Abstract:
A method of treating a patient, involving
       a) injecting a flowable material into a cancellous bone region of a bone, wherein the material is adapted to facilitate tissue regeneration, and   b) irradiating the cancellous bone region with an effective amount of NIR/red light.       
 
     The irradiation may be carried out from a light source located inside the bone. The light may enter the bone via a transmitter located underneath the skin of the patient.

Description:
CONTINUING DATA 
       [0001]    This application claims priority and is a continuation from co-pending patent application U.S. Ser. No. 14/499,520, entitled “Red Light Implants for Treating Osteoporosis”, filed Sep. 29, 2014 (Attawia) (Docket No. DEP5578USCNT2), which is a continuation from U.S. Ser. No. 13/587,542, filed Aug. 16, 2012, entitled “Red Light Implants for Treating Osteoporosis”, (Attawia)(now U.S. Pat. No. 8,845,703), (Docket No. DEP5578USCNT1), which is a continuation from U.S. Ser. No. 11/235,674, filed Sep. 26, 2005, entitled Red Light Implants for Treating Osteoporosis”, (Attawia), (Docket No. DEP5578USNP) (now U.S. Pat. No. 8,262,713), the specifications of which are incorporated by reference in their entireties. 
     
    
     BACKGROUND OF THE INVENTION 
       [0002]    Osteoporosis is a disease that results in the weakening of bone and an increase in the risk of fracture. It has been reported that American females over the age of 50 have about a 50% chance of breaking a bone during their lifetime, and a 40% chance of breaking either a hip, vertebra or wrist. Post-menopausal women lose about 1-3% of their bone mass for each of the first 5-7 years after menopause. Osteoporosis is believed to contribute to about 1.5 million fractures a year in the United States, including about 700,000 spinal fractures and about 300,000 hip fractures. According to the Mayo Clinic, about 25% of the people over 50 who fracture a hip die within a year of the incident. The risk of breaking a bone for an osteoporotic individual doubles after the first fracture. The risk of breaking a second vertebra for an osteoporotic individual increases about four-fold after the first spinal fracture. 
         [0003]    Human bone comprises hard mineralized tissue and softer collagenous tissue. The combination of these tissues provides bone with both a structural, weight-bearing capability and a shock-absorption capability. As the bone ages, however, the collagenous portion of the bone is slowly mineralized, thereby making the entire bone more brittle. To compensate for this, bone constantly undergoes a process called “remodeling” in which older, more mineralized bone is replaced by new, more collagenous bone. 
         [0004]    Bone remodeling is undertaken by two competing processes: bone formation and bone resorption. Bone formation is largely achieved by bone-forming cells called osteoblasts, while bone resorption is largely achieved by bone-eating (bone-resorbing) cells called osteoclasts. In the normal desired situation, the rate of bone formation is essentially equal to the rate of bone resorption, so that bone mass in the body is maintained. 
         [0005]    Osteoporosis occurs when the rate of bone resorption exceeds the rate of bone formation. The rate of bone resorption is largely dependent upon the local production of osteoclasts. 
         [0006]    Current treatments for osteoporosis have focused upon arresting the activity of the osteoclast cells. In particular, osteoporosis therapy has focused upon administering drugs called “anti-resorptive agents” or ARA&#39;s. The most common classes of anti-resorptive drugs include estrogen, selective estrogen receptor modulators (SERMs), biphosphonates, calcitonin, osteoprotegrin (OPG), cathespin K and statins. Current products include FOSAMAX® (alendronate) in the U.S., Biphosphonate DIDRONEL® (etidronate), and ACTONEL® (risedronate). 
         [0007]    Despite the promise provided by these anti-resorptives, there still remain serious issues. First, many anti-resorptives act in a manner that wholly eliminates osteoclast activity. Thus, the delicate balance between bone formation and bone-resorption is again upset, and older, highly mineralized tissue remains within the bone. Although this has the effect of increasing bone mineral density (BMD), the bone that remains is fragile and prone to microdamage. 
