OBJECTIVES: To determine the effectiveness of a 16-week community-based tai chi program in reducing falls and improving balance in people aged 60 and older. DESIGN: Randomized, controlled trial with waiting list control group. SETTING: Community in Sydney, Australia. PARTICIPANTS: Seven hundred two relatively healthy community-dwelling people aged 60 and older (mean age 69). INTERVENTION: Sixteen-week program of community-based tai chi classes of 1 hour duration per week. MEASUREMENTS: Falls during 16 and 24 weeks of follow-up were assessed using a calendar method. Balance was measured at baseline and 16-week follow-up using six balance tests. RESULTS: Falls were less frequent in the tai chi group than in the control group. Using Cox regression and time to first fall, the hazard ratio after 16 weeks was 0.72 (95% confidence interval (CI)=0.51-1.01, P=.06), and after 24 weeks it was 0.67 (95% CI=0.49-0.93, P=.02). There was no difference in the percentage of participants who had one or more falls. There were statistically significant differences in changes in balance favoring the tai chi group on five of six balance tests. CONCLUSION: Participation in once per week tai chi classes for 16 weeks can prevent falls in relatively healthy community-dwelling older people.

Aim of the study was to investigate the effect of magnetic fields on bone fracture healing and biochemical indices of bone turnover. Young male "White Newzealand Rabbits" were exposed after osteotomy of the femur of the hind-paw in narcosis for 31 days in a low-frequency magnetic field (field parameters: frequency 15.3 Hz, signal form: sine, magnetic field strength: 50 microT peak value). Eight animals each were assigned randomly for a single blind study to 3 groups. Controls were kept in a sham-exposition cage without magnetic field influence and were compared with a group in (Pseudo-) Helmholtz-coil arrangement with a horizontal magnetic field and a further group in a cylinder coil (vertical magnetic field). The daily duration of stay in the (sham-) exposition arrangements amounted to 30 minutes respectively. The activities of the alkaline phosphatase (AP) and creatinkinase (CK) were evaluated preoperatively, after the 19th and 31st experimental day, the callus density by means of computertomography after the 31st experimental day (two-tailed t-test). The densitometrically assessed callus densities of the magnetically treated groups were highly significant (p < 0.0001) compared with the controls. In spite of accelerated fracture healing the activities of the ALP were lower at both postoperative examinations than preoperatively, in the cylinder-coil the activity proved to be significantly lower (p < 0.05) compared with the controls after 31 days. Significant differences in CK were detected at no time. In conclusion, we confirm the positive magnetic field effects on fracture healing. The mechanisms of interaction of magnetic field and bone fracture healing remain to be clarified.

BACKGROUND AND AIMS: Loss of balance is a major risk factor for falls in the elderly, and physical exercise may improve balance in both elderly and middle-aged people. We propose a clinical trial to test the efficacy of an exercise program based on dance in improving balance in adult and young old subjects.

METHODS: We carried out a mono-institutional, randomized, controlled clinical trial. 40 subjects (aged 58 to 68 yr) were randomly allocated in two separate groups: the exercise group (n = 20) followed a 3-month exercise program; the control group (n = 20) did not engage in physical activities. Differences in balance between the end of the training period and the baseline were assessed using four different balance tests: Tinetti, Romberg, improved Romberg, Sit up and go.

RESULTS: Results showed a significant improvement in balance in the exercise group at the end of the exercise program, whereas the control group did not show any significant changes. The comparison between exercise and control group variations in balance test scores showed a highly significant difference. 17 out of 20 subjects in the exercise group reported great or moderate satisfaction with the dance activity.

CONCLUSIONS: Results suggest that physical activity based on dance may improve balance and hence be a useful tool in reducing the risk of falling in the elderly. The exercise program also revealed interesting psychosocial benefits.

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.

OBJECTIVE:To investigate the effect of whole-body vibration exercise (WBV) on fracture risk in adults≥50 years of age.

DESIGN:A systematic review and meta-analysis calculating relative risk ratios, fall rate ratio and absolute weighted mean difference using random effects models. Heterogeneity was estimated using I2 statistics, and the Cochrane Collaboration's risk of bias tool and the GRADE approach were used to evaluate quality of evidence and summarise conclusions.

