CROSS REFERENCE TO RELATED APPLICATION 
   The present application is a continuation of U.S. patent application Ser. No. 10/419,005, filed Apr. 18, 2003, which claims the benefit of U.S. provisional patent application No. 60/373,546 filed on Apr. 18, 2002, the entirety of which are incorporated herein by reference. 


   STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH 
   This invention was made with United States Government support from the National Institute of Health through Grant No. 1R15HL67787-01. The United States Government has certain rights in this invention. 


   FIELD OF THE INVENTION 
   This invention relates generally to non-invasive musculoskeletal loading devices which provide adjustable loading. 
   BACKGROUND OF THE INVENTION 
   The health of human bones is of enormous importance. Bones provide support and protection for the human body. Osteoporosis is a disease characterized by low bone mass and structural deterioration of bone tissue which can seriously impede the ability of osteoporotic bones to provide support and protection for the body. An increased risk of bone fracture is present in individuals with osteoporosis. In 1995 alone, the cost of treatment for osteoporotic bone fractures was $13.8 billion. Around 28 million American&#39;s suffer from low bone mass or osteoporosis and are at risk of adding to the yearly cost of treatment for the disease. One in every 2 women and 1 in every 8 men over the age of 50 will develop a fracture in their lifetime due to the disease. With changing demographics and the aging of America, the significance of this national as well as international concern will only increase. 
   Bone disuse atrophy is a disease that can also lead to osteoporosis. While undergoing long flights in space, astronauts suffer from a lack of weight bearing on their bones. Bone disuse atrophy has been seen to cause decreases in bone mass from 1-2% per month in astronauts. Decreases in bone mass of this magnitude could seriously impede an astronaut&#39;s bone health during long duration space flight, such as what will someday be incurred by astronauts on roundtrip missions to Mars or other planets. With the closest medical assistance for an astronaut being millions of miles away, it is of key importance that an astronaut&#39;s bones do not degrade to a point where they risk fracture during missions. 
   The majority of current countermeasures for bone disuse atrophy are not entirely effective. Mineral and hormone treatments have been administered as attempts to maintain bone mass, but have had little benefit in the long run. Mechanical stimulation of bone has been shown to achieve the goal of maintaining bone mass and structure. However, some methods of applying mechanical stimuli may be more damaging than good, while others may only partially aid in the maintenance of bone strength. 
   Recent research involving the effects of vibrational bone loading have proved successful at increasing bone density in sheep. This and related research have utilized a vibrating platform upon which the sheep or other subject stands. Because this arrangement relies on gravity, the arrangement does not provide an adjustable load and loses its effectiveness as gravity is reduced. 
   SUMMARY 
   A device for non-invasively mechanically stimulating bone or muscle includes a vibrational energy generator for applying vibrational energy to a first end of a length of a tissue which includes bone and/or muscle. The vibrational energy is for inducing strain in at least one region within the length of tissue. A restraint is disposed opposite the first end of the length to resist translation of the tissue length or the device during operation of the device, and to provide compressive or tensile loading to the bone or muscle. The restraint can be disposed on a variety of bodily regions, including the knee, waist and shoulder. 
   A connecting structure couples the restraint across the tissue to be treated. The device does not require gravity to operate and as a result is expected to have applications in space, such as with astronauts, with those having bone ailments such as bed-ridden patients, persons with osteoporosis or disuse atrophy, athletes, recovering bone cancer patients, and persons with musculoskeletal disorders. 
   The level or frequency of the vibrational energy applied can be adjustable. The length of the connecting structure also can include structure for adjustment, wherein shortening the length provides compression and lengthening the length provides tension to the tissue region. The connecting structure can include a sensor for measuring a level of applied compression or tension. 
   The vibrational energy generator can comprises an adjustable cam driven by a motor. A speed controller is preferably provided and connected to the motor for controlling a speed of the motor. The arrangement provides an adjustable frequency spectrum output by the vibrational energy generator. The motor can drive a follower plate. 
   The connecting structure can comprises a plurality of structures which are each disposed circumferentially along a volume which includes the tissue length. The plurality of structures can be activateable independently, wherein activation of some but not all of the plurality of structures provides circumferential compression which varies as a function of angular position along at least a portion of the tissue length being treated. 
