期刊
ARCHIVES OF ENDOCRINOLOGY METABOLISM
卷 60, 期 4, 页码 391-401出版社
SBEM-SOC BRASIL ENDOCRINOLOGIA & METABOLOGIA
DOI: 10.1590/2359-3997000000178
关键词
GWAS; mutation; fracture; low bone mass; bone remodeling
资金
- Capes scholarship [33002010062P5]
- Sao Paulo Research Foundation (Fapesp) Young Investigator award [2011/12696-4]
- Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [11/12696-4] Funding Source: FAPESP
The pathogenesis of osteoporosis, a common disease with great morbidity and mortality, comprises environmental and genetic factors. As with other complex disorders, the genetic basis of osteoporosis has been difficult to identify. Nevertheless, several approaches have been undertaken in the past decades in order to identify candidate genes for bone fragility, including the study of rare monogenic syndromes with striking bone phenotypes (e.g. osteogenesis imperfecta and osteopetroses), the analysis of individuals or families with extreme osteoporotic phenotypes (e.g. idiopathic juvenile and pregnancy-related osteoporosis), and, chiefly, genome-wide association studies (GWAS) in large populations. Altogether, these efforts have greatly increased the understanding of molecular mechanisms behind bone remodelling, which has rapidly translated into the development of novel therapeutic strategies, exemplified by the tales of cathepsin K (CTSK) and sclerostin (SOST). Additional biological evidence of involvement in bone physiology still lacks for several candidate genes arisen from GWAS, opening an opportunity for the discovery of new mechanisms regulating bone strength, particularly with the advent of high-throughput genomic technologies. In this review, candidate genes for bone fragility will be presented in comprehensive tables and discussed with regard to how their association with osteoporosis emerged, highlighting key players such as LRP5, WNT1 and PLS3. Current limitations in our understanding of the genetic contribution to osteoporosis, such as yet unidentified genetic modifiers, may be overcome in the near future with better genotypic and phenotypic characterisation of large populations and the detailed study of candidate genes in informative individuals with marked phenotype.
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