A method for continuous adherence and duration signals for bone healing

Abstract

A method of treating a bone fracture in a patient with a co-morbidity and in need of bone fracture treatment, comprising administering to the patient 30 consecutive treatments of low-intensity pulsed ultrasound to the bone, wherein the consecutive treatments are consecutive daily treatments. The method may further include reducing the incidence of non-union fractures of the bone in a patient in need thereof, tracking the treatment of the patient, and healing the bone to complete healing.

Description

[Technical Field]

[0001] Described herein is a novel method for treating bone fractures using low intensity pulsed ultrasound. [Background technology]

[0002] Fractures are common injuries for individuals worldwide. Rehabilitation after injury can be a lengthy process, resulting in impaired mobility and function. Patients may also experience delayed union or nonunion, respectively. An estimated 10% of individuals suffer from improper healing (Einhorn et al., 2014). The normal healing process begins with an inflammatory phase after injury, which initiates matrix formation and solidification. This is followed by a fibrovascular phase to remodel damaged blood vessels and restore nutrient supply. Revascularization leads to the bone formation phase. Stem cells necessary for bone growth are then recruited and can differentiate into either osteoblasts, chondrocytes, or other bone-forming cells to complete the restoration of bone structure at the fracture site (Bahney et al., 2019).

[0003] One approach to treating fractures is the use of therapeutic ultrasound to accelerate and support proper healing. A typical treatment consists of low-intensity pulsed ultrasound in an optimal frequency range for an optimal duration. Ultrasound provides cyclical mechanical sound waves passing through tissue, which may support all biological stages of bone healing. Vascular remodeling and early bone growth are also promoted by ultrasound therapy through modulation of growth-related and differentiation signaling. Finally, ultrasound is thought to support the bone remodeling phase in a manner similar to mechanical force or physical loading (Jiang et al., 2018).

[0004] Poor patient compliance presents an additional hurdle to recovery and healing, especially when patients are required to self-administer the therapy. However, direct feedback compliance of patients self-administering ultrasound therapy has been found to significantly impact patient compliance (Pounder et al., 2016).

[0005] Incorporation by Reference All publications, patents, and patent applications mentioned in this specification are herein incorporated by reference for their background teachings to the same extent as if each individual publication, patent, or patent application was specifically and individually indicated to be incorporated by reference. Summary of the Invention

[0006] In one embodiment described herein, a method of treating a bone fracture in a patient with a co-morbidity and in need of bone fracture treatment comprises administering 30 consecutive treatments of low intensity pulsed ultrasound to the bone to the patient. In one aspect of this method, the co-morbidity includes smoking, diabetes, obesity, or cardiovascular disease. In another aspect of this method, the bone includes a short bone and a long bone. In another aspect of this method, the short bone includes a navicular bone. In another aspect of this method, the long bone includes a tibia.

[0007] In another aspect, the method further includes tracking the patient's treatment. In another aspect, the tracking includes using a compliance calendar, a goal progress tracker, or a continuity tracker.

[0008] In another embodiment, the method further comprises administering about 60 to about 120 successive treatments to the patient. In another embodiment, the method further comprises administering about 60 successive treatments to the patient. In another embodiment, the method further comprises administering about 90 successive treatments to the patient. In another embodiment, the method further comprises administering about 120 successive treatments to the patient.

[0009] In another aspect, the method further comprises allowing the bone to heal to complete the healing, hi another aspect, the method further comprises clinically significant healing.

[0010] Another embodiment described herein is a method of reducing the incidence of nonunion fractures of a bone in a patient in need thereof, the method comprising: a) administering 30 successive treatments of low-intensity pulsed ultrasound to the bone; b) tracking the treatments of the patient; and c) allowing the bone to heal to complete healing. In another aspect, the bone comprises the navicular bone or the tibia. In another aspect, tracking comprises using a compliance calendar, a goal progress tracker, or a continuity tracker. In another aspect, the method further comprises administering an additional 30 successive treatments.

