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8. Implants in Irradiated Tissues
         John Beumer III, DDS, MS
      Division of Advanced Prosthodontics,
      Biomaterials and Hospital Dentistry
            UCLA School of Dentistry




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Implants in Irradiated Tissues
                   Table of Contents
 Radiation effects and impact on osseointegration
 Changing methods of radiation delivery and the
  impact of chemoradiation
 Patient selection criteria
 Animal studies
 Human data
 Osteoradionecrosis
 Role of HBO
 Timing of implant placement
 Irradiation of existing implants
Osseointegration
 Success requires primary implant anchorage and immobilization, the
 formation of a clot between the surface of the implant and the osteotomy
 site, release of growth factors, angiogenesis and migration of
 osteoprogenitor cells to and deposition of bone on the surface of the
 implant and in the osteotomy site.


Osteoblasts




Mineral deposition
                          Non-collagenous
                              matrix
                                                  Collagen matrix
Osseointegrated Implants
   These biologic processes may be compromised or
    absent in patients exposed to high dose radiation
    and as a result anchorage of implants in bone is
    probably mechanical as opposed to biological.

   In addition, long term function of osseointegrated
    implants is dependent on the presence of viable
    bone that is capable of remodeling and turnover as
    the implant is subjected to stresses associated with
    supporting, retaining, and stabilizing prosthetic
    restorations. These processes are compromised or
    perhaps entirely lacking in heavily irradiated bone.
Radiation effects
 Reduced vasculature            Lamellar bone
 Loss of osteoprogenitor             • Loss of central artery in
                                      Haversian systems
  cells                               • Death of osteocytes
 Marrow undergoes fatty
  and fibrous degeneration
 Periosteum becomes
  acellular and loss of
  vasculature
                                               Trabecular bone
 Root
 surface




                             Marrow
Radiation effects
These tissue changes lead to:          Lamellar bone
                                           • Loss of central artery in
     Compromised remodeling               Haversian systems
                                           • Death of osteocytes
     Response to infection is
      compromised ie
      osteoradionecrosis
     Continuing osteolytic activity
  Root
                                        Trabecular bone
  surface




                                  Marrow
Why are these changes important?
 Anchorage may be mechanical as opposed to biologic
 Response to infection is compromised
 Remodeling apparatus is not fully functional
       Response to occlusal forces is compromised
 Osteolytic activity continues and compromises the density
  of the bone
Root                                    Trabecular bone
surface




                                   Marrow
Continued osteolytic activity
   The density of bone is diminished because bone resorption
    continues secondary to the presence of isolated osteoclasts
    making it more difficult to achieve primary stability of the
    implant.
Remodeling apparatus – Osteolytic Activity
                             This patient received 70 Gy
                             to the mandible for an anterior
                             floor of mouth Sq Ca.

                             Note the dramatic change in
                             the prominence of the cortical
                 Preradiationplates (arrows) and the
                             differences in trabecular
                             patterns between preradiaton
                             and postradiation radiographs.

                             Osteolytic activity seems
                             more prominent in patients
                             treated with chemoRT
                 Postradiation
Remodeling apparatus – Osteolytic Activity




                                      Postradiation


 Hence in irradiated sites initial stabilization of
      the implants is more difficult to achieve
 In edentulous patients the irradiated mandible is
      more susceptible to fracture
Remodeling apparatus – Osteolytic Activity
   Patient received 60 Gy. The mandible fractured through the left
    posterior implant site (arrow) two weeks following implant
    placement.




                                It was reduced and repaired as
                                shown with eventual healing. An
                                implant assisted overlay denture
                                was later fabricated and used
                                successfully by the patient.
The tissue changes are dose dependent and the
          dose depends in part upon:
Mode of therapy
   CRT (Conventional radiation therapy)
   IMRT (Intensely modulated radiation therapy)
   Brachytherapy

In edentulous patients the preferred implant
sites are:
  Symphyseal region of the mandible
  Premaxilla
   The mode of therapy will determine the dose
   delivered to these regions and dose is the best
   predictor of long term success and the risk of ORN.
Changing methods of radiation delivery
Conventional radiation therapy (CRT)
      200 cGy per fraction
      Bilateral opposed equally weighted fields
      Total doses                                         Source: www.beaumonthospital.com
           7000 cGy definitive dose
           5000-6000 cGy post op
Intensity modulated radiation therapy (IMRT)

                                    This technique uses multiple radiation
                                    beams of non-uniform intensities. The
                                    beams are modulated to the required
                                    intensity maps for delivering highly
                                    conformal doses of radiation to the
                                    treatment targets, while limiting dose
                                    normal tissue structures.
 Source: www.beaumonthospital.com
IMRT dosimetry diagrams




Note the hot spot on anterior mandible (oval).
 With IMRT the dose distribution is not uniform.
(CRT)                        Chemoradiation                         (IMRT)




       Source: www.beaumonthospital.com      Source: www.beaumonthospital.com


 • Used in combination with CRT or IMRT
 • Full course of concomitant chemoradiation is theoretically
 equivalent to an additional 7-10 Gy (Kashibhatla, 2006; Fowler,
 2008).

