Healing of fracture nonunions treated with low-intensity pulsed ultrasound (LIPUS): A systematic review and meta-analysis

Introduction: Bone fractures fail to heal and form nonunions in roughly 5% of cases, with little expectation of spontaneous healing thereafter. We present a systematic review and meta-analysis of published papers that describe nonunions treated with low-intensity pulsed ultrasound (LIPUS). Methods: Articles in PubMed, Ovid MEDLINE, CINAHL, AMED, EMBASE, Cochrane Library, and Scopus databases were searched, using an approach recommended by the Methodological Index for Non-Randomized Studies (MINORS), with a Level of Evidence rating by two reviewers independently. Studies are included here if they reported fractures older than 3 months, presented new data with a sample N ≥ 12, and reported fracture outcome (Heal/Fail). Results: Thirteen eligible papers reporting LIPUS treatment of 1,441 nonunions were evaluated. The pooled estimate of effect size for heal rate was 82% (95% CI: 77-87%), for any anatomical site and fracture age of at least 3 months, with statistical heterogeneity detected across all primary studies (Q = 41.2 (df = 12), p < 0.001, Tau2 = 0.006, I2 = 71). With a stricter definition of nonunion as fracture age of at least 8 months duration, the pooled estimate of effect size was 84% (95% CI: 77% − 91.6%; heterogeneity present: Q = 21 (df = 8), p < 0.001, Tau2 = 0.007, I2 = 62). Hypertrophic nonunions benefitted more than biologically inactive atrophic nonunions. An interval without surgery of <6 months prior to LIPUS was associated with a more favorable result. Stratification of nonunions by anatomical site revealed no statistically significant differences between upper and lower extremity long bone nonunions. Conclusions: LIPUS treatment can be an alternative to surgery for established nonunions. Given that no spontaneous healing of established nonunions is expected, and that it is challenging to test the efficacy of LIPUS for nonunion by randomized clinical trial, findings are compelling. LIPUS may be most useful in patients for whom surgery is high risk, including elderly patients at risk of delirium, or patients with dementia, extreme hypertension, extensive soft-tissue trauma, mechanical ventilation, metabolic acidosis, multiple organ failure, or coma. With an overall average success rate for LIPUS >80% this is comparable to the success of surgical treatment of non-infected nonunions

Effects of low power laser irradiation on bone healing in animals: a meta-analysis

<p>Abstract</p> <p>Purpose</p> <p>The meta-analysis was performed to identify animal research defining the effects of low power laser irradiation on biomechanical indicators of bone regeneration and the impact of dosage.</p> <p>Methods</p> <p>We searched five electronic databases (MEDLINE, EMBASE, PubMed, CINAHL, and Cochrane Database of Randomised Clinical Trials) for studies in the area of laser and bone healing published from 1966 to October 2008. Included studies had to investigate fracture healing in any animal model, using any type of low power laser irradiation, and use at least one quantitative biomechanical measures of bone strength. There were 880 abstracts related to the laser irradiation and bone issues (healing, surgery and assessment). Five studies met our inclusion criteria and were critically appraised by two raters independently using a structured tool designed for rating the quality of animal research studies. After full text review, two articles were deemed ineligible for meta-analysis because of the type of injury method and biomechanical variables used, leaving three studies for meta-analysis. Maximum bone tolerance force before the point of fracture during the biomechanical test, 4 weeks after bone deficiency was our main biomechanical bone properties for the Meta analysis.</p> <p>Results</p> <p>Studies indicate that low power laser irradiation can enhance biomechanical properties of bone during fracture healing in animal models. Maximum bone tolerance was statistically improved following low level laser irradiation (average random effect size 0.726, 95% CI 0.08 - 1.37, p 0.028). While conclusions are limited by the low number of studies, there is concordance across limited evidence that laser improves the strength of bone tissue during the healing process in animal models.</p

The effect of low level laser on condylar growth during mandibular advancement in rabbits

<p>Abstract</p> <p>Introduction</p> <p>It has been shown that Low Level Laser (LLL) has a positive effect on bone formation. The aim of this study was to evaluate the effect of low level laser on condylar growth during mandibular advancement in rabbits.</p> <p>Materials and methods</p> <p>Continuous forward mandibular advancement was performed in fourteen male Albino rabbits with the mean age of 8 weeks and the mean weight of 1.5 ± 0.5 kg, with acrylic inclined planes. The rabbits were randomly assigned into two groups after 4 weeks. LLL (KLO3: wave length 630 nm) was irradiated at 3 points around the TMJ, through the skin in the first group. The exposure was performed for 3 minutes at each point (a total of 9 minutes) once a day for 3 weeks. The control group was not exposed to any irradiation. The rabbits in both groups were sacrificed after two months and the histological evaluation of TMJ was performed to compare fibrous tissue, cartilage, and new bone formation in condylar region in both groups. Disc displacement was also detected in both groups. Student's t-test, Exact Fisher and Chi square tests were used for the statistical analysis.</p> <p>Results</p> <p>The formation of fibrous tissue was significantly lower, while bone formation was significantly greater in lased group as compared with control group. The thickness of cartilage did not differ significantly between two groups.</p> <p>Conclusion</p> <p>Irradiation of LLL (KLO3) during mandibular advancement in rabbits, increases bone formation in condylar region, while neither increase in the cartilage thickness nor fibrous tissues was observed.</p