[0011] The features of the present disclosure are set forth with particularity in the appended claims. A better understanding of the features and advantages of the present disclosure will be obtained by reference to the following detailed description that sets forth illustrative embodiments, in which the principles of the disclosure are utilized, and the accompanying drawings. [Brief explanation of the drawings]

[0012] [Figure 1] We describe the results of a clinician survey demonstrating the average number of days of low-intensity pulsed ultrasound use to treat fractures. [Figure 2] Describe tracking tools that patients can use to track treatment and ensure adherence. [Figure 3] The odds ratios (ITT) of pseudarthrosis for patients using EXOGEN® versus the matched cohort are described. DETAILED DESCRIPTION OF THE INVENTION

[0013] The following description and examples illustrate in detail embodiments of the present disclosure.

[0014] It should be understood that the present disclosure is not limited to the particular embodiments described herein, as such may vary, and those skilled in the art will recognize that there are variations and modifications of the present disclosure that are encompassed within the scope of the present disclosure.

[0015] All terms are intended to be understood as understood by one of ordinary skill in the art. Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this disclosure pertains.

[0016] The section headings used herein are for organizational purposes only and are not to be construed as limiting the subject matter described.

[0017] Although various features of the present disclosure may be described in the context of a single embodiment, these features may also be provided separately or in any suitable combination. Conversely, although the present disclosure may be described herein with respect to separate embodiments for clarity, the present disclosure may also be implemented in a single embodiment. The following definitions supplement definitions in the art and are directed to this application and should not be attributed to any related or unrelated case, for example, any commonly owned patent or application. Although any methods and materials similar or equivalent to those described herein can be used in the practice of testing the present disclosure, preferred materials and methods are described herein. Therefore, the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting.

[0018] In this application, the use of the singular includes the plural unless specifically stated otherwise. It must be noted that as used herein, the singular forms "a," "an," and "the" include plural references unless the context clearly indicates otherwise.

[0019] In this application, the use of "or" means "and / or" unless stated otherwise. As used herein, the terms "and / or" and "any combinations thereof," and their grammatical equivalents, may be used interchangeably. These terms may convey that any combination is specifically contemplated. For illustrative purposes only, the following phrases "A, B, and / or C" or "A, B, C, or any combinations thereof" may mean "individually A, individually B, individually C, A and B, B and C, A and C, and A, B, and C." The term "or" may be used conjunctively or disjunctively unless the context specifically dictates disjunctive use.

[0020] Furthermore, the use of the term "including" and other forms such as "include," "includes," and "included" is not limiting.

[0021] References herein to "some embodiments," "some aspects," "embodiments," "aspects," "another aspect," "one embodiment," "one aspect," or "other embodiments" or "other aspects" mean that a particular feature, structure, or characteristic described in connection with an embodiment is included in at least some, but not necessarily all, embodiments of the present disclosure.

[0022] As used in the specification and claim(s), the words "comprising" (and any form of "comprising," such as "comprise" and "comprises"), "having" (and any form of "having," such as "have," "has"), including (and any form of "including," such as includes, include), or "containing" (and any form of "containing," such as "contains" and contain) are inclusive or open-ended and do not exclude additional, unrecited elements or method steps. It is contemplated that any embodiment discussed herein can be implemented with respect to any method or configuration of the disclosure, and vice versa. Furthermore, the compositions of the disclosure can be used to achieve the methods of the disclosure.

[0023] The term "about" or "approximately" means within an acceptable error range for a particular value as determined by one of ordinary skill in the art, which depends in part on how the value is measured or determined, i.e., the limitations of the measurement system. For example, "about" can mean within 1 or more than 1 standard deviation, as is customary in the art. Alternatively, "about" can mean a range of up to 20%, up to 10%, up to 5%, or up to 1% of a given value. In another example, the amount "about 10" includes 10 and any amount from 9 to 11. In yet another example, the term "about" in reference to a numerical reference can also include a range of values ​​of plus or minus 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% from that value. Alternatively, particularly with respect to biological systems or processes, the term "about" can mean within an order of magnitude of a value, preferably within 5-fold, and more preferably within 2-fold. Where specific values ​​are recited in this application and claims, unless otherwise stated, the term "about" should be assumed to mean within an acceptable range of error for the particular value.

