Distinct frequency dependent effects of whole‐body vibration on non‐fractured bone and fracture healing in mice

Abstract

Low-magnitude high-frequency vibration (LMHFV) provokes anabolic effects in non-fractured bone; however, in fracture healing, inconsistent results were reported and optimum vibration conditions remain unidentified. Here, we investigated frequency dependent effects of LMHFV on fracture healing. Twelve-week-old, female C57BL/6 mice received a femur osteotomy stabilized using an external fixator. The mice received whole-body vibrations (20 min/day) with 0.3g peak-to-peak acceleration and a frequency of either 35 or 45 Hz. After 10 and 21 days, the osteotomized femurs and intact bones (contra-lateral femurs, lumbar spine) were evaluated using bending-testing, m-computed tomography, and histomorphometry. In non-fractured trabecular bone, vibration with 35 Hz significantly increased the relative amount of bone (þ28%) and the trabecular number (þ29%), whereas cortical bone was not influenced. LMHFV with 45 Hz failed to provoke anabolic effects in trabecular or cortical bone. Fracture healing was not significantly influenced by whole-body vibration with 35 Hz, whereas 45 Hz significantly reduced bone formation (À64%) and flexural rigidity (À34%) of the callus. Although the exact mechanisms remain open, our results suggest that small vibration setting changes could considerably influence LMHFV effects on bone formation in remodeling and repair, and even disrupt fracture healing, implicating caution when treating patients with impaired fracture healing. Keywords: whole-body vibration; LMHFV; fracture healing; bone formation Delayed or incomplete fracture healing is a major issue in orthopedic surgery, with an incidence of about 10% of patients and a high socioeconomic burden, implicating the need for effective treatment strategies.1 Because bone metabolism is partly regulated by mechanical factors and suitable mechanical stimuli can improve bone repair, 2,3 non-invasive physical methods, among them low-magnitude high-frequency vibration (LMHFV), 2,4 could provide a readily applicable and cost-effective approach to prevent or treat delayed fracture healing.LMHFV is characterized by a sinusoidal waveform with an acceleration of <1g (g ¼ gravitational acceleration, 1g ¼ 9.81 m/s 2 ) and a frequency range between 20 and 90 Hz, 5 inducing extremely small strains in bone tissue (approximately 10 me), much less than the peak strains generated during locomotion (2,000-3,000 me). 2LMHFV provoked anabolic effects in both healthy and osteoporotic bone in preclinical 6-9 and clinical studies. 11 In both healthy 12 and ovariectomized rats, 13 LMHFV (35 Hz/0.3g) was shown to improve bone repair by inducing a large callus with more bone and improved mechanical quality. The same authors found that LMHFV stimulated callus angiogenesis 14 and, in the late healing phase, bone resorption. 15 In a model of metaphyseal bone healing, vibrations with both high frequency (90 Hz) and acceleration (4g) provoked some positive effects in ovariectomized rats, but resulted in delayed callus bridging in healthy animals, and was therefore consi...

The effect of whole body vibration on fracture healing – a systematic review

“…Ten (Butezloff et al, 2015;Cheung et al, 2012;Chow et al, 2011;Chung et al, 2014;Leung et al, 2009;Shi et al, 2010;Wehrle et al, 2015;Wehrle et al, 2014;Wei et al, 2016) of the nineteen studies adopt a 20 min/d treatment, four (Bilgin et al, 2017;Komrakova et al, 2013;Stuermer et al, 2014;Stuermer et al, 2010) In this review, vibration regimes with a magnitude lower than 1 ×g were regarded as LMHFV and those with a magnitude greater than 1 ×g were regarded as HMHFV (high magnitude high frequency vibration). Six (Butezloff et al, 2015;Komrakova et al, 2016;Komrakova et al, 2013;Stuermer et al, 2014;Stuermer et al, 2010;Usui et al, 1989) of the included studies use HMHFV and twelve (Bilgin et al, 2017;Cheung et al, 2012;Chow et al, 2011;Chung et al, 2014;Gao et al, 2016;Leung et al, 2009;Shi et al, 2010;Wehrle et al, 2015;Wehrle et al, 2014;Wolf et al, 2001) adopt LMHFV. One study uses both LMHFV and HMHFV (Uchida et al, 2017).…”

“…Exclusion criteria were: 1) non-English-language papers; 2) not vibration treatment-related; 3) not Cheung et al, 2012;Chow et al, 2011;Chung et al, 2014;Gao et al, 2016;Komrakova et al, 2016;Komrakova et al, 2013;Leung et al, 2009;Shi et al, 2010;Stuermer et al, 2014;Stuermer et al, 2010;Uchida et al, 2017;Wei et al, 2016), two mouse studies (Wehrle et al, 2015;Wehrle et al, 2014), one sheep study (Wolf et al, 2001) and one rabbit study (Usui et al, 1989). No clinical study was found, based on our search criteria on publications prior to the 12 th March 2017.…”

“…Three studies (Gao et al, 2016;Leung et al, 2009;Uchida et al, 2017) use only non-OVX rats as research subjects. Among the two mouse studies, one (Wehrle et al, 2015) investigate the effects of vibration on both OVX and sham-OVX mice and the other (Wehrle et al, 2014) uses non-OVX models only. Both, the sheep study (2-3 years old female sheep) and the rabbit study (adult female rabbit) do not report the use of an osteoporosis/osteopenia model (Table 1A,B,C).…”

“…Nine of them use closed fracture models with Kirschner wire (K-wire) internal fixation; of those, eight are carried out on the femur of the animals (Butezloff et al, 2015;Cheung et al, 2012;Chow et al, 2011;Chung et al, 2014;Leung et al, 2009;Shi et al, 2010;Wei et al, 2016) and one uses the tibia fracture model (Gao et al, 2016). The other ten studies include two femoral fracture models (Wehrle et al, 2015;Wehrle et al, 2014), five tibial fracture models (Bilgin et al, 2017;Komrakova et al, 2016;Komrakova et al, 2013;Stuermer et al, 2014;Stuermer et al, 2010), one metatarsal fracture model [in which researchers conducted osteotomy with external fixators or titanium plates (Wolf et al, 2001)], one rib fracture model without fixation (Uchida et al, 2017) and one fibular osteotomy model without fixation (Usui et al, 1989). Fifteen diaphyseal fracture models and four metaphyseal fracture models are used in the included studies (Table 1A,B,C).…”

“…A summary of the vibration regimes is shown in Table 2A (Komrakova et al, 2013;Wehrle et al, 2014) and one study compares low and high magnitude vibration during fracture healing (Uchida et al, 2017). Most studies (12 out of 19) report starting vibration treatment at day 5 postoperatively, four studies commence at day 3 postfracture, two studies at day 7 and day 14 respectively and the final study does not report the exact start time.…”