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Osteoporosis and Fragility Fractures: Risk Factors, Underlying Mechanisms and Clinical Interventions - An Integrated Approach

Principal investigator; Åkesson, Kristina, Professor, MD/PhD

Clinical speciality: Orthopaedics

Phone: ++4640332370

Co-workers, Lund University: Holmberg Anna H, Karlsson Magnus, Luthman Holger, McGuigan Fiona, Rogmark Cecilia

Co-workers, not Lund University: Bouxsein Mary, Grynpas Marc, Kenny Anne, Kindmark Andreas, Marsh David, Piehl Fredrik, Reid David, Skerry Tim, Uitterlinden André, Woolf Anthony

International networks: GENOMOS (international collaboration of leading researchers in osteoporosis)

Research area/areas: Cell and Molecular Biology, Medical Genetics, Orthopaedics

The aim of this project is to improve risk assessment by evaluating genetic and environmental influences at different stages of life in both women and men. Identifying underlying mechanisms may also offer future possibilities for prevention and molecular targets for pharmaceutical treatment of osteoporosis and fracture risk.

The project is expected to quantify the association between genetic markers, bone density, and fragility fractures; to define genetic variants in metabolic pathways related to treatment response; and to define the functional mechanisms by which genetic polymorphisms regulate bone cell function, bone mass and bone strength.

The major focus of our research is on risk factors related to osteoporosis and fragility fractures with an emphasis on delineating gene-environment interactions and interactions between bone and skeletal muscle, adipose tissue, glucose metabolism, and inflammation.

Several, also by international standards, very large and well-characterized population-based cohorts of women and men are followed prospectively by extensive examinations focusing on risk factors for osteoporosis and fracture (n=3800). Allelic variants of genes related to regulation of bone metabolism and bone cell activity are determined and compared for age- and gender-related difference. In addition, we have developed a methord for mRNA extraction from bone samples obtained at surgery for evaluation of functional effects.

The identification of genes predisposing to osteoporosis is a prime focus, since this may both identify possible targets for pharmaceutical intervention and allow for genetic markers to be used as additional diagnostic tools, identifying those at risk at an earlier stage.

Effective treatments with defined mechanisms of action are now available for prevention of osteoporosis; customizing drug treatment by targeting existing and future drugs more effectively will be the ultimate outcome from advances in bone genetics. The functional studies will add to the insight in pathogenesis

Link to project homepage: http://www.med.lu.se/klinvetmalmo/osteoporosforskning

5 recent original publications

Lagerholm Sofia, Park Hee-Bok, Luthman Holger, Grynpas Marc, McGuigan Fiona, Swanberg Maria, Åkesson Kristina
Identification of Candidate Gene Regions in the Rat by Co-Localization of QTLs for Bone Density, Size, Structure and Strength
PLoS One. 2011; 6: -

McGuigan Fiona, Kumar Jitender, Ivaska Kaisa, Obrant Karl, Gerdhem Paul, Åkesson Kristina
Osteocalcin gene polymorphisms influence concentration of serum osteocalcin and enhance fracture identification.
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2010; Apr 7: -

Large-scale analysis of association between LRP5 and LRP6 variants and osteoporosis
JAMA Journal of the American Medical Association. 2008; 299: 1277 - 1290

Tenne MD Max, McGuigan Fiona, Jansson Lisa, Gerdhem Paul, Obrant Karl, Luthman Holger, Åkesson Kristina
Genetic variation in the PTH pathway and bone phenotypes in elderly women: Evaluation of PTH, PTHLH, PTHR1 and PTHR2 genes.
Bone. 2008; Dec 23: -

Friesendorff v M, Besjakov J, Åkesson K.
Long-term survival and fracture risk in women with hip fracture. A 22-year follow-up
J Bone Min Res. 2008; 11: 1832-41

IGrundberg E, ,Lau E, Lorentzson, Karlsson M, Holmberg A, Groop L, Mellström D, Orwoll E, Mallmin H, Ohlsson C, Ljunggren Ö, Åkesson K.
Large-scale Association Study between Polymorphic Variations in the LRP5 Gene and Bone Mineral Density in Young and Elderly Men
Osteoporosis Int.. 2007; 306: Ehead Nov 17

Further publications here (new window)

Financing/year