Osteoporosis medication with striking additional benefits

For decades, bisphosphonates have been the standard treatment for progressive bone loss in old age. Studies suggest that these drugs also have a life-prolonging effect beyond osteoporosis. Researchers at the Medical University of Vienna have used a new animal model to investigate the underlying mechanisms.

Biology and Medicine

by Alois Pumhösel

October 13, 2025

The active ingredient alendronate helped achieve a breakthrough in the treatment of osteoporosis. In the 1990s, researchers discovered that the substance can significantly reduce the progressive bone loss associated with this disease in old age. The group of bisphosphonates, to which this substance belongs, was originally developed for other purposes – including that of an additive in detergents to prevent calcification. In the medical context, doctors found that bisphosphonates such as alendronate could also effectively inhibit the activity of osteoclasts, which are responsible for the degeneration of bone structures in the body. The result was a significant reduction in femoral neck and vertebral fractures connected with severe osteoporosis.

Osteoporotic fractures are associated with increased mortality, which is why a reduction of the frequency of fractures could lower mortality rates. Surprisingly, several studies suggest that the mortality rate of patients treated with bisphosphonates could even improve beyond this fracture-related rate. To this day, the mechanisms behind this apparent life-prolonging effect of this group of drugs remain unclear. In the context of the FWF-funded project “Bisphosphonates effect on Nothobranchius furzeri,” researchers at the Medical University of Vienna have now established a new research approach in this field. With the help of an animal model, used for this purpose for the first time worldwide, the team sought to confirm the life-prolonging effect of bisphosphonates and investigate the underlying cellular processes.

“Observations to date suggest that bisphosphonates have effects not only on osteoporosis, but also on oncological and cardiovascular diseases,” notes Peter Pietschmann, who heads the project in his capacity as director of the Department of Cellular and Molecular Pathophysiology at the Medical University of Vienna. “We conducted a comprehensive series of tests on the fish species Nothobranchius furzeri to look for clues as to what is responsible for this general mortality-reducing effect.”

The project

The active ingredient alendronate, which is successfully used to treat osteoporosis, may also have a positive effect on the immune system and the regulation of tumor cells. This is indicated by studies conducted on the turquoise killifish animal model at the Medical University of Vienna.

“Observations to date suggest that bisphosphonates have effects not only on osteoporosis, but also on oncological and cardiovascular diseases.” Peter Pietschmann

The short life cycle of the turquoise killifish

The life of the animal used for this new model, also known as turquoise killifish, is aligned with the sequence of wet and dry seasons in Central Africa, as it lives in pools that evaporate every year. “As a vertebrate, the fish has an extremely short lifespan. It has to complete its entire life cycle within a few months,” explains Pietschmann. “That’s why it is ideal for mortality research, and it is already established internationally as a model for studies on aging processes.” In Austria, the fish has previously been used at the Medical University of Vienna in research in the field of toxicology. Initial metabolic processes in bones relevant to osteoporosis have also been characterized. The experiments now carried out in connection with osteoporosis, on the other hand, are an absolute novelty.

The small turquoise killifish, also popular for aquariums, with its distinctive yellow fins. — With an average life expectancy of just 12 months, the turquoise killifish Nothobranchius furzeri is one of the world’s fastest aging vertebrates. The fish shows aging processes similar to those observed in humans and is easy to keep in captivity, which is why it is often used as a model system in research on aging.
© Leibniz FLI / Nadine Grimm

In Pietschmann's study, 44 Nothobranchius furzeri of advanced age were administered alendronate – analogous to human osteoporosis patients who also take the active ingredient in the second half of their lives. The dose added to the water in the habitat was proportionate to the size of the organisms. Forty-five additional animals served as a control group and were given a placebo. One of the clearest results was revealed by the comparison of lifespan, which actually differed significantly. “We were able to produce a concentration of the active ingredient that prolonged the animals' lives: the fish in the control group survived an average of 18 weeks, whereas those given alendronate survived 19 weeks.”

Analysis of the animals' bones showed that the active ingredient caused changes in bone mineralization. Although this factor was not decisive for the lifespan achieved, it confirmed that the alendronate was actually absorbed by the fish organisms. Histological examinations also showed an increase in cells responsible for bone formation. While no relevant effects on the cardiovascular system were found, genetic tests such as RNA sequencing and real-time PCR analyses yielded particularly interesting results with regard to the immune system and the regulation of tumor development.

Genetic analysis shows possible cancer effect

“We selected a number of molecules that are produced in varying amounts based on genetic information for our analysis,” explains Pietschmann. “In doing so, we discovered a compound that belongs to the group of so-called zinc finger proteins and which occurred in smaller quantities in the treated fish. According to previous studies, this particular protein is likely to play a role in the development of breast cancer. Manifestly, such a cancer-causing factor was less pronounced in the treated fish.”

Future studies should examine the significance and regulation of the protein in more detail. In the best case scenario, the protein could become a lynchpin for the development of new cancer therapies. An additional achievement of the project is the establishment of Nothobranchius furzeri as a model organism for osteoporosis research – Pietschmann hopes that this animal model will be widely used in future.

But the scientist also wants to convey another important message: “The study results are further encouragement to treat osteoporosis consistently,” emphasizes Pietschmann. “In Austria, the disease is still often not taken seriously enough. I hope that the findings on the additional positive effects of treatment will contribute to a rethinking and increased use of the already effective existing drugs.”

About the researcher

Peter Pietschmann heads the Department of Cellular and Molecular Pathophysiology at the Center for Pathophysiology, Infectiology, and Immunology at the Medical University of Vienna. With his research group, the physician investigates bone biology and pathophysiology with the help of molecular, cellular, and translational approaches. Since 2023, Pietschmann has also been president of the European Calcified Tissue Society (ECTS), a leading society for bone research in Europe. The project “Effect of bisphosphonates on Nothobranchius furzeri,” which ran from 2022 to 2025, received EUR 182,000 in funding from the Austrian Science Fund FWF.