In the paper, Obesity variants in the GIPR gene do not associate with risk of fracture or bone mineral density” published in the JCEM, The Journal of Clinical Endocrinology & Metabolism, scientists from deCODE genetics, a subsidiary of Amgen, and collaborators, investigate if obesity variants in GIPR are associated with reduced BMD and/or risk of fractures.
The incretin hormonal system has recently been the focus of several treatment strategies for obesity and type 2 diabetes.
Sequence variants in one of the incretin receptor genes, GIPR, are associated with lower body mass index (BMI) and more favorable glycaemic traits. These variants disrupt the function of the receptor, leading to the notion that diminishing the activity of GIPR may be a way to treat obesity.
It is not clear if such inhibition of GIPR could lead to reduced bone mineral density (BMD) beyond what is expected with rapid weight loss, with an increased risk of fracture as a consequence.
The scientists gathered data on fractures and BMD from up-to 1.2 million individuals from 4 populations: Iceland, Denmark (CHB/DBDS studies), the United Kingdom (UK Biobank study), and the United States (Intermountain Health study).
The results from this large collaborative effort show that none of these obesity-related variants in the GIPR gene are associated with an increased risk of fracture or lowered BMD.