         [0008]    Second, many of the anti-resorptives are administered systemically, through either oral or intravenous means. Accordingly, side effects associated with systemic administration are often seen. For example, the systemic administration of hormone replacement therapy (“HRT”) has been associated with an elevated cancer risk. In response to this concern, some anti-resorptive drugs, such as biphosphonates, have been engineered to be selective for bone tissue. However, in many cases, the amount of such tissue selective drug that actually reaches bone is often less than 100%. 
         [0009]    With respect to the spine, one of the manifestations of osteoporosis is the low pullout strength of pedicle screws. Simply, the lower density of the cancellous bone in the vertebral body reduces the amount of purchase available to a pedicle screw implant. 
         [0010]    The art has described a number of different methods for enhancing the pull out strength of pedicle screws. These methods include the use of expandable screws (Cook,  Spine Journal,  1(2001) 109-114 and Cook,  Spine Journal,  4 (2004) 402-8), and of injectable, settable fluids around the pedicle screw (Bai,  Spine,  26(24) 2679-83). 
       SUMMARY OF THE INVENTION 
       [0011]    The present inventors have developed methods and devices for enhancing the integration of pedicle screws into vertebrae. In particular, the present inventors have developed inventions using red light irradiation of the bone-pedicle screw interface to enhance the integration of the pedicle screw into the vertebra. 
         [0012]    The literature reports that red light irradiation enhances the pull-out strength of dental implants. For example,  Khandra, Clin. Oral Implants Res.,  2004, June: 15(3):325-332, reports that in vivo red light irradiation of dental implants increased the pullout strength of these implants by about 40%. See also, Khandra,  Swed. Dent. J. Suppl.,  2005, (172) 1-63. Guzzardella,  Int. J. Artif. Organs,  2001, December 24(12): 898-902 reports that red light irradiation of HA nails drilled into rabbit femurs resulted in a higher degree of HA-bone integration, and concluded that low power laser treatment can be considered a good tool to enhance the bone-implant interface in orthopedic surgery. 
         [0013]    The literature has further reported on possible reasons why red light irradiation of implants results in enhanced osteointergration. Khandra,  Clin Oral Implants Res.  2005, April 16(2) 168-75 reports that red light irradiation of human fibroblasts cultured upon titanium implant material produces results in a significantly higher incidence of cell attachment. Lopes,  Photomed. Laser Surg.  2005 February 23(1) 27-31 reports that red light irradiation of dental implants implanted into rabbit femurs resulted in a significant increase in calcium HA concentration. Dortbudak,  Clin. Oral Implants Res.,  2002, June 13(3) 288-92, reports that red light irradation of wounded bone resulted in a nearly 20% increase in viable osteocyte count, while not affecting bone resorption rate. 
         [0014]    Therefore, in accordance with the present invention, there is provided method of treating a vertebra, comprising the steps of:
   a) implanting an implant into a cancellous bone region of the vertebra, and   b) irradiating the cancellous bone region with an effective amount of red light.   
 
     
    
     
       DESCRIPTION OF THE FIGURES 
         [0017]    FIG. 1  discloses a glass screw embodiment of the present invention. 
           [0018]      FIG. 2  discloses a cannulated screw with glass cylinder. 
           [0019]      FIG. 3A  discloses a cap-screw assembly, wherein the cap transmits light through the screw. 
           [0020]      FIGS. 3B-3C  each disclose a cap for a screw, wherein the cap transmits light through the screw. 
           [0021]      FIG. 4  discloses a cap for a screw, wherein the cap transmits light directly into bone. 
           [0022]      FIG. 5  discloses a collar for a screw, wherein the collar transmits light through the screw. 
           [0023]      FIG. 6  discloses a helical embodiment of the present invention. 
           [0024]      FIG. 7  discloses a helical embodiment of the present invention adapted to irradiate a pedicle screw augmented with cement. 
           [0025]      FIG. 8  discloses an exemplary implant powered by an external light source. 
           [0026]      FIG. 9  discloses a red light implant of the present invention powered by an external Rf antenna. 
           [0027]      FIG. 10  discloses a red light implant of the present invention powered by an internal power source. 
           [0028]      FIG. 11  discloses exemplary circuit that may accommodate an LED component of the present invention. 
       
