Vibration Therapy as an Intervention for Enhancing Trochanteric Hip Fracture Healing in Elderly Patients

Study Overview
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Brief Summary
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Currently, there are approximately 300,000 hip fractures per year in the US with a mortality rate of 20% within 1 year. In Hong Kong, around 6,000 hip fractures occur yearly with costs approximately 52 million USD, and these numbers are projected to double by 2050. The treatment of osteoporotic fractures is a major challenge as bone healing is delayed due to the impaired healing properties with respect to bone formation, angiogenesis and mineralization. Failure to unite results in pain, weakness, reduced mobility and fixation failure, and these complications are most common in elderly patients. Enhancement of osteoporotic fracture healing even after surgical fixation is therefore critical as a major goal in modern fracture management. Low-magnitude high-frequency vibration (LMHFV) is a biophysical intervention that provides non-invasive, systemic mechanical stimulation and we are the first group to study its effect on fracture healing. Our previous animal studies have shown LMHFV to enhance healing from the early inflammation stage to the late phases of remodeling in osteoporotic diaphyseal fracture healing. Using our newly developed clinically relevant metaphyseal fracture model, we further proved the efficacy of LMHFV. Our results show LMHFV significantly enhanced fracture healing in both osteoporotic and normal rats radiologically by X-ray and micro-CT, histologically and biomechanically. Justified with our preclinical studies, we hypothesize LMHFV can accelerate the time to fracture healing and enhance functional recovery. In this study, we propose to study the efficacy of LMHFV in trochanteric hip fracture healing by conducting a randomized double-blinded placebo-controlled clinical trial. Elderly patients aged 65 years or older of either gender, after surgical fixation, will be treated with LMHFV at 35Hz, 0.3g, 20 minutes/day, 5 days/week for 6 months. Results will be evaluated by clinical assessments, radiologically with X-rays, Computed Tomography (CT) and dynamic perfusion Magnetic Resonance Imaging (MRI) for blood circulation evaluation, Dual-energy X-ray absorptiometry (DXA), functional outcomes, and mortality. Positive findings from the study would have huge impact and change clinical practice.

Detailed Description
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Osteoporosis predisposes patients to increased risk of fragility fractures, which affects clinical outcomes and functional recovery. In fact, the lifetime fracture risk of osteoporotic patients reaches as high as 40%. There are approximately 2.5 million osteoporotic fractures each year in the United States (US), with costs estimated at $15 billion USD in 2010. Currently, there are approximately 300,000 hip fractures per year in the US with a mortality rate of 20% within 1 year. Low-magnitude high-frequency vibration (LMHFV) is a promising biophysical intervention that provides non-invasive, systemic mechanical stimulation. We previously conducted a randomized controlled trial with 710 healthy, active and independent postmenopausal women over 60 years old. The LMHFV group had significant improvements in reaction time, movement velocity, maximum excursion of balancing ability assessment and also quadriceps muscle strength (p<0.001). There were significantly lower fall incidences with 18.6% of 334 vibration group subjects compared with 28.7% of 327 control group subjects (adjusted HR=0.56, p=0.001). Benefits of LMHFV for balancing ability, muscle strength and risk of falling were retained 1 year after cessation of the treatment. This is a randomized double-blinded placebo-controlled clinical trial to investigate the use of LMHFV to enhance trochanteric hip fracture healing and will provide impactful findings for the future management of osteoporotic fractures. Objectives To investigate the efficacy of LMHFV in trochanteric hip fractures on the time to radiological healing by conducting a randomized double-blinded placebo-controlled controlled clinical trial To assess the effects of LMHFV in trochanteric hip fractures compared with control on clinical outcomes, densitometry, blood circulation, and mortality Research Plan and Methodology A total of 120 unilateral trochanteric hip fracture (AO classification A1-A3) patients due to unintentional fall, aged 65 years or older, will be recruited. Patients will be randomized into either vibration or placebo group after surgical fixation with a cephalomedullary nail. Radiology will be taken after fixation and regular follow-up X-rays will be taken. CTs will also be taken to assess fracture healing. Blood circulation will be assessed by dynamic perfusion MR. BMD and Bone mineral content (BMC) at fracture site will be measured by Dual X-ray Absorptiometry (DXA) scan. Clinically, vital signs, wound condition and pain intensity will be monitored. Functional outcomes including Short Form-36 (SF-36), muscle strength, Timed up and go (TUG) test and balancing ability are evaluated. Mortality will be documented. Throughout the study, complications and safety issues will be documented and in case adverse events occur, treatment will be terminated immediately. The above parameters will be compared between pre- and post-treatment and between the 2 groups.

