Endocrinology and mineral metabolism
We are working with clinical and preclinical studies on metabolic bone diseases as well as genetic bone diseases such as Osteogenesis imperfecta. Through studies of the basic biology of bone cells, genetic studies on bone mineral density, epidemiological population studies and through involvement in clinical trials we try to understand the causes of bone diseases, to identify risk factors, and also to develop new treatment strategies.
The research is mainly focused on male osteoporosis, osteogenesis imperfecta and phosphate homeostasis.
These investigations are based on the clinical cohort, Mr OS. This is a collaboration between Sweden, US and Hong Kong. In total 11 000 elderly men are followed prospectively to fracture. In Uppsala 1000 men are gathered. The baseline sampling of the cohort and 5 year follow up is now completed. Current research is mostly on regulation of calcium and phosphate, influence of sex hormones and genetic determinants for fracture.
Osteogenesis Imperfecta (OI) is an inherited disease that is causes by mutations in the genes encoding collagen type I. In collaboration with the children’s hospital in Stockholm a cohort of patients with OI is collected. The mutations causing OI are determined, and at present large amount of clinical data are gathered to investigate genotype-phenotype interaction in this disease. Also, individual patients with new sorts of mutations causing defect collagen are investigated, and we have recently identified OI-causing mutations in the type I procollagen C-propeptide cleavage site. Finally in this project we are investigating the possibility to use gene silencing to interrupt dominant negative mutations in the genes for collagen type I.
In collaboration with nephrologists at Uppsala hospital, hormonal regulation of serum phosphate is investigated. Focus is on the recently discovered putative hormone FGF-23. Again the research is based on clinical cases or groups of patients. To date most interest has been on studies in patients with oncogenic phosphate wasting osteomalacia, and in patient groups with renal impairment. In the Mr OS cohort we have demonstrated that low serum levels of FGF-23 is a risk factor for fracture.