US 6,416,737 B1Granted

Increasing bone strength with selected bisphosphonates

AssigneeBoard of Trustees of the University of Arkansas

InventorsStavros C. Manolagas, Teresita Bellido

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Abstract

The present invention is a method and composition to increase bone strength in a manner that decreases fracture incidence, which may or may not include increasing bone mineral density (“BMD”). The invention includes administering an effective amount of a bisphosphonate to a host in need thereof to increase bone strength, which inhibits the apoptosis of osteoblasts and osteocytes, without a significant effect on osteoclasts. In one embodiment, the bisphosphonate is not 1-amino-3-(N,N-dimethylamino)-propyliden-1,1-bisphosphonic acid or its pharmaceutically acceptable salt. An increase in osteoblast life span can lead to an increase in bone mass, i.e., an anabolic effect. Preservation of osteocyte life span can increase bone strength, which may be disproportional to the increase in bone mass.

Claims7

Dependent claims

A method of screening for a compound that increases bone strength, that includes the steps of:

i. a) contacting osteocytes with a test compound;
and b) comparing the number of apoptotic osteocytes contacted with the test compound with the number of apoptotic osteocytes in a control wherein osteocytes are not contacted with the compound;
ii. a) contacting osteoblasts with the test compound;
and b) comparing the number of apoptotic osteoblasts contacted with the test compound with the number of apoptotic osteoblasts in a control wherein osteoblasts are not contacted with the test compound;
iii. a) contacting osteoclasts with the test compound;
and b) comparing the number of apoptotic osteoclasts contacted with the test compound with the number of apoptotic osteoclasts in a control wherein osteoclasts are not contacted with the test compound;
and
iv. selecting a test compound that inhibits the apoptosis of osteocytes and osteoblasts and does not substantially affect the apoptosis of osteoclasts.

5 more elements

Dependencies are inferred from the claim text.

Facts

Application: 09/443,841Filed 19 Nov 1999 · us provisional application
Priority: 19 Nov 1998
Granted: 9 Jul 2002
Term ends: Not estimatedThe source records don’t support an estimate.

Classification18 codes

G01N 33/5044
For testing or evaluating the effect of chemical or biological compounds, e.g. drugs, cosmetics: involving specific cell types
A61K 31/57
Compounds containing cyclopenta[a]hydrophenanthrene ring systems; Derivatives thereof, e.g. steroids: substituted in position 17 beta by a chain…
A61K 31/663
Phosphorus acids or esters thereof having P—C bonds, e.g. foscarnet, trichlorfon: compounds having two or more phosphorus acid groups or esters…
A61P 19/08
Drugs for skeletal disorders: for bone diseases, e.g. rachitism, Paget's disease