Emerging Options for Biologic Enhancement of Stress Fracture Healing in Athletes

Timothy L. Miller, MD; Christopher C. Kaeding, MD; Scott A. Rodeo, MD


J Am Acad Orthop Surg. 2020;28(1):1-9. 

In This Article

Pulsed Parathyroid Hormone

Pulsed recombinant human parathyroid hormone (PTH, −34) is an endocrine-based injectable treatment strategy that has been shown to increase fracture callus formation in multiple animal models.[33–36] It is a regulator of calcium and phosphate homeostasis and induces an anabolic response in bone when applied at intermittent low doses.[34] PTH acts within the pathway of bone morphogenic proteins (BMP's). It is FDA-approved for the treatment of osteoporosis, although its off-label use has included poorly healing fractures and nonunions. Topical gel alternatives that can be applied locally are currently in development to increase ease of use and patient compliance.

The effect of PTH on fracture healing in humans has been evaluated with mixed results. However, it has been shown to achieve the primary end point of accelerated healing with improved early fracture callus formation compared with placebo in distal radius fractures.[37] Although evaluation of its administration in animal models has shown that supraphysiologic doses of PTH increase fracture site strength, callus size, and bone remodeling along with increased bone mineralization, its effect on fracture healing in humans remains indeterminate.[38]