Osteoporosis: Focusing on bones

Osteoporosis is one of the most common diseases of old age and the most frequent disorder of bone metabolism, with an estimated 27 million cases per year in Europe. The impact on the lives of those affected can be severe: pain, limited mobility, spinal changes and even the need for nursing care. The best-known consequence of osteoporosis is the increased incidence of bone fractures. At LBI Trauma, osteoporosis is studied on both a large and a small scale. Insights are gained at the macroscopic level of a society as well as at the microscopic level of cell biology.

Osteoporosis is characterised by low bone mass and deterioration of the microarchitecture of bone tissue. Bones become less stable and the risk of fractures increases tremendously. The average lifetime risk of a 50-year-old woman to suffer an osteoporotic fracture is estimated at almost 50%, the corresponding risk in men at 22%. Frequently, so-called fragility fractures occur, i.e. bone fractures occurring due to a minimal application of force, for example when falling from a standing position.

A group of researchers has now taken the first epidemiological look at osteoporotic fragility fractures in Austria. Besides Gesundheit Österreich GmbH, the Barmherzige Schwestern Hospital Vienna, the Medical University of Graz and Hemetsberger Medical Services, AUVA was also involved in the study. Johannes Grillari, head of the Ludwig Boltzmann Institute of Traumatology, the research center in cooperation with AUVA, coordinated the partners’ collaboration, which was largely based on the outstanding quality of AUVA’s patient data. The article recently appeared in “Im Blickpunkt,” the magazine for contract partners of the Austrian health insurance fund in Burgenland, as well as in the renowned journal Osteoporosis International.

Figures on bone fracture diagnoses from all public hospitals in Austria were combined with data from the MEDOK system of AUVA, which contains information on the type of injury, such as falls from the same height. In particular, the high data quality of AUVA thanks to the 4-eyes principle for diagnoses contributes to the high relevance of this study. This made it possible to derive the proportion of fragility fractures in the total number of fractures and to assign them to age groups. The calculations showed that out of a total of about 115,000 fragility fractures in 2018, 92,000 cases occurred in people aged 50 years or older which can be attributed to osteoporosis. Thus, the authors were able to demonstrate the enormous burden that osteoporosis places on both the healthcare system and the quality of life of so many people. They deduce from this the enormous importance of fall prevention, especially in light of our ageing society with an increasing prevalence of osteoporosis.

But what kind of processes happen in an osteoporotic bone in the first place? A research team led by Darja Marolt-Presen, head of the Bone Regeneration Group at LBI Trauma, has turned its attention to the question of how adult stem cells in bone change with age, and what impact that has on bone and joint health. The study appeared in the journal Mechanisms of Ageing and Development.

Mesenchymal stem cells, the driving force behind the formation of musculoskeletal tissue, remain active in adults to help broken bones heal. When needed, they can develop into bone cells themselves and energetically assist, or they regulate the behaviour of neighbouring cells by using signals such as microRNAs (miRNAs for short).

Maintenance processes take place continuously in every adult tissue. Around the clock, cells are busy replacing old tissue matrix with new ones. In old age, and especially in osteoporosis, the balance in this process shifts. More bone matrix is broken down than is regenerated. This out-of-balance process is also reflected in the mesenchymal stem cells, possibly even originating there.

Stem cell exhaustion is a well-known process and a main characteristic of the aging body. It has been shown that aging stem cells in the bone marrow develop less well towards bone, preferring instead to become fat cells. However, these can do little to build healthy bone, and bone density decreases. The altered environment in turn affects stem cells that still exist. When studying the gene expression profile of stem cells in osteoporotic bone, it was observed that those transduce different genes than stem cells in healthy bone from older donors. Followingly, there is a downward spiral once the bone is out of balance.

However, it is possible to intervene in this spiral. Understanding the cellular and subcellular mechanisms of osteoporosis is crucial at this point. Roland Kojican, a scientist at the LBI for Osteology as well as at the LBI Trauma – a manifestation of the excellent cooperation between these two LBIs – has been dedicating himself to the role of cell communication in osteoporosis for years. He was supported in his work by the Viennese StartUp TAmiRNA. He could demonstrate that osteoporosis not only affects miRNAs, the signaling molecules, in bone, but also miRNAs circulating in the body. This also helps to explain why osteoporosis does not simply affect individual bones, but the patient’s entire bone metabolism. In follow-up studies, Kocijan observed that drugs used to treat osteoporosis also bring the profile of circulating miRNAs closer to normal. Because a blood draw is much easier and gentler to perform than a bone biopsy, these findings are highly significant. After all, this means that the blood can be used to determine whether a patient is suffering from osteoporosis – and preventive measures can be taken accordingly. Drug treatment could also be monitored via the blood. The findings caused quite a stir in the scientific community and led to publications in the best journals in the bone field. Kocijan’s first study was awarded the prestigious Copp Prize of the German Society of Osteology in Erlangen in 2017.