Consequences (particularly with CRT):
       The biologically equivalent dose (BED) is raised leading to more short
       term and long term side effects (mucositis, fibrosis, trismus,
velopharyngeal incompetence, osteoradionecrosis etc).
Implants in Irradiated Tissues
Issues to consider
 Potential benefit to the patient
     What are the objectives and wishes of
      the patient?
     Risk – reward ratio?

   Risk of osteoradionecrosis?
       Morbidity?
   Short term success rates?
   Long term success rates?
Risk vs Reward Edentulous
                          Maxillectomy Patients
   As indicated by the following data, without implants to help retain and
    stabilize the complete denture-obturator prosthesis, mastication is not
    restored
   With the retention provided by the implants mastication levels are restored
    to presurgical levels of function (Garrett et al, 2008).
   The risk of osteoradionecrosis secondary to implant placement is very low.
   Since the risk is minimal and the rewards are significant we do not hesitate
    to recommend the use of implants in patients with palatal defects that have
    been irradiated.
Masticatory Performance
                                            Maxillectomy
                                                   N=5
                                      (‘0’ score if not able to chew)



                50                                                 46.2
                45                                                        40.5
% performance




                40
                35
                30
                                                                                 Defect
                25
                                                                                 Intact
                20                          15.6
                15
                           8.2        8.8
                10   6.2                            6.6 8.1
                 5
                 0
                      Entry         Post-Surgery    Post-CP         Post-IP
                                 Garret et al, 2008                              *p<0.01
Masticatory Performance
                                    Maxillectomy
                                               N=5
                                  (‘0’ score if not able to chew)          * *

                50                                                  46.2
                45
% performance




                                                                           40.5
                40
                35
                30
                                                                                  Defect
                25
                                                                                  Intact
                20                          15.6
                15
                            8.2       8.8
                10    6.2                            6.6 8.1
                 5
                 0
                       Entry        Post-Surgery     Post-CP        Post-IP
                      Garret et al, 2008; Garrett et al, 2009                     *p<0.01
Tongue-Mandible Defects
                    Reconstructed with Free Flaps
             Patients with dentition on the unresected side
   As indicated from the following data you can see that patients retain their
    ability to masticate effectively on the nonresected side after mandibular
    reconstruction.
   Implant placement on the fibula side does not add substantially to their
    mastication efficiency.
   In addition if the tongue is restored with the flap the patient lacks the
    sensory and motor innervation to control the food bolus on the resected
    side.
   The risk reward ratio is not as favorable and therefore in most such
    situations we therefore recommend a conventional RPD when the implant
    sites have been heavily irradiated.
Masticatory Performance
                Fibula free flaps - Mandible (dentate patients)


                     (“0” if unable to attempt test; n=15)
% performance




                45                          Defect
                40                          Intact                  41.6
                        36
                35                                                  34.5
                30                                       32.7
                25
                        21.1         24.9
                20                                       20.3
                15
                10
                 5                   7.3
                 0
                     Entry     Post-Surgery          Post-CP    Post-IP    Garrett et al, 2005
Tongue-Mandible Defects Reconstructed
        with Free Flaps - Edentulous Patients
The functional benefit derived from implant placement in
irradiated edentulous patients depends on several factors, the
most important being the status of tongue function.
   If the tongue and/or mandible has been resected and reconstructed and the bulk,
    mobility and control of the reconstructed tongue results in reasonable tongue
    function, the placement of implants may significantly improve mastication
    performance particularly if the denture bearing surface has been compromised or is
    not ideal.
Tongue-Mandible Defects Reconstructed with
              Free Flaps - Edentulous Patients
   Patient had hemiglossectomy and reconstruction of tongue with
    a free flap and received 55 Gy post operatively.
   Tongue bulk is restored and tongue mobility is excellent
   Without implants use of a lower complete denture would have
    been problematic.
   The dose is low. The risk reward ratio is favorable and
    therefore in such patients implants were placed to stabilize and
    retain the denture.




