Osteoclast inhibitors for knee conditions
View Patent ↗Oral dosage forms of osteoclast inhibitors, such as zoledronic acid, in an acid or a salt form can be used to treat or alleviate pain or related conditions, such as knee pain.
1. A method of treating osteoarthritis comprising orally administering zoledronic acid to a person suffering from osteoarthritis and having a bone marrow lesion, wherein the person has knee pain, and a pain intensity of 5 or greater measured using the 0-10 numerical rating scale (NRS) or 5 cm or greater using the 10 cm visual analog scale (VAS), and wherein about 200 mg to about 400 mg of the zoledronic acid is administered within 2 months.
2. The method of claim 1 , wherein an equivalent to 50 mg of the zoledronic acid is orally administered weekly in a salt form.
3. The method of claim 2 , wherein the salt form of zoledronic acid is orally administered weekly for 6 weeks.
4. The method of claim 2 , wherein orally administering the zoledronic acid in the salt form to the person results in a C max of zoledronic acid of about 30 ng/mL to about 40 ng/mL.
5. The method of claim 1 , wherein the person has a normal joint space in the knee, with OARSI Grade 0, or Kellgren and Lawrence Grades 0 or 1, joint space narrowing.
6. The method of claim 1 , wherein the zoledronic acid is orally administered at an interval of 6 to 8 days.
7. The method of claim 1 , wherein the zoledronic acid is orally administered at an interval of 12 to 16 days.
8. The method of claim 1 , wherein the zoledronic acid is orally administered at an interval of 26 to 35 days.
9. The method of claim 1 , wherein the zoledronic acid is orally administered to the person in an acid form.
10. The method of claim 1 , wherein the zoledronic acid is orally administered to the person in a salt form.
11. The method of claim 1 , wherein the zoledronic acid is orally administered to the person in a disodium salt form.
12. The method of claim 9 , wherein the person experiences a reduction in pain intensity of at least about 1.5 cm, using the 10 cm VAS, as compared to a placebo.
13. The method of claim 10 , wherein the person experiences a reduction in pain intensity of at least about 1.5 cm, using the 10 cm VAS, as compared to a placebo.
14. The method of claim 1 , wherein the first time a salt form of zoledronic acid is orally administered, the person has a C max of zoledronic acid of about 5 ng/mL to about 80 ng/mL.
15. The method of claim 11 , wherein the person experiences a reduction in pain intensity of at least about 1.5 cm, using the 10 cm VAS, as compared to a placebo.
16. The method of claim 15 , wherein about 50 mg to about 60 mg of the disodium salt form of zoledronic acid is orally administered about once a week.
17. The method of claim 16 , wherein the disodium salt form of zoledronic acid is orally administered about once a week for 3 to 6 weeks.
18. The method of claim 17 , wherein the first time the disodium salt form of zoledronic acid is orally administered, the person has a C max of zoledronic acid of about 30 ng/mL to about 50 ng/mL.
19. The method of claim 1 , wherein the zoledronic acid is orally administered to provide a C max of zoledronic acid of about 20 ng/mL to about 50 ng/mL.
20. The method of claim 1 , wherein the zoledronic acid is orally administered to provide a C max of zoledronic acid of about 5 ng/mL to about 50 ng/mL.
21. The method of claim 3 , wherein the C max of zoledronic acid in the person, measured after the salt form of zoledronic acid is orally administered weekly for 6 weeks, is about 30 ng/mL to about 80 ng/mL.
22. The method of claim 1 , wherein orally administering the zoledronic acid to the person results in a C max of zoledronic acid of about 30 ng/mL to about 50 ng/mL.
23. The method of claim 1 , wherein orally administering zoledronic acid in a salt form or an acid form to the person results in a C max of zoledronic acid of about 50 ng/mL to about 80 ng/mL.
24. The method of claim 1 , wherein orally administering zoledronic acid in a salt form or an acid form to the person results in a C max of zoledronic acid of about 80 ng/mL to about 120 ng/mL.