The present invention relates generally to the field of implant related risk of revision, in particular implant related risk of revision not caused by an infection or metal on metal reaction. The present invention provides methods of diagnosing implant related risk of revision, use of kits for such diagnostic purposes and compositions for use in the treatment of implant related risk of revision, in particular implant related risk of revision not caused by an infection or metal on metal reaction.

This invention relates, in part, to unique and newly identified genetic polynucleotides involved in the process of bone remodeling; variants and derivatives of the polynucleotides and corresponding polypeptides; uses of the polynucleotides, polypeptides, variants and derivatives; and methods and compositions for the amelioration of symptoms caused by bone remodeling disorders. Disclosed in particular are, the isolation and identification of polynucleotides, polypeptides, variants and derivatives involved in osteoclast activity, validation of the identified polynucleotides for their potential as therapeutic targets and use of the polynucleotides, polypeptides, variants and derivatives for the amelioration of disease states and research purposes.

The present invention discloses a novel therapeutic intervention for osteoporosis. The present invention discloses that Interleukin-3 (IL-3) can be utilized as a therapeutic intervention against osteoporosis and for regulating bone homeostasis. The present invention also provides a method for determining the pre-disposition of a subject for osteoporosis by measuring the RANKL/OPG level.

Methods for treating diseases such as cancer comprising administering a Wnt pathway inhibitor, either alone or in combination with other anti-cancer agents, and monitoring for skeletal-related side effects and/or toxicity.

A compound of Formula I has the structure:

##STR00001##

wherein G is a straight, branched or cyclic alkyl group having 2 to 50 carbon atoms or an ether group, and R is a fluorescent dye. In some embodiments, G is selected from the group consisting of (CH.sub.2).sub.n and (CH.sub.2OCH.sub.2).sub.m, wherein n is an integer from 2 to 18, m is an integer from 2 to 18.

Methods of diagnosing and preventing bone loss and/or enhancing bone formation are disclosed. The invention additionally provides methods of diagnosing a predisposition to bone loss. The methods mathematically combine the information provided by imaging tests with the information provided by biomarkers to provide an index value. The index value is used for diagnosis of bone diseases, and to assess the progress of treatment of bone diseases.

The present invention relates to biological markers of metabolic bone diseases or disorders such as osteoporosis and related methods using thereof. The invention further relates to the use of those biomarkers and related material and assays in the diagnosis of subjects at risk of developing such disorders or monitoring the effects of a treatment thereof.

Disclosed are methods of identifying subjects with osteoporosis or osteopenia, subjects at risk for developing osteoporosis, osteopenia, and bone fractures, methods of evaluating the effectiveness of osteoporosis treatments in subjects with osteoporosis or osteopenia, and methods of selecting therapies for treating osteoporosis or osteopenia, using biomarkers.

Disclosed herein is a marker composition that includes sphingosine 1-phosphate (S1P) lipid and that may be used to predict the risk of fracture or osteoporosis; a kit that includes an antibody that specifically binds to the S1P lipid and that can be used to predict the risk of fracture or osteoporosis; and a method that can be used to obtain information that allows prediction of the risk of fracture or osteoporosis and includes measurements of S1P lipid concentrations by measuring the binding of a S1P-specific antibody to SIP lipid. The S1P lipid disclosed herein is highly expressed in individuals with fracture, regardless of their bone mineral density. Accordingly, it may be useful as a biomarker of the risk of fracture or osteoporosis.

Methods for treating diseases such as cancer comprising administering a Wnt pathway inhibitor, either alone or in combination with other anti-cancer agents, and monitoring for skeletal-related side effects and/or toxicity.