Diagnostics and therapeutics for osteoporosis

Abstract

Diagnostics and therapeutics for osteoporosis, which are based on the identification of the subject's IL-1 haplotype pattern are described.

What is claimed is:  
     
         1 . A method for determining whether a female subject is predisposed to developing osteoporosis, comprising identifying the IL-1 haplotype pattern of the female, wherein the presence of haplotype pattern 1 indicates that the female is susceptible to larger bone loss and/or increased risk of fracture during the early menopausal years and the presence of haplotype pattern 2 indicates that the female is susceptible to larger bone loss and/or increased risk of fracture during post-menopause.  
     
     
         2 . A method of  claim 1 , wherein said identifying step is selected from the group consisting of: 
 a) allele specific oligonucleotide hybridization;    b) size analysis;    c) sequencing;    d) hybridization;    e) 5′ nuclease digestion;    f) single-stranded conformation polymorphism;    g) allele specific hybridization;    h) primer specific extension; and    j) oligonucleotide ligation assay.    
     
     
         3 . A method of  claim 1 , wherein prior to or in conjunction with the identifying step, the nucleic acid sample is subject to an amplification step.  
     
     
         4 . A method of  claim 2 , wherein said size analysis is preceded by a restriction enzyme digestion.  
     
     
         5 . A method for selecting an appropriate osteoporosis therapy for a female subject, comprising the steps of: (a) identifying the IL-1 haplotype pattern of the female, wherein the presence of haplotype pattern 1 indicates that the female is susceptible to larger bone loss and/or increased risk of fracture during the early menopausal years and the presence of haplotype pattern 2 indicates that the female is susceptible to larger bone loss and/or increased risk of fracture during post-menopause ; and (b) and selecting a therapeutic that compensates for or otherwise modulates the net bioactivity resulting from the haplotype pattern.  
     
     
         6 . A method of  claim 5 , wherein said identifying step is performed using a technique selected from the group consisting of: 
 a) allele specific oligonucleotide hybridization;    b) size analysis;    c) sequencing;    d) hybridization;    e) 5′ nuclease digestion;    f) single-stranded conformation polymorphism;    g) allele specific hybridization;    h) primer specific extension; and    j) oligonucleotide ligation assay.    
     
     
         7 . A method of  claim 5 , wherein prior to or in conjunction with the identifying step, the nucleic acid sample is subjected to an amplification step.  
     
     
         8 . A method of  claim 6 , wherein said size analysis is preceded by a restriction enzyme digestion.  
     
     
         9 . A method of  claim 5 , wherein the therapeutic is a modulator of an IL-1 activity.  
     
     
         10 . A method of  claim 9 , wherein the IL-1 activity is IL-1α.  
     
     
         11 . A method of  claim 9 , wherein the IL-1 activity is IL-1β.  
     
     
         12 . A method of  claim 9 , wherein the IL-1 activity is IL-1RN.  
     
     
         13 . A method of  claim 9 , wherein the modulator of an IL-1 activity is a protein, peptide, peptidomimetic, small molecule, nucleic acid or a nutraceutical.  
     
     
         14 . A method of  claim 9 , wherein the modulator is an agonist.  
     
     
         15 . A method of  claim 9 , wherein the modulator is an antagonist.  
     
     
         16 . A method for determining the effectiveness of treating a subject that has or is predisposed to developing osteoporosis with a particular dose of a particular therapeutic, comprising the steps of: 
 a) detecting the level, amount or activity of an IL-1 protein; or an IL-1 mRNA or DNA in a sample obtained from a subject;    b) administering the particular dose of the particular therapeutic to the subject; detecting the level, amount or activity of an IL-1 protein; or an IL-1 mRNA or DNA in a sample obtained from a subject; and    c) comparing the relative level, amount or activity obtained in step a) with the level, amount or activity obtained in step b).    
     
     
         17 . A method of  claim 16 , wherein the therapeutic is a modulator of an IL-1 activity.  
     
     
         18 . A method of  claim 17 , wherein the IL-1 activity is IL-1α.  
     
     
         19 . A method of  claim 17 , wherein the IL-1 activity is IL-1β.  
     
     
         20 . A method of  claim 17 , wherein the IL-1 activity is IL-1RN  
     
     
         21 . A method of  claim 16 , wherein the therapeutic is a protein, peptide, peptidomimetic, small molecule or a nucleic acid.  
     
     
         22 . A method of  claim 17 , wherein the modulator is an agonist.  
     
     
         23 . A method of  claim 17 , wherein the modulator is an antagonist.  
     
     
         24 . A method for treating or preventing the development of osteoporosis in a female subject comprising the steps of: (a) identifying the IL-1 haplotype pattern of the female, wherein the presence of haplotype pattern 1 indicates that the female is susceptible to larger bone loss and/or increased risk of fracture during the early menopausal years and the presence of haplotype pattern 2 indicates that the female is susceptible to larger bone loss and/or increased risk of fracture during post-menopause; and (b) administering to the subject a therapeutic that compensates for or otherwise modulates the net bioactivity resulting from the haplotype pattern.  
     
     
         25 . A method of  claim 24 , wherein the identifying step is selected from the group consisting of: 
 a) allele specific oligonucleotide hybridization;    b) size analysis;    c) sequencing;    d) hybridization;    e) 5′ nuclease digestion;    f) single-stranded conformation polymorphism;    g) allele specific hybridization;    h) primer specific extension; and    j) oligonucleotide ligation assay.    
     
     
         26 . A method of  claim 24 , wherein prior to or in conjunction with identifying, the nucleic acid sample is subjected to an amplification step.  
     
     
         27 . A method of  claim 25 , wherein said size analysis is preceded by a restriction enzyme digestion.  
     
     
         28 . A method of  claim 24 , wherein the therapeutic is selected from the group consisting of: a modulator of an IL-1 activity.  
     
     
         29 . A method of  claim 28 , wherein the IL-1 activity is IL-1α.  
     
     
         30 . A method of  claim 28 , wherein the IL-1 activity is IL-1β.  
     
     
         31 . A method of  claim 28 , wherein the IL-1 activity is IL-1Ra.  
     
     
         32 . A method of  claim 24 , wherein the therapeutic is a protein, peptide, peptidomimetic, small molecule or a nucleic acid.  
     
     
         33 . A method of  claim 28 , wherein the modulator is an agonist.  
     
     
         34 . A method of  claim 28 , wherein the modulator is an antagonist.