Note: The patient must masticate on the sensate unresected side.
Facial Prostheses – Quality of retention
                          Quality of life




When patients present with facial defects implant retention improves
patient satisfaction and frequency of use (Chang et al, 2005).
With large combination facial defects adhesive retention is ineffective and
         implant retention is required for most patients
Although the implant loss rates are high the benefits are great particularly in
         patients with large facial defects such as this one.
Therefore, we recommend the placement of implants in most patients with
         large facial defects even though the implant sites have been irradiated.
Facial Prostheses - Retention During Daily Activities




                                       *             Adhesive Implant
                                                                                   *
                                  95                                                                *
                       100                                                   89
                        90                      84                                             85
                                                              79
                        80
                        70                 63
                             57
                        60
       % 'Excellent'




                        50                               44                               44
                                                                        38
                        40
                        30
                        20
                        10
                         0
Chang et al, 2005            Home          Eating       Exercise        Perspire       Sneeze/Cough
Frequency of Wear Facial Prostheses
                                                          Chang et al, 2005


                                  Adhesive Implant
            120
                       95                    100
            100                   89                 88
            80              *63
% Wearing




            60    44
            40
            20
                                                              3    0
             0
                  Home       Work             Social          Never
Implants in Irradiated Tissues

Biologic viability (animal studies)
   Hum  and Larsen, (1990)
   Weinlander et al, (2006)
   Nishimura et al, (1996)
   Asikainen et al, (1993)
   Ohrnell et al, (1997)
   Jacobsson et al, (1988)
Implants in Irradiated Tissues
Biologic viability (animal studies)
  Asikainen, 1998
     Dogs  received either 4000, 5000, or 6000 cGy
     Two months later TPS screw type implants were
      inserted
     Four months later the implants were loaded
     Success rates:
          4000 cGy group – 100%
          5000 cGy group – 20%
          6000 cGy group – 0 %
Implants in Irradiated Tissues
                Weinlander et al, (2006)




 Dogs were partially edentulated
 Following a suitable healing period three implants were
placed on each side
 All seven dogs received radiation therapy, starting three
weeks post implantation on one side of the     mandible,
consisting of a dose equivalent to 5000 cGy delivered in 4
fractions during a 2 week period
Methods – Histomorphometric Calculations
   A scanning electron
    microscope was used
    to image the
    background electron
    density of the three
    elements – bone, soft
    tissue and implant.


 The histometry calculation yielded volume
 and boundary fractions for the implant, bone
 and soft tissue components.
                             Weinlander et al, 2006
Bone contact area in control specimens
      80
      70
      60
      50
      40                                  Bone
      30                                  Appositional
                                          Index %
      20
      10
       0
           Machined   Plasma    HA
            Surface   Spray    Coated



                                   Weinlander et al,
Bone contact area in irradiated tissue
     70
     60
     50
     40
                                             Bone
     30                                      Appositional
     20                                      Index %

     10
      0
          Machined   Plasma    HA
           Surface   Spray    Coated


                                       Weinlander et al,
                                       2006
Nishimura et al,1996
   Dosage of Radiation Therapy Administered
A rabbit tibia model was used in this study. The rat tibia were
exposed to equivalents of the following doses and implants were
placed 3 months following completion of radiation treatments.
Polyfluorochrome labeling was performed three months after
implant placement and the animals sacrificed 2 days later,

                          (cGy)
             4000                      5800
             4600                      6400
             5200                      7000
Nishimura et al, 1996

                     Results
   Normal              5200 cGy           5800 cGy




Three months after implant placement the tissue samples were
harvested and were evaluated with light and fluorescent
microscopy. Fluorochrome labeling documented a steady
decrease in biologic activity at the higher doses.
Nishimura et al, 1996
                   Results
  Normal bone                  Irradiated bone




At lower doses irradiated specimens had more
woven bone at the bone implant interface than did
the normal specimens at the time of sacrifice.
Additional animal studies (summaries)
   Jacobsson et al (1988) - Reduction in bone
    formation capacity, an increase in bone
    resorption and a reduction in the number of
    capillaries.

   Ohrnell et al (1997) - Fibrosis of the bone
    marrow, bone resorption, less bone adjacent to
    the implants and an overall reduction in the
    remodeling capacity of bone.

   Hum and Larsen (1990) - The bone contact area
    for irradiated specimens was significantly less
    than nonirradiated specimens
Summary of tissue changes affecting
       osseointegration based on animal studies
 At higher doses (70 Gy) virtually little or no bone will be
  deposited on the implant surface. Anchorage is primarily
  mechanical as opposed to biologically driven.

