Enhancement of fracture healing after citrulline supplementation in mice.

Around 10 % of long bone fractures show inadequate bone healing resulting in non-union development. A deregulated arginine-citrulline-nitric oxide metabolism caused by a poor nutritional status of the patients is a risk factor for non-unions. Additionally, previous research in mice with a disrupted arginine to citrulline conversion showed delayed healing. The study hypothesis was that stimulating said metabolism could positively influence the healing process through promotion of collagen synthesis and angiogenesis. Adult wild-type mice underwent a femur osteotomy and plate-screw osteosynthesis. Mice were randomly divided into three groups and received daily oral supplementation of arginine, citrulline or 0.9 % saline (control). Body weight and food intake were measured daily. After 14 d, the mice were euthanised and femora collected. Callus formation was assessed by micro-computed tomography and concentrations of amino acids and enzymes in the femora were measured. Only citrulline-treated mice showed significantly increased bridging of the fracture gap when compared to control mice. Femur citrulline and ornithine concentrations were increased in citrulline-treated animals. qPCR showed significantly decreased expression of inflammatory markers, whereas increased expression of angiogenic and collagen-producing factors was observed in citrulline-treated mice. Although food intake did not show any difference between the three groups, animals treated with citrulline showed a weight gain of 0.3 g, compared with a 0.1 g decline in the control group. Daily oral citrulline supplementation stimulated callus formation and improved the inflammatory response, positively contributing to the enhanced healing response. Finally, the increased weight gain pointed toward a better post-operative recovery.

CT scan-evaluated outcome of pulsed electromagnetic fields in the treatment of acute scaphoid fractures: a randomised, multicentre, double-blind, placebo-controlled trial.

We hypothesised that the use of pulsed electromagnetic field (PEMF) bone growth stimulation in acute scaphoid fractures would significantly shorten the time to union and reduce the number of nonunions in a randomised, double-blind, placebo-controlled multicentre trial. A total of 102 patients (78 male, 24 female; mean age 35 years (18 to 77)) from five different medical centres with a unilateral undisplaced acute scaphoid fracture were randomly allocated to PEMF (n = 51) or placebo (n = 51) and assessed with regard to functional and radiological outcomes (multiplanar reconstructed CT scans) at 6, 9, 12, 24 and 52 weeks. The overall time to clinical and radiological healing did not differ significantly between the active PEMF group and the placebo group. We concluded that the addition of PEMF bone growth stimulation to the conservative treatment of acute scaphoid fractures does not accelerate bone healing.

The effects of low-intensity pulsed ultrasound and pulsed electromagnetic fields bone growth stimulation in acute fractures: a systematic review and meta-analysis of randomized controlled trials.

INTRODUCTION: The aim of this systematic review and meta-analysis was to evaluate the best currently available evidence from randomized controlled trials comparing pulsed electromagnetic fields (PEMF) or low-intensity pulsed ultrasound (LIPUS) bone growth stimulation with placebo for acute fractures. MATERIALS AND METHODS: We performed a systematic literature search of the medical literature from 1980 to 2013 for randomized clinical trials concerning acute fractures in adults treated with PEMF or LIPUS. Two reviewers independently determined the strength of the included studies by assessing the risk of bias according to the criteria in the Cochrane Handbook for Systematic Reviews of Interventions. RESULTS: Seven hundred and thirty-seven patients from 13 trials were included. Pooled results from 13 trials reporting proportion of nonunion showed no significant difference between PEMF or LIPUS and control. With regard to time to radiological union, we found heterogeneous results that significantly favoured PEMF or LIPUS bone growth stimulation only in non-operatively treated fractures or fractures of the upper limb. Furthermore, we found significant results that suggest that the use of PEMF or LIPUS in acute diaphyseal fractures may accelerate the time to clinical union. CONCLUSIONS: Current evidence from randomized trials is insufficient to conclude a benefit of PEMF or LIPUS bone growth stimulation in reducing the incidence of nonunions when used for treatment in acute fractures. However, our systematic review and meta-analysis suggest that PEMF or LIPUS can be beneficial in the treatment of acute fractures regarding time to radiological and clinical union. PEMF and LIPUS significantly shorten time to radiological union for acute fractures undergoing non-operative treatment and acute fractures of the upper limb. Furthermore, PEMF or LIPUS bone growth stimulation accelerates the time to clinical union for acute diaphyseal fractures.

The clinical and radiological outcome of pulsed electromagnetic field treatment for acute scaphoid fractures: a randomised double-blind placebo-controlled multicentre trial.

The use of pulsed electromagnetic fields (PEMF) to stimulate bone growth has been recommended as an alternative to the surgical treatment of ununited scaphoid fractures, but has never been examined in acute fractures. We hypothesised that the use of PEMF in acute scaphoid fractures would accelerate the time to union by 30% in a randomised, double-blind, placebo-controlled, multicentre trial. A total of 53 patients in three different medical centres with a unilateral undisplaced acute scaphoid fracture were randomly assigned to receive either treatment with PEMF (n = 24) or a placebo (n = 29). The clinical and radiological outcomes were assessed at four, six, nine, 12, 24 and 52 weeks. A log-rank analysis showed that neither time to clinical and radiological union nor the functional outcome differed significantly between the groups. The clinical assessment of union indicated that at six weeks tenderness in the anatomic snuffbox (p = 0.03) as well as tenderness on longitudinal compression of the scaphoid (p = 0.008) differed significantly in favour of the placebo group. We conclude that stimulation of bone growth by PEMF has no additional value in the conservative treatment of acute scaphoid fractures.