APC Mutations Are Associated With Increased Bone Mineral Density in Patients With Familial Adenomatous Polyposis

作者：Miclea Razvan L; Karperien Marcel; Langers Alexandra M; Robanus Maandag Els C; van Lierop Antoon; van der Hiel Bernies; Stokkel Marcel P; Ballieux Bart E; Oostdijk Wilma; Wit Jan M; Vasen Hans F; Hamdy Neveen A^*

来源：Journal of Bone and Mineral Research, 2010, 25(12): 2348-2356.

DOI：10.1002/jbmr.153

• APC FAP
• beta CATENIN
• BMD BONE TURNOVER

The canonical Wnt pathway plays a key regulatory role in osteoblastogenesis and bone mass acquisition through its main effector, beta-catenin Adenomatous polyposis coli (APC) represents the key intracellular gatekeeper of beta-catenin turnover, and heterozygous germline 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 (545% 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 beta-crosslaps (beta-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" activat

• 出版日期2010-12