Low-intensity continuous ultrasound triggers effective bisphosphonate anticancer activity in breast cancer

Ultrasound (US) is a non-ionizing pressure wave that can produce mechanical and thermal effects. Bisphosphonates have demonstrated clinical utility in bone metastases treatment. Preclinical studies suggest that bisphosphonates have anticancer activity. However, bisphosphonates exhibit a high affinity for bone mineral, which reduces their bioavailability for tumor cells. Ultrasound has been shown to be effective for drug delivery but in interaction with gas bubbles or encapsulated drugs. We examined the effects of a clinically relevant dose of bisphosphonate zoledronate (ZOL) in combination with US. In a bone metastasis model, mice treated with ZOL+US had osteolytic lesions that were 58% smaller than those of ZOL-treated animals as well as a reduced skeletal tumor burden. In a model of primary tumors, ZOL+US treatment reduced by 42% the tumor volume, compared with ZOL-treated animals. Using a fluorescent bisphosphonate, we demonstrated that US forced the release of bisphosphonate from the bone surface, enabling a continuous impregnation of the bone marrow. Additionally, US forced the penetration of ZOL within tumors, as demonstrated by the intratumoral accumulation of unprenylated Rap1A, a surrogate marker of ZOL antitumor activity. Our findings made US a promising modality to trigger bisphosphonate anticancer activity in bone metastases and in primary tumors

Comparison of the lower limb inter-segmental coordination during walking between healthy controls and people with multiple sclerosis with and without fall history

Background: This research aims to compare lower limb inter-segmental coordination, a higher order property of the human movement system, during walking between healthy controls and people with multiple sclerosis (PwMS) with and without fall history. Methods: Fifty PwMS (25 patients with fall history and 25 patients without fall history) and 25 healthy controls participated in the present study. Three-dimensional coordinate data of the lower limbs were collected during treadmill walking at a preferred walking speed. The phasing relationship and its variability between lower limb segments were evaluated using the mean absolute relative phase (MARP) and deviation phase (DP) during the stance and swing phases of gait. Results: Compared to healthy controls, both groups of PwMS demonstrated significantly greater shank-thigh MARP values during the stance phase (p < 0.001). In addition, MARP values of foot-shank coordination were significantly smaller in both groups of PwMS than the healthy controls during both the stance and swing phases (p < 0.001). For the DP of shank-thigh coordination, our analysis revealed greater values in both MS fallers and non-fallers compared to healthy controls during the stance (p < 0.001) and swing phases (p < 0.001, p = 0.004, respectively). Moreover, MS fallers demonstrated greater DP values than non-fallers in swing phase (p = 0.02). For the DP of foot-shank coordination, MS fallers showed greater values compared to non-fallers and healthy controls during the stance (p = 0.009, p = 0.001, respectively) and swing phases (p = 0.01, p = 0.006, respectively). Conclusion: Our results suggest that in addition to traditional gait parameters, examining and also facilitating lower limb inter-segmental coordination should be considered in future studies aimed at improving gait performance and reducing risk of falling in PwMS. © 2020 Elsevier B.V

Lack of association between NOD2 rs3135500 and IL12b rs1368439 microRNA binding site SNPs and colorectal cancer susceptibility in an Iranian population

Objective: The purpose of this study was to evaluate the potential association between single nucleotide polymorphisms (SNPs) in microRNA (miRNA) binding sites in the NOD2 and IL12B gene 3�-untranslated regions and colorectal cancer (CRC) susceptibility in an Iranian population. Methods: We genotyped NOD2 rs3135500 3� untranslated region (UTR) A/G and IL12B rs1368439 (3�UTR G/T) in a hospital-based study of 92 colorectal cancer cases and 105 healthy controls. All samples were genotyped by TaqMan assay via an ABI 7500 Real Time PCR System (Applied Biosystems) with DNA from FFPE tissue and peripheral blood. Results: our results showed similar distribution of genotype and allelic frequencies of the NOD2 and IL12B polymorphisms between patients and controls. When the more common rs3135500 AA genotype was used as the reference, the rs3135500 AG and rs3135500 GG genotypes were not significantly associated with the risk of CRC (OR = 1.294, 95% CI: 0.524 -3.197; and OR = 2.230, 95% CI: 0.87 - 5.715, respectively), and The IL12B rs1368439 TG and IL12B rs1368439 GG genotypes were not significantly associated with the risk of CRC compared with the IL12B rs1368439 TT genotype (OR = 1.547 95% CI: 0.187- 12.771; and OR = 1.753, 95% CI: 0.217-14.157, respectively). Conclusion: NOD2 rs3135500 and IL12B rs1368439 SNPs were not genetic risk factors for colorectal cancer in the studied Iranian population. � 2016 Bentham Science Publishers