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Non-Union Fractures and PRP

By December 2, 2022April 16th, 2024No Comments

The FDA defines a long bone non -union fracture  as a fracture that has failed to heal within the first 9 months following the injury. There is currently no standardized system to define a non- union however there is a classification from 2005 which defines the types of non- union:

  • Hypertrophic- inadequate immobilization, yet adequate blood supply. In x-rays, callous formation is decreased
  • Atrophic- poorly vascularized non- union, resulting in poor potential for forming boney cells and therefore delaying healing. There is little callous formation around the fracture gap.
  • Oligotrophic- The body can initiate a healing response but is unable to complete the fracture formed between the two ends of bones
  • Septic- A bacterial infection impedes the healing process.
  • Pseudoarthrosis- Persistent motion at fracture site causes formation of a false joint

Patients whose bony fractures fail to heal routinely have greater healthcare resource use and higher medical costs.

In a review of 5000 patients with long bone fractures, 3% had the diagnosis of non–union within 2 years of the trauma.

Impaired healing occurs in 10-15% of fracture patients.

The average health care cost was greater than triple than those without non -union. ($35,000 vs $103,000)

The greatest non -union rates by site were.

  • Humeral Shaft 18%
  • Tibial Shaft 10%
  • Femoral Shaft 9%

The lowest rates of non -union were:

  • Radius/Ulna 2%
  • Elbow 2%

Risk factors for non-union of fractures

  • Increasing age
  • Alcohol consumption
  • Smoking
  • Deficiencies in Vit D, Calcium or Protein
  • Other systemic disease states

The current gold standard for the treatment on non-union of fractures is the use of autologous bone grafts. Bone from another part of the body is transplanted to the non-union site and acts as a scaffold for the growth of new bone. The downside of this treatment is the limited supply and donor site morbidity associated with autologous grafting.

Platelet Rich Plasma in Non-Union Fractures

Over the last 20 years, there has been 38 articles written concerning the use of Platelet Rich Plasma and non-union of fractures. Due to the diversity of protocols implemented and significant variation in outcome measures, the author of this review found it extremely difficult to directly compare the studies. However, the vast majority of the studies reported beneficial outcomes when PRP was used.

The use of PRP is rapidly evolving in many medical fields especially in bone regeneration. The primary reason is because autologous platelet concentrations offer an easy cost- effective method to obtain high concentrations of growth factors employed in the bodies tissue regeneration. These include.

  • Platelet derived growth factor (PDGF)
  • Vascular endothelial growth factor (VEGF)
  • Transforming growth factor (TGF BETA 1)
  • Insulin like growth factor (IGF-1)

All of the above are needed for tissue healing and regeneration.

Contained in the platelets are granules which contain numerous growth factors and cytokines that are relevant in bone healing and repair. Upon Activation, these platelets release these growth factors which play a critical role in the production of bio-active proteins required for the regenerative process. Leukocytes are also present and aid in the removal of dead or damaged molecules then help with cellular proliferation, matrix formation, osteoid production and collagen synthesis.

The literature concerning the use of PRP specifically for the treatment of non-union fractures demonstrates a lack of large randomized clinical trials. However, studies are predominantly in the form of case studies. The advantage of case studies is that they are relatively easy to conduct and require less time and financial resources when compared to large trials. The majority of published PRP studies on non-union are favorable.

Key aspects of the use of PRP are platelet concentration, leukocyte components and activation modalities.

Chen demonstrated how a medium concentration of PRP induces osteogenic differentiation of bone marrow stem cells improving fracture healing while high concentrations can inhibit bone formation and delay callus remodeling.

Labibzadeh reported that leukocyte rich PRP induced higher proliferation of bone marrow stem cells while other studies in the literature have found activation to influence the molecules released by PRP . This highlights and confirms that differing concentrations released by the platelet granules after activation will affect the efficacy of the therapy.