[0024] As used herein, the term "comorbidity" refers to the simultaneous presence of two or more medical conditions and / or diseases in a patient. In the present disclosure, comorbidity may refer to diseases or medical conditions in addition to fractures. Any comorbidity is contemplated herein, including, for example, cardiovascular disease, cirrhosis, chronic obstructive pulmonary disease (COPD), osteoporosis, diabetes, cancer, renal failure, obesity, or arthritis. Furthermore, comorbidity may also include concomitant medication use, including, for example, anticoagulant use, anticonvulsant use, benzodiazepine use, bisphosphonate use, cardiac mediator use, diuretic use, hormone replacement therapy use, insulin use, antidiabetic (non-insulin) use, nonsteroidal anti-inflammatory drug (NSAID) use, opioid use, oral contraceptive use, steroid use, smoking cessation product use, proton pump inhibitor use, SSRI antidepressant use, or thyroid medication use.

[0025] As used herein, the term "composition" is intended to encompass a product containing the specified ingredients in the specified amounts, as well as any product resulting, directly or indirectly, from combining the specified ingredients in the specified amounts. "Pharmaceutically acceptable" means that the carrier, diluent, or excipient must be compatible with the other ingredients of the formulation, including the vector described herein, and not deleterious to the recipient thereof. A "pharmaceutically acceptable carrier" is any carrier that is relatively non-toxic and innocuous to a patient at concentrations consistent with the effective activity of the active ingredient, such that any adverse side effects attributable to the carrier do not impair the beneficial effects of the active ingredient.

[0026] As used herein, the term "continuous treatment" refers to continuous daily treatment using low intensity pulsed ultrasound in a particular setting.

[0027] As used herein, the term "pseudounion" refers to a fracture that has not healed. The most agreed-upon definition of a nonunion is a fracture that persists for three months without signs of healing. A nonunion may also refer to a nonhealed fracture that shows no signs of healing after clinical evaluation when examined by a physician and using serial radiographs taken at 45-90 day intervals.

[0028] "Patient" or "subject," as used herein, refers to a mammalian subject who has been diagnosed with or is suspected of having a fracture. In some embodiments, the term "patient" refers to a mammalian subject who has a higher-than-average likelihood of developing a non-union fracture. Exemplary patients can be humans, apes, dogs, pigs, cows, cats, horses, goats, sheep, rodents, and other mammals that may benefit from the therapies disclosed herein. Exemplary human patients can be male and / or female. "Patient in need thereof" or "subject in need thereof," as used herein, refers to a patient who has been diagnosed with or is suspected of having a disease or disorder, such as, but not limited to, rheumatoid arthritis.

[0029] "Administering," as used herein, refers to providing one or more compositions or therapies described herein to a patient or subject. By way of example and not limitation, administration, e.g., injection, of a composition can be performed by intravenous (i.v.), subcutaneous (i.c.), intradermal (i.d.), intraperitoneal (i.p.), or intramuscular (i.m.) injection. One or more such routes can be used. Parenteral administration can be, for example, by bolus injection or slow perfusion over time. Alternatively, or concurrently, administration can be by oral route. Additionally, administration can also be by surgical deposition of a bolus or pellet of cells or positioning of a medical device. In one embodiment, a composition of the present disclosure can comprise a gel used with a low-intensity pulsed ultrasound device in an amount effective to treat or heal a fracture. Administering may further refer to administering a therapy of the present disclosure, which may include administering low intensity ultrasound in an amount effective to treat, repair, or promote healing of a bone fracture in a patient in need of treatment of the bone fracture.

[0030] As used herein, the terms "treatment," "treating," or grammatical equivalents thereof, refer to obtaining a desired pharmacological and / or physiological effect. In some embodiments, the effect is therapeutic, i.e., the effect partially or completely cures a disease and / or condition. In some embodiments, the term "treating" can include inhibiting or "preventing" a disease or condition, including treating a bone fracture. In some embodiments, the term "treating" can include "repairing" or "healing" a bone fracture.

