SBIR-STTR Award

Osteoporosis affects 10 million Americans over the age of 50 and leads to 1.5 million bone fractures per year, primarily in women. For senior citizens who suffer fractures of the hip, 20% will die within one year. Unfortunately, pharmacological treatments for osteoporosis have been met with resistance due to significant adverse side effects. This project aims to develop and test a non-invasive device to prevent bone loss in postmenopausal women by delivering vibrational stimulus to skeletal sites that are at high risk for fractures, particularly the hip and spine. Existing vibration devices require patients to stand on a platform for extended periods of time, which can lead to noncompliance, especially in the home setting. Moreover, when delivered through the feet, vibrations are attenuated significantly by the time they reach the hip and spine. The proposed device offers to more directly stimulate these skeletal sites of interest using accelerometer- based feedback while allowing patients to wear the device during many everyday activities, which is hypothesized to increase compliance. TheraNova will test this hypothesis through an initial feasibility study involving 20 postmenopausal women who will use the device 10 minutes per day for 16 weeks. Before beginning the study, refinements to the device will be made with user input to ensure that it will be comfortable for the study participants. Compliance rates during the16-week study will be tracked and compared with rates from prior studies that have used vibration platforms. It is expected that the wearable vibration device will have higher rates of compliance than the platform devices. In addition to tracking compliance, this proposal aims to measure changes in levels of bone turnover in the study participants through analysis of urinary collagen cross-linked N-telopeptide (NTx) and bone-specific alkaline phosphatase (ALP), biochemical markers for bone resorption and formation. It is expected that NTx levels will decrease and ALP levels will increase over the course of the 16-week study, which will support the therapeutic feasibility of the wearable vibration device. Furthermore, effectiveness of the device in decreasing NTx and increasing ALP is expected to correlate with levels of compliance. Successful completion of this research will form the basis for a much larger study that will investigate the effect of the wearable vibration device on bone mineral density (BMD) and fracture rates in postmenopausal women.

Thesaurus Terms:
Activities Of Daily Living;Address;Adverse Effects;Affect;Age;Alkaline Phosphatase;American;Attenuated;Attenuation;Base;Biochemical Markers;Bisphosphonate;Bone;Bone Density;Bone Growth;Bone Loss;Bone Necrosis;Bone Resorption;Bone Turnover;Clinical;Collagen;Commercialization;Computers;Cost;Crosslink;Design;Development;Devices;Direct Costs;Disease;Effectiveness;Elderly;Elements;Enrollment;Ensure;Ergonomics;Esophagus;Experience;Feasibility Studies;Feedback;Femoral Fractures;Foot;Foundations;Fracture;Frequencies (Time Pattern);Health;High Risk;Hip Fractures;Hip Region Structure;Home Environment;Improved;Innovation;Interest;Jaw;Knee;Lead;Leg;Literature;Manikins;Marketing;Measures;Meetings;Motor;N-Telopeptide;Non-Compliance;Osteogenesis;Osteoporosis;Osteoporosis With Pathological Fracture;Outcome;Participant;Patients;Pharmacological Treatment;Phase;Pilot Projects;Positioning Attribute;Postmenopause;Prevent;Protocols Documentation;Prototype;Public Health Medicine (Field);Public Health Relevance;Questionnaires;Randomized Controlled Trials;Reading;Research;Resistance;Serum;Site;Skeletal;Stimulus;Success;Testing;Therapeutic;Time;Transmission Process;United States;Urinary;User-Friendly;Validation Studies;Vertebral Column;Vibration;Walking;Weight;Woman;Wrist;