In studies where PRP was ineffective, the subjects (20) were treated with a low dose of PRP and activated with calcium chloride. The size of the non-union was not standardized and a total of 2.5 cc of PRP was used. The size of the non-union is widely varying when comparing patients in these study groups. Also, the volume of the PRP is not standardized in published studies. PRP has been reported to be successful with at least 5cc applied in three separate occasions. In addition, activation with calcium chloride has been found to be inferior to bovine/ autologous thrombin. Therefore, the volume and activation process with the size of the non-union could determine success with the treatment of PRP for this condition.

Despite its common use especially in countries other than the US, bovine thrombin as an activator has been questioned in clinical application since disease transmission, possible carcinogenesis and overall cost are all issues related to bovine thrombin.

In 2008, Bielecki concluded that PRP is a sufficient method to achieve union as long as the treatment occurs less than 11 months following initial surgery.

A more recent study by Tawfik, criteria of (more than 90% contact between the fracture fragments) and a dose of 20cc PRP produced 85% of union among patients.

Another study by Malhotra found exactly the same union rates of 87% using the same criteria of patients and dose of PRP.


The consensus from the literature is that PRP is effective in accelerating the healing of non-union fractures. This success was demonstrated when used with doses between 2.5 cc and 20 cc. The overall implication is PRP could potentially become the primary form of treatment in these patients. Success with the use of PRP, has also been demonstrated with combined treatment of surgery with PRP.


Injury 2014 Feb;45(2): 418-423  PMID 24119491

Introduction- Non-union rate in forearm fractures is generally less than 2% when a proper technique is used; this rate increases when ulnar lesions are involved. This was a case study of 7 patients. The purpose of this case series was to establish a better treatment and find a technique that could avoid the use of bone grafts.

Conclusion- All patients in this study showed complete recovery with excellent clinical outcomes. This study showed that the use of specific locking nail system can provide proper stability and when combined with autologous PRP is sufficient to promote bone healing without the necessity to take autologous bone grafts.

Bull Emerg Trauma 2016 Jul;4(3): 134-140  PMID 27540547

Objective- To determine the effects of platelet rich plasma on healing rates of long bone fractures.

Method- Randomized double-blind clinical trial on 75 adult patients suffering from non-union long bone fractures. Patients received 5ml of PRP or 5cc NSS in the site of fracture after intramedullary nailing or open reduction and internal fixation along with autologous bone graft.

Conclusion- Application of PRP along with autologous bone graft in the site of non-union of long bone after intramedullary rod or ORIF results in a higher cure rate, shorter healing duration, lower limb shortening and less postoperative pain.

Curr Osteoporos Rep 2021 Feb;19(1):1-14. PMID 33393012

Purpose of review- The treatment of non-union fractures represents a significant challenge for orthopedic surgeons. In recent years, biologic agents have been investigated and utilized to support and improve bone healing. Among these agents, Platelet Rich Plasma is an emerging strategy that is gaining popularity. The aim of this review is the evaluate the current literature regarding the application and clinical effectiveness of PRP injections specifically for the treatment of non-union fractures.

Recent findings- The majority of published studies reported PRP accelerated fracture healing with the evidence predominantly level IV. The lack of randomized clinical trials is currently hampering the successful clinical translation of PRP as a therapy for non-union fractures. This is despite the positive reports regarding the potential to heal non-union fractures when used in isolation or in combination with other forms of treatment. Future recommendations to facilitate clinical translation and acceptance of PRP therapy include the need to investigate higher volumes of PRP and the need for more prolonged studies.


Juventix Regenerative Medical is an industry leader in the regenerative medical field. Our FDA approved Platelet Rich Plasma Kits are designed for safety and effectiveness. Platelet Rich Plasma has been well documented in the osteoarthritis arena. The effectiveness far surpasses other therapies in the longevity of relief of symptoms caused by this disease.

Juventix Regenerative Medical offers a patent pending LED Activator to activate the platelets and begin the regenerative process. Activation is a critical step in the ultimate release of growth factors and cytokines. There are no extraneous chemicals used in this production.

Juventix Regenerative Medical supplies a Bio-Incubator that transforms Platelet Rich Plasma into an anti-inflammatory Platelet Rich Fibrin. PRF has different cytokines and growth factors than PRP which allows these products to be used interchangeably depending on the disease state.




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