Pulsed electromagnetic field (PEMF): A potential adjuvant treatment for infected nonunion.

Infected nonunion is still a challenge for orthopaedic surgeons. The goal of treatment is to eliminate infection and achieve bone union. Surgery is the only effective method currently. However, it is invasive and the results are still unsatisfactory. Therefore, seeking a noninvasive and effective method to resolve infected nonunion is necessary. Pulsed electromagnetic field (PEMF) has been used for the treatment of nonunion for more than 40 years. PEMF could promote bone formation at tissue, cell and subcellular levels. Furthermore, our study showed that PEMF had bactericidal effect. The hypothesis we proposed herein is that PEMF may be an adjuvant treatment for infected nonunion by controlling infection and inducing bone formation.

Vitamin D and Metabolic Supplementation in Orthopedic Trauma.

Active assessment and management of hypovitaminosis D among orthopedic patients is low-risk and low-cost while retaining significant potential to improve patient care. Vitamin D has an established role in musculoskeletal development and calcium homeostasis, and vitamin D deficiency is pervasive in orthopedic trauma populations. Clinical guidelines for screening and supplementation for hypovitaminosis D are lacking. Literature on the effects of vitamin K on bone health is limited. Anabolic hormone analogues may have a future role in delayed union or nonunion treatment. Vitamin D deficiency and other endocrine abnormalities should be considered in orthopedic trauma patients presenting with fracture nonunion of uncertain cause.

Role of isolated percutaneous autologous platelet concentrate in delayed union of long bones.

PURPOSE: The objective of this study is to evaluate the efficacy of percutaneous platelet concentrate (PC) injection in increasing the chances of attaining union in delayed union of long bones and to know whether the time taken for union decreases with use of PC. METHODS: Forty delayed unions (15-30 weeks old) were randomized into a study group in which autologous PC prepared by blood bank centrifuge was percutaneously injected at the fracture site under image intensifier after activation with 10% calcium gluconate and a control group where patients were observed over time. Follow-up was every 6 weeks till fracture union. At each follow-up visit clinical and radiological parameters of union were assessed. RESULTS: Percentage union was 78% (18/23) in PC group and 59% (10/17) in control group, respectively (p = 0.296). The mean time to fracture union treated with PC (15.33 ± 9.91 weeks) was not different from the control group (13.10 ± 7.21 weeks; p = 0.540). In the PC group union is seen in 12 weeks after PC injection in 60 per cent of the cases. CONCLUSION: Isolated percutaneous PC injection increases union rates in delayed union of long bones. The results were, however, not statistically significant but show high positive association. Further studies are required to recommend routine use of PC injection.

Evaluation of bone turnover markers and serum minerals variations for predicting fracture healing versus non-union processes in adult sheep as a model for orthopedic research.

Bone turnover markers (BTMs) have been considered as an auxiliary method of following the fracture healing process and for early prediction of impaired bone healing. A better understanding of the potential of BTMs in this application could allow for earlier interventions and improved patient care. The aim of this study with a large animal experimental model was to assess the variation of bone formation markers - namely the total alkaline phosphatase (ALP) and its bone-specific isoform (BALP), serum concentration of intact osteocalcin (OC), N-terminal propeptide type III procollagen (PIIINP) and of bone resorption markers - namely tartrate resistant acid phosphatase (TRAP) and deoxypyridinoline crosslink (DPD) during the first stages of a normal fracture healing process and of a segmental critical size defect (CSD), which progresses to a non-union process. Thirty healthy female sheep (Portuguese Churra-da-Terra-Quente breed), approximately 4-years-old, were enrolled in this study. Jugular venous blood samples were collected pre-operatively and at 1, 2, 3, 4, 6, 8, 10 and 12 post-operative weeks. The animals of the CSD group showed significant lower serum levels of BALP, OC and significant higher serum PIIINP levels at early stages of the fracture healing process, compared with animals that progressed in a normal fracture healing process. Serum BALP, OC and PIIINP levels could be useful as non-invasive auxiliary tools with other complementary methods for predicting the outcome of traumatic bone fractures.