 At lower doses a greater component of woven bone is seen in
  the interface. Compromise of the remodeling apparatus may
  preclude this woven bone from being replaced with lamellar
  bone

 Death of osteocytes, loss of osteoprogenitor cells and the basic
  multi-cellular unit of the remodeling apparatus (BMU)
  compromises the remodeling of bone at the bone implant
  interface and compromises the bone’s response to occlusal
  load.
Summary of tissue changes affecting
 osseointegration based on animal studies

• Poor blood supply in the marrow predisposes
  to infection and implant loss

• At lower doses radiation induced tissue effects
  significantly reduced the bone appositional
  index as compared to controls and probably
  compromise implants load bearing capacity.
Disclaimer
 No animal model truly reflects human biology. Lower form
vertebrates are more tissue and vascular tolerant of radiation
damage than humans.

Using the mathematical biologic equivalent of human doses
in a single administration or using fewer fractions with large
doses, serves a mathematical purpose but does not
guarantee biologically equivalent outcomes.



 Animal studies have yet to be reported assessing
 the impact of chemoradiation on osseointegration.
Anticipated outcomes in humans based on
                   animal studies
   Because anchorage is essentially mechanical as opposed to
    biologic, the load carrying capabilities of osseointegrated
    implants in irradiated bone will be less than seen in
    nonirradiated bone.
   The success rates of osseointegrated implants in irradiated
    bone should be less than that seen in nonirradiated bone. The
    higher the dose, the more profound the tissue changes and the
    lower the success rates.
Anticipated outcomes in humans based on
              animal studies
   In the mandible at higher doses (above 6500 cGy with
    conventional fractionation) the risk of osteoradionecrosis
    is most likely quite significant.
   Because of essentially mechanical anchorage and
    compromise of the remodeling apparatus of bone, late
    implant failures should be expected, even in good quality
    bone sites such as the anterior mandible
Anticipated outcomes in humans based on
                  animal studies
   Persistent osteoclastic activity secondary to residual
    functioning osteoclasts leads to bone which is less dense,
    and therefore initial anchorage and stabilization may be
    difficult to achieve in irradiated sites.
   Because of the compromised remodeling apparatus and
    impaired anchorage, long term clinical observations will be
    needed to properly assess the success-failure rates of
    implants in irradiated tissues
Human studies

   Yerit et al, 2006
   Roumanas et al, 1997 (Maxilla)
   Roumanas et al, 2002 (Craniofacial sites)
   Nimi et al, 1998 (Maxilla)
   Esser et al, 1997 (Mandible, maxilla)
   Granstrom et al, 1994 (Craniofacial sites)
   Granstrom, 2005 (All sites)
Implants in irradiated mandible
Yerit et al, 2006 (Pt base 1990-2003)*
 Patients – 71
 Dose 5000 cGY
 Number of implants - 316
 Implant survival
    •   Nonirradiated – 95%
    •   Irradiated sites – 72%




 *HBO was not used
Implants in irradiated mandible
Yerit et al, 2006 (Pt base 1990-2003)*
Success rates – Irradiated sites -154 implants)
     93% at 1 year
     90% at 2 years
     84% at 5 years
     72% at 8 years followup. The survival rates for the 84
      implants placed
Success rates - nonirradiated residual mandibular
  sites (84 implants)
     99% at one year
     99% at 2 years
     99% at 5 years
     95% at 8 years followup
Implants in irradiated mandible
Esser and Wagner, 1997
 Post op dose (CRT) – up to 6000 cGy
 Opposed mandibular fields – Symphysis?
 Pts - 58 (from 1985-1995)
 Implants placed – 221
 Implants lost – 32
     Before loading - 18
     After loading -17
     Success rate 84.2%
Granstrom, 2005
 63% survival rate for 15 implants placed in
 the mandible                         *HBO was not used
Implants in the irradiated maxilla

Predictability-Maxilla          %
   Roumanas     et al, 1997*   55

   Nimi   et al, 1998*         63




  *Without   HBO
Implants in edentulous maxillectomy patients

          Patients           Number of implants            Success
        Treated placed      uncovered    buried   failed     %
Irradiated 13      50           29          3       10      55.2
Non-
Irradiated 10      35          25          3        2       80.0

Totals      23         85       54         6        12      66.7




Roumanas et al, 1997


Failures in the irradiated group tend to be late, after the implants
                         have been loaded.
Implants in nonirradiated tissues
                 Craniofacial sites*

Implant     Pts   Implants Implants Implants Implants Survival
sites              placed uncovered buried    failed  rates (%)

Auricular 35      111        97       8         5         94
Nasal     16
 Piriform          27        25       0         5         80
 Glabella          2         2        0         2         0
Orbital    9       28        25       2         7         70