   A gravity-independent method for non-invasively mechanically stimulating bone or muscle, includes the steps of restraining a tissue region of a subject comprising at least one of bone and muscle, and applying vibrational energy through the region to induce strain in the region. The method can include the step of imposing a compressive or tensile force on the region during the applying step. The magnitude of the compressive or tensile force can be adjustable. 
   The method can be performed in a substantially weightless environment, such as space. The method can also be performed on earth, such as applied to supine subjects as no gravity is required to practice the claimed method. 
   The method can include the step of providing a vibrational energy generator, wherein a frequency spectrum provided by the vibrational energy generator is adjustable. The method can be applied to only a portion of the subject thus providing site-specific treatment. The frequency of vibrational energy can be 20, 30, 40, 50, 60 ,70, 80, 90, 100 Hz, or other frequencies. 


   
     BRIEF DESCRIPTION OF THE DRAWINGS 
     A fuller understanding of the present invention and the features and benefits thereof will be accomplished upon review of the following detailed description together with the accompanying drawings, in which: 
       FIG. 1  illustrates an exemplary bone loading device, according to an embodiment of the invention. 
       FIG. 2  shows an exemplary embodiment of a frame, according to an embodiment of the invention. 
       FIG. 3  shows a driving structure which comprises a motor to induce motion in a cam-follower which couples to a follower plate to apply vibrations to a subject, according to an embodiment of the invention. 
       FIG. 4  shows an exemplary connecting structure, according to an embodiment of the invention. 
       FIGS. 5(   a ) and ( b ) show therapy applied at two different knee angles using the invention. 
       FIG. 6  shows an alternative connecting structure which comprises a plurality of separate compression-loading units, according to yet another embodiment of the invention. 
       FIG. 7  shows a restraint for use in connection with the bone loading device of  FIG. 1 . 
       FIG. 8  shows an alternative embodiment of a restraint for use in connection with the bone loading device of  FIG. 1 . 
   


   DETAILED DESCRIPTION OF THE INVENTION 
     FIG. 1  illustrates a device  100  for non-invasively mechanically stimulating bone or muscle in a subject, according to an embodiment of the invention. Device  100  can be used to mechanically stimulate an osteogenic effect in bone or the development of muscle. Device  100  includes a vibrational energy generator  105  for applying vibrational energy to a first end  108  of a length of a tissue to be treated  110  which includes bone and/or muscle therein (not shown). The vibrational energy is for inducing strain in at least one region within the length of the tissue  110 . 
   A restraint  115  is disposed opposite the first end of the length  110  to resist translation of the length during operation of the device  100 . Restraint  115  is coupled to connecting structure  130  which couples restraint  115  to the first end of the length of tissue to be treated, such as through connection to frame  120 . Connecting structure  130  also provides a compressional coupling force and localized tensile forces to the region to be treated, the force preferably being adjustable, such as through variation of its length. Straps  135 , such as Velcro® straps (or equivalent) are preferably provided for securing the connecting structure  130  to the length of tissue to be treated  110 . 
   Unlike earlier vibrational loading devices, device  100  does not require gravity to operate and can be used in microgravity environments (e.g. space) or by supine (e.g. bedridden) individuals on earth. For vibrational treatment, bodily regions must have some coupling force (e.g. compression or tension) acting on them in order for the vibrational energy to transfer through the targeted region. On earth, a person capable of standing upright can utilize their body weight to provide the coupling force to permit vibrational energy to transfer through their body. However, for the gravity reliant systems while in space, when the first vibrational oscillation is applied, the subject would be sent adrift by the vibrational forces because no forces would be holding the vibration-inducing device to the person. In contrast, connecting structure  130 , through its connection across of length of tissue to be treated  110 , provides both a coupling and restraining force which does not depend on gravity. 
   Another advantage provided by device  100  is the ability to treat discrete portions (site-specific treatment) of a subject, rather than the entire subject treated when the individual stands on a vibrational plate. Thus, conventional vibrational loading devices gravitationally load the subject from head to toe, or from a seated position the spine of the subject is loaded. In contrast, device  100  can treat a single discrete tissue length, such as tissue length  110  disposed between the knee and the foot of an individual. 
