Method for inhibiting bone resorption

Abstract

Disclosed are methods for inhibiting bone resorption in mammals while minimizing the occurrence of or potential for adverse gastrointestinal effects. Also disclosed are pharmaceutical compositions and kits for carrying out the therapeutic methods disclosed herein.

What is claimed is:  
     
         1 . A method for inhibiting bone resorption in a mammal, said method comprising orally administering to said mammal a pharmaceutically effective amount of a bisphosphonate as a unit dosage according to a continuous schedule having a dosing interval selected from the group consisting of once-weekly dosing, twice-weekly dosing, biweekly dosing, and twice-monthly dosing.  
     
     
         2 . A method according to  claim 1  wherein said bisphosphonate is selected from the group consisting of alendronate, cimadronate, clodronate, tiludronate, etidronate, ibandronate, risedronate, piridronate, pamidronate, zolendronate, pharmaceutically acceptable salts thereof, and mixtures thereof.  
     
     
         3 . A method according to  claim 1  wherein said bisphosphonate is selected from the group consisting of alendronate, pharmaceutically acceptable salts thereof, and mixtures thereof.  
     
     
         4 . A method according to  claim 3  wherein said pharmaceutically acceptable salt is alendronate monosodium trihydrate.  
     
     
         5 . A method according to  claim 4  wherein said mammal is a human.  
     
     
         6 . A method for treating osteoporosis in a mammal in need of such treatment, said method comprising orally administering to said mammal a pharmaceutically effective amount of a bisphosphonate as a unit dosage according to a continuous schedule having a dosing interval selected from the group consisting of once-weekly dosing, twice-weekly dosing, biweekly dosing, and twice-monthly dosing.  
     
     
         7 . A method according to  claim 6  wherein said mammal is a human.  
     
     
         8 . A method according to  claim 7  wherein said dosing interval is once-weekly and said unit dosage comprises about 70 mg of alendronate monosodium trihydrate, on an alendronic acid active basis.  
     
     
         9 . A method according to  claim 7  wherein said dosing interval is twice-weekly and said unit dosage comprises about 35. mg of alendronate monosodium trihydrate, on an alendronic acid active basis.  
     
     
         10 . A method according to  claim 7  wherein said dosing interval is biweekly and said unit dosage comprises about 140 mg of alendronate monosodium trihydrate, on an alendronic acid active basis.  
     
     
         11 . A method according to  claim 7  wherein said dosing interval is twice-monthly and said unit dosage comprises about 140 mg of alendronate monosodium trihydrate, on an alendronic acid active basis.  
     
     
         12 . A method for preventing osteoporosis in a mammal in need of such treatment, said method comprising orally administering to said mammal a pharmaceutically effective amount of a bisphosphonate as a unit dosage according to a continuous schedule having a dosing interval selected from the group consisting of once-weekly dosing, twice-weekly dosing, biweekly dosing, and twice-monthly dosing.  
     
     
         13 . A method according to  claim 12  wherein said mammal is a human.  
     
     
         14 . A method according to  claim 13  wherein said dosing interval is once-weekly and said unit dosage comprises about 35 mg of alendronate monosodium trihydrate, on an alendronic acid active basis.  
     
     
         15 . A method according to  claim 13  wherein said dosing interval is twice-weekly and said unit dosage comprises about 17.5 mg of alendronate monosodium trihydrate, on an alendronic acid active basis.  
     
     
         16 . A method according to  claim 13  wherein said dosing interval is biweekly and said unit dosage comprises about 70 mg of alendronate monosodium trihydrate, on an alendronic acid active basis.  
     
     
         17 . A method according to  claim 13  wherein said dosing interval is twice-monthly and said unit dosage comprises about 70 mg of alendronate monosodium trihydrate, on an alendronic acid active basis.  
     
     
         18 . A method for treating abnormal bone resorption in a human in need of such treatment comprising orally administering to said human a unit dosage of a bisphosphonate, said unit dosage comprising from about 17.5 mg to about 140 mg, on an alendronic acid basis, of a bisphosphonate selected from the group consisting of alendronate, pharmaceutically acceptable salts thereof, and mixtures thereof.  
     
     
         19 . A method according to  claim 18  wherein said unit dosage comprises about 35 mg of the bisphosphonate.  
     
     
         20 . A method according to  claim 18  wherein said unit dosage comprises about 70 mg of the bisphosphonate.  
     
     
         21 . A method according to  claim 20  wherein said unit dosage is administered once-weekly.  
     
     
         22 . A method according to  claim 18  wherein said unit dosage comprises about 140 mg of the bisphosphonate.  
     
     
         23 . A method for preventing abnormal bone resorption in a human in need of such treatment comprising orally administering to said human a unit dosage of a bisphosphonate, said unit dosage comprising from about 8.75 mg to about 70 mg, on an alendronic acid basis, of a bisphosphonate selected from the group consisting of alendronate, pharmaceutically acceptable salts thereof, and mixtures thereof, on an alendronic acid active weight basis.  
     
     
         24 . A method according to  claim 23  wherein said unit S dosage comprises about 17.5 mg of the bisphosphonate.  
     
     
         25 . A method according to  claim 23  wherein said unit dosage comprises about 35 mg of the bisphosphonate.  
     
     
         26 . A method according to  claim 25  wherein said unit dosage is administered once-weekly.  
     
     
         27 . A method according to  claim 23  wherein said unit dosage comprises about 70 mg of the bisphosphonate.  
     
     
         28 . A method for inhibiting bone resorption in a mammal, said method comprising sequentially orally administering to said mammal a pharmaceutically effective amount of a unit dosage of a histamine H2 blocker or a proton pump inhibitor and a unit dosage of a bisphosphonate according to a continuous schedule having a dosing interval selected from the group consisting of once-weekly dosing, twice-weekly dosing, biweekly dosing, twice-monthly dosing.  
     
     
         29 . A method according to  claim 28  wherein said histamine H2 blocker or said proton pump inhibitor is administered from about 30 minutes to about 24 hours prior to the administration of said bisphosphonate.  
     
     
         30 . A pharmaceutical composition comprising about 70 mg, on an alendronic acid active basis, of a bisphosphonate selected from the group consisting of alendronate, pharmaceutically acceptable salts thereof, and mixtures thereof.  
     
     
         31 . A pharmaceutical composition comprising about 140 mg, on an alendronic acid active basis, of a bisphosphonate selected from the group consisting of alendronate, pharmaceutically acceptable salts thereof, and mixtures thereof.  
     
     
         32 . A kit for inhibiting bone resorption in a mammal, said kit comprising at least one pharmaceutically effective unit dosage of a bisphosphonate for oral administration according to a continuous schedule having a dosing interval selected from the group consisting of once-weekly dosing, twice-weekly dosing, biweekly dosing, and twice-monthly dosing.  
     
     
         33 . A method for inhibiting bone resorption in a mammal, said method comprising orally administering to said mammal a pharmaceutically effective amount of a bisphosphonate as a unit dosage according to a continuous schedule having a periodicity from about once every 3 days to about once every 16 days.