Combined therapy could revolutionize the prevention of osteoporosis fractures

Osteoporosis is a disease in which bone resorbs faster than it is formed, gradually weakening its structure over time and leading to fractures. Although the condition is well recognized, Dominique Pioletti, head of the Laboratory of Biomechanical Orthopedics in EPFL's School of Engineering, emphasizes that the economic and societal impacts of osteoporosis fractures are often underestimated.

"In the absence of effective preventive measures, around 40% of women aged 50 will suffer at least one major osteoporotic fracture; in men, the percentage is around 20%," he says. "Moreover, people often do not realize the severity of the condition. In the elderly, fractures of the femoral neck, near the hip, have a 20% mortality rate in the year following the fracture, and over half of those affected are never able to return to pre-fracture activities."

A diagnosis of osteoporosis is usually followed by treatment with systemic drugs that work either by decreasing the resorption rate of old bone (anti-catabolism) or boosting new bone production (anabolism). But both types of treatment can take up to a year to have an effect, leaving patients vulnerable to fracture in the meantime.

Pioletti and colleagues at EPFL start-up flowbone have developed an injectable hydrogel that targets rapid, localized increase in bone density. The team, in collaboration with Vincent Stadelmann at the Schulthess Klinik, Zurich, have recently reported a novel therapy that combines these hydrogel injections with traditional systemic drugs. The results, published in the journal Bone, show a four- to five-fold increase in bone density in the legs of rats with bone loss.

In this work, we demonstrate for the first time that a combined therapy of a systemically delivered drug and local injection of our hydrogel delivers a rapid increase in bone density, and could therefore revolutionize the prevention of osteoporosis fractures."

Dominique Pioletti, Head of the Laboratory of Biomechanical Orthopedics, EPFL's School of Engineering

Boosting build-up while blocking breakdown

Most current osteoporosis treatments are systemic, and the few local treatments available take the form of pastes that harden into a kind of cement. The easily injectable hydrogel developed at EPFL and flowbone, on the other hand, is made of hyaluronic acid and hydroxyapatite nanoparticles, and is designed to mimic the natural minerals in bone.

The study results showed that standalone hydrogel injections significantly densified local bone two- to three-fold, independent of systemic therapy. But the most potent effect was seen in rats that received a systemic anabolic treatment (parathyroid hormone), plus the hydrogel mixed with the anti-catabolic drug Zoledronate: at the injection site, their bone density increased up to 4.8-fold in just 2-4 weeks.

"Our findings suggest that injectable hydrogels with localized anti-catabolic drug delivery can complement systemic anti-catabolic treatment, or bone-boosting systemic anabolic treatment, by rapidly increasing local bone density," Pioletti summarizes.

He adds that the flowbone team is now awaiting regulatory approval to move ahead with a clinical study in human patients. "We hope that such a study will allow us to demonstrate the benefit of our hydrogel in cases where patients require rapid bone densification, for example to support an implant where the bone is weak. Then, we want to build on this evidence, ultimately to develop therapies to prevent fractures due to osteoporosis."