Effects of the amylin analog pramlintide on bone remodeling and fracture healing in healthy and osteoporotic conditions.

• Applicants: Shan Jiang, Ph.D.; Professor Dr. Johannes Keller
• Subject Area: Orthopaedics, Traumatology, Reconstructive Surgery
• Term: since 2026
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 578397347

Postmenopausal osteoporosis is associated with reduced stability of the skeleton and an increased risk of fractures. In addition to reduced bone strength, osteoporosis is also characterised by impaired bone healing. Amylin, a polypeptide produced in the pancreas, not only plays an important role in diabetes mellitus, but is also associated with the pathogenesis of osteoporosis. Previous studies have shown that amylin inhibits the activity of bone-degrading osteoclasts on the one hand and supports blood glucose control in diabetes on the other. Although numerous in vitro studies have shown that amylin acts via the calcitonin receptor (CTR), the identity of the biologically relevant amylin receptor in vivo remains unclear. As amylin is unstable and not amenable to pharmacological application, its euglycemic effect led to the development of pramlintide, an FDA-approved amylin analogue used as an adjunct to insulin in patients with diabetes. However, although a number of beneficial effects of amylin in the skeleton have been described, the potential impact of the anti-diabetic drug pramlintide on bone remodeling and fracture healing remains unknown. By combining three work packages, this project aims to explore the drug repurposing of pramlintide in the indications of osteoporosis and fracture healing. First, we will investigate the effects of pramlintide on bone remodeling in healthy and osteoporotic conditions. We will then test whether pramlintide accelerates fracture healing in healthy mice and improves healing outcome in mice with mimicked postmenopausal osteoporosis. Finally, we will determine whether these effects are mediated in a CTR-dependent manner and further elucidate the cellular and molecular signaling events involved in the action of pramlintide. Overall, the project is expected to provide the necessary scientific and translational evidence from a preclinical perspective to further decide whether prospective, randomized trials investigating novel applications of pramlintide in orthopedic trauma surgery may indeed be promising.

• DFG Programme: Research Grants