Local intraosseous administration of bone forming agents and anti-resorptive agents, and devices therefor

Abstract

This invention relates to local administration of a bone-forming agent and at least one anti-resorptive agent to treat osteoporosis and related disorders.

What is claimed is: 
     
       1. A method of therapeutically treating an uncoupled resorbing bone in a patient, comprising the steps of:
 a) administering an effective amount of a first formulation comprising a bone forming agent into the cancellous or cortical portion of the uncoupled resorbing bone, and 
 b) administering an effective amount of a second formulation comprising an anti-resorptive agent in a sustained release form into the cancellous or cortical portion of the uncoupled resorbing bone, wherein the anti-resorptive agent is a highly specific cytokine antagonist comprising REMICADE® infliximab and wherein an effective amount of the anti-resorptive agent remains within the bone for at least one month after administration of the second formulation. 
 
     
     
       2. The method of  claim 1  wherein the bone is non-fractured. 
     
     
       3. The method of  claim 1  wherein the amount of the first formulation comprising the bone forming agent is effective to increase the density of the bone. 
     
     
       4. The method of  claim 1  wherein the patient is post-menopausal. 
     
     
       5. The method of  claim 1  wherein the uncoupled resorbing bone is a vertebral body. 
     
     
       6. The method of  claim 1  wherein the uncoupled resorbing bone is a vertebral body and is adjacent to a fractured vertebral body. 
     
     
       7. The method of  claim 1  wherein the uncoupled resorbing bone is a hip bone. 
     
     
       8. A method of treating osteoporosis in a patient, comprising administering an effective amount of a sustained release formulation comprising an effective amount of a highly specific cytokine antagonist into the cancellous or cortical portion of at least one uncoupled resorbing bone, wherein the highly specific cytokine antagonist comprises REMICADE® infliximab and wherein an effective amount of the highly specific cytokine antagonist remains within the bone for at least one month after administration of the formulation. 
     
     
       9. The method of  claim 8  wherein at least one bone into which the formulation is administered is non-fractured. 
     
     
       10. The method of  claim 8  wherein the amount is effective to increase the bone mineral density of the bone. 
     
     
       11. The method of  claim 8  wherein the patient is post-menopausal. 
     
     
       12. The method of  claim 8  wherein the bone is a vertebral body. 
     
     
       13. The method of  claim 8  wherein the uncoupled resorbing bone is a vertebral body and is adjacent to a fractured vertebral body. 
     
     
       14. The method of  claim 8  wherein the bone is osteoporotic. 
     
     
       15. The method of  claim 8  wherein the bone is a hip bone. 
     
     
       16. A method of treating an osteoporotic patient having a spinal unit comprising an upper vertebral body, a lower vertebral body, and an intervertebral disc therebetween, comprising: inserting a sustained release device into at least one vertebral body adjacent to the intervertebral disc, wherein the device is adapted to deliver an effective amount of a bone forming agent and an anti-resorptive agent into the cancellous or cortical portion of the vertebral body, and the anti-resorptive agent comprises REMICADE® infliximab and wherein an effective amount of the bone forming agent and anti-resorptive agent remains within the bone for at least one month after administration. 
     
     
       17. A method of therapeutically treating an uncoupled resorbing bone in a patient, comprising administering an effective amount of a sustained release formulation comprising an anti-resorptive agent into the cancellous or cortical portion of the uncoupled resorbing bone, wherein the bone is nontumorous and wherein the anti-resorptive agent is a highly specific cytokine antagonist comprising REMICADE® infliximab and wherein an effective amount of the anti-resorptive agent remains within the bone for at least one month after administration of the formulation. 
     
     
       18. A method of therapeutically treating an uncoupled resorbing bone in a patient, comprising the steps of:
 a) administering an effective amount of a first formulation comprising a bone forming agent into the cancellous or cortical portion of the uncoupled resorbing bone, and 
 b) administering an effective amount of a second formulation comprising an anti-resorptive agent in a sustained release form into the cancellous or cortical portion of the uncoupled resorbing bone, wherein the anti-resorptive agent is a highly specific cytokine antagonist comprising REMICADE® infliximab, wherein the second formulation remains in the bone in an effective amount for at least one month. 
 
     
     
       19. The method of  claim 1 , wherein the bone forming agent is released from a sustained release device. 
     
     
       20. The method of  claim 1 , wherein the uncoupled resorbing bone is osteoporotic or osteopenic. 
     
     
       21. The method of  claim 8  wherein the anti-resorptive agent remains in the bone in an effective amount for at least two months. 
     
     
       22. The method of  claim 16  wherein the device is adapted to deliver the bone forming agent and the anti-resorptive agent into the vertebral body for at least two months. 
     
     
       23. The method of  claim 17  wherein the anti-resorptive agent remains in the bone in an effective amount for at least two months. 
     
     
       24. A method of treating a patient having a spinal condition, the method comprising:
 administering a first treatment of a pain-relieving therapy for a first period of time from a first plurality of locations at a vertebra of the patient; and   administering a second treatment of the pain-relieving therapy for a second period of time from a second plurality of locations at the vertebra of the patient,   wherein the first plurality of locations is greater in number than the second plurality of locations, wherein the administering of the first and second treatments is of a common modality of delivery.   
     
     
       25. The method of claim 24, wherein the first and second plurality of locations have at least one location in common. 
     
     
       26. The method of claim 24, further comprising sensing with a sensor a condition predicate to administering the first treatment, the second treatment, or a combination thereof. 
     
     
       27. The method of claim 26, wherein the sensor is a biosensor. 
     
     
       28. The method of claim 24, wherein an implant implanted in the patient administers the first and second treatments. 
     
     
       29. The method of claim 28, wherein the implant includes a first component and a second component, and wherein administering the first treatment includes stimulating tissue of the patient at the vertebra of the patient in at least one of an axial direction relative to the first and second components and a radial direction relative to the first and second components. 
     
     
       30. The method of claim 28, wherein the implant includes a first component and a second component, and wherein administering the first treatment includes stimulating tissue of the patient at the vertebra of the patient in both an axial direction relative to the first and second components and a radial direction relative to the first and second components. 
     
     
       31. The method of claim 28, wherein the implant includes a first component and a second component, and wherein administering the second treatment therapy includes stimulating tissue of the patient at the vertebra of the patient in a radial direction relative to the first and second components. 
     
     
       32. The method of claim 28, wherein at least a portion of the implant is implanted in a vertebral body of the patient. 
     
     
       33. The method of claim 28, wherein at least a portion of the implant is implanted at a location adjacent to a vertebral body of the patient.