The role of extracellular modulators of canonical Wnt signaling in bone metabolism and diseases.

Objectives: The Wnt signaling pathway is a key pathway in various processes, including bone metabolism. In this review, current knowledge of all extracellular modulators of the canonical Wnt signaling in bone metabolism is summarized and discussed.

Methods: The PubMed database was searched using the following keywords: canonical Wnt signaling, β-catenin bone metabolism, BMD, osteoblast, osteoporosis, Wnt, LRPs, Frizzleds, sFRPs, sclerostin or SOST, dickkopfs, Wif1, R-spondins, glypicans, SOST-dc1 and kremen, all separately as well as in different combinations.

A common LRP4 haplotype is associated with bone mineral density and hip geometry in men-data from the Odense Androgen Study (OAS).

Osteoporosis is a common disease characterized by an increased susceptibility to fracture. It is a complex disorder resulting from the interaction of several polymorphisms in different genes and environmental factors. Since we recently reported a role for low density lipoprotein-related protein (LRP)-4 in monogenic disorders with bone overgrowth, we now wanted to evaluate whether genetic variation in the LRP4 gene has an effect on the susceptibility to osteoporosis in a population based cohort from the Odense Androgen Study.

Mutations in sFRP1 or sFRP4 are not a common cause of craniotubular hyperostosis.

Sclerosing bone dysplasias are a heterogeneous group of rare diseases marked by increased BMD caused by either increased bone formation or by decreased bone resorption. In this study we have focused on craniotubular hyperostoses mainly affecting the long bones and the skull. Currently, there are three causative genes identified namely LRP5, SOST and LRP4.

Single nucleotide polymorphisms in sFRP4 are associated with bone and body composition related parameters in Danish but not in Belgian men.

The senescence accelerated mouse P6 (SAMP6) has a low bone mass and has previously shown to be a good model for senile osteoporosis in humans. In addition to a reduced bone mass, SAMP6 mice are obese and have hyperlipidemia. Using positional cloning and expression studies, an increased expression of sfrp4 was found in these mice.

Association study of common variants in the sFRP1 gene region and parameters of bone strength and body composition in two independent healthy Caucasian male cohorts.

Bone mineral density (BMD) and bone strength are predictive parameters for the development of osteoporosis and related fracture later in life. Although it is well known that BMD and bone strength have a high heritability, not much of the variation is already explained. Mice models showed that sFRP1 has an influence on bone formation.