09:21am Sunday 26 January 2020

Discovery of genes underlying fracture susceptibility and osteoporosis

Osteoporosis is a frequent and devastating age-related disease: 50% of subjects that fracture their hip after age 80 years die within 12 months after the event. Actually, women older than 65 years are at greater risk for death after hip fracture than after breast cancer. While the consequences of osteoporosis are well established, the causes of the disease remain elusive. The disease is strongly genetically determined, but the responsible genes are largely unknown. However, this situation has changed dramatically today.

This is the first time such a large number of genetic variants have been robustly found associated with fracture risk. An international consortium, co-led by researchers from the Sahlgrenska Academy at Gothenburg University and also involving researchers from Umeå, Uppsala and Malmö, has studied more than 80,000 individuals with DXA scans (to measure bone mineral density) and examined the relation with fracture in approximately 30,000 cases and 100,000 controls. This constitutes the largest genetic study in osteoporosis performed to date.

This research leads to better understanding of the biology of skeletal health and fracture susceptibility. “In addition to the known proteins and pathways we have identified we are also confronted with completely new biology”, says Dr Ulrika Pettersson, Associate Professor at Umeå University and co-author of the publication.

“Our genetic study on BMD has allowed an unprecedented leap in sheer number of discoveries on human skeletal biology” explains Dr. Claes Ohlsson, Professor at the Sahlgrenska Academy, shared senior author of the study. “We have now pinpointed many factors in critical molecular pathways which are candidates for therapeutic applications.” he adds. “Such potential is highlighted by the identification (among others) of genes encoding proteins that are currently subject to novel bone medications. This is the case for denosumab (commercial name Prolia), a human monoclonal antibody against RANKL, a protein mediating the activation of bone resorption.”

“We also established that, as compared to women carrying the normal range of genetic factors, women with an excess of BMD-decreasing genetic variants had up to 56% higher risk of having osteoporosis adds Liesbeth Vandenput, Assistant Professor at the Sahlgrenska Academy and co-author of the study.

This study is part of the GEnetic Factors of OSteoporosis (GEFOS) project sponsored by the European Commission (FP7-HEALTH- F2-2008-201865-GEFOS). The article is authored by about 180 researchers, 10 of them in Sweden. Contributors at Umeå University, besides Ulrika Pettersson Kymmer, are Professor Göran Hallmans, Department of Public Health and Clinical Medicine, and Professor Olle Svensson, Department of Surgical and Perioperative Sciences.

Scientific contacts

Associate Professor Ulrika Pettersson-Kymmer, Clinical Pharmacology, Department of Pharmacology and Clinical Neuroscience, Umeå University, SE-901 87, Umeå, Sweden,
Tel: +46 702 313679, E-mail: ulrika.pettersson@pharm.umu.se

Professor Claes Ohlsson, Center for Bone and Arthritis Research, Department of Internal Medicine, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, Vita Stråket 11, S-41345, Gothenburg, Sweden,
Tel.: +46 706 832966, E-mail: claes.ohlsson@medic.gu.se


F Rivadeneira et. al. Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture
Nature Genetics, online-publishing 15 april 2012

Editor: David Meyers


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