Blood Biomarkers for Bone Fracture and Cartilage Injury

Abstract

Blood biomarkers are described for use in methods and compositions to determine whether an individual has sustained a bone fracture or a cartilage injury.

1 . A method of detecting an injury to cartilage in a human individual comprising measuring the level of cartilage acidic protein 1 (CRTAC-1) in a first blood sample obtained from a first individual and comparing the level of CRTAC-1 in the first blood sample to the level of CRTAC-1 determined in a second blood sample from the first individual or a second individual when the first or second individual did not have a cartilage injury, wherein a level of CRTAC-1 in the first blood sample that is at least about 20% higher than the level of CRTAC-1 in the second blood sample indicates that the first individual has sustained a cartilage injury. 
     
     
         2 . The method according to  claim 1 , wherein the step of measuring the level of CRTAC-1 in the first blood sample comprises contacting the first blood sample with a binding partner for CRTAC-1 to form a binding complex between the binding partner and CRTAC-1 present in the first blood sample. 
     
     
         3 . The method according to  claim 2 , wherein the binding complex formed between the binding partner and CRTAC-1 present in the first blood sample is detected by a detectable label present on the binding partner. 
     
     
         4 . The method according to  claim 2 , wherein the binding complex formed between the binding partner and CRTAC-1 present in the first blood sample is detected by adding an antibody that binds to said binding partner or that binds to said CRTAC-1 present in said binding complex and detecting said antibody by a detectable label present on said antibody. 
     
     
         5 . The method according to any one of  claims 2 - 4 , wherein the binding partner for CRTAC-1 is a binding protein or an aptamer that binds CRTAC-1. 
     
     
         6 . The method according to  claim 5 , wherein said binding protein for CRTAC-1 is an antibody to CRTAC-1. 
     
     
         7 . A method of monitoring the state of a cartilage injury in an individual comprising measuring the level of cartilage acidic protein 1 (CRTAC-1) in a first blood sample previously obtained from the individual and comparing the level of CRTAC-1 in the first blood sample with the level of CRTAC-1 measured in a second blood sample, wherein the second blood sample was obtained within two weeks, inclusive, after the first blood sample from the individual, and determining whether the level of CRTAC-1 in the second blood sample has increased, decreased, or remained the same relative to the level in the first blood sample. 
     
     
         8 . A method for determining the time proximity of an individual from a cartilage injury comprising:
 (a) obtaining a blood sample from said individual at a first time point,   (b) obtaining at least one additional blood sample from said individual at a later time point,   (c) determining the concentration of cartilage acidic protein 1 (CRTAC-1) in at least said first blood sample and said at least one additional blood sample, wherein said first time point and said later time point are within two weeks of each other,   wherein a determination that an increase in CRTAC-1 concentration of at least about 20% has occurred between said first time point and said later time point indicates that the individual has suffered a cartilage injury within two weeks prior to said later time point,   wherein a determination that a decrease in CRTAC-1 concentration of at least about 4.5% has occurred between said first time point and said later time point indicates that the individual has suffered a cartilage injury more than six weeks but less than ten weeks prior to said later time point,   wherein a determination that the concentration of CRTAC-1 has neither increased or decreased more than about 2% between said first time point and said later time point indicates that the individual has not suffered a cartilage injury for at least ten weeks prior to said later time point.   
     
     
         9 . The method according to  claim 8 , wherein said first time point and said at later time point are within one week of each other. 
     
     
         10 . A kit for use in measuring the level of cartilage acidic protein 1 (CRTAC-1) in a blood sample previously obtained from an individual to determine whether said individual has sustained a cartilage injury comprising:
 a binding partner that binds to cartilage acidic protein 1 (CRTAC-1);   an antibody that binds the binding partner when the binding partner is bound to CRTAC-1;   instructions for using the kit to measure the level of CRTAC-1 in a blood sample previously obtained from an individual to determine if said individual has sustained a cartilage injury.   
     
     
         11 . A kit for use in detecting the presence of transforming growth factor beta receptor III (TGFβrIII) in a blood sample previously obtained from an individual to determine whether said individual has sustained a bone fracture comprising:
 a binding partner that binds to transforming growth factor beta receptor III (TGFβrIII); 
 an antibody that binds the binding partner when the binding partner is bound to TGFβrIII; 
 instructions for using the kit to detect TGFβrIII in a blood sample previously obtained from an individual to determine if said individual has sustained a bone fracture. 
 
     
     
         12 . The kit according to  claim 10  or  claim 11 , further comprising a device to obtain a sample of blood from an individual.