Method of treating osteoporosis and other bone disorders with upfront loading of bisphosphonates, and kits for such treatment

• US 20040097468A1
• Filed: 11/20/2002
• Published: 05/20/2004
• Est. Priority Date: 11/20/2002
• Status: Abandoned Application

• Current Assignee: Sunil J. Wimalawansa
• Original Assignee: Sunil J. Wimalawansa
• Inventors: Wimalawansa, Sunil J.
• Application Number:
  US10/299,975
• Publication Number:
  US 20040097468A1
• Time in Patent Office: Days
• US Class Current: 514/89
• CPC Class Codes: A61K 31/66 Phosphorus compounds
• CPC Class Codes: A61K 31/663 Compounds having two or more phosphorus acid groups or esters thereof, e.g. clodronic acid, pamidronic acid

Abstract

Administering thereto-upfront loading of a bisphosphonate agent can be used to treat primary and secondary osteoporosis, other metabolic bone diseases, alleviation of bone pain, transplant and drug-induced bone loss, Paget'"'"'s disease of bone, loosening of prosthesis, or metastatic bone diseases in mammals, preferably a human female or a male. A bisphosphonate drug can be administered as a loading dose upfront. Bisphosphonates can be administered by themselves or combined with, one or more other medications acting on bone, such as HRT, selective estrogen receptor modulating drug, calcitonin, parathyroid hormone, fluoride, androgen, sex-steroid hormone analogues, nitroglycerin growth factors and their analogs, peptides and proteins and their analogues, or any other novel therapeutic agents.

This new regimen of administration of an anti-osteoporosis drug (e.g., a bisphosphonate) by itself, or in combination with other medications, can be used in mammals, preferably human (in women and men) for prevention and treatment of osteoporosis (e.g., postmenopausal, glucocorticoid- or drug-induced osteoporosis and osteoporosis in men, etc.) and other metabolic bone disorders, metastatic bone disease, transplant bone disease, Paget'"'"'s disease, and prevention and treatment of loosening of prosthesis. Disclosed are methods for rapid inhibition of bone resorption in mammals while obtaining a rapid reduction of bone turnover and biomarkers, rapid increase of bone mineral density, and rapid reduction of fractures. Also disclosed are pharmaceutical compositions and kits for carrying out the therapeutic methods disclosed herein.

Claims

1. A method comprising at least one pharmaceutically effective dosage of a bisphosphonate selected from the group consisting of alendronate, cimadronate, clodronate, tiludronate, etidronate, ibandronate, risedronate, piridronate, olpandronate, pamidronate, zoledronate or any other new bisphosphonates in a pharmaceutically acceptable salts, acid, or esters thereof, and mixtures thereof, for oral tablets or liquid form or intravenous administration, or administration via other parenteral means to a mammal having a loading dosing interval selected depending on the potency of the agent.

3. A method of claims 1 and 2, where a loading dose of a bisphosphonate or an another bone acting agent is administered orally tablets or liquid form (daily, several days a week, weekly, etc.), or the agent is administered intravenously or another parenteral route as a loading dose to rapidly reduce bone turnover, increase BMD and decrease fracture rates.

4. A method of claims 1 through 3 for prevention or treatment of primary and secondary osteoporosis of a female or male mammal comprising administering to an afflicted mammal, or one in need thereof, loading dose of oral tablets or liquid form or parenterally administered bisphosphonate by itself.

5. A method claims 1 through 3, for prevention or treatment of primary and secondary osteoporosis of a female or male mammal comprising administering to an afflicted mammal, or one in need thereof, loading dose of a bisphosphonate together with another agent acting on bone, including any estrogenic compound administered continuously or cyclically with or without a progestin agent (progesterone, dyprogesterone, medroxyprogesterone, norethisterone, levonorgestrel, or norgestrel, etc.) or both;

tibolone;

any androgen, testosterone or testosterone analogue;

anabolic steroid (nandrolone decanoate);

estrogen receptor modulating agent SERMs;

PTH or its analogues;

any calcitonin;

vitamin D or its analogues;

bone active growth factors, peptides or proteins, or their analogues;

fluoride (fluoride salt is a rapid or slow release sodium fluoride formulation);

an nitric oxide donor, it'"'"'s substrate, or a pharmacologically acceptable nitrate, any of these agents administered continuously, intermittently, or cyclically.

6. The method of claims 1 through 3, wherein the mammal is a female or male human suffering from primary or secondary osteoporosis, and/or preventing or alleviating pain associated with osteoporosis.

7. The method of claims 1 through 3, wherein the mammal is a human and the treatment further comprises a loading dose of a bisphosphonate is administered at least with calcitonin, HRT, SERMs, nitroglycerin, PTH, fluoride, or anabolic steroid, administered continuously or cyclically.