    
    
     DETAILED DESCRIPTION OF THE INVENTION 
       [0029]    In some embodiments, the red light is delivered to the implant-bone interface through the pedicle screw. In these situations, it is preferred that the pedicle screw be made of a material capable of transmitting red light, such a single crystal alumina. Now referring to  FIG. 1 , there is provided a red light implant  1 , comprising:
       a) a pedicle screw  3  made of a red light transmitting material and having:
           i) a distal tip  5 ,   ii) an intermediate shaft  7  having a distal threaded portion  9  and a proximal smooth portion  11 , and   iii) a proximal end portion  13  adapted for receiving a rod or other static or dynamic fixation device (e.g., a plate or a tether),   
           b) a red light LED  15  abutting the proximal portion of the screw,   c) an Rf antenna  17  for receiving Rf energy positioned upon the proximal smooth portion of the and electrically connected to the red light LED, and   d) a red light reflective coating  19  the proximal end portion and the proximal smooth portion of the screw.       
 
         [0037]    The red light reflective coating (such as a metal) directs red light emitted by the LED distally towards the threaded portion of the screw. 
         [0038]    In use, the screw is implanted and Rf energy is directed towards the Rf antenna portion of the implant. The Rf energy activates the LED which then emits red light, which travels throughout the screw. The red light exits the screw and irradiates the adjacent cancellous bone, thereby stimulating bone repair and osteointegration of the implant. Although the illustrated pedicle screw  3  is a monoaxial pedicle screw, the pedicle screw of the present invention can be any type of pedicle screw, including for example, a polyaxial pedicle screw. 
         [0039]    In other embodiments wherein the red light is delivered through the screw, the red light is delivered through a cannulated pedicle screw. Now referring to  FIG. 2 , there is provided a red light implant  21 , comprising:
       a) a pedicle screw  23  made of a metallic material and having:
           i. a distal tip  25 ,   ii. an intermediate shaft  27  having an outer surface  28  having a distal threaded portion  29 , a proximal smooth portion  31  and throughholes  32 ,   iii. a proximal end portion  33  adapted for receiving a rod or other static or dynamic fixation device,   iv. a longitudinal bore  36  communicating with the throughholes,   
           b) a red light LED  35  abutting the proximal portion of the screw,   c) an Rf antenna  37  for receiving Rf energy positioned upon the proximal smooth portion of the and electrically connected to the red light LED, and   d) a rod  39  comprising a red light transmitting material and disposed within the longitudinal bore.       
 
         [0048]    Within the bore, the rod of red light transmitting material may be inserted so that red light can be shined upon the proximal end portion of the screw and delivered through the red light transmitting rod and throughholes to the cancellous regions surrounding the screw. 
         [0049]    In some embodiments, a conventional pedicle screw is implanted and the red light is delivered via a second implant that preferably surrounds the pedicle screw 
         [0050]    In some embodiments, the second implant is a cap that rests against the proximal end of the pedicle screw. 
         [0051]    In some embodiments, the cap transmits light through the screw. Now referring to  FIG. 3 a   , there is provided a there is provided a red light implant  41 , comprising:
       a) a pedicle screw  43  made of a red light transmitting material and having:
           i. a distal tip  45 ,   ii. an intermediate shaft  47  having an outer surface  48  having a distal threaded portion  49  and a proximal smooth portion  51 ,   iii. a proximal end portion  53  adapted for receiving a rod or other static or dynamic fixation device and having a threaded outer surface  54 , and   
           b) a cap  55  having a threaded inner surface  56  adapted to engage the threaded outer surface of the proximal end portion of the screw and made of a red light transmitting material.       
 