DATA SOURCES:The databases PubMed, Embase and the Cochrane Central Register from inception to April 2016 and reference lists of retrieved publications.

ELIGIBILITY CRITERIA FOR SELECTING STUDIES:Randomised controlled trials examining the effect of WBV on fracture risk in adults≥50 years of age. The primary outcomes were fractures, fall rates and the proportion of participants who fell. Secondary outcomes were bone mineral density (BMD), bone microarchitecture, bone turnover markers and calcaneal broadband attenuation (BUA).

RESULTS:15 papers (14 trials) met the inclusion criteria. Only one study had fracture data reporting a non-significant fracture reduction (risk ratio (RR)=0.47, 95% CI 0.14 to 1.57, P=0.22) (moderate quality of evidence). Four studies (n=746) showed that WBV reduced the rate of falls with a rate ratio of 0.67 (95% CI 0.50 to 0.89, P=0.0006; I2=19%) (moderate quality of evidence). Furthermore, data from three studies (n=805) found a trend towards falls reduction (RR=0.76, 95% CI 0.48 to 1.20, P=0.24; I2=24%) (low quality of evidence). Finally, moderate to low quality of evidence showed no overall effect on BMD and only sparse data were available regarding microarchitecture parameters, bone turnover markers and BUA.

CONCLUSIONS:WBV reduces fall rate but seems to have no overall effect on BMD or microarchitecture. The impact of WBV on fractures requires further larger adequately powered studies. This meta-analysis suggests that WBV may prevent fractures by reducing falls.

PROSPERO REGISTRATION NUMBER:CRD42016036320; Pre-results.

OBJECTIVE: To observe the effect of acupuncture on fracture in the ovariectomized rat and the mechanism. METHODS: Sixty SD female rats were randomly divided into 4 groups: normal group (group A), model group (group B), acupuncture group (group C) and Nilestriol group (group D). In all the groups, except the group A which received sham operation, the rats were overiectomized for preparing the osteoporosis model. Three months after the ovariectomy, the left femurs of the rats were closely fractured. Then, the group A and B were treated with oral administration of normal saline solution, 3 mL, weekly. The rats in the group C were treated daily with acupuncture at "Huantiao"(GB 30), "Housanli" (ST 36), "Yanglingquan"(GB 34) and "Weizhong"(BL 40) on the left hind legs; the rats in the group D were given orally Nilestriol solution (0.2 mg/mL) in a dose of 0.6 mL/100 g body weight, weekly. At the 7th, 14th, 21st and 28th days, some rats were sacrificed and their fractural callus and blood samples were taken for histological examinations and immunohistochemical examination of brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB). RESULTS: HE stained callus slides observed by optical microscope showed that the process of fracture healing in the group A, C, D was faster than that in the group B. Positive immuno-stalning of BDNF and TrkB could be seen in the all groups, mainly on the 7 and 14 days after the fracture. The expression levels from high to low in turn were group A, C, D and B. CONCLUSION: Expressions of BDNF and TrkB in callus of osteoporotic fracture were less than that of the normal fracture; acupuncture can elevate the expression levels and accelerate the process of fracture healing.

OBJECTIVE: To observe the effect of acupuncture on fracture in the ovariectomized rat and the mechanism. METHODS: Sixty SD female rats were randomly divided into 4 groups: normal group (group A), model group (group B), acupuncture group (group C) and Nilestriol group (group D). In all the groups, except the group A which received sham operation, the rats were overiectomized for preparing the osteoporosis model. Three months after the ovariectomy, the left femurs of the rats were closely fractured. Then, the group A and B were treated with oral administration of normal saline solution, 3 mL, weekly. The rats in the group C were treated daily with acupuncture at "Huantiao"(GB 30), "Housanli" (ST 36), "Yanglingquan"(GB 34) and "Weizhong"(BL 40) on the left hind legs; the rats in the group D were given orally Nilestriol solution (0.2 mg/mL) in a dose of 0.6 mL/100 g body weight, weekly. At the 7th, 14th, 21st and 28th days, some rats were sacrificed and their fractural callus and blood samples were taken for histological examinations and immunohistochemical examination of brain-derived neurotrophic factor (BDNF) and tyrosine kinase B (TrkB). RESULTS: HE stained callus slides observed by optical microscope showed that the process of fracture healing in the group A, C, D was faster than that in the group B. Positive immuno-stalning of BDNF and TrkB could be seen in the all groups, mainly on the 7 and 14 days after the fracture. The expression levels from high to low in turn were group A, C, D and B. CONCLUSION: Expressions of BDNF and TrkB in callus of osteoporotic fracture were less than that of the normal fracture; acupuncture can elevate the expression levels and accelerate the process of fracture healing.