   Although connecting structure  130  shown in  FIG. 1  physically connects across the length of tissue to be treated  110  to provide a load, physical connection is not required. Loading can also be provided using an electromagnetic attractive force to induce compressive loading, such as using an electrical or magnetic field. For example, restraint  115  and a portion of frame  120  can each be electrodes which if biased with opposite polarities, will produce an attractive force which can provide a compressive load across tissue length  110 . 
     FIG. 2  shows an exemplary embodiment of frame  120  with vibrational energy generator  105  removed. Frame  120  includes a follower plate  215  upon which the first end  108  of a length of a tissue to be treated  110  is placed during operation of the device. However, those having ordinary skill in the art will realize that loading can be applied by structures other than follower plate  215 . Optional strap  235  can be included to further secure the first end  108  of a length of a tissue to be treated  110  to frame  120 . In operation, follower plate  215  is vibrated up and down by a suitable driving structure. 
   In one embodiment shown in  FIG. 3 , vibrational energy to drive follower plate  215  can be produced via driving structure  300  which comprises a motor  315  to induce motion in a cam-follower  320  which couples to follower plate (not shown in  FIG. 3 ). Although not shown, electromagnetic linear actuators and other vibrational energy sources can also be used with the invention. Applied to tissue  110  shown in  FIG. 1 , the mechanical vibrations at the follower plate will transfer the vibrations from the heel or ball of the subject&#39;s foot through tissue length  110 . 
   Although described generally as for treating the region of tissue between the knee and the foot, the invention is in no way limited in this way. Those having ordinary skill in the art will realize a variety of other regions, such as the knee, waist, shoulder, arms and spine can be treated using device  100 . In fact as illustrated in  FIG. 7 , a back restraint  700  with a lower back coupling pad  720 , connecting structures  730 , knee coupling pads  740  and leg pad  750  is shown as one example of a restraint for use in connection with the device  100 . This embodiment of a restraint provides two non-invasive points of coupling at the back and the knees. To provide another alternative restraint for use in connection with device  100 .  FIG. 8  shows a waist restraint  800  having a waist restraint pad  820 , connecting structures  830  and knee coupling pads  840 . 
     FIG. 4  shows an exemplary connecting structure  130 . Connecting structure  130  includes a fastener  408  to connect to restraint  115 . Fastener  408  can be coupled to an optional force sensor  412 . Force sensor  412  is shown coupled to adjustable knob  414  which is attached to a bar  410 . Bar  410  connects to frame  120  (not shown). Adjustable knob  414  can increase or decrease the length of connecting structure  130  to provide adjustable levels of compressive or localized tensile loading. Although not shown, electronic controls can be integrated with connecting structure  130  to provide automatic coupling force adjustments. 
   Adjustability of device  100  is thus provided by connecting structure  130  shown in  FIG. 4  as it is capable of providing a compressive or localized tensile force capable of variation. As used herein, the applied force is also referred to as a preload. The preload, when present, acts on the targeted tissue region, such as a region of bone. A preload acting on the targeted bone region can be used to induce larger strains and to more effectively control the directions of strains in the bones or muscles of a subject as compared to applied vibrations alone. 
   Although not shown, device  100  can also include one or more strain gauges to monitor the strain induced along tissue length  110 , such as disposed on the skin of a subject. Together with a conventional feedback and control system, the level of preload and/or vibrational energy parameters applied by vibrational energy generator  105  can be dynamically adjusted to provide a desired level of strain. 
   By providing larger strains to targeted tissue regions using preloads according to the invention, the time required for therapy to achieve a desired level of bone (or muscle) strengthening may be reduced. In particular, the addition of preloads acting on bones can produce larger strains at the midshaft of the diaphysis of long bones because of the curved shape of long bones. Thus, the use of preloads with the loading device  100  increases the efficacy of the process of increasing bone (or muscle) strength. 
   Further treatment adjustability provided by device  100  results from the ability to operate the device when the foot (or other tissue length) is flexed at different angles.  FIGS. 5(   a ) and ( b ) show therapy applied using device  100  at two different knee angles.  FIG. 5(   a ) shows a minimum muscle stretch on the posterior side of the lower leg, while  FIG. 5(   b ) shows a maximum muscle stretch of the same region. The maximum muscle stretch shown in  FIG. 5  ( b ) provides enhanced therapy in the calf region. An alternate embodiment includes active adjustment of the tissue length flexure during therapy to better simulate gravitational forces acting on the body during activities such as walking. 