The 6-Hour Rule for Surgical Debridement of Open Tibial Fractures: A Systematic Review and Meta-Analysis of Infection and Nonunion Rates.

OBJECTIVES: The aim of this study was a systematic review and meta-analysis of studies comparing early (<6 hours) versus late (>6 hours) surgical debridement of open tibial fractures, with regards to infection and nonunion rates. METHODS: A systematic literature search of MEDLINE, Excerpta Medica Database, Cumulative Index to Nursing and Allied Health Literature (1961 to present), Allied and Complementary Medicine, and COCHRANE databases was conducted using any combination of the key words: "open," "tibial," and "fractures." After appropriate screening, 7 studies were included for analysis. Inclusion criteria were studies assessing the relation between time to debridement from injury and infection and/or nonunion rates. RESULTS: Three studies (n = 365) evaluated overall infection rates that varied from 7.7% to 8.9% in the early group versus 1%-18.5% in the late group. Three studies (n = 197) evaluated deep infection rates that varied from 13% to 18.5% in the early group versus 7.1%-18.6% in the late group. Four studies (n = 245) evaluated nonunion rates that varied from 13.2% to 26.1% in the early group versus 0%-32.6% in the late group. Meta-analysis showed no statistical difference between groups with regards to overall infection rates (risk ratio = 1.32; 95% CI, 0.54-3.23; P = 0.55), deep infection rates (risk ratio = 0.99; 95% CI, 0.48-2.07; P = 0.98), and nonunion rates (risk ratio = 1.49; 95% CI, 0.64-3.49; P = 0.36). CONCLUSIONS: The available literature suggests that there is no obvious difference in the overall/deep infection and nonunion rates between open tibial fractures debrided within 6 hours and those debrided at more than 6 hours. The findings presented here would appear to indicate that judicious delays of greater than 6 hours may not result in a significantly increased risk of adverse events or peri-operative morbidity. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Do smokers have greater risk of delayed and non-union after fracture, osteotomy and arthrodesis? A systematic review with meta-analysis.

OBJECTIVES: Systematic review and meta-analysis of published observational cohort studies. To quantify the increased risk smokers have of experiencing a delayed and/or non-union in fractures, spinal fusion, osteotomy, arthrodesis or established non-unions. SETTING: Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica database (EMBASE), Allied and Complementary Medicine Database (AMED) and Web of Science Core Collection from 1966 to 2015. STUDY ELIGIBILITY CRITERIA, PARTICIPANTS AND INTERVENTIONS: Observational cohort studies that reported adult smokers and non-smokers with delayed and/or non-union or time to union of the fracture, spinal fusion, osteotomy, arthrodesis or established non-union were eligible. DATA EXTRACTION AND OUTCOME MEASURES: 2 authors screen titles, abstracts and full papers. Data were extracted by 1 author and checked independently by a second. The relative risk ratios of smoking versus non-smoking and the mean difference in time to union patients developing a delayed and/or non-union were calculated. RESULTS: The search identified 3013 articles; of which, 40 studies were included. The meta-analysis of 7516 procedures revealed that smoking is linked to an increased risk of delayed and/or non-union. When considered collectively, smokers have 2.2 (1.9 to 2.6) times the risk of experiencing delayed and/or non-union. In all the subgroups, the increased risk was always ≥1.6 times that of non-smokers. In the patients where union did occur, it was a longer process in the smokers. The data from 923 procedures were included and revealed an increase in time to union of 27.7 days (14.2 to 41.3). CONCLUSIONS: Smokers have twice the risk of experiencing a non-union after fracture, spinal fusion, osteotomy, arthrodesis or treatment of non-union. Time to union following fracture, osteotomy, arthrodesis or treatment of an established non-union is longer in smokers. Smokers should be encouraged to abstain from smoking to improve the outcome of these orthopaedic treatments.

Does intrawound application of vancomycin influence bone healing in spinal surgery?