In view of the controversy of the clinical use of hyperbaric oxygen (HBO) treatment to stimulate fracture healing and bone regeneration, we have analyzed the effects of daily exposure to HBO on the proliferation and differentiation of human osteoblasts in vitro. HBO stimulated proliferation when osteoblasts were cultured in 10% fetal calf serum (FCS), whereas an inhibitory effect of HBO was observed when cultures were supplemented with 2% FCS. On the other hand, HBO enhanced biomineralization with an increase in bone nodule formation, calcium deposition, and alkaline phosphatase activity, whereas no cytotoxic effect was detected using a lactate dehydrogenase activity assay. The data suggest that the exposure of osteoblasts to HBO enhances differentiation toward the osteogenic phenotype, providing cellular evidence of the potential application of HBO in fracture healing and bone regeneration.

OBJECTIVE:To explore the effect and mechanism of hyperbaric oxygen (HBO₂) therapy of open tibial fractures in rabbits after transient seawater immersion.

METHODS:Forty-eight (48) New Zealand rabbits were randomly and averagely divided into an HBO₂ therapy group (Group A) and a control group (Group B). All rabbits were subjected to unilateral open tibial fractures, while immersed in artificial seawater (20-22 °C) for three hours prior to debridement and external fixation. Group A was treated with HBO₂ at 2 atmospheres absolute (ATA) for50 minutes once daily for two weeks; Group B received postoperative routine treatments only. The fracture zone in each group was compared by radiological, histological and immunohistochemical examinations.

RESULTS:In Group A, bony callus and mature osteocytes without infiltration of inflammatory cells were observed in the fracture zone. Vascular endothelial growth factor (VEGF) was expressed mainly in the cytoplasm of osteoblasts, chondrocytes and osteocytes, and exhibited significant changes at different time points. The gray value of bony callus in Group A was 190.58± 7.52; that of Group B was 144 ± 8.11. Difference between the groups was statistically significant (P ⟨ 0.01). The content of malondialdehyde (MDA) in Group A was significantly lower than Group B (P ⟨ 0.01), and the activity of superoxide dismutase (SOD) in Group A was higher than Group B (P⟨ 0.01) at four weeks. There were no significant differences in MDA content and SOD activity between groups at eight and 12 weeks.

CONCLUSIONS:HBO₂ treatment of open tibial fractures in seawater can reduce the inflammatory reaction and reperfusion injury, and promote osteocytic proliferation and fracture healing.

BACKGROUND:Complex regional pain syndrome type I (CRPS-I), previously known as reflex sympathetic dystrophy, is common after conservatively or surgicallytreatedwrist fractures. Several studies support the efficacy of vitamin C in preventing CRPS-I, although the data are somewhat conflicting. The primary objective of this systematic literature review and meta-analysis was to assess the efficacy of vitamin C therapy in preventing CRPS-I after a wrist fracture.

METHODS:Randomised, placebo-controlled trials of vitamin C to prevent CRPS-I after wrist fractureswere sought in the three main databases: PubMed (1980 to December 2015), CENTRAL (Central 2015, number 12), andEmbase (1980 to December 2015). Two authors worked independently to select articles. Data from selected articles were collected independently.

RESULTS:Three randomisedplacebo-controlled trials in a total of 875 patients were included.Treatment was non-operative in758/890(85.1%)fracturesand operative in 132(14.9%)fractures. Vitamin C supplementation was started on the day of the injury and continued for 50 days. In the group given 500mg of vitamin C daily, the risk ratio for CRPS-I was 0.54 (95%CI, 0.33-0.91;p=0.02).Thus, the risk of developing CRPS-I was significantly decreased by prophylactic treatment with 500mg of vitamin C per day. The heterogeneity rate was 65% (non-significant).

CONCLUSION:Daily supplementation with 500mg of vitamin C per day for 50 days decreases the 1-year risk of CRPS-I after wrist fracture.

