APC Mutations are Associated with Increased Bone Mineral Density in Patients with Familial Adenomatous Polyposis | oneFAPvoice

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APC Mutations are Associated with Increased Bone Mineral Density in Patients with Familial Adenomatous Polyposis

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source: Journal of bone and mineral research

year: 2010

authors: Miclea R L, Karperien M, Langers A M, Robanus-Maandag E C, van Lierop A, van der Hiel B, Stokkel M P, Ballieux B E, Oostdijk W, Wit J M, Vasen H F, Hamdy N A


The canonical Wnt pathway plays a key regulatory role in osteoblastogenesis and bone mass acquisition through its main effector, β-catenin. Adenomatous polyposis coli (APC) represents the key intracellular gatekeeper of β-catenin turnover, and heterozygous germ-line mutations in the APC gene cause familial adenomatous polyposis (FAP). Whether APC mutations affect bone mass has not been previously investigated. We conducted a cross-sectional study evaluating skeletal status in FAP patients with a documented APC mutation. Twenty-two FAP patients with a mean age of 42 years (54.5% women) were included in this study. Mean bone mineral density (BMD) Z-scores were significantly increased above normal at all measured sites: lumbar spine (p < .01), total hip (p < .01), femoral neck (p < .05), and trochanter (p < .01). Z-scores were +1 or greater in 14 patients (63.6%) and +2 or greater in 5 (22.7%). Mean values of bone turnover markers were within normal ranges. There was a significant positive correlation between procollagen type I N-terminal propeptide (P1NP) and β-crosslaps (β-CTX) (r = 0.70, p < .001) and between these markers and sclerostin and BMD measurements. We demonstrate that FAP patients display a significantly higher than normal mean BMD compared with age- and sex-matched healthy controls in the presence of a balanced bone turnover. Our data suggest a state of “controlled” activation of the Wnt signaling pathway in heterozygous carriers of APC mutations, most likely owing to upregulation of cytoplasmic β-catenin levels.

organization: Leiden University Medical Centre

DOI: 10.1002/jbmr.153

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