"The goal is to use the discoveries for the benefit of everyone affected by osteoporosis"

How common is osteoporosis among children and what is currently known about the causes?

Although osteoporosis is considered a disease of the elderly, affecting particularly postmenopausal women, it is becoming increasingly recognized as a health problem also among children and young adults. Excessive bone fragility and osteoporosis in a child is in most cases caused by an underlying chronic illness or its treatment. Fortunately, even in children with chronic illnesses, osteoporosis is relatively rare. However, in our earlier studies up to 20–25% of children with a severe chronic illness, such as rheumatological disease, inflammatory bowel disease, or leukemia, develop osteoporotic fractures.

When a child without any other illness sustains several fractures caused by minor or moderate trauma, these can also be a sign of osteoporosis. In such cases genetic factors play an important role. Several genetic forms of osteoporosis have been recognized. In such cases a mutation in a single gene with a major role in the bone development can be the cause of osteoporosis. These monogenic forms of osteoporosis are considered rare diseases and affect less than 5% of all those children who sustain a fracture.

How can your research help ensure that children with osteoporosis are diagnosed earlier and receive better treatment?

Our research on early-onset osteoporosis has two major goals. The first one is to identify new genes and gene variants that are responsible for early-onset osteoporosis. The second goal is to describe the clinical features, disease course, and treatment results in monogenic osteoporosis. Our research has already resulted in discovery of several completely new genetic forms of osteoporosis. Using these findings, we can provide genetic testing to family members to identify as early as possible those at risk. Early diagnosis makes it possible to prevent fractures and treat osteoporosis before it causes permanent complications, such as painful spinal fractures that lead to height loss and spinal deformities.

In studies on natural course and treatment effects, we have learned that osteoporosis treatment needs to be individually tailored because all monogenic forms of osteoporosis behave differentially and the medications that are effective in one type might not be the optimal choice for another genetic form of osteoporosis. Furthermore, we have found out that monogenic osteoporosis may not be only a disease of the skeleton but there may be other non-skeletal manifestations that need to be evaluated and treated. In this way our research helps to improve diagnostics, treatment and follow up of children with osteoporosis.

In what ways will the results from your research on early-onset osteoporosis also be applicable in the treatment of more common forms of osteoporosis in adults? 

Research on rare bone disorders has significantly benefitted not only individuals affected by rare diseases but also the general population. For example, the so called WNT-signaling pathway is presently regarded as a key regulator of bone metabolism. Its role was discovered by studying rare monogenic diseases with abnormal bone mass. These genetic and molecular discoveries led to development of a new osteoporosis medication targeting the WNT pathway. This medication is now widely used to treat postmenopausal osteoporosis.

Similarly, I anticipate our results to modify the present conception of pathogenic mechanisms in osteoporosis and reveal novel therapeutic targets that could be used in drug development. Our research applies several methods to learn more about the pathology in bone, muscle, and their interactions in early-onset osteoporosis. We also develop zebrafish models for the investigated monogenic forms of osteoporosis; these models can then be used for preclinical testing of the known and potential novel therapeutic molecules. So the goal is to improve management not only in these rare diseases but to use these discoveries for the benefit of those affected by osteoporosis in the general population.