[0031] As used herein, a "treatment interval" refers to a treatment cycle, e.g., a course of administration of a therapeutic agent or therapy, which may be repeated on a regular schedule. In some embodiments, a dosing regimen may have one or more periods without administration of a therapeutic agent during the treatment interval.

[0032] The terms "therapeutically effective amount," "therapeutic amount," or grammatical equivalents thereof, refer to an amount effective, at a dosage or setting, for a period of time necessary, to achieve a desired therapeutic result. A therapeutically effective amount may vary depending on factors such as an individual's disease state, age, sex, and weight, and the ability of the compositions described herein to induce a desired response in one or more subjects. The exact amount of a composition or therapy of the present disclosure to be administered can be determined by a physician, taking into account the patient's (subject's) age, weight, tumor size, degree of inflammation, infection, or metastasis, and individual differences in the condition. For example, a therapeutically effective amount of low-intensity pulsed ultrasound may be the amount, specific setting, recommended by a medical device manufacturer or prescribed by a physician over a treatment period.

[0033] As used herein, the term "treatment period" refers to the administration of a specific medical treatment, e.g., low-intensity pulsed ultrasound treatment for a bone fracture, administered in a specific setting over a period of time, e.g., several days. Thus, a treatment period can include the administration of low-intensity pulsed ultrasound over a treatment period of, e.g., 1-120 days, 1-90 days, 1-60 days, 1-30 days, or 1-15 days.

[0034] For the recitation of numerical ranges herein, each intervening number is expressly contemplated to the same degree of precision. For example, for the range 6 to 9, the numbers 7 and 8 are contemplated in addition to 6 and 9, and for the range 6.0 to 7.0, the numbers 6.0, 6.1, 6.2, 6.3, 6.4, 6.5, 6.6, 6.7, 6.8, 6.9, and 7.0 are expressly contemplated.

[0035] This disclosure describes a novel method for treating bone fractures using low-intensity ultrasound that includes tracking tools to aid patient adherence and results in clinically significant healing in a shorter time than the current standard of care.

[0036] While successful treatments for fractures currently exist, the duration of treatment after injury remains a challenge to positive patient outcomes. Elderly patients or those with comorbidities are more susceptible to complications in healing and recurrence than those without. The use of ultrasound to therapeutically treat and evaluate bone injuries is known. However, the success of ultrasound treatment depends on patient compliance with the treatment regimen. (Harrison et al., 2021) A shorter treatment period has been shown to increase patient compliance and provide positive economic benefits due to shorter healing times and reduced risk of improper healing. (Sklar et al., 2008) Accordingly, one embodiment described herein is a method of treating a fracture in a patient in need of treatment using low-intensity pulsed ultrasound.

[0037] Ultrasound delivery systems generally use pulsed high-frequency waves (in the MHz range) to treat bone fractures. These systems utilize the piezoelectric properties of bone. When ultrasound waves are applied to a fractured bone, they are converted into electrical currents within the bone to promote healing through small deflections within the bone. Such systems are well known, including those described in, for example, U.S. Pat. Nos. 5,003,965, 5,186,162, 5,556,372, and the EXOGEN® Ultrasound System, all of which are incorporated herein by reference for their general teachings. However, other ultrasound application devices can be used in the methods described herein. In one aspect, the ultrasound waves are low-intensity pulsed ultrasound waves.

[0038] Ultrasound therapy can be used to treat fractures of any bone type, including the long and short bones of the arms and legs, the short bones of the wrist and ankle, flat bones such as the scapula, sternum, and skull, and irregular bones such as the vertebrae. In one aspect, the bone includes the humerus, metatarsal, and ankle. In one aspect, the bone includes the distal phalanx of the thumb, the proximal phalanx of the thumb, or a phalange, including any of the distal, middle, or proximal phalanges. In another aspect, the bone includes a metacarpal. In another aspect, the bone includes the carpal bones, including the ulna and radius, the trapezoid, the trapezoid, the capitate, the navicular, the lunate, the triquetrum, the hamate, or the uncinate. In another aspect, the bone includes any of the bones of the leg, including the femur, patella, tibia, or fibula. In one aspect, the bone includes the navicular or tibia.