Overall      60   172        153     10        21         85

                                            *Roumanas et al, 2002
*Roumanas et al, 2002


              Implants in irradiated tissues
                   Craniofacial sites*

  Implant       Pts    Implants Implants Implants Implants Survival
  sites                 placed uncovered buried    failed  rates (%)
  Auricular 2              6              6           0           0          100
  Nasal     4
   Piriform               8               6           0           1           83
   Glabella               2               2           0           2           0
  Orbital   6            19              15           0           11          27

  Overall        12      35              29           0           14          52

Failures in the irradiated group tend to be late, after the implants have been loaded.
                                                                               loaded
Implants in the Irradiated
                   Supraorbital Rim
Success is poor and
 failures are late
 because:
   Mostly cortical bone
    •   Blood supply from periosteum
        and is compromised
    •   Anchorage is primarily
        mechanical
 More radiation absorption
 Compromised remodeling
Implant failures -Irradiated sites
             Case report




Flange exposure   Eventually led to loss of
                         implants
  This patient received more than
  6000 cGy to the implant sites
Implant failures – Irradiated sites
          Auricular defects
               Flange   exposure led to
                loss of implants three
                years post insertion

               Noteexposed bone
                (ORN) (arrows)
Risk of osteoradionecrosis

Esser et al, 1997.
In this retrospective
analysis, 2 patients out
60 (3.4%), developed
osteoradionecrosis, both
in the mandible. All
patients received 6000
cGy with CRT
postoperatively via
opposed mandibular
fields.
Risk of osteoradionecrosis
Granstrom (2009)
   10 out of 116 patients – 8.6%
   Dose
    •   Mean 79 Gy
    •   4 had two courses of radiation
    •   23- 145 Gy
   Sites
    •   Mandible
    •   Orbit
    •   Mastoid
    •   Frontal bone
Osteoradionecrosis
                       Case report
                        This patient received 6600 cGy for a
                        squamous carcinoma of the lateral
                        tongue. Three years later implants
                        were placed.


               Three years after
               implant placement the
               patient developed an
               infection associated
               with left posterior
               implant.

Eventually, the patient developed an osteoradionecrosis, a
pathologic fracture of the mandible and subsequently the
mandible was resected.
Osteoradionecrosis - Mastoid


            Note exposed bone (ORN)
             (arrows)
            The necrosis eventually
             resolved with conservative
             measures and the two
             inferiorly positioned
             implants failed.
Implants in irradiated mandible
         Role of hyperbaric oxygen

The data is all retrospective, but based on the reports of
Granstrom et al (1993, 2005), there appears to be an
advantage. Success rates appear to be higher and the risk of
osteoradionecrosis may be reduced depending upon the
dosage to the implant sites.

   • 63% survival rate for 15 implants placed in the mandible
       without HBO
   • 100% survival rate for 30 implants placed in the mandible
       with pre-operative HBO therapy.
Impact of HBO
Granstrom 2005 -- All sites – 25 years
               Implants placed Implants lost   ORN
Without HBO          291        117             5
With HBO             340         29             0
Impact of HBO
   Periosteal blood supply improvement vs revascularizing the
    marrow and repopulating it with stem cells?
       It is not known which of these two phenomenon is most important
   Success rates improved over the short term particularly in
    ideal sites such as the anterior mandible
   Experience in the orbit
       Late failures with short implants even with HBO
Impact of HBO - Maxilla
Implants can be inserted with little or no risk of
 osteoradionecrosis regardless of dose as long as
 the dosage is within customary therapeutic levels.




The use of hyperbaric oxygen can be justified only
on the basis of improving success rates.
Time from irradiation
Impact of time – After cancerocial doses of
  radiation do the tissues recover?
     At cancericidal doses the irradiated tissues do
      not recover. With time the irradiated tissues
      continue to deteriorate and become less
      vascular, more fibrotic etc.

     The longer the time from radiotherapy the
      poorer the results (Granstrom, 2005)
Implants in Irradiated Tissues
Recommendations
   Patient selection
     Edentulous  patients receive
      the most benefit
     Consider risk – reward ratio
     Determine tumor status – 80%
      of recurrences occur within the
      1st year
     Check the dosimetry of the
      radiation
Implants in Irradiated Tissues
Recommendations
   Longer  implants are recommended
   Use more implants than the usual
    number
   Splint implants together with rigid
    frameworks
   Implant assisted tissue bar designs
    are preferred with overlay dentures
   No cantilevers
   HBO or pentoxyfilline-tocopherol
    protocol recommended to improve
    success rates and reduce risk of
    ORN
Implants in the irradiated mandible
Doses 5500 cGy and below
     Implants can be inserted with little or no risk of osteoradionecrosis
     Success rates will be probably be 15