RANDOMISED CONTROLLED CLINICAL TRIAL 233 pyri Co gh Not for Publicationt b y Q u i N n o t t r f ess o ce Mohamed Badr, Paul Coulthard, Rami Alissa, Richard Oliver en The efficacy of platelet-rich plasma in grafted maxillae. A randomised clinical trial Mohamed Badr, BDS, MSc Doctoral Researcher, Oral and Maxillofacial Surgery, School of Dentistry, Man- chester Academic Health Science Centre, The University of Manchester, Manchester, UK Key words bone graft, iliac crest, implant stability, maxilla, platelet-rich plasma Paul Coulthard, BDS, MDS, PhD Conflict-of-interest statement: There is no financial conflict of interest. Professor in Oral and Maxil- lofacial Surgery and Editor, Cochrane Oral Health Purpose: The aim of this randomised, controlled, parallel-group clinical trial was to evaluate the clini- Group, School of Dentistry, The University of Manches- cal effect of platelet-rich plasma (PRP) on bone graft healing and implant integration in iliac crest ter, Manchester, UK grafted maxillae. Rami Alissa, PhD Materials and methods: Twenty-two consenting patients were randomised to PRP (13 patients) and Clinical Assistant, Oral and control (9 patients) groups. Both groups received onlays and 16 patients had their maxillary sinus Maxillofacial Surgery, School of Dentistry, Manchester grafted with particulate bone (lateral window approach) with iliac crest bone grafts. Autologous Academic Health Science platelet concentrates were prepared from the patients’ blood and autologous thrombin was pro- Centre, The University of Manchester, Manchester, duced. PRP was mixed with the test group bone grafts. Outcome measures were implant integration, UK implant stability, soft tissue healing, graft resorption, and donor and recipient site complications. Richard J Oliver, Implant stability measurements were recorded at placement and exposure using a resonance fre- BDS, BSc, PhD Private practice, quency analysis device. Patients were followed up to abutment connection. Multiple linear regression Shrewsbury, UK analyses using robust standard error were performed, taking the patient as the unit of measurement. Correspondence to: The t test was also used where appropriate. Mohamed Badr Results: One bone graft failed in the PRP group and regrafting was required. No statistically signifi- School of Dentistry, The University of Manchester, cant differences were observed for soft tissue healing indices (P = 0.4) and mean graft resorption Higher Cambridge Street, (P = 0.5) between groups. All implants were found clinically integrated at time of exposure. No statis- Manchester, UK M15 6FH Email: tically significant differences in implant stability were observed between groups at implant placement [email protected] (P = 0.059) and exposure (P = 0.1). Using a post-hoc analysis, posterior implants in the PRP group showed statistically significantly higher stability values (61 ± 2.6) than anterior implants (60 ± 2.4) at implant placement (mean difference -0.95, P = 0.04). However, this difference was not clinically significant. Conclusion: No appreciable clinical effect could be observed when using PRP with autologous iliac crest bone graft in the maxilla. Eur J Oral Implantol 2010;3(3):233–244 234 Badr et al Platelet-rich plasma in grafted maxillae pyri Co gh Not for Publicationt b y Although the surplus platelet-poorQ plasma (PPP) Introduction u available after PRP preparation is expected to containN i n o Bone volume and quality significantly affect the a significantly lower number of plateletst and conse-t r f ess o e clinical outcome of dental implants together with quently lower levels of growth factors, it shouldenc con- other implant-related factors1. Losing teeth for any tain a fairly high concentration of fibrinogen. Fibrin, reason usually results in losing the supporting bone which is the activated form of fibrinogen, is known as well. Insufficient bone volume often necessitates to play an important role in wound healing. Not only augmenting the site before implant placement and does the fibrin network contribute to haemostasis is frequently undertaken using an autologous bone after capillary injury, but it also acts as an extracellu- graft. However, the need for a second surgical site, lar matrix which is essential for cell migration during with the donor site associated comorbidity, together angiogenesis and other wound-healing processes14. with the inherent tendency for graft resorption dur- Nonetheless, the clinical efficacy of fibrin sealants on ing healing might limit this reconstructive option2. wound healing is still controversial15. One of the most important factors influencing The aim of the present study was to investigate implant success rates is the stability of the implant the effect of PRP on autologous bone graft heal- immediately after insertion, which is referred to as ing and implant stability. The authors carried out a the primary stability3. The primary stability can also randomised clinical trial to test the null hypothesis influence the implant optimal loading time4. An of no differences in hard and soft tissue healing, estimate