[0039] Ultrasound therapy treatment may involve the administration of ultrasound therapy at specific settings and for a defined treatment period. Treatment settings include specified intensity, frequency, and wavelength. For example, the EXOGEN® Ultrasound Bone Healing System (Model Number 71034400) device provides 30 mW / cm 2 The standard settings are used: power density of 1 kHz, a 1.5 MHz signal, and punctuality of 1 kHz, 20% duty cycle. Thus, in one aspect, treatment may include daily treatment with standard settings for a low intensity pulsed ultrasound device.

[0040] The current standard of care for fractures includes cast immobilization and non-surgical treatment (e.g., https: / / www.aafp.org / pubs / afp / issues / 2004 / 0901 / p879.html). The standard of care for low-intensity pulsed ultrasound is limited to treatment with a device set for a prescribed number of minutes for daily use. However, clinicians vary in the number of days such treatment should be continued (i.e., the treatment duration over several days). Thus, while patients may comply with daily use, adherence to the treatment duration appropriate for complete healing remains uncertain. Furthermore, patient adherence to the set treatment duration is difficult. A survey of clinicians using low-intensity pulsed ultrasound devices to treat fractures found that clinicians continue using such therapy until complete healing, but generally prescribe use for 70 to 90 days, as seen in Figure 1.

[0041] In one embodiment of the methods described herein, the administration of low intensity pulsed ultrasound to the patient comprises a daily treatment for about 10 minutes to about 30 minutes, about 15 minutes to about 20 minutes, about 10 minutes, about 15 minutes, about 20 minutes, about 25 minutes, or about 30 minutes. In one embodiment, the administration of low intensity pulsed ultrasound to the patient comprises a daily treatment for about 20 minutes. In another embodiment of the methods described herein, the administration of low intensity pulsed ultrasound to the patient comprises a once-daily, twice-daily, or three-daily treatment. A treatment period can include one or more treatments over a specific time interval. In one aspect, the treatment period comprises daily treatment with standard device settings for about 1 to about 10 consecutive days, about 1 to about 15 consecutive days, about 1 to about 20 consecutive days, about 1 to about 25 consecutive days, about 1 to about 30 consecutive days, about 1 to about 45 consecutive days, about 1 to about 50 consecutive days, about 1 to about 65 consecutive days, about 1 to about 75 consecutive days, about 1 to about 80 consecutive days, about 1 to about 90 consecutive days, about 1 to about 100 consecutive days, about 1 to about 115 consecutive days, about 1 to about 120 consecutive days, about 1 to about 125 consecutive days, about 1 to about 135 consecutive days, or about 1 to about 150 consecutive days.

[0042] In yet another embodiment of the methods described herein, the patient is administered low intensity pulsed ultrasound for 1 to about 120 consecutive treatments ("consecutive treatments" refers to consecutive daily treatments), 1 to about 90 consecutive treatments, 1 to about 60 consecutive treatments, 1 to about 30 consecutive treatments, 1 to about 15 consecutive treatments, about 2 to about 10 consecutive treatments, about 5 to about 20 consecutive treatments, about 10 to about 25 consecutive treatments, about 15 to about 25 consecutive treatments, about 20 to about 30 consecutive treatments, about 25 to about 35 consecutive treatments, about 30 to about 40 consecutive treatments, about 35 to about 45 consecutive treatments, about 40 to about 50 consecutive treatments, or the like. The preferred treatments include about 10 consecutive treatments, about 18 consecutive treatments, about 25 consecutive treatments, about 30 consecutive treatments, about 45 consecutive treatments, about 60 consecutive treatments, about 75 consecutive treatments, about 80 consecutive treatments, about 90 consecutive treatments, about 100 consecutive treatments, about 18 consecutive treatments, about 25 consecutive treatments, about 30 consecutive treatments, about 45 consecutive treatments, about 60 consecutive treatments, about 75 consecutive treatments, about 90 consecutive treatments, or about 120 consecutive treatments. In one aspect of the methods described herein, the administration of low intensity pulsed ultrasound to the patient comprises a single treatment per day for 20 minutes, for 30 days, for 45 days, for 60 days, for 75 days, for 90 days, or for 120 days. In another aspect, the administration of low intensity pulsed ultrasound to the patient comprises continuous treatment (continuous daily treatment for a defined period of days). In another aspect of the methods described herein, the administration of low intensity pulsed ultrasound to the patient comprises a treatment interval.

