Treatment of osteoporosis

• US 4,812,304 A
• Filed: 09/12/1986
• Issued: 03/14/1989
• Est. Priority Date: 12/21/1984
• Status: Expired due to Term

• Current Assignee: The Procter & Gamble Company
• Original Assignee: The Procter & Gamble Company
• Inventors: Anderson, Colin, Flora, Lawrence
• Primary Examiner(s): Schenkman, Leonard
• Application Number:
  US06/906,858
• Time in Patent Office: 914 Days
• Field of Search: 424/128, 424/112, 514/167, 514/141
• US Class Current: 514/141
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/557 Eicosanoids, e.g. leukotrienes or prostaglandins
• CPC Class Codes: A61K 31/59 Compounds containing 9, 10- seco- cyclopenta[a]hydrophenanthrene ring systems
• CPC Class Codes: A61K 31/66 Phosphorus compounds
• CPC Class Codes: A61K 33/16 Fluorine compounds
• CPC Class Codes: A61K 33/42 Phosphorus; Compounds thereof

Abstract

A method for treating or preventing osteoporosis is disclosed. Bone cells are synchronized during a bone cell activating period; bone resorption, which normally follows activation, is inhibited using a polyphosphonate; bone formation is allowed to occur in the rest period during which nutrient supplements may be administered to the patient.

Claims

1. A method for treating or preventing osteoporosis in humans comprising administering to a subject afflicted with or at risk to osteoporosis a bone cell activating compound and a bone resorption inhibiting polyphosphonate according to a regimen consisting of one or more cycles, whereby each cycle consists of:

(a) a bone activating period of from about 1 day to about 5 days during which a bone activating amount of a bone cell activating compound is administered daily to said subject;

followed by (b) a bone resorption inhibition period of from about 10 days to about 20 days during which ethane-1-hydroxy-1,1-diphosphonic acid, or a pharmaceutically-acceptable salt or ester thereof, is administered daily to said subject in an amount of from about 0.25 mgP/kg/day to about 3.3 mgP/kg/day;

followed by (c) a rest period of from about 70 days to about 180 days during which the subject receives neither a bone cell activating compound nor a bone resorption inhibiting polyphosphonate.

2. The method of claim 1 wherein during the bone resorption inhibition period the ethane-1-hydroxy-1,1-diphosphonic acid, or pharmaceutically-acceptable salt or ester thereof, is administered daily in an amount of from about 0.25 mgP/kg/day to about 2.5 mgP/kg/day.

3. The method of claim 2 wherein the bone cell activating compound is an inorganic phosphate and the bone activating amount is from about 4 mg/kg/day to about 60 mg/kg/day of phosphorous, and not to exceed about 3600 mg P/day.

4. The method of claim 3 wherein the bone cell activating compound is an organic phosphate and the bone activating amount is from about 30 mg/kg/day to about 40 mg/kg/day of phosphorous, and not to exceed about 3600 mg P/day.

5. The method of claim 2 wherein the bone cell activating compound is 1,25-dihydroxy vitamin D₃ and the bone activating amount is from about 0.001 microgram/kg/day to about 0.03 microgram/kg/day.

6. The method of claim 2 wherein the bone cell activating compound is 25-hydroxy vitamin D₃ and the bone activating amount is from about 0.1 microgram/kg/day to about 3 microgram/kg/day.

7. The method of claim 2 wherein the bone cell activating compound is an inorganic fluoride and the bone activating amount is from about 0.1 mg F/kg/day to about 1.0 mg F/kg/day.

8. The method of claim 2 wherein the bone cell activating compound is thyroxine and the bone activating amount is from about 0.01 mg/kg/day to about 0.5 mg/kg/day.

9. The method of claim 2 wherein the bone cell activating compound is triiodothyroxine and the bone activating amount is from about 0.1 microgram/kg/day to about 2.5 microgram/kg/day.

10. The method of claim 2 wherein the bone cell activating compound is prostaglandin PGE₂ and the bone activating amount is from about 0.1 mg/kg/day to about 25 mg/kg/day.

11. The method of claim 2 wherein the bone cell activating compound is parathyroid hormone 1-34 and the bone activating amount is from about 0.1 microgram/kg/day to about 3.0 microgram/kg/day administered subcutaneously.

12. The method of claim 1 wherein during the bone resorption inhibition period the ethane-1-hydroxy-1,1-diphosphonic acid, or pharmaceutically-acceptable salt or ester thereof, is administered daily in an amount from about 0.5 mgP/kg/day to about 2.0 mgP/kg/day.

13. The method of claim 4 wherein during the bone resorption inhibition period of ethane-1-hydroxy-1,1-diphosphonic acid, or pharmaceutically-acceptable salt or ester thereof, is administered daily in an amount from about 0.5 mgP/kg/day to about 2.0 mgP/kg/day.

14. A method for treating or preventing osteoporosis in humans comprising administering to a subject afflicted with or at risk to osteoporosis inorganic phosphate and ethane-1-hydroxy-1,1-diphosphonic acid according to a regimen consisting of one or more cycles, whereby each cycle consists of:

(a) a bone activating period of about 3 days during which about 30 mg P/kg, in the form of inorganic phosphate, is administered daily to said subject;

followed by (b) a bone resorption inhibition period of about 14 days during which said diphosphonic acid, or a pharmaceutically acceptable salt thereof, is administered daily to said subject at a rate of about 1.24 mgP/kg/day;

followed by (c) a rest period of about 80 days during which the subject received calcium at a rate of from about 500 mg/day to about 1000 mg/day and vitamin D at a rate of about 400 units per day.