LEVEL OF EVIDENCE:II, systematic review of level I and II studies.

AIM AND METHOD: The objective of this research was to study the effect of homeopathic treatment with Plumbum metallicum (Plumbum met.) on mandibular bone repair in rats. MATERIALS AND METHODS: We analyzed the mandibles of 60 male rats, approximately 3-month-old, randomly divided into three groups of 20 animals each: control, treated with calcitonin, and treated with a homeopathic medicine. A circumscribed bone defect measuring 4mm in diameter was made in the mandible and covered with a polytetrafluorethylene (PTFE) barrier. The group treated with calcitonin received 2IU/kg intramuscularly three times a week; the group treated with Plumbum met. 30c received three drops in water every day. The animals were sacrificed after 7, 14, 21 and 28 days. The mandibles were removed and submitted to histologic and histomorphometric analyses. RESULTS: Data were analyzed statistically by two-way ANOVA and by the Tukey test. The interaction effect (ANOVA, F df(6; 48)=4.64; p=0.001<0.05) indicated that the relationship between treatments was not the same at each time of sacrifice. Although statistical analysis of the histomorphometric data showed a similar results for the treated and control groups. But histological analysis showed complete filling of the surgical defect throughout its extent was only for the group treated with Plumbum met. CONCLUSION: The study demonstrated that for repair of surgical defects in rat mandibles Plumbum met. 30c and control did not differ significantly in histomorphometric terms.

Objective:Healing of bone fractures is a prolonged process that can be affected by nutrition. Our objective was to critically evaluate the effect of supplementation with an essential nutrient complex, containing ascorbic acid, lysine, proline, and vitamin B6 on healing time of tibial fractures.

Design:Random double-blind placebo-controlled study

Setting: Dr. Jamdar Hospital, Jabalpur, India

Subjects and Intervention:113 patients with unilateral displaced closed or grade I open tibial fractures were randomized to receive either standard care with placebo or with supplementation with an essential nutrient complex containing ascorbic acid, lysine, proline, and vitamin B6. Qualifying patients, on admission to the study, were clinically examined, radiographs of the affected limbs taken, fractures reduced under anesthesia, and above knee plaster casts applied. Radiographs were taken at each follow-up visit to confirm reduced alignment of fracture and proper callus formation.
Primary Outcome Measure: The primary outcome measure was the number of weeks required for fracture to be healed. Healing was defined as absence of abnormal mobility at fracture site clinically, absence of pain elicited by stressing the fracture or by walking, and radiographic confirmation of callus formation.

Results:Data analysis demonstrated reduced fracture-healing time associated with experimental supplementation. For PP analysis group, fracture healing time in 75% of the supplemented group of patients (N=21) was 17 weeks or less and 19 weeks or less in 75% of the placebo group patients (N=36). The percentage of patients with fractures healing in 10 weeks or less was 33.3% for the supplemented group and 11.1% for the placebo group. However, the difference in healing time between the two groups did not reach statistical significance.

Conclusion:

Results showed encouraging trends that fracture-healing time is reduced by supplementation with an essential nutrient complex containing ascorbic acid, lysine, proline, and vitamin B6. In addition, the nutrient supplemented participants reported improved feeling of well-being with use of the supplement.

BACKGROUND: The authors' objective was to evaluate the efficacy of a 6-month Tai Chi intervention for decreasing the number of falls and the risk for falling in older persons. METHODS: This randomized controlled trial involved a sample of 256 physically inactive, community-dwelling adults aged 70 to 92 (mean age, 77.48 years; standard deviation, 4.95 years) who were recruited through a patient database in Portland, Oregon. Participants were randomized to participate in a three-times-per-week Tai Chi group or to a stretching control group for 6 months. The primary outcome measure was the number of falls; the secondary outcome measures included functional balance (Berg Balance Scale, Dynamic Gait Index, Functional Reach, and single-leg standing), physical performance (50-foot speed walk, Up&Go), and fear of falling, assessed at baseline, 3 months, 6 months (intervention termination), and at a 6-month postintervention follow-up. RESULTS: At the end of the 6-month intervention, significantly fewer falls (n=38 vs 73; p=.007), lower proportions of fallers (28% vs 46%; p=.01), and fewer injurious falls (7% vs 18%; p=.03) were observed in the Tai Chi group compared with the stretching control group. After adjusting for baseline covariates, the risk for multiple falls in the Tai Chi group was 55% lower than that of the stretching control group (risk ratio,.45; 95% confidence interval, 0.30 to 0.70). Compared with the stretching control participants, the Tai Chi participants showed significant improvements (p<.001) in all measures of functional balance, physical performance, and reduced fear of falling. Intervention gains in these measures were maintained at a 6-month postintervention follow-up in the Tai Chi group. CONCLUSIONS: A three-times-per-week, 6-month Tai Chi program is effective in decreasing the number of falls, the risk for falling, and the fear of falling, and it improves functional balance and physical performance in physically inactive persons aged 70 years or older.

