A Review of Bone Growth Stimulation for Fracture Treatment

Steve B. Behrens; Matthew E. Deren; Keith O. Monchik


Curr Orthop Pract. 2013;24(1):84-91. 

In This Article

Low-intensity Pulsed Ultrasound

A large number of clinical studies have examined the effects of LIPUS on fresh fractures, as well as delayed unions and nonunions. Overall, the evidence is Level II because of the heterogeneity of clinical trials and outcomes, with somewhat conflicting results as assessed by meta-analyses. LIPUS for the treatment of fresh fractures has a Grade B recommendation, while a Grade C recommendation can be made for its use in treating delayed or nonunited fractures.

A meta-analysis of five randomized, controlled trials reported decreased time to union with LIPUS compared with placebo by 36 days in fresh fractures.[80] The authors concluded that these results should be interpreted with caution, as the pooled results failed tests for heterogeneity. A previous meta-analysis pooled three double-blind, randomized, placebo-controlled trials and reported that LIPUS significantly decreased time to union by 64 days on average.[81] Other authors have noted, however, that two of the three pooled trials were industry-supported, and the other trial had flaws in patient selection.[82] Another recent meta-analysis was unable to pool data for delayed and nonunited fractures treated with LIPUS, but reported that weak evidence exists for its use.[83] Bashardoust et al.[76] performed a meta-analysis of seven trials of LIPUS treatment of fresh fractures, reporting decreased time to healing compared with placebo.

In 1994, Heckman et al.[76] reported the acceleration of tubercle fracture healing by LIPUS. In this randomized, controlled, double-blinded, multi-center center study, 33 fractures underwent ultrasound treatment compared with 34 placebo in acute, Grade 1, open tibia oblique or transverse fractures with less than 50 percent displacement. The treatment was 20 minutes per day until healing, which was defined as a three-cortices bridge. The results were a 38% faster healing time for fractures in the experimental compared with placebo patients. Patients undergoing ultrasound healed at 94 days, and patients receiving placebo at 154 days, which was statistically significant. The incidence of delayed union was reduced 83%. Older patients, younger patients, smokers, and nonsmokers saw decreased healing times of 65, 42, 72, and 33 days, respectively. In patients in whom there was a 2-mm gap, healing time decreased by 21 days. Patients with 3 to 4-mm gaps had a 58-day decrease and patients with a 5-mm gap had a 121-day decrease.

.Strauss et al.[76] published a prospective, randomized, placebo-controlled study of 20 patients in which all 10 experimental patients treated by LIPUS healed by 8 weeks. In the placebo group, six healed by 13 weeks, eight healed by 16 weeks, and two had delayed unions defined as not healed by 20 weeks. The only critique in this study is its small sample size of only 10 patients in both the experimental and placebo groups.

Kristiansen et al.[76] studied LIPUS in a randomized, doubleblinded, placebo-controlled trial of 60 patients with fresh metaphyseal distal radial fractures and reported significantly decreased time to union (61 days compared with 98 days) and decreased loss of reduction (20% compared with 43%) in those treated with LIPUS compared with placebo. Rue et al.[76] tested LIPUS against placebo in a randomized, double-blind trial of 43 tibial stress fractures in athletes and determined that LIPUS did not significantly reduce time to healing. A case series of five athletes with anterior midtibial stress fractures reported decreased pain and full return to activity at 3 months with LIPUS treatments. However, bony healing did not coincide with pain-free activity, and the authors urged close follow-up for treated patients.[88]

A randomized, placebo-controlled trial reported decreased time to callus formation (9.5 to 6.5 weeks) and full weightbearing status (15.5 to 9.3 weeks) in complex tibial fractures when comparing placebo with LIPUS.[89] However, LIPUS did not demonstrate any increased fracture healing, resumption of activities of daily living, or pain scores when compared with placebo in a randomized, double-blind, controlled trial of 101 patients with fresh clavicular fractures.[90] Likewise, in lateral malleolar fractures treated with bioabsorbable fixation devices and randomized, double-blinded to treatment with placebo or LIPUS, Handolin et al.[76] did not observe a statistically significant difference in fracture healing despite a small trend towards increased callus in 12 weeks of follow-up.

A multicenter, randomized, double-blinded, placebo-controlled trial of 91 patients with tibial nonunion demonstrated increased bone mineral density and decreased bone gap area with LIPUS treatment.[92] This study did not report functional outcomes or time to healing for either treatment group. Mayr et al.,[93] in 2002, published on low-intensity ultrasound effectiveness for treating fracture healing disorders in a prospective case series of 100 nonunions. Inclusion criteria consisted of greater than 90 days from the last surgery or treatment change and 120 days since fracture. LIPUS treatment of 20 minutes per day was the only change in treatment. The authors reported an 86% rate of fracture healing. Patient selection was a shortcoming of this study, with the possibility that the sample of patients chosen might have been expected to respond well to treatment.

Nolte et al.[76] published a study on LIPUS in a prospective case series of 29 nonunions: 5 atrophic, 12 hypertrophic, and 12 oligotrophic. The average fracture was 1.2 years old, the average time after prior surgery was 1 year, and the average number of previous surgeries was 1.4. Ultrasound was used for 20 minutes per day and was the only change in the treatment, resulting in 86% of cases healed. The average time to healing with ultrasound was 4 months, and 75% of smokers or ex-smokers had healed. Hemery et al.[76] reported a retrospective case series of 14 patients with surgically treated tibial nonunions, 11 of which reached union within 9 months of LIPUS treatment with no reported complications. 95 In a case series of 29 various nonunions treated with daily, 20-minute treatments of LIPUS, 25 fractures went on to union, with only tobacco use as a significant risk for failure to union after treatment.[94]

Gebauer et al.,[25] in 2005, published a prospective case series of 67 patients with nonunions that were stable, with no evidence of infection.[25] The minimal fracture age was 8 months; 4 months or more had passed since the date of last intervention, and radiographs demonstrated greater than 3 months with no evidence of healing.[25] Fractures were, on average, 39 months old, and patients averaged two prior failed surgeries. The ultrasound treatment was 20 minutes per day, resulting in 85% of fractures healed with an average of 168 days of treatment. Another cohort of 67 established nonunions were treated with LIPUS for an average of 168 days, with 85% successful healing, excluding malaligned, infected, segmental bone loss, or grossly unstable fractures. 25 Reanalysis of a multicentered cohort on LIPUS in long-bone fracture nonunions determined that the union rate was increased from 75% to 89.7% overall if treatment was started within 6 months of surgery.[96] A retrospective cohort of 71 tibial nonunions consequently treated with LIPUS demonstrated union in 73%, increased over the authors' quoted spontaneous union rate of 5–30%.[97]