   In another embodiment of the invention, preloads can be directed through specific circumferential positions.  FIGS. 6(   a ),  6 ( b ), and  6 ( c ) show connecting structure  600  adapted to provide preloads directed through specific circumferential positions. Rather than using two (2) connecting structures shown in  FIG. 1 , with each connecting structure covering only a small percentage of the circumference of tissue length  110 , devices according to the invention can include a plurality of connecting structures which collectively cover an arc length spanning substantially the entire circumference of tissue length  110 . This embodiment can induce equal or unequal stress or strain along the entire tissue length being treated. 
   For simplicity,  FIG. 6  shows an alternate connecting structure  600 , which comprises a plurality of separate connecting structures, referred to in this embodiment as force-loading units  610 - 614 . Force-loading units  610 - 614  are placed circumferentially around a bodily region to be treated  640 . Each force loading unit  610 - 614  is disposed between restraint  630  and frame  620  and preferably includes an adjustable knob or other structure (not shown) to independently increase or decrease their respective lengths to provide adjustable levels of compressive or localized tensile loading. 
   Loading units  610 - 614  can be activated one-by-one or in multiple succession to apply bending, tensile and/or compression loads to target bone (or muscle) regions  640 . This permits key regions of bone to be strengthened as a function of angular position. 
   The top depictions in  FIGS. 6(   a )-( c ) represent cross-sections of a long bone  640 , while the pictures at the bottom show a lateral view of the same bone  640 .  FIG. 6(   a ) depicts bone  640  subject to no compressive load.  FIG. 6(   b ) depicts bone  640  subject to uniform compression since all the compressional-loading units are actively providing the same level of compression. The arrows shown indicate the direction of loading.  FIG. 6(   c ) depicts bone  640  subject to site-specific circumferential loading. Here, force-loading units  612  and  613  are actively applying compression, while force-loading units  610 ,  611  and  614  are inactive (not applying compression). Loading bone  640  as shown in  FIG. 6(   c ) creates a bending moment about the bone, thus circumferentially influencing bone morphology. 
   This method of loading bone can be advantageous particularly when one side of a bone is weaker than another. The location where stresses in a bone are the highest generally are the sites where bone adaptations are most necessary, so that new bone will be deposited most readily. Therefore loading a bone such that bending is induced will allow new bone to be deposited more readily at the site where additional support is necessary. 
   By actively changing the circumferential loading direction during vibration-induced bone strengthening sessions, the bone  640  will be subjected to loading in multiple directions, which may prove advantageous to uniaxial loading (i.e., compression loading alone). Preferential stiffness of a bone loaded uniaxially can cause deleterious effects if the bone is later subjected to loading in shear. This is because the bone is only geared to absorb loading in the direction it has been “trained” to absorb loads in. 
   The invention has many potential uses. For example, U.S. Pat. No. 6,061,597 to Reiman et al discloses a method and device for healing bone fracture. The invention can likely be used to enhance the healing bone fracture through the coupling of vibrational energy through the region in healing. Thus, using the present invention, bone can experience increased mass, density, and structural strength, while muscle can experience increased strength, size, flexibility. Joints/ligaments/tendons can also benefit from the invention and receive increased flexibility. Skin toning is also possible using the invention. 
   While the preferred embodiments of the invention have been illustrated and described, it will be clear that the invention is not so limited. Numerous modifications, changes, variations, substitutions and equivalents will occur to those skilled in the art without departing from the spirit and scope of the present invention.
A device for non-invasively mechanically stimulating bone or muscle includes a vibrational energy generator for applying vibrational energy to a first end of a length of a tissue which includes bone and/or muscle. The vibrational energy is for inducing strain in at least one region within the length of tissue. A restraint is disposed opposite the first end of the length to resist translation of the length during operation of the device and to provide loading to the bone or muscle. A connecting structure couples the restraint to the vibrational energy generator. The device does not require gravity to operate and as a result is expected to have applications in space, such as with astronauts, with those having bone ailments such as bed-ridden patients, persons with osteoporosis or disuse atrophy, athletes, recovering bone cancer patients, and persons with muscoskeletal disorders.