Osteopenia is a highly common skeletal condition with accelerated loss of bone mass that leads to osteoporosis. Characterized by below normal bone mineral density (BMD), osteopenia affects 43 million Americans. If BMD loss is not mitigated, patients become osteoporotic and are at increased risk of bone fractures, particularly of the hip and spine. Such fractures decrease independent living, shorten life and increase morbidity. Clinical guidelines for treating osteopenia include both dietary modifications and high impact exercise. While diet and exercise are highly effective in maintaining BMD, compliance is low. The alternative is prescribed bisphosphonates, which effectively inhibit bone resorption. However, serious adverse events with prolonged use limit their use to patients with osteoporotic levels of BMD, when their antifracture benefits considerably outweigh their potential for harm. Our scientific premise is that delivering mechanical stimulation to the hips and spine via a wearable vibration device can serve as a surrogate for exercise and thus, an effective non-drug intervention for osteopenia. Whole body vibration, which is administered by standing on a vibrating platform, has demonstrated significant improvement in BMD in some cases. However, with substantial attenuation of vibration as it passes through the body, a high and unsafe vibration magnitude is required to elicit an improvement in hip and spine BMD in older individuals. TheraNova has developed Mimetix, a novel wearable vibration device designed to provide controlled, safe and therapeutic mechanical stimulation localized to the hip and spine in order to mitigate bone mass loss and fracture risk. In our clinical Phase I studies, we successfully demonstrated that Mimetix provides: (1) Delivery of consistent mechanical stimulation localized to the hips and spine, (2) Effective mitigation of bone resorption (observed via bone turnover markers (BTMs)) using safe magnitudes of vibration and (3) Enhanced potential for patient compliance based on ease-of-use and comfort. The goal of this proposal is to validate the efficacy of Mimetix treatment on improving bone resistance to fracture (bone strength) and BMD. In Specific Aim 1, we will conduct a 6-week study with 20 postmenopausal patients to verify that the Mimetix device can be tuned to apply a consistent acceleration dose to each patient. During both in-clinic and at-home use, accelerations will be monitored via body worn accelerometers to validate personalized device calibration for delivery of consistent levels of vibrational acceleration that are both therapeutic and safe (a) across different patients; (b) over an extended time period; and (c) during at-home daily activities. In Specific Aim 2, we will conduct an 18-month, prospective, single-blinded, at-home study to validate the efficacy of mechanical stimulation via the Mimetix device compared to a sham device in 110 postmenopausal, osteopenic patients. Efficacy will be evaluated based on (a) hip bone strength, (b) hip and spine BMD and (c) BTMs indicative of both bone formation and resorption. Once completed, the results from these studies support regulatory approval and commercialization, allowing Mimetix to meet the large, unmet clinical need for a simple, non-invasive, effective treatment for osteopenia.

Public Health Relevance Statement:
Narrative Osteopenia is a highly common skeletal condition with accelerated loss of bone mass, which affects about 43 million Americans. If bone mass loss is not mitigated, patients become osteoporotic with serious clinical consequences due to fractured bones. There is a need for an effective non-drug intervention to prevent early progression of bone loss prior to patients reaching an osteoporotic state. We propose a novel wearable vibration device that is designed to provide controlled, safe and consistent mechanical stimulation to the hip and spine to mitigate bone mass loss and fracture risk.

Project Terms:
Acceleration; Accelerometer; Affect; age related; Aging; American; Animals; Attenuated; attenuation; base; bisphosphonate; bone; Bone Density; bone loss; bone mass; Bone Resorption; bone strength; bone turnover; Calibration; Clinic; Clinical; Collaborations; commercialization; Compliance behavior; Control Groups; Data; design; Device Designs; Devices; diet and exercise; Diet Modification; Doctor of Philosophy; Dose; Dual-Energy X-Ray Absorptiometry; effective therapy; Ensure; Exercise; Feedback; Fracture; fracture risk; Future; Goals; Guidelines; hip bone; Hip region structure; Home environment; Human; Image Analysis; improved; Incidence; Independent Living; Individual; Intervention; Joints; Life; Mechanical Stimulation; Medical center; Monitor; Morbidity - disease rate; Motor; Nebraska; non-drug; novel; Osteoclasts; Osteogenesis; Osteopenia; Osteoporosis; Osteoporotic; Patients; Phase; phase 1 study; Placebos; Population; Postmenopause; prevent; prospective; Randomized; Resistance; Risk; Serious Adverse Event; Single-Blind Study; skeletal; Therapeutic; Time; Universities; Vertebral column; vibration; Woman; Work; X-Ray Computed Tomography