Methods for the Treatment and Diagnosis of Bone Mineral Density Related Diseases

Abstract

The present invention relates to methods of the treatment and diagnosis of bone mineral density related disorders. More particularly, the present invention relates to a method of diagnosing or predicting a bone mineral density related disease, or a risk of a bone mineral density related disease, in a subject, which method comprises detecting a mutation in the TBXAS1 gene, wherein the presence of said mutation is indicative of a bone mineral density related disease or of a risk of a bone mineral density related disease. The invention also relates to a compound selected in the group consisting of a thromboxane synthase (TXAS) encoding polynucleotide, a TXAS, thromboxane A2 or an analog thereof for treating or preventing a disease associated with an increased bone mineral density (e.g., Ghosal hematodiaphyseal dysplasia syndrome). The invention also relates to a compound selected from the group consisting of an inhibitor of TBXAS1 gene expression or a thromboxane inhibitor for treating or preventing a disease associated with a decreased bone mineral density (e.g., osteoporosis).

1 . A method of diagnosing or predicting a bone mineral density related disease, or a risk of a bone mineral density related disease, in a subject, which method comprises detecting a mutation in the TBXAS1 gene, wherein the presence of said mutation is indicative of a bone mineral density related disease or of a risk of a bone mineral density related disease, wherein said method comprises the step of detecting a TBXAS1 mutation in a nucleic acid sample obtained from said subject. 
     
     
         2 . The method according to  claim 1 , wherein the bone mineral density related disease is a disease associated with an increased bone mineral density and the mutation in the TBXAS1 gene is associated with a decrease of the Thromboxane synthase activity. 
     
     
         3 . The method of  claim 2  wherein said disease associated with an increased bone mineral density is Ghosal hematodiaphyseal dysplasia syndrome. 
     
     
         4 . The method of  claim 2  wherein the mutation is selected from the group consisting of 1463T>C, 248T>C, 1444G>T and 1238G>A. 
     
     
         5 . The method of  claim 2  wherein the mutation is selected from the group consisting of mutations which result in Leu488Pro, Leu83Pro, Gly482Trp and Arg413Glu mutants of thromboxane synthase (TXAS). 
     
     
         6 . The method according to  claim 1 , wherein the bone mineral density related disease is a disease associated with a decreased bone mineral density and the mutation in the TBXAS1 gene is associated with an increase of the Thromboxane synthase activity. 
     
     
         7 . The method of  claim 6  wherein said disease associated with a decreased bone mineral density is selected from the group consisting of osteoporosis, osteogenesis imperfecta, bone metastasis, primitive bone cancers and osteosarcoma. 
     
     
         8 . The method of  claim 6  wherein said disease associated with a decreased bone mineral density is osteoporosis. 
     
     
         9 . A method for treating or preventing a disease associated with an increased bone mineral density comprising administering to a subject in need thereof a compound selected in the group consisting of a TXAS encoding polynucleotide, TXAS, thromboxane A2 or an analog thereof. 
     
     
         10 . The method of  claim 9  wherein said disease associated with an increased bone mineral density is Ghosal hematodiaphyseal dysplasia syndrome. 
     
     
         11 . A method for treating or preventing a disease associated with a decreased bone mineral density comprising administering to a subject in need thereof a compound selected from the group consisting of an inhibitor of TBXAS1 gene expression or a thromboxane inhibitor. 
     
     
         12 . The method of  claim 11 , wherein said disease associated with a decreased bone mineral density is selected from the group consisting of osteoporosis, osteogenesis imperfecta, bone metastasis, primitive bone cancers and osteosarcoma. 
     
     
         13 . The method of  claim 11  wherein said disease associated with a decreased bone mineral density is osteoporosis.