PURPOSE: Surgical site infections represent a major complication of spinal surgery. The application of lyophilised vancomycin into the wound is reported to significantly decrease infection rates. As concentrations applied locally can exceed the minimal bacterial inhibitory concentration for more than a 1000-fold, toxic side effects on local tissue may be possible. METHODS: Primary osteoblast cell cultures were generated from bone tissue samples of 10 patients. Samples were incubated in absence or presence of either 3, 6 or 12 mg/cm(2) vancomycin according to a planned phase I clinical trial protocol. Changes in pH, osteoblast migration, proliferation and viability were analysed. Alkaline phosphatase as well as mineralisation patterns was studied. RESULTS: The application of more than 3 mg/cm(2) vancomycin induced a decline of pH. The migration potential of osteoblasts was decreased from 100% (control samples) to zero (12 mg/cm(2) vancomycin) in a dose-dependant manner. Cell proliferation was significantly inhibited at dosages above 3 mg/cm(2). Significant cell death was observed if the dosage applied exceeded 6 mg/cm(2). The synthesis of alkaline phosphatase was markedly reduced in all dosages applied and calcium deposition was significantly decreased in dosages above 3 mg/cm(2). CONCLUSION: As bone remodelling requires the immigration, proliferation and differentiation of osteoblasts at the fusion site, high dosages of intrawound vancomycin might interfere with regenerative processes and increase the risk of non-union. To allow an appropriate balance of infection risk and the risk of non-union, the minimal local concentration required should be determined by controlled in vivo studies.

Hyperbaric oxygen therapy for promoting fracture healing and treating fracture non-union.

BACKGROUND: Hyperbaric oxygen therapy (HBOT) consists of intermittently administering 100% oxygen at pressures greater than one atmosphere absolute (ATA) in a pressure vessel. This technology has been used to treat a variety of diseases and has been described as helping patients who have delayed healing or established non-union of bony fractures. This is an update of a Cochrane Review first published in 2005, and previously updated in 2008. OBJECTIVES: The aim of this review is to assess the evidence for the benefit of hyperbaric oxygen treatment (HBOT) for the treatment of delayed bony healing and established non-union of bony fractures. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (July 2012), the Cochrane Register of Controlled Trials (CENTRAL) (The Cochrane Library 2012, Issue 7), MEDLINE (1946 to July Week 1 2012), EMBASE (1974 to 2012 July 16), CINAHL (1937 to 17 July 2012), the Database of Randomised Controlled Trials in Hyperbaric Medicine (accessed July 2012), the WHO International Clinical Trials Registry Platform (17 July 2012) and reference lists of articles. SELECTION CRITERIA: We aimed to include all randomised controlled trials comparing the clinical effects of HBOT with no HBOT (no treatment or sham) for healing of bony fractures and fracture non-unions. DATA COLLECTION AND ANALYSIS: Two review authors independently screened electronic search results, and all three authors independently performed study selection. We planned independent data collection and risk of bias assessment by two authors using standardised forms. MAIN RESULTS: No trials met the inclusion criteria. In this update, we identified three ongoing randomised controlled trials. Among the eight excluded studies were three randomised trials comparing HBOT with no treatment that included patients with fractures. One of these trials had been abandoned and the other two did not report on fracture healing outcomes. AUTHORS' CONCLUSIONS: This systematic review failed to locate any relevant clinical evidence to support or refute the effectiveness of HBOT for the management of delayed union or established non-union of bony fractures. Good quality clinical trials are needed to define the role, if any, of HBOT in the treatment of these injuries. There are three randomised controlled trials underway and we anticipate these will help provide some relevant clinical evidence to address this issue in the future.

WITHDRAWN: Hyperbaric oxygen therapy for promoting fracture healing and treating fracture non-union.