OBJECTIVE:The evidence of tai chi for balance improvement and fall reduction in older adults was updated and reviewed.

METHOD:A systematic review was carried out by two independent reviewers among nine electronic databases to identify randomized controlled trials (RCTs) that examined the effects of tai chi on balance improvement and fall reduction in older adults using such key words as tai chi, falls, balance, and randomized trial.

RESULTS:The results based on 13 RCTs indicated that tai chi was effective in improving balance of older adults but may not necessarily be superior to other interventions. Results also showed that in the absence of other interventions, tai chi reduced falls in the nonfrail elderly.

CONCLUSION:Tai chi is recommended as an alternative treatment for improving balance so as to reduce falls. Future research with improved research designs such as more consistent outcome measures on balance and fall reduction and longer postintervention follow-up should be conducted to unravel the efficacy of different types of tai chi.

The benefits of various minerals and vitamins on fracture healing have been demonstrated in animal models. Vitamin C is an essential substance in fracture healing but has not been studied previously on an experimental basis. Sixteen rats were grouped randomly into control and vitamin C-supplemented groups. The right tibias of all rats were fractured by digital manipulation. One group received single high dose of vitamin C intramuscularly. On the 5th, 10th, 15th, and 20th days, two rats from each group were killed and the tibias examined under light microscopy. It was seen that the vitamin C-supplemented group went through the stages of fracture healing faster compared with the control group.

OBJECTIVES:The objective was to study the effect of the add-on yogic prana energization technique (YPET) on healing of fresh fractures.

MATERIALS AND METHODS:Thirty (30) patients (22 men and 8 women) between 18 and 55 years with simple extra-articular fractures of long and short bones were selected from the outpatient department of Ebnezar Orthopaedic Centre and Parimala Speciality Hospital, Bengaluru. They were randomized into yoga (n = 15) and control (n = 15) groups. Compound, complicated, pathologic fractures, old fractures, and those associated with dislocations were excluded. Both groups received the conventional plaster of paris immobilization of the fracture site as the primary treatment. The yoga group, in addition, practiced YPET twice a day (30 minutes/session) for 2 weeks using taped audio instructions after learning under supervision for 1 week. YPET is an advanced yoga relaxation practice that involves breath regulation, chanting, and visualization, which according to yogic science revitalizes the tissues by activating the subtle energies (prana) within the body. Both the groups were assessed on the 1st and 21st day by the Numerical Pain Rating Scale for pain (NRS), tenderness (0-4), swelling (0-4), fracture line density (1-4), and the bridging of cortices (1-4).

RESULTS:Two (2) groups were matched on all variables. The Wilcoxon test showed significant improvement in both groups on all variables. Pain reduction (NRS) was better (p = 0.001 Mann-Whitney test) in the YPET group (94.5%) than in the control group (58.6%); Tenderness reduced (p = 0.001) better in the YPET group (94.4 %) than in the control group (69.12%); Swelling reduced by 93% in the YPET group and by 69.4% in controls (between-groups p = 0.093, i.e., nonsignificant); increase in fracture line density was better (p = 0.001) in the YPET group (48%) than in the control group (18.25%). The number of cortices united was significantly better (p = 0.001) in the YPET group (81.4%) than in controls (39.7 %).

CONCLUSIONS:Add-on yoga-based YPET accelerates fracture healing.

