Topical administration of statins for treatment of bone disorders

1. A method for treating bone disorders in a vertebrate animal subject which method comprises topically administering a pharmaceutical formulation suitable for topical application to a subject in need of such treatment comprising, as active ingredient, a compound of the formula:

wherein X in each of formulas (1) and (2) represents a substituted or unsubstituted alkylene, alkenylene, or alkynylene linker of 2–6C;

Y represents one or more carbocyclic or heterocyclic rings; when two or more rings are present in Y, they may optionally be fused; and

R′ represents a cation, H or a substituted or unsubstituted alkyl group of 1–6C; and

the dotted lines represent optional π-bonds.

2. The method of claim 1 , wherein the formulation is a transdermal patch.

3. The method of claim 1 , wherein the formulation is an aerosol spray, a lotion, a gel or an ointment.

4. The method of claim 3 , wherein the formulation comprises as a vehicle, lower aliphatic alcohols, polyglycols, esters of fatty acids, oils, fats and/or silicones.

5. The method of claim 1 , wherein X in each of formulas (1) and (2) represents an unsubstituted alkylene, alkenylene or alkynylene linker of 2–6C.

6. The formulation of claim 1 , wherein Y is

wherein R 1 is substituted or unsubstituted alkyl;

each R 2 is independently a noninterfering substituent;

R 3 is H, hydroxy, or alkoxy (1–6C);

each m is independently an integer of 0–6, wherein each R 2 may reside in any of positions 2–7; and

p is 0 or 1, depending on the position of any π-bonds indicated by the dotted lines.

7. The method of claim 6 , wherein each m is independently 1 or 2 and wherein each R 2 resides in positions 2, 5 or 6.

8. The method of claim 7 , wherein Y is

9. The method of claim 1 , wherein Y is

wherein each n is 0 or 1, but wherein at least one n in formula (5) and in formula (9) must be 1;

Z is CH or N, when n associated with its extra-ring substituent is 1 and is S or O when said n is 0;

each K comprises a substituted or unsubstituted aromatic or nonaromatic carbocyclic or heterocyclic ring system which may optionally be spaced from the linkage position shown in formulas (5)–(9) by a linker of 1–2C;

each of R 4 and R 5 is independently H or linear or branched chain alkyl.

10. The method of claim 9 , wherein Y is of the formula

wherein each n is 1,

Z is N,

K comprises a substituted or unsubstituted aromatic carbocyclic or heterocyclic ring system which may optionally be spaced from the linkage position shown in formula (7) by a linker of 1–2C, or in formula (7), Z may be spaced from the carbon bonded to X by ═CR 6 — wherein R 6 is H or linear, branded or cyclic alkyl (1–6C), and

R 5 is H or linear, branched or cyclic alkyl.

11. The method of claim 1 , wherein said active ingredient is lovastatin, mevastatin, simvastatin, pravastatin, cerivastatin, NK104, or atorvastatin.

12. The method of claim 1 , wherein the bone disorder is a bone deficit.

13. The method of claim 1 , wherein the bone disorder is a cartilage deficit.

14. The method of claim 1 , wherein the formation of new bone is enhanced.