenuating neutrophil respiratory burst activity

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

Compartment syndrome is a unique form of ischaemia of skeletal muscle which occurs despite patency of the large vessels. Decompression allows the influx of activated leucocytes which cause further injury. Vitamin C is a powerful antioxidant which concentrates preferentially in leucocytes and attenuates reperfusion-induced muscle injury. We have evaluated the use of pretreatment with oral vitamin C in the prevention of injury caused by compartment syndrome in a rat cremasteric muscle model. Acute and delayed effects of pretreatment with vitamin C were assessed at one and 24 hours after decompression of compartment syndrome. Muscle function was assessed electrophysiologically. Vascular, cellular and tissue inflammation was assessed by staining of intercellular adhesion molecule-1 (ICAM-1) and by determination of the activity of myeloperoxidase (MPO) in neutrophils and tissue oedema. Compartment syndrome impaired skeletal muscle function and increased the expression of ICAM-1, activity of MPO and muscle weight increased significantly. Pretreatment with vitamin C preserved muscle function and reduced the expression of ICAM-1, infiltration of the neutrophils and oedema

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

We explored the role of iron overload, deficiency of vitamin C and alcohol abuse in the aetiology of cervical and intertrochanteric fractures of the neck of the femur as a result of minor trauma. We studied prospectively 72 patients (45 men, 27 women). Levels of serum iron markers, vitamin C and alcohol markers were measured. Consumption of alcohol was estimated using questionnaires. The findings were compared with those of an age- and gender-matched control group. The mean age of the men was 59.5 years and of the women 66.9 years, with a male predominance. In the men, iron overload, as shown by high levels of serum ferritin (p < 0.001) and deficiency of vitamin C (p < 0.03), as well as abuse of both Western and the traditional type of alcohol, appear to be important aetiological factors. In women, alcohol abuse was also common, but iron markers and levels of vitamin C did not differ significantly from the control group

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

The December 2014 Trauma Roundup. 360 . looks at: infection and temporising external fixation; Vitamin C in distal radial fractures; DRAFFT: Cheap and cheerful Kirschner wires win out; femoral neck fractures not as stable as they might be; displaced sacral fractures give high morbidity and mortality; sanders and calcaneal fractures: a 20-year experience; bleeding and pelvic fractures; optimising timing for acetabular fractures; and tibial plateau fractures

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

Relating the results of our investigations to the knowledge hitherto acquired about the etiology of osteoporosis (which I have already referred to), I am inclined to interpret the pathogenesis of osteoporosis in the following way: 1) Primary osteoblastic deficiency: congenital (Lobstein); involutive (senile osteoporosis?); 2) Reduced osteoblastic activity from absence of trophic stimuli: (inactivity, ovarian agenesia, eunuchoidism, menopause); 3) Reduced osteoblastic activity from inhibitory stimuli: (cortisone, adrenocorticotrophic hormone (A.C.T.H.), stress, Cushing's disease, thyrotoxicosis); 4) Normal osteoblastic activity but insufficiency of constructive material: (malnutrition, disturbances of the digestive system, insufficiency of vitamin C, diabetes, thyrotoxicosis, cortisone, A.C.T.H., stress, Cushing's disease). Osteoporosis may therefore be the consequence either of a congenital osteoblastic deficiency, such as that found in cases of osteogenesis imperfecta, or of reduced osteoblastic activity due to absence of trophic stimuli such as mechanical stress and the sex hormones, or of reduced activity of the bone cells due to anti-anabolic substances which inhibit them, such as cortisone and its derivatives and the thyroid hormone in strong doses, or lastly of reduced availability of construction material due to its introduction in reduced quantities (starvation, dysfunction of the digestive system) or due to hindering of synthesis (deficiency of vitamin C, diabetes, cortisone and its derivatives) or due to an excessive degree of destruction (thyrotoxicosis). In the case of anti-anabolic hormones from the adrenal cortex, the mechanism may thus be twofold: inhibition of the osteoblasts and deprivation of the osteoblasts of glucoprotein material due to a general anomaly of metabolism. This may perhaps explain the most serious forms of bone atrophy which are usually observable in cases of hyperfunction of the adrenal cortex. Senile osteoporosis should, in my opinion, be included in the first of our groups because it cannot be said to be brought about by any of the causes usually cited for osteoporosis– such as deficiency of sex hormones, excess of hormones from the adrenal cortex, deficiency of calcium, etc.–and in all probability it will depend on a progressive involution of the osteoblasts brought about by old age. Senile involution is an expression of the descending phase of life's parabola and it involves all the organs and all the parenchymatous tissues in the human body, but it does not cause a parallel reduction of functions and activities on all of them equally. The skeletal system is one of the first to feel these reductions, because in old age life necessarily becomes less intense. Consequently in the economy of the ageing subject the generally reduced level of metabolism brings about a sort of selection in the nourishment of the different organs and systems, and sometimes almost a dismantling of some of these in an attempt to fall in with the new and reduced level of activities of some of the parenchymatous tissues, activities which may be incomplete or even transferred elsewhere. We believe that the moment which originally determines the beginning of senile osteoporosis coincides with the involutional process of cellular metabolism that strikes at all parenchymatous tissue during old age–striking, in the case of osteoporosis, hardest of all at the bony tissues. There is, indeed, no doubt that certain essential processes of cellular metabolism do alter with age, and that the reduction in the activity of the gonads does have considerable importance. In any case, just as adolescence and old age cannot be explained only in terms of gonadal activity, so the involution of the skeleton cannot be due merely to the involution of the gonads. How should one then interpret the well known benefit afforded by administration of sex hormones in cases of osteoporosis? Probably the action of oestrogens and androgens is, in this case, of a pharmacological nature, and comparable, for instance, to the action of digitalis on the cardiac muscle. It will be remembered how digitalis acts almost exclusively on myofibrils which have become inadequate, and has little or no effect on a normal myocardium. Similarly, the sex hormones would seem to exert a stimulating action on osteoblasts that are on the way to involution, while they exert little or no action on normal osteoblasts. In support of this we have the findings of Urist and other workers, who demonstrated that the administration of sex hormones produces calcium and nitrogen retention only in osteoporotics, while in non-osteoporotic subjects of the same age it produces no effect. On the other hand, the action of the sex hormones might act in cases of senile osteoporosis by returning the changed level of protein metabolism to normal. From the data in the literature and from the results of our own investigations, I conclude that osteoporosis in general, and senile osteoporosis in particular, are first and foremost the result of a disturbance in the metabolism of bone, and that the metabolic disturbance is closely and exclusively related to the degree of activity and the state of activity of the cells in the bone. Lastly, I believe that senile osteoporosis should not be considered an actual disease but rather as one limited aspect of the normal descending parabola which affects to a greater or less degree all the tissues of the body

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

Aims

Accumulated evidence indicates that local cell origins may ingrain differences in the phenotypic activity of human osteoblasts. We hypothesized that these differences may also exist in osteoblasts harvested from the same bone type at periarticular sites, including those adjacent to the fixation sites for total joint implant components.

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