         [0057]    In use, the cap transmits light from itself to the screw via the threaded surface interface. 
         [0058]    In some embodiments, and now referring to  FIG. 3 b   , the cap is adapted to transmit red light that has been transdermally applied. Such a cap comprises a light reflective coating  57  upon the various surfaces of the cap, but has an uncoated proximal end portion that accepts the transdermally delivered light. 
         [0059]    In some embodiments, and now referring to  FIG. 3 c   , the cap contains a red light light emitting diode (LED)  58  and a power source  59  (such an antenna or battery). 
         [0060]    Now referring to  FIG. 4 , there is provided a there is provided a red light implant  61 , comprising:
       a) a pedicle screw  63  made of a metallic material and having:
           i. a distal tip  65 ,   ii. an intermediate shaft  67  having an outer surface  68  having a distal threaded portion  69  and a proximal smooth portion  71 ,   iv. a proximal end portion  73  adapted for receiving a rod, and   
           b) a cap  75  adapted to fit around the proximal end portion of the screw and made of a red light transmitting material, the cap comprising:
           i. an uncoated distal end portion  77 ,   ii. an intermediate portion  79  coated with a light reflective material  81 , and   iii. an uncoated proximal end portion  83 .   
               
 
         [0069]    In some embodiments, the second implant is a collar that sits distal to the head of the screw. The collar contains a red light LED and a power source. Now referring to  FIG. 5 , there is provided a red light implant  101 , comprising:
       a) a pedicle screw  103  made of a red light transmitting material and having:
           i) a distal tip  105 ,   ii) an intermediate shaft  107  having a distal threaded portion  109  and a proximal smooth portion  111 , and   iii) a proximal end portion  113  adapted for receiving a rod,   
           b) a red light LED  115  surrounding the proximal smooth portion of the shaft,   c) an Rf antenna  117  for receiving Rf energy positioned upon the proximal smooth portion and proximal to the LED, and   d) a red light reflective layer coating  119  covering the LED.       
 
         [0077]    In some embodiments, it is preferred that the second implant has a helical shape and is implanted around the pedicle screw. The helical shape is preferred because it can be delivered in a minimally invasive manner, and can irradiate essentially the entire surface area of the pedicle screw. 
         [0078]    Now referring to FIG. 6 , there is provided an implant  121  for delivering red light to an implant-vertebra interface, comprising:
       a) a helix  123  comprising a red light transmitting material and having a proximal end portion  125  and a distal end portion  127 , and   b) a red light source  131  connected to the proximal end portion of the helix and comprising i) a red light LED  135  and ii) a power source  137  electrically connected to the red light LED.       
 
         [0081]    Still referring to  FIG. 6 , the helical implant is implanted in a vertebral body along with a pedicle screw  139 . As shown, the helix is co-axial with the pedicle screw. The helical nature of the implant allows red light irradiation of the full diameter of the screw along its longitudinal axis. 
         [0082]    In some embodiments, the red light implant may be a double helix in order to provide a more even illumination of the cancellous bone. 
         [0083]    In some embodiments, the red light treatment of the present invention can be used in conjunction with the injection of a settable paste around the pedicle screw. It is believed that the red light will enhance the osteointegration of the paste to the surrounding bone. 
         [0084]    Preferably, the settable paste comprises calcium phosphate (CaP) or hydroxyapatite (HA). As noted above, Guzzardella,  Int. J. Artif. Organs,  2001, December 24(12): 898-902 reported that red light irradiation of HA nails drilled into rabbit femurs resulted in a higher degree of HA-bone integration, and concluded that low power laser treatment can be considered a good tool to enhance the bone-implant interface in orthopedic surgery. 
         [0085]    Therefore, in accordance with the present invention, there is provided a method of treating a vertebra, comprising the steps of:
       a) implanting an implant into the vertebra,   b) injecting a paste around the implant, and   c) irradiating the paste with an effective amount of red light.       
 
         [0089]    In preferred embodiments, and now referring to  FIG. 7 , the pedicle screw  139  is cannulated and comprises holes  141  and the injectable, settable paste  143  is injected through the cannula of the screw and then irradiated with red light delivered from the helix  123 . 
         [0090]    Therefore, in preferred embodiments of the present invention, there is provided a method of treating a vertebra, comprising the steps of:
       a) implanting a pedicle screw having an outer surface, a central bore, and a plurality of throughholes extending between the outer surface and the central bore,   b) injecting a settable paste into the bore so that the paste extrudes through the throughholes, and   c) irradiating the extruded paste with an effective amount of red light.       
 
