Combined therapy could revolutionize fracture prevention in osteoporosis.

Although this disease is well-known, Dominique Pioletti, the head of the Biomechanical Orthopedics Laboratory at EPFL's School of Engineering, emphasizes that the economic and social consequences of fractures due to osteoporosis are often underestimated.

“In the absence of effective preventive measures, about 40% of women aged 50 experience at least one serious osteoporotic fracture; for men, this figure is around 20%,” he states. “Moreover, people often do not realize the severity of this condition. In elderly patients, the mortality rate within a year after a hip fracture is 20%, and more than half of those affected are unable to return to their previous activities.”

The diagnosis of "osteoporosis" typically comes with treatment involving systemic medications that either work by slowing down the resorption of old bone tissue (anticatabolism) or by accelerating the production of new bone tissue (anabolism). However, achieving the desired effect from both types of treatment can take up to a year, during which time patients become more prone to fractures.

Pioletti and his colleagues have developed an injectable hydrogel for rapid local increases in bone density. Recently, the team, in collaboration with Vincent Stadelmann from the Schultes Clinic in Zurich, reported on a new therapy combining hydrogel injections with traditional systemic medications. Results published in the journal Bone indicate a four to fivefold increase in bone density in the legs of rats that had previously experienced bone loss.

In this study, the researchers demonstrated for the first time that a combined therapy, which includes systemic drug delivery and local injection of the new hydrogel, provides a rapid increase in bone density and could thus revolutionize fracture prevention in osteoporosis.

Enhancing Synthesis and Preventing Destruction

Most modern treatments for osteoporosis are systemic, while the few available local treatments take the form of pastes that harden, resembling cement. The easily injectable hydrogel developed at EPFL consists of hyaluronic acid and hydroxyapatite nanoparticles, mimicking the natural minerals found in bone.

Research results showed that self-administered hydrogel injections significantly increased bone density by two to three times, regardless of the use of systemic therapy. However, the strongest effect was observed in animals receiving systemic anabolic treatment (parathyroid hormone) along with a hydrogel mixed with the anticatabolic drug zoledronate: at the injection site, bone density increased nearly 4.8 times in just 2-4 weeks.

The findings of this study suggest that injectable hydrogels with local delivery of anticatabolic drugs could complement systemic anticatabolic treatment or systemic anabolic treatment that promotes bone strengthening, rapidly increasing bone density locally.

The research team is currently awaiting regulatory approval to conduct clinical trials in humans.

The researchers hope that such trials will allow them to demonstrate the benefits of the hydrogel in cases where patients require rapid increases in bone density, for example, to support an implant in conditions of bone weakness. Based on the data obtained, they plan to develop a therapy aimed at preventing fractures caused by osteoporosis.