Local delivery of parathyroid hormone counter balances microgravity-associated bone loss

Osteoporosis is a skeletal disorder characterized by compromised bone strength predisposing to an increased risk of fracture.  During the space flight, figures indicate a reduction in bone mass associated with microgravity of 2% per month.  This would be devastating for long duration space flights. There is a clear need for preventive and treatment strategies to address this dysregulation and protect the integrity of the musculoskeletal system during space flight.  Parathyroid Hormone (PTH), a peptide hormone, has been shown to be effective for treatment of osteoporosis. PTH has both anabolic and catabolic effects on bone, which depend on dosage and mode of administration. Various administration methods have been applied for PTH delivery, for instance, injections, osmotic pumping, oral administration, pulmonary route and others. Still, bioavailability is lacking with some, and inconvenient administration protocols compromise others. There is a clear need for alternate approaches for the delivery of PTH.  Our research goal is to develop a local delivery regime for PTH that can counteract   bone loss associated with microgravity. Biocompatible polymers, such as poly(L-lactide), poly(lactide-co-glycolide) and polyanhydrides will be used to prepare different polymer-based devices in which PTH is encapsulated and protected. The local delivery of PTH will be achieved with the degradation of polymers. Furthermore, the delivery pattern will be tailored by means of controlling of composition and molar mass of polymers, structures and component devices.  Meanwhile, the degraded product from the PTH carrier device will have readily assessed biologic activity and will be excluded easily through normal metabolic processes.  These studies will provide valuable information that can be used to address situations of bone loss in general and in particular, that associated with altered gravity states as in space flight.