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The present invention provides a genetic test for assaying predisposition to and/or resistance to high rates of bone turnover, development of low bone mass and responsiveness or otherwise to therapeutic modalities. This is a specific model for use in prediction of osteoporosis and likely response to preventive or therapeutic modalities. It is a general model of allelic variation in transcriptional regulators determining physiological set-points and thus susceptibility or resistance to certain pathophysiological states.