BACKGROUND: Hyperbaric oxygen therapy (HBOT) consists of intermittently administering 100% oxygen at pressures greater than one atmosphere absolute (ATA) in a pressure vessel. This technology has been used to treat a variety of diseases and has been described as helping patients who have delayed healing or established non-union of bony fractures. OBJECTIVES: The aim of this review was to assess the evidence for the benefit of hyperbaric oxygen treatment (HBOT) for the treatment of delayed bony healing and established non-union of bony fractures. SEARCH METHODS: We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register (April 2008), the Cochrane Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 2, 2008), MEDLINE (OVID 1966 to April week 3, 2008), CINAHL (OVID 1982 to April week 3, 2008), EMBASE (OVID 1980 to week 17 2008), the locally developed Database of Randomised Controlled Trials in Hyperbaric Medicine (available at www.hboevidence.com) from inception to May 2008, and reference lists of articles. SELECTION CRITERIA: We aimed to include all randomised controlled trials that compared the effect of HBOT with no HBOT (no treatment or sham). DATA COLLECTION AND ANALYSIS: We planned independent data collection by two authors using standardised forms. MAIN RESULTS: No trials met the inclusion criteria. We excluded one trial that compared HBOT with no treatment because no clinical outcomes were reported. AUTHORS' CONCLUSIONS: This systematic review failed to locate any relevant clinical evidence to support or refute the effectiveness of HBOT for the management of delayed union or established non-union of bony fractures. Good quality clinical trials are needed to define the role, if any, of HBOT in the treatment of these injuries.

Hyperbaric oxygen therapy for promoting fracture healing and treating fracture non-union.

BACKGROUND: Hyperbaric oxygen therapy (HBOT) consists of intermittently administering 100% oxygen at pressures greater than one atmosphere absolute (ATA) in a pressure vessel. This technology has been used to treat a variety of diseases and has been described as helping patients who have delayed healing or established non-union of bony fractures. OBJECTIVES: The aim of this review was to assess the evidence for the benefit of hyperbaric oxygen treatment (HBOT) for the treatment of delayed bony healing and established non-union of bony fractures. SEARCH STRATEGY: We searched the Cochrane Musculoskeletal Injuries Group trials register (to January week 3, 2004), the Cochrane Central Register of Controlled Trials (The Cochrane Library Issue 4, 2003), MEDLINE (OVID 1966 to January week 3, 2004), CINAHL (OVID 1982 to January week 3, 2004), EMBASE (OVID 1980 to February 2004), the locally developed Database of Randomised Controlled Trials in Hyperbaric Medicine (available at www.hboevidence.com) from inception to March 2004, and reference lists of articles. SELECTION CRITERIA: We aimed to include all randomised controlled trials that compared the effect of HBOT with no HBOT (no treatment or sham). DATA COLLECTION AND ANALYSIS: Two authors using standardised forms attempted to extract data independently. MAIN RESULTS: No trials met the inclusion criteria. We excluded one trial that compared HBOT with no treatment because no clinical outcomes were reported. AUTHORS' CONCLUSIONS: This systematic review failed to locate any relevant clinical evidence to support or refute the effectiveness of HBOT for the management of delayed union or established non-union of bony fractures. Good quality clinical trials are needed to define the role, if any, of HBOT in the treatment of these injuries.

Treatment of nonunions with electric and electromagnetic fields.

Electric and electromagnetic fields are, collectively, one form of biophysical technique which regulate extracellular matrix (ECM) synthesis and may be useful in clinically stimulating repair of fractures and nonunions. Preclinical studies have shown that electric and electromagnetic fields regulate proteoglycan (PG) and collagen synthesis in models of endochondral ossification, and increase bone formation in vivo and in vitro. A substantial number of clinical studies have been done that suggest acceleration of bone formation and healing, particularly osteotomies and spine fusions, by electric and electromagnetic fields. Many of these studies have used randomized, placebo controlled designs. In osteotomy trials, greater bone density, trabecular maturation, and radiographic healing were observed in actively treated, compared with placebo-treated patients. In spine fusions, average union rates of 80% to 90% were observed in actively treated patients across numerous studies compared with 65% to 75% in placebo-treated patients. Uncontrolled, longitudinal cohort studies of delayed and nonunions report mean union rates of approximately 75% to 85% in fractures previously refractory to healing. The few randomized controlled studies in delayed and nonunions suggest improved results with electric and electromagnetic fields compared with placebo treatment, and equivalent to bone grafts.

