Outimaija Mäkitie

Osteoporosis is characterized by compromised bone strength and fractures. The associated morbidity and mortality have significant human and economic implications. Genetic factors play an important role but the underlying genes remain inadequately characterized. We aim to identify novel genes with a major effect on the skeleton and explore the mechanisms through which these genes lead to skeletal fragility. We use a family-based approach and focus on osteoporosis presenting in childhood or early adulthood. We recruit individuals and families with early-onset osteoporosis of unknown cause. After phenotyping with bone densitometry, radiography and biochemistry we use genetic analyses, including whole-genome sequencing, to identify the genetic cause of osteoporosis. Functional consequences of gene defects are studied on the tissue level and in patient-derived cell lines. We analyze transiliac bone biopsies for bone cell function and mineralization. Mesenchymal stem cells are obtained from bone marrow and analyzed for osteogenic and adipogenic potential. Osteocyte cell lines are used to gain further insight to the pathogenic mechanisms. This project involves several international collaborators. Discovery of new genes underlying osteoporosis enables development of new diagnostic, preventive and therapeutic methods. Markers that enable early diagnosis of osteoporosis and preventive measures in predisposed individuals will have significant positive human and economic implications.