Investigational drugs for fracture healing: preclinical & clinical data

ABSTRACT

Introduction: The need for fracture healing enhancement for the management of fracture complications such as non-union and for the achievement of early function in fracture patients is constantly increasing. Therefore, the development and evaluation of novel pharmaceutical agents is mandatory in order to accelerate the process and increase bone union rates.

Areas covered: This review summarizes the most recent knowledge on the pharmacological enhancement of fracture repair. It provides a synopsis of the most important preclinical and clinical studies published over the past five years on long bone fracture healing.

Expert opinion: To date, limited drugs seem to have the potential for clinical use in fracture healing enhancement and the field is progressing very slowly. Among anti-osteoporotic drugs, only PTH and anti-sclerostin antibodies have such a potential but further research is needed before clinical use. The same applies also to BMPs, the use of which still carries major drawbacks that should be overcome before their widespread clinical utilization. Other drugs and growth factors, such as statins, VEGF, FGF, EPO, could be future key players in fracture healing but evidence is still lacking. Further in depth understanding of the healing process is essential in order to identify novel effective pharmacological agents.

KEYWORDS:

• Fracture healing
• fracture repair
• drugs
• clinical
• preclinical
• bone morphogenetic proteins/bmp
• growth factors
• anti-osteoporotics
• statins
• bisphosphonates

Article highlights

• The field of pharmacological enhancement of fracture healing is progressing very slowly.

• Antiosteoporotics seem to have low potential for use in fracture healing apart from PTH and anti-sclerostin antibodies.

• The use of BMPs, despite their FDA approval, is still limited by their major drawbacks.

• Statins may have a potential for fracture healing enhancement but further research is still needed.

• Further delineation of the cascade of events leading to fracture healing will lead to the development of novel pharmacological agents.

This box summarizes key points contained in the article.

Declaration of interest

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.