Official Title
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Vibration Therapy as an Intervention for Enhancing Trochanteric Hip Fracture Healing in Elderly Patients: A Randomized Double-Blinded, Placebo-Controlled Clinical Trial

Conditions
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Hip Fractures

Intervention / Treatment
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* Device: Low-magnitude high-frequency vibration (LMHFV)
* Device: Low-magnitude high-frequency vibration (LMHFV)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Elderly male or females aged 65 years or older Unilateral trochanteric hip fractures (AO classification A1-A3) Due to unintentional fall Fractures fixed with cephalomedullary nail (Gamma nail, Stryker - usual practise at our unit) Willing and able to comply with study protocol Exclusion Criteria: Open fracture Bilateral fractures Patient with multiple injuries Pathological fractures e.g. tumour, infection, etc. History of medication or disease affecting bone metabolism such as hypo/hyperthyroidism, hypo/hyperparathyroidism, etc. Malignancy Chairbound or bedbound (unable to comply for LMHFV therapy) Cognitive problems e.g. dementia (unable to agree for consent)

Ages Eligible for Study
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Minimum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Randomized Double-Blinded, Placebo-Controlled Clinical Trial
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo-Controlled<br>Placebo group will have placebo treatment by standing on the LMHFV platform for 20 minutes/day | Device: Low-magnitude high-frequency vibration (LMHFV)<br>* Placebo group will have sham treatment by standing on the LMHFV platform for 20 minutes/day<br>|
| Experimental: Vibration Group<br>Vibration group is treated with LMHFV at 35Hz, 0.3g, for 20 minutes/day, 5 times/week | Device: Low-magnitude high-frequency vibration (LMHFV)<br>* Low-magnitude high-frequency vibration (LMHFV) is a biophysical intervention that provides non-invasive, systemic mechanical stimulation and has been reported to have no adverse effect.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in time to healing | X-ray | X-ray: baseline, 12, 52 weeks post-operation | 
| Change in time to healing | Computed Tomography | 6 weeks post-operation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Densitometry | Bone Mineral Density | baseline, 6, 12 and 26 weeks post-operation | 
| Densitometry | Bone mineral content | baseline, 6, 12 and 26 weeks post-operation | 
| Blood circulation at fracture site | Measured by dynamic contrast-enhanced MR imaging | 6 weeks post-operation | 
| Pain scale | Verbal Descriptor Scale (Pain Thermometer): scale ranges from 0 to 10, higher score indicates more pain | 2, 6, 12, 16, 20, 26, 36, 52 weeks post-operation | 
| Quality of life questionnaire (SF-36) | Functional status questionnaire to measure health-related quality of life in eight domains (physical functoning, physicial and emotional limitations, social functioning, bodily pain, general and mental health; Scores ranges from 0-100, higher score indicates better result. | 2, 6, 12, 16, 20, 26, 36, 52 weeks post-operation | 
| Quadriceps muscle strength | Dynamometer | 2, 6, 12, 16, 20, 26, 36, 52 weeks post-operation | 
| Balancing ability | Basic Balance Master System | 2, 6, 12, 16, 20, 26, 36, 52 weeks post-operation | 
| Time up and go test (TUG) | The subject will stand from a chair, walk 3 meters and travel back and sit back on the chair. The time is recorded | 2, 6, 12, 16, 20, 26, 36, 52 weeks post-operation | 
| Mortality |  | 1 month, 3 months and 1 year post-operation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Fracture healing, Osteoporosis, Vibration treatment