8. The method of claims 1 through 3, a pharmaceutical composition comprising synergistic effective amounts of a loading dose of a bisphosphonate, is administered with other bone-acting compound.

14. A method in claims 1 though 3, wherein said unit dosage of said bisphosphonate kits comprise about 1.0 to 6000 μ

/kg body weight, or the unit dosage of said bisphosphonate comprises about 5 to 2000 μ

g/kg body weight.

2. A kit comprising at least one pharmaceutically effective dosage of a bisphosphonate selected from the group consisting of alendronate, cimadronate, clodronate, tiludronate, etidronate, ibandronate, risedronate, piridronate, olpandronate, pamidronate, zoledronate, or any other new bisphosphonates in a pharmaceutically acceptable salts, acid, or esters thereof, and mixtures thereof, for oral tablets or liquid form or intravenous administration, or administration via other parenteral means to a mammal, preferably a human male or female, having a loading dosing interval selected depending on the potency of the agent.

15. A kit according to claim 2 wherein said bisphosphonate is selected from the group consisting of alendronate, risedronate, zolendronate, cimadronate, clodronate, tiludronate, etidronate, ibandronate, piridronate, olpandronate, pamidronate, or any other new bisphosphonates in a pharmaceutically acceptable salt, acid, or an esters thereof, and mixtures thereof.

16. A kit according to claim 2 and 15, wherein said pharmaceutically acceptable salt is selected from the group (e.g., of any bisphosphonate) consisting of sodium, potassium, calcium, magnesium, and ammonium salt or an acid, or esters thereof, and mixtures thereof.

17. A kit according to claim 2 comprising at least one pharmaceutically effective unit dosage of a loading doses of an orally tablets or liquid form, parenterally, or intravenously administered bisphosphonate selected from the group consisting of alendronate, cimadronate, clodronate, tiludronate, etidronate, risedronate, ibandronate, zolendronate, olpandronate, piridronate, pamidronate, or any other bisphosphonate agent, pharmaceutically acceptable salts, acid, or esters thereof, and mixtures thereof, for administration to a mammal according to a continuous or intermittent schedule.

18. A kit according to claim 2 wherein said unit dosage of a kit comprises a memory aid form in a tablet or capsule, a blister pack, unit dosages and are oriented in the order of their intended use.

9. A method of preventing and treating any metabolic bone diseases in a mammal preferably human, comprising administering to the subject a loading dose of a bone resorption inhibiting agent (e.g., a bisphosphonate), or a bone stimulating agent (i.e., anabolic agent), as a pharmaceutically acceptable salt, acid or thereof, or another bone-acting agent either orally or parenteralily including intravenously administered bisphosphonate or a pharmaceutically acceptable salt, acid, or thereof.

10. A method of preventing and treating any metastatic bone disease in a mammal, preferably a human, administering to the subject a bone resorption inhibiting amount of a loading dose of an oral tablets or liquid form, or parenterally or intravenously administered bisphosphonate as a pharmaceutically acceptable salt, acid, or thereof.

11. A method of preventing or alleviating pain associated with any metabolic bone disease, crush fracture syndrome, metastatic bone disease, or Paget'"'"'s disease of bone in a mammal, preferably human, using administering a bone resorption inhibiting amount of a loading dose of an oral tablets or liquid form, intravenously or intra arterially administered bisphosphonate as a pharmaceutically acceptable salt, acid, or thereof.

12. A method of treating or preventing recurrences of Paget'"'"'s disease as well as pain associated with the Paget'"'"'s disease of bone in a mammal, preferably human, using administering a bone resorption inhibiting amount of a loading dose of an oral, parenterally, or intravenously administered bisphosphonate as a pharmaceutically acceptable salt, acid, or thereof.

13. A method of preventing bone losses associated with microgravity, bed-ridden conditions such as following stokes or a fracture, or for astronauts in long-duration space flights using administering a bone resorption inhibiting amount of a loading dose of an oral, intravenously or intra arterially (parenteral) as a pharmaceutically acceptable bisphosphonate salt, acid, or thereof.

19. Loading dose of bisphosphonate therapy in patients who have an orthopedic implant device and a method of retarding loosening of an orthopedic prosthesis in a subject for treating and for preventing peri-prosthetic bone loss and/or pain by the administration of a loading dose of an oral, intravenous, or parenterally administered bisphosphonate, or an anabolic agent, or another bone acting agent in by itself or in combination with a bisphosphonate of a pharmaceutically acceptable salt, acid or, thereof, to decrease bone resorption and fracture reduction.

20. Loading dose of bisphosphonate therapy for treating, retarding, or preventing transplant- or drug-induced bone loss and/or bone pain by the administration of an oral tablets or liquid form, or parenterally administered bisphosphonate, or an anabolic agent, or another bone acting agent by itself or in combination with a bisphosphonate of a pharmaceutically acceptable salt, acid or, thereof, to decrease bone resorption and fracture reduction.