of the degree of implant stability can be implant stability, and complications, using PRP or performed by measuring insertion torque or using not, against the alternative hypothesis of a differ- Periotest, as well as by a resonance frequency analy- ence between the two procedures. sis (RFA) device which detects the implant’s reso- nance frequency and translates this into an implant stability quotient (ISQ). The higher the ISQ value, Materials and methods the more stable the implant is expected to be5,6. Lower implant stability and lower success rates were The CONSORT guidelines16 were followed for observed in less dense and/or in grafted bone and reporting the present study. It was a balanced ran- have been reported in a number of studies7,8. domised, controlled, parallel-group trial. The proto- Recently introduced regenerative treatment col of the present study was reviewed and approved options using biological mediators have gained inter- by the Tameside and Glossop Local Research Ethics est from oral and maxillofacial surgeons. Amongst Committee (Ref.No.05/Q1402/29). This study was those biological mediators are the recombinant part of a research degree course. bone morphogenic proteins and the platelet-derived growth factor preparations; both are now commer- Patient recruitment cially available9. However, the technique of human recombinant growth factor preparation is quite Eligible patients were adults with a deficient maxil- expensive and has led to considering more cost- lary ridge who were to receive dental implants for effective alternatives10. fixed or removable prosthetic reconstruction. Eligi- Platelets are considered a rich source of growth ble patients were to receive maxillary augmentation factors which are stored in their alpha granules and using an autologous iliac crest bone graft. Patients released upon platelet activation in areas of tissue were to be excluded from the study if they had any damage11. Platelet-rich plasma (PRP) is an economic of the following: i) abnormal platelet count (less than autologous source for such growth factors and is 150,000 or more than 400,000 platelets/mm3); ii) believed to enhance soft and hard tissue healing, any bleeding and/or clotting disorder (e.g. haemo- leading to a faster graft consolidation11,12. It is also philia, platelet dysfunction syndrome); iii) allergy to thought that it might lead to a lower degree of bone tetracycline (in order to be suitable for bone label- resorption, which is considered a main shortcoming ling procedure); iv) regular or recent aspirin intake frequently seen in autologous bone grafts13. (within the last 10 days); v) heavy smokers (more Eur J Oral Implantol 2010;3(3):233–244 Badr et al Platelet-rich plasma in grafted maxillae 235 pyri Co gh Not for Publicationt b Fig 1 PRP (bottom,y than 20 cigarettes/day); vi) any general medical con- Q with noozle) and PPP u dition that contraindicates general anaesthesia; vii) N i (top, in tray) loaded in n o the applicators provided under treatment with NSAIDs, antibiotics, systemic t t r f e o bys these manufacturer.nce corticosteroids, anticoagulants or immunosuppres- The applicator provides sive drugs; viii) neoplasia or haematological malig- the PRP/PPP and nancy; ix) metabolic bone disease such as osteoma- thrombin in a 10:1 ratio, respectively. lacia, hypocalcaemia or hypercalcaemia, x) Jehovah’s Witness; or xi) participation in another trial. Patients were referred to the Oral and Maxillo- facial Surgery Unit, University Dental Hospital of Manchester. From the period of July 2007 to Janu- ary 2010, patients were approached and asked to participate in the present study. Patients were asked to sign an informed consent form and, using a com- width augmentation. Grafts were fixed using tita- puterised random allocation process, patients were nium screws (diameter 1.5 mm, Martin Medizintech- allocated to either a test or control group. nik, Tuttlingen, Germany) to ensure graft immobility In the test group patients, PRP was mixed with the during the healing period. bone graft during and after graft fixation. Patients’ allocation was placed in a sealed opaque envelope PRP preparation by the department secretary. Immediately before the induction of anaesthesia for the bone graft surgery, For patients in the test group, PRP was prepared at the envelope corresponding to the current participant the same time as graft harvesting by one of the study was opened and the patient’s group was revealed investigators (MB). by Mohamed Badr (MB). All patients were blind to After anaesthetic induction, 54 ml of blood was their group of study. All surgeries were undertaken drawn using a green aphaeresis needle into a 60 ml by one of two surgeons (Richard Oliver [RO] or Paul syringe pre-filled with 6 ml of anticoagulant citrate Coulthard [PC]) and their surgical teams. dextrose solution. The syringe was gently agitated The need for onlay with or without inlay maxil- several times to insure even distribution of the anti- lary bone grafting was mandatory for patient par- coagulant. The citrated blood was then loaded into ticipation.