Electrical stimulation with bone and wound healing.

Electrical stimulation has been used to heal fractures and ulcers and reduce pain through modulation of local body processes. It has been recognized that mechanical forces and bioelectricity have an intimate relationship in influencing the production of bone. Science has developed techniques to affect change in the electrical charge of fractures to positively affect the healing process. Electrical stimulation, through invasive and noninvasive applications, has produced excellent results in the treatment of nonunions and ulcer care. A thorough review of the electrical properties of bone and soft tissue and the influence of electrical stimulation on healing is presented here.

Pulsed electromagnetic fields for the treatment of bone fractures.

The effectiveness of electrical stimulation and Pulsed Electro Magnetic Field (PEMF) stimulation for enhancement of bone healing has been reported by many workers. The mechanism of osteogenesis is not clear, therefore, studies look for empirical evidence. The present study involved a clinical trial using low amplitude PEMF on 19 patients with non-union or delayed union of the long bones. The pulse system used was similar in shape to Bassett's single pulse system where the electric voltage pulse was 0.3 mSec wide repeating every 12 mSec making a frequency of about 80 Hz. The peak magnetic fields were of the order of 0.01 to 0.1 m Tesla, hundred to thousand times smaller than that of Bassett. Among the 13 who completed this treatment schedule the history of non-union was an average of 41.3 weeks. Within an average treatment period of 14 weeks, 11 of the 13 patients had successful bone healing. The two unsuccessful cases had bone gaps greater than 1 cm following removal of dead bone after infection. However, use of such a low field negates Bassett's claim for a narrow window for shape and amplitude of wave form, and justifies further experimental study and an attempt to understand the underlying mechanism.

Electrical stimulation of bone nonunion with the presence of a gap.

A total of 22 established nonunions was treated with a capacitively-coupled electrical signal. A gap of 0.5 cm or more between the fragments was present in all of these nonunions. After an average of 26 weeks of treatment with capacitive coupling, radiographic assessment showed solid bone union in 72.7% of the cases. The results were better when the fracture site was metaphyseal. When the site was diaphyseal, bone healing was mainly achieved by bone trabeculae invading the gap. When the site was metaphyseal, healing occurred by the formation of a peripheral callus. The results were not affected by the presence of infection. In 8 of the cases osteomyelitis occurred, but all healed.

Comparison of asymmetrical and symmetrical pulse waveforms in electromagnetic stimulation.

Pulsing electromagnetic field (PEMF) stimulation is a noninvasive therapeutic modality that has been successfully used to stimulate healing of surgically resistant human bone fracture nonunions. Asymmetry of the stimulus pulse waveform was thought to be necessary for therapeutic effectiveness, but asymmetrical pulses require significant electrical energy that constrains clinical delivery systems to suboptimal designs. Development of low-energy consuming stimuli will enable clinical device improvements and may provide additional information about the interaction of electromagnetic fields with tissues. The objectives of this study were (a) to determine if asymmetry of the stimulus pulse waveform is needed for efficacy and (b) to determine if symmetrical pulse waveform stimuli also can produce a beneficial therapeutic response. The rabbit fibular osteotomy model was used to answer these questions and to identify which components of the clinically used asymmetrical PEMF produce the therapeutic response. The results suggest that asymmetry is not necessary and that a narrow pulse width, symmetrical square wave signal can also stimulate stiffness increases in this model. The data also suggest that the high-amplitude, narrow-pulse portion of the asymmetrical PEMF is the principal component of the signal pulse that is responsible for the clinical therapeutic effect.

Electrical stimulation of bone repair.

Interest in methods of accelerating bone healing persists. Electrical stimulation has demonstrated consistently high success rates in recalcitrant, complicated nonunions. The promise of successful noninvasive alternatives for treating nonunions continues to be realized. Given the rapidity of advances in this field, it appears likely that acceleration of fracture repair by electrical stimulation will become more widespread in the future.