[0043] Thus, in another aspect, the method further includes tracking the patient's treatment. Tracking includes recording the patient's treatment, including ongoing treatment, and progress toward treatment goals. Thus, tracking provides a means for patient compliance and encouragement. Various tools can be used to accomplish the recording and tracking. In one aspect, tracking includes the use of a compliance calendar. The compliance calendar includes a calendar that the patient uses not only to remind them of their treatment, but also to record their treatment and thus monitor their progress. The compliance calendar can include tracking treatments administered out of the total treatments required to reach a goal. In another aspect, tracking includes the use of a progress toward goal tool. The progress toward goal tool includes the number of treatments completed, the total treatment goal, and a timer to assist the patient in completing the treatment regimen. In another aspect, tracking includes the use of an adherence tracker that counts the number of complete treatments per day since the first treatment. In another aspect, tracking includes a continuity tracker that tracks the total number of consecutive treatment days to track and encourage the patient to adhere to continuous, uninterrupted daily treatment. An exemplary tracking tool is shown in FIG. 2.

[0044] In one aspect, bone healing includes complete healing. Complete healing refers to when a clinician determines that a fracture has healed, typically using radiographic and clinical evaluations to assess pain, range of motion, strength, and other parameters. Assessment of complete healing may result in cessation of further treatment. If complete healing is not achieved, the patient may continue treatment for an additional period of treatment as determined by the physician. In another aspect, bone healing includes clinically significant healing. Clinically significant healing refers to healing with a pseudarthrosis odds ratio of 1.5, meaning that patients not using low-intensity pulsed ultrasound are 1.5 times more likely to develop a pseudarthrosis than patients using low-intensity pulsed ultrasound.

[0045] It will be readily apparent to those skilled in the relevant art that suitable modifications and adaptations to the compositions, methods, and applications described herein can be made without departing from the scope of any embodiment or aspect thereof. The compositions and methods provided are exemplary and are not intended to limit the scope of any of the specified embodiments. All of the various embodiments, aspects, and options disclosed herein can be combined in any and all variations or iterations. The scope of the compositions, formulations, methods, and processes described herein includes all actual or potential combinations of the embodiments, aspects, options, examples, and preferences described herein. [Example]

[0046] Example 1 Low-Intensity Pulsed Ultrasound (LIPUS) Therapy to Reduce the Risk of Pseudoarthrosis in At-Risk Patients A 9-month study was conducted to demonstrate that treatment of scaphoid fractures with EXOGEN® is effective in reducing the incidence of fracture pseudarthrosis in patients at risk for scaphoid fractures compared to standard of care alone (including conservative fracture management with cast immobilization or surgical repair) using low-intensity pulsed ultrasound (LIPUS). The primary study endpoint was based on the incidence of scaphoid fracture pseudarthrosis, as measured by clinician diagnosis in the form of an International Classification of Diseases (ICD) pseudarthrosis diagnosis.

[0047] Target population: EXOGEN Treatment Cohort: Adult patients (ages 21-60) in the United States (US) at risk for developing a fracture nonunion who were prescribed EXOGEN® as adjunctive treatment for scaphoid fractures.

