Low-Intensity Pulsed Ultrasound and Pulsed Electromagnetic Field in the Treatment of Tibial Fractures: A Systematic Review

Abstract

METHODS

Two authors (N.A.W. and J.P.) independently identified relevant randomized clinical trials through a systematic search of several electronic databases: MEDLINE (1966 through 2004), Physiotherapy Evidence Database (PEDro) (1929 through 2004), and ProQuest (1987 through 2004) (Figure). The key words we used were ultrasound, fracture, and tibial with limits of human, clinical trials, and written in English. We initially focused on the tibia because a cursory review of the literature suggested that this bone would allow for the best opportunity to compare responses to the devices. However, this search yielded only 4 papers. Therefore, we removed the limits from the search criteria and found 5 additional studies. The authors of 4 of the studies used ultrasound for imaging; authors of the fifth provided a cost analysis.

To find additional studies of LIPUS, we performed a hand search of the references within the clinical reports and added 2 papers. We conducted a similar search using the key words electric current, fracture, and tibialin addition to the previously mentioned limits. This search yielded 2 papers. In an attempt to locate additional research, we dropped the limits and found 13 studies, but of these, 2 were diagnostic in nature, 3 related to imaging, 2 involved muscular healing, and 1 addressed vascular response. Thus, a total of 5 clinical trials of PEMF for fracture healing remained for further investigation.

Due to the small number of trials relating to tibial fracture healing that were identified, we expanded our search to include treatment of fractures in all bones with LIPUS or PEMF. First, we searched using the aforementioned limits with ultrasound, fracture, and bone. This yielded 58 papers. The key word healingwas added to the list, resulting in 7 studies. Four involved only treatment of tibial fractures, 1 was an imaging study, another was specific to diagnostics, and 1 reported on healing of the femur, radius, ulna, humerus, metatarsal, and clavicle with LIPUS.⁸ A similar search was then done for electric current, in place ofultrasound in the previous search. This yielded 3 papers, 2 of which concentrated on the tibia only, and 1 related to the femur, tibia, radius, and humerus.¹⁴ These additional studies were retained for this review.

We independently applied previously established inclusion criteria to assess the methods of each potentially eligible study. The following criteria had to be met: random allocation of treatments, inclusion of skeletally mature patients of either sex with a current fracture, blinding of both the patient and the assessors as to treatment group, administration of either LIPUS or PEMF treatments to one of the treatment groups, and assessment of time to fracture healing or proportion of fractures healed as determined radiographically, clinically, or both.

We assessed the quality of the selected studies and independently abstracted the data. For a checklist, we adopted the PEDro 10-point scale.¹⁷ The PEDro scale is based on 2 premises, internal validity and adequate statistical information to allow for interpretation.¹⁷ In a subsequent consensus meeting, we discussed each criterion. Because the articles already were rated in PEDro, the ratings were used as a third voice in the assessment process. When we disagreed about assessments, we discussed our concerns until we attained a consensus.

RESULTS

We identified 159 studies related to LIPUS (135) and PEMF (24), of which 14 were human clinical trials published in English (Figure). Of the 14 studies, 2 were excluded from the final analysis because another form of electric stimulation was studied.^12,13 Four were excluded^8,10,11,14 due to lack of a control group for comparison (Table 1). The PEDro scores for the 8 retained and 6 excluded studies are found in Table 1.

DISCUSSION

Low-intensity pulsed ultrasound and PEMF are used to treat fractures of all types. However, a relatively limited number of randomized, controlled clinical trials have been used to investigate the efficacy of these treatments. Focusing on tibial fractures, we found 6 studies suggesting a benefit to using LIPUS and PEMF for fracture union.^{3,6,7,9,15,16} Others, however, have failed to show a beneficial effect.^4,5 The studies we included in our review were of generally high methodologic quality (rating 8 or higher on the PEDro scale). To our knowledge, ours is the first systematic review attempting to compare the efficacy of LIPUS with that of PEMF. Unfortunately, such a comparison is not possible due to the heterogeneity in the outcomes measured and the timing of assessments. Moreover, the PEMF studies involved treatment of nonunions (Table 4), whereas the studies of LIPUS involved treatment of acute fractures.

