Clinical Trial: Validation of Laboratory Test for Predicting Bone Tissue Regeneration
Study Status: Completed
Recruit Status: Completed
Study Type: Observational
Official Title: Validation of Laboratory Test for Predicting Bone Tissue Regeneration in Patient Affected by Aseptic Pseudarthrosis and Treated With Platelet Gel
Brief Summary:
The aim of the study is to determine whether the evaluation of pro-osteogenic activity of autologous serum may predict the effectiveness of platelet gel in regenerating bone tissue in patients with nonunions of long bones.
Serum samples will be collected before the surgery, and their pro-osteogenic activity will be evaluated by using a bioactivity test (mineralization assay).
In order to determine whether the pro-osteogenic activity of the serum is able to discriminate between individuals who will achieve or will not achieve bone consolidation, the laboratory results will be correlated with clinical and radiographic results at 12 months, when patients will be considered as healed or not healed.
Detailed Summary:
Pseudarthrosis (or 'nonunions') is defined as a bone movement which occurs after about 6 months from the traumatic event as consequence of the inadequate healing of a fracture. The use of regenerative medicine for treating recalcitrant pseudarthrosis is considered a promising strategy to promote bone consolidation. Among the various approaches used, the local cell therapy based on autologous mesenchymal stromal cells (MSC), combined with or without growth factors, has been extensively used. MSC reside within the stromal compartment of bone marrow which may be obtained from the iliac crest. Growth factors may be discharged from platelet gel (PG) which is obtained after activation of autologous platelet concentrates. Nevertheless, the results of recent clinical studies show that the above mentioned regenerative approach shows a failure rate of approximately 30% (Calori et al, 2008). The availability of a laboratory test which may predict the regenerative capacity of the PG may help the orthopaedic surgeon in addressing the decisions regarding the regenerative approach, e.g. to use or non use autologous platelet concentrates or to enhance the use of autologous derivatives with recombinant factors.The rationale for the use of platelet concentrates in pseudarthrosis is the significant reduction of osteoinductive growth factors observed at the lesion site (Gandhi et al., 2005). Platelet gel mimics what happens physiologically after any bone injury, when platelets are entrapped in a clot within a fibrin matrix. Platelet activation determines the release of various growth factors promoting bone healing. The optimal level and ratio of growth factors and their synergistic effects should be more efficient than single recombinant molecules, even though no data are available on the most relevant molecules and on their optimal amount. In this context, the in vitro mineralization assay could be a valid tool to assess the pro-osteogenic
Sponsor: Istituto Ortopedico Rizzoli
Current Primary Outcome: Correlation between laboratory results at the surgery and clinical and radiographic results at 12 months, when patients will be considered as healed or not healed. [ Time Frame: 13 months, for each patient ]
The pro-osteogenic ability of autologous serum will be evaluated by using a bioactivity test (mineralization assay). For this purpose serum samples will be collected 1 day before the surgery and used for culturing osteogenic cells. The ability of inducing the mineralization will be assessed after 10 days of culture.
At 12 months, clinical outcome will be evaluated as follows:
- anteroposterior and lateral X-rays to assess the continuity of bone in the various plans;
- semeiotics of the consolidation;
- assessment of pain during loading (Visual Analogue Scale).
Original Primary Outcome: Correlation between laboratory results at 1 month before the surgery and clinical and radiographic results at 12 months, when patients will be considered as healed or not healed. [ Time Frame: 13 months, for each patient ]
The pro-osteogenic ability of autologous serum will be evaluated by using a bioactivity test (mineralization assay). For this purpose serum samples will be collected 1 month before the surgery and used for culturing osteogenic cells. The ability of inducing the mineralization will be assessed after 10 days of culture.
At 12 months, clinical outcome will be evaluated as follows:
- anteroposterior and lateral X-rays to assess the continuity of bone in the various plans;
- semeiotics of the consolidation;
- assessment of pain during loading (Visual Analogue Scale).
Current Secondary Outcome:
- Assessment of the pro-osteogenic properties of serum over time. [ Time Frame: 1 month before surgery ]
In order to determine whether the pro-osteogenic properties are maintained over time, we planned to collect other serum samples, namely preoperatively, 1 month before the surgery.
The pro-osteogenic activity will be evaluated as previously described.
- Correlation between laboratory testing and timing of healing. [ Time Frame: 1, 3, 6, and 9 months postoperatively ]Clinical and radiographic results will be assessed at intermediate end points, as previously described.
Original Secondary Outcome:
- Assessment of the pro-osteogenic properties of serum over time. [ Time Frame: 1 day before surgery; 1 month postoperatively; 12 month postoperatively ]
In order to determine whether the pro-osteogenic properties are maintained over time, we planned to collect other serum samples, namely preoperatively, 1 day before the surgery, and postoperatively, after 1 and 12 months.
The pro-osteogenic activity will be evaluated as previously described.
- Correlation between laboratory testing and timing of healing. [ Time Frame: 1, 3, 6, and 9 months postoperatively ]Clinical and radiographic results will be assessed at intermediate end points, as previously described.
Information By: Istituto Ortopedico Rizzoli
Dates:
Date Received: May 26, 2011
Date Started: January 2011
Date Completion:
Last Updated: March 27, 2015
Last Verified: March 2015
