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APC mutations are associated with increased bone mineral density in patients with familial adenomatous polyposis
Author(s) -
Miclea Razvan L,
Karperien Marcel,
Langers Alexandra M,
RobanusMaandag 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
Publication year - 2010
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1002/jbmr.153
Subject(s) - familial adenomatous polyposis , adenomatous polyposis coli , procollagen peptidase , medicine , bone mineral , bone remodeling , endocrinology , wnt signaling pathway , sclerostin , gene mutation , femoral neck , mutation , osteoporosis , colorectal cancer , biology , cancer , gene , genetics
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. © 2010 American Society for Bone and Mineral Research.