         [0094]    In some embodiments, the power source can be a battery. 
         [0095]    In other embodiments, the power source can be an Rf antenna adapted to receive Rf energy for an external Rf antenna. 
         [0096]    In order to protect the active elements of the device from the CSF, in some embodiments, the red light LED is encased in a casing. This casing both protects the LED components from body fluids, and also prevents the LED components from elicting a violent immune reaction In some embodiments, the casing is made of a red light transparent material. The red light transparent material may be placed adjacent the LED component so that red light may be easily transmitted therethrough. In some embodiments, the red light transparent casing is selected from the group consisting of silica, alumina and sapphire. In some embodiments, the light transmissible material is selected from the group consisting of a ceramic and a polymer. Suitable red light-transmissible ceramics include alumina, silica, CaF, titania and single crystal-sapphire. Suitable red light transmissible polymers are preferably selected from the group consisting of polypropylene and polyesters. 
         [0097]    In some embodiments, the red light-transmissible implant comprises a red light transmissible polymer. In other embodiments, the red light-transmissible implant comprises a UVB-transmissible ceramic, such as glass. The glass content of the implant is preferably in the range of 20-40 volume percent (“v/o”). At higher glass glass contents, the implant becomes relatively inelastic. At lower implants, red light transmission is more problematic. The red light transmissible component of the implant may be in the form of beads, long fibers or chopped fibers. 
         [0098]    In some embodiments, energy (such as Rf energy or red light) is delivered transdermally and collected near the skin layer of the patient. Such a configuration would allow light to be delivered deep within the patient, or in or near critical organs or tissues, and yet have the light source and associated components in a less sensitive region. This configuration allows easier access to the light/controller should the need arise for service or maintenance, and also allow for more efficient transdermal energy transmission. Moreover, by using a hollow tube with reflective internal surfaces, light and therapeutic fluids could be delivered to the implanted device. The light source/controller implanted near the patient&#39;s skin could also be a simple, hollow chamber made to facilitate the percutaneous access described above. The advantages and benefits of this system include:
       a) further removal from the deep site of the functional implant, thereby reducing risk of contamination of the deeper site by percutaneous access;   b) easier precutaneous access by being closer to the skin surface and having a larger surface area or target to access with the needle;   c) a larger volume could hold more therapeutic fluid to provide a longer duration of activity; and   d) a central reservoir could provide therapy to multiple implants throughout the body.       
 