The difference in the findings of Emami et al^4,5 and the other LIPUS investigators^3,6,7 could be the result of other factors, including management. The descriptions of the natures of the fractures were similar across studies (Table 4), however, except that those in the Leung et al⁷ report sustained more complex fractures. The patients included in the reports by Emami et al^4,5 were all treated with intramedullary nails. The effect of intramedullary nailing on responses to LIPUS has not, to our knowledge, been reported.

Other than the reports by Emami et al,^4,5 the papers^3,6,7 we included in our review are in agreement with a previous meta-analysis by Heckman et al.¹ The authors¹ concluded that LIPUS may reduce the time to fracture healing for fractures treated nonoperatively. Effect sizes were calculated to estimate the magnitude of the treatment effect.²⁰ Cohen¹⁹proposed that effect sizes of 0.2 represent small differences; 0.5, moderate differences; and 0.8+, large differences. Effect sizes for radiographic and clinical healing ranged from 1.9 magnitude⁷ to 4.2 magnitude,⁶ whereas reports of clinical healing alone ranged from 0.5 magnitude⁷ to 2.7 magnitude.⁶

The meta-analysis by Heckman et al¹ and the studies we included investigated healing of tibial fractures. Kristiansen et al²¹ reported accelerated healing (38% less time to union than in controls) of dorsally angulated radial fractures in a multicenter, prospective, controlled clinical trial. We found no randomized, controlled clinical trials involving LIPUS in the treatment of fracture nonunions.

We limited our search to clinical trials that included a control group and were written in English. In 2002, LIPUS was approved by the Food and Drug Administration for the treatment of established nonunions.²²The use of patients as their own controls in studies investigating the treatment of nonunion fractures is now accepted research practice. Nolte et al⁸ reported that 80% of the femur, radius, and scaphoid fractures treated with LIPUS healed in an average of 155 days and 75% of “other” bones healed in approximately 167 days, despite a long period of nonunion.

Authors of each of the randomized, controlled trials related to healing of nonunion fractures with PEMF, however, reported cases of healing with placebo stimulation. The lack of control groups precludes conclusions that no healing would have occurred without intervention. Yet the high success rates reported by Nolte et al⁸ certainly suggests that LIPUS is effective in the treatment of delayed healing and nonunion fractures.

Few high-quality controlled clinical trials of PEMF exist. We found 2 reports of PEMF fracture treatments that did not involve a control group, in addition to those we included. Each group reported high rates of long-bone union between 14 weeks and 5.2 months. Regarding long-bone fractures, Satter Syed et al¹⁴ found that 84.6% (11 of 13) experienced successful bone healing within an average treatment period of 14 weeks. Similarly, when Bassett et al¹⁰ studied the effects of PEMF on the tibia and the femur, the healing rate was 93% (65 of 70) or greater in an average of 4 months. Bassett et al¹⁰ performed additional work with the tibia and once again found that, in an average of 5.2 months, 87% (110 of 127) of all nonunions had healed with non–weight-bearing treatment. In addition to the results of the randomized clinical trials, the findings of Satter Syed et al¹⁴ and Bassett et al¹⁰suggest that PEMF speeds healing of tibial and other long-bone fractures.

CONCLUSIONS

Because the authors of the controlled LIPUS trials reported days to healing and those studying PEMF provided proportions of the groups with united fractures, it is not possible to compare the effects of these interventions. We recommend that investigators in future PEMF studies record time to healing in days, similar to what is done in LIPUS research.

Low-intensity pulsed ultrasound speeds acute fracture healing and promotes healing in nonunion fractures. At present, the efficacy of this treatment is best supported by the randomized, controlled clinical trials of acute tibial fractures^3,14,15 available. Controlled clinical trials assessing the management of other acute fractures are needed. Evidence suggests that PEMF also increases the proportion of nonunion fractures that heal without additional intervention.

Comparison studies of these 2 modalities may prove useful in helping clinicians to select the most effective treatments for various fractures across a spectrum of patients. We also recommend that investigators stratify patients based on fracture status (acute versus nonunion), fixation (internal versus external), and smoking. Smoking tobacco slows down the regeneration of bone tissue,⁷ and a disproportionate number of smokers in either a treatment or a control group may bias the results in favor or disfavor of fracture treatments.

REFERENCES