In one aspect, the present invention provides methods of determining
susceptibility to bone fracture in a mammalian subject, wherein the
methods comprise analyzing nucleic acid molecules obtained from the
mammalian subject to determine which of the P, p X, and x alleles of the
estrogen receptor .alpha. gene are present, wherein the presence of a
haplotype comprising the p and x alleles is indicative of an increased
susceptibility to bone fracture. The present invention also provides kits
for determining susceptibility to bone fracture in a mammalian subject.