[0048] Treatment regimen: Patients received prescribed therapy with the EXOGEN® Ultrasound Bone Healing System (Model Number 71034400) for scaphoid fractures as identified by ICD-10-CM codes. The EXOGEN® product was used as administered, once daily for 20 consecutive minutes, through patient self-administered therapy at home or at work. Each patient was periodically evaluated by a physician and radiographed for this data. If a patient was not seen by a physician within the allotted time, they were excluded from the study.

[0049] The length of the treatment window was variable and determined by the treating clinician's assessment of the healing process. Clinicians generally recommend using the EXOGEN® System for the treatment of scaphoid fractures for 90 days to achieve complete healing, which refers to when the clinician determines that the fracture has healed. This is typically done through a combination of x-rays and clinical evaluation to determine pain, range of motion, strength, etc.

[0050] result: Figure 3 describes the results as the odds ratio (ITT) of nonunion for patients using EXOGEN® compared to the matched cohort. For this study, clinical significance was defined as an odds ratio of 1.5, indicating that the outcome of the control group with a nonunion fracture was 1.5 times that of the group using the EXOGEN® System for treatment. The p-value demonstrates statistical significance.

[0051] A correlation between clinical effectiveness and patient compliance with the use of low-intensity pulsed ultrasound has been reported (Pounder et al., 2016), with data showing that 8 out of 10 clinical trials with patient compliance greater than 72% reported successful outcomes, while 2 clinical trials reported insufficient patient compliance and resulted in unsuccessful outcomes. However, compliance was based on daily usage. Thus, while the results indicate that patients can achieve 100% treatment compliance with daily treatments, there is no indication of the total number of daily treatments required for complete cure. Therefore, the results described in Figure 2 further suggest that complete cure may occur with more days of daily treatment than the current standard of care prescribed by physicians.

[0052] Example 2 Future studies similar to those described above will be conducted using patients with tibial fractures.

[0053] Although the above disclosure has been described in some detail by way of illustration and example for purposes of clarity of understanding, it will be readily apparent to those skilled in the art that, in light of the teachings of the present invention, certain changes and modifications can be made thereto without departing from the spirit or scope of the appended claims. The following examples are provided by way of illustration only, and not by way of limitation. Those skilled in the art will readily recognize a variety of non-critical parameters that can be changed or modified to yield essentially similar results.

Claims

1. 1. A method of treating a bone fracture in a patient having a co-morbidity and in need of bone fracture treatment, comprising administering to the patient 30 successive treatments of low intensity pulsed ultrasound to the bone.

2. 10. The method of claim 1, wherein the comorbidity comprises smoking, diabetes, obesity, or cardiovascular disease.

3. The method of claim 1 , wherein the bones include short bones and long bones.

4. The method of claim 3 , wherein the short bone comprises a navicular bone.

5. The method of claim 3 , wherein the long bone comprises a tibia.

6. The method of claim 1 , further comprising tracking treatment of the patient.

7. The method of claim 6 , wherein the tracking includes using a compliance calendar, a goal progress tracker, or a continuity tracker.

8. 8. The method of claim 7, further comprising administering about 60 to about 120 successive treatments to the patient.

9. 10. The method of claim 8, further comprising administering about 60 successive treatments to the patient.

10. 10. The method of claim 9, further comprising administering about 90 successive treatments to the patient.

11. 10. The method of claim 9, further comprising administering about 120 successive treatments to the patient.

12. The method of claim 1 , wherein the method further comprises allowing the bone to heal to complete healing.

13. 10. The method of claim 1, wherein the method further comprises a clinically significant cure.

14. 1. A method of reducing the incidence of non-union fractures of a bone in a patient in need thereof, comprising: a) administering 30 consecutive treatments of low intensity pulsed ultrasound to bone; b) tracking the treatment of said patient; c) allowing the bone to heal to complete healing.

15. The method of claim 14 , wherein the bone comprises a navicular bone or a tibia.

16. The method of claim 14 , wherein the tracking includes using a compliance calendar, a goal progress tracker, or a continuity tracker.

17. 15. The method of claim 14, further comprising administering an additional 30 subsequent treatments.

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