         [0103]    In use, the surgeon implants the implant into the spine of the patient so that the Rf receiving antenna is adjacent the posterior portion of the vertebral body. 
         [0104]    In some embodiments wherein the red light is delivered transdermally, it may be advantageous to provide the red light collection closer to the skin. Now referring to  FIG. 8 , there is provided a first exemplary implant having an external light source. The externally based-control device has a light source  101  for generating light within the device. The light generated by this source is transmitted through fiber optic cable  103  through the patient&#39;s skin to an internally-based light port  109 . The light port is adapted to be in light-communication with fiber optic cable  221  disposed upon the proximal surface  203  of the helical implant  201 . The helix receives the light and transmits the light to the adjacent cancellous tissue. 
         [0105]    Now referring to  FIG. 9 , there is provided a second exemplary UV unit having an internal light source. Externally based-control device  222  has an RF energy source  224  and an antenna  230  for transmitting signals to an internally-based antenna  232  provided on the prosthesis. These antennae  230 ,  232  may be electro-magnetically coupled to each other. The internal antenna  232  sends electrical power to a light emitting diode (LED)  234  disposed internally on the implant in response to the transmitted signal transmitted by the external antenna  230 . The light generated by the LED travels across the red light transparent—single crystal alumina implant  238  and into the cancellous tissue. 
         [0106]    In some embodiments, and now referring to  FIG. 10 , the prosthesis having an internal light source further contains an internal power source  300 , such as a battery (which could be re-chargeable), which is controlled by an internal receiver and has sufficient energy stored therein to deliver electrical power to the light source  234  in an amount sufficient to cause the desired light output. 
         [0107]    When the implant is coupled with external energy, power can be transmitted into the internal device to re-charge the battery. 
         [0108]    In some embodiments, the light generated by the implant is powered by wireless telemetry integrated onto or into the implant itself. In the  FIG. 9  embodiment, the LED  234  may comprise a radiofrequency-to-DC converter and modulator. When radiofrequency signals are emitted by the external antenna  230  and picked up by the internal antenna  232 , these signals are then converted by the receiver (not shown) into electrical current to activate the light source of the PCO unit. 
         [0109]    In one embodiment, the implant may have an internal processor adapted to intermittently activate the LED. 
         [0110]    In some embodiments, the telemetry portion of the device is provided by conventional, commercially-available components. For example, the externally-based power control device can be any conventional transmitter, preferably capable of transmitting at least about  40  milliwatts of energy to the internally-based antenna. Examples of such commercially available transmitters include those available from Microstrain, Inc. Burlington, Vt. Likewise, the internally-based power antenna can be any conventional antenna capable of producing at least about 40 milliwatts of energy in response to coupling with the externally-generated Rf signal. Examples of such commercially available antennae include those used in the Microstrain Strainlink™ device. Conventional transmitter-receiver telemetry is capable of transmitting up to about 500 milliwatts of energy to the internally-based antenna. 
         [0111]    In some embodiments, and now referring to  FIG. 11 , the implant includes a light emitting diode (LED)  234  built upon a portion  307  of the implant, along with the required components to achieve trans-dermal activation and powering of the device. These components can include, but are not limited to, RF coils  301 , control circuitry  303 , a battery  305 , and a capacitor. Such a device could be capable of intermittent or sustained activation without penetrating the skin, thereby avoiding trauma to the patient and/or risk of infection from skin-borne bacteria. As shown above, the accessory items needed to power and control the LED may be embedded within the implant. However, they could also be located on the surface(s) of the implant, or at a site adjacent to or near the implant, and in communication with the implant. 
         [0112]    To enhance the propagation of light emitted from the end of the device, a lens could be placed at the distal end of the device to spread the light, or a diffuser such as a small sheet or plate of optical material could be used to create more surface area. Alternatively, one could create a series of lateral diffusers, such as grooves or ridges, along the distal portion of end of the device to spread light out from 360 degrees perpendicular to the axis of the device, as well as emanating directly out from the end of the fiber. 
         [0113]    Preferably, the red light of the present invention has a wavelength of between about 600 nm and about 1000 nm. In some embodiments, the wavelength of light is between 800 and 900 nm, more preferably between 800 nm and 835 nm. In some embodiments, the wavelength of light is between 600 nm and 700 nm. 
         [0114]    In some embodiments, the light source is situated to irradiate adjacent tissue with between about 0.02 J/cm 2  and 200 J/cm 2  energy. In some embodiments, the light source is situated to irradiate adjacent tissue with between about 0.2 J/cm 2  and 50 J/cm 2  energy, more preferably between about 1 J/cm 2  and 10 J/cm 2  energy. In some embodiments, the light source is situated to produce an energy intensity of between 0.1 watts/cm 2  and 10 watts/cm 2 . In some embodiments, the light source is situated to produce about 1 milliwatt/cm 2 . 
         [0115]    In some embodiments, the light source emits lights consisting essentially of red light having a wavelength between 600 nm and 1000 nm. In others, the light source emits a wide spectrum of light and includes the emission of red light having a wavelength between 600 nm and 1000 nm with a strength of between about 0.02 J/cm 2  and 200 J/cm 2  energy. In one of these wide spectrum embodiments, white light is used as the light source. In some embodiments thereof, the device includes a filter that filters out at least some of the wavelengths outside of the 600-1000 nm range. 
         [0116]    Therefore, in some embodiments of the present invention, the therapeutic dose of red light is provided on approximately a daily basis, preferably no more than 3 times a day, more preferably no more than twice a day, more preferably once a day. 
         [0117]    In some embodiments of the present invention, he implant comprises an intervetebral motion disc and a red light source adapted to enhance the osteointegration of the endplates of the motion disc to the adjacent vertebrae.