AIM: To investigate the effects of free oxygen radicals and various antioxidants on bone healing after experimental formation of fracture. MATERIALS AND METHODS: Fifty male rats were used and divided into five groups (ten rats in each). The right forelimbs of the rats were broken by bimanual compression method. One hour before this procedure, 5 ml/kg of intraperitoneal (i.p.) physiologic saline were given to the control Group 1. All 40 rats in the experimental Groups 2, 3, 4 and 5 were treated with i.p. zymosan at a dosage of 100 mg/kg to induce the production of free radicals by stimulating NADPH oxidase in polymorphonuclear leukocytes. Zymosan induction was stopped on the fifth post-fracture day. In addition to the zymosan, i.p. 1 g/kg/day of dimethyl sulfoxide were given to the animals in Group 3, 50 mg/kg/d of Ginko biloba Extract (EGb 761) in Group 4 and 500 mg/kg/day of vitamin C in Group 5. Radiographs of the fractures of all animals were obtained to assess callus formation, remodeling and bridging bone formation under ether anesthetics on postfracture day 7, 14 and 21. All rats were euthanized on day 22, and sections of the radius and ulna were examined both histologically with light and electron microscopy and ultrastructurally. Statistical analysis was made with Kruskal-Wallis variance analyze test and comparison between groups was performed by Dunn's multiple comparison test. RESULTS: An impairment of bone healing was observed in Group 2 inducted with purely zymosan. Variable results were obtained for bone healing in the groups treated with various antioxidants. There was very significant difference of fracture healing between Groups 1 and 2 both histologically and radiologically (P < 0.001). There was significant difference between Groups 2 and 5 radiologically (P < 0.05). CONCLUSION: Free oxygen radicals demonstrate a negative effect on fracture healing and vitamin C (an antioxidant) partially prevents the negative effect of zymosan on fracture healing.

BACKGROUND: Phytoestrogens are plant-derived natural molecules having some bone forming and bone substituting effects. In the present study, the role of phytoestrogens on bone healing was investigated in a rabbit fracture model. METHODS: Twenty-two New Zealand white rabbits with right tibia fracture were divided into two groups randomly. The plant derived extract of Vitex agnus-castus L. (Verbenaceae) prepared before the study was administered intramuscularly in group 1 and group 2 was chosen as control. Fracture healing was monitored in weekly basis with blood alkaline phosphatase level, radiographs of extremities and 99m-Tc MDP bone scintigraphy. The study was finished at the end of the 3rd week. The extremities including tibial fractures were collected for histological examination. RESULTS: Radiographic evidence of fracture healing obtained on postoperative day seven was superior in group 1 than control group (p<0.01). The 99m-Tc MDP bone scintigraphy uptake ratios on postoperative seventh day showed higher uptake in group 1 than in group 2 (p<0.05). The differences of scintigraphic uptakes in fractured tibias calculated on postoperative seventh day and postoperative 14th in group 1 were higher than group 2 (p=0.04). The histopathologic evaluation performed after sacrification of all rabbits on postoperative 25th day showed no significant difference between both groups. No statistical difference was determined related to the other variables. CONCLUSION: Flavonoids affected positively the early periods of fracture healing mechanism in New Zealand white rabbits. We suggest further studies with phytoestrogens to determine the effects of various dosages and administration ways.

Vitamin C is an important antioxidant and cofactor which is involved in the regulation of development, function and maintenance of several cell types in the body. Deficiencies in vitamin C can lead to conditions such as scurvy, which, among other ailments, causes gingivia, bone pain and impaired wound healing. This review examines the functional importance of vitamin C as it relates to the development and maintenance of bone tissues. Analysis of several epidemiological studies and genetic mouse models regarding the effect of vitamin C shows a positive effect on bone health. Overall, vitamin C exerts a positive effect on trabecular bone formation by influencing expression of bone matrix genes in osteoblasts. Recent studies on the molecular pathway for vitamin C actions that include direct effects of vitamin C on transcriptional regulation of target genes by influencing the activity of transcription factors and by epigenetic modification of key genes involved in skeletal development and maintenance are discussed. With an understanding of mechanisms involved in the uptake and metabolism of vitamin C and knowledge of precise molecular pathways for vitamin C actions in bone cells, it is possible that novel therapeutic strategies can be developed or existing therapies can be modified for the treatment of osteoporotic fractures. This article is protected by copyright. All rights reserved.