Fracture Repair
ZT-031 [Ostabolin-C™, cyclic PTH-(1-31)] is a novel 31-amino acid PTH analog with an established safety profile and clearly demonstrated bone formation activity and increased bone mineral density (BMD) in a Phase 2 study in postmenopausal women with osteoporosis1. In particular, the highest dose of ZT-031 caused a highly significant increase in hip BMD after 4 months of therapy. PTH appears to be an important regulator of osteogenic precursor cells, which contribute to fracture healing. A growing body of research has demonstrated that PTH has the potential to function as a bone anabolic agent capable of building mechanically strong new bone and accelerating and/or repairing fractures in osteoporosis patients undergoing surgical fixation.
PTH has been shown to:
- Enhance the implant-bone fixation of stainless steel screws in animal bones2
- Accelerate fracture healing in an experimental animal model of fracture. In the model, PTH increased callous volume (thickening/hardening of bone), and improved bone density, stiffness and torsional strength (ability to twist one end of a limb while the other end is held fast or turned in the opposite direction)3
Zelos therefore believes that with further successful study, ZT-031 could prove to be an important addition to the treatment armamentarium for osteoporotic fracture.
Osteoporotic Fracture Overview
According to the American Academy of Family Physicians, the lifetime risk of sustaining an osteoporotic fracture, defined as a fracture of the hip, spine or forearm, is as high as 50%, and the risk of fracture increases two to three times for every 10% drop in bone density4. The elderly are most at risk, as bone mass declines with age, and, of this population, women are at the greatest risk due to additional loss of bone density caused by the onset of menopause. Hospital admissions for fractures of the vertebrae and hip increase 10-fold between the ages of 65 and 904 and will continue to climb as the baby-boomer population ages, with some studies estimating more than 500,000 hip fractures annually by the year 20405.
Costs of osteoporotic fracture are high on all levels:
- Loss of independence—half of all older adults who suffer a hip fracture never regain their previous level of function6
- 25% of adults who suffer a hip fracture remain in a nursing home more than one year after their injury6
- Elevated risk of suffering subsequent fractures6
- 20% of all individuals who suffer a hip fracture will die within a year of their injury6
- For hip fractures alone, the total annual cost, assuming a 5% inflation rate, is estimated by to reach $240 billion by 20405.
Currently available agents and technologies to treat osteoporotic fracture, such as recombinant human bone morphogenetic protein (rhBMP), have limited indications for use and/or require a surgical procedure to administer. An agent with the ability to accelerate healing, improve outcomes and enhance the quality of life in patients suffering osteoporotic fractures would be an important advance.
1Hodsman, A., et al, “Ostabolin-C™ Increases Lumbar Spine and Hip BMD after 1 Year of Therapy: Results of a Phase II Clinical Trial,” Abstract 1130: 29th Annual Meeting of the American Society for Bone and Mineral Research, September 2007
2Skripitz, R., Aspenberg, P., “Implant fixation enhanced by intermittent treatment with parathyroid hormone,” The Journal of Bone & Joint Surgery (Rr), April 2001
3Alkhiary, Y., et al, “Enhancement of Experimental Fracture-Healing by Systemic Administration of Recombinant Human Parathyroid Hormone (PTH 1-34),” The Journal of Bone & Joint Surgery (Rr), April 2005
4Ullom-Minnich, Paul, MD, MPH, “Prevention of Osteoporosis and Fractures,” American Family Physician, July 1999
5Cornell University, Environmental Geriatrics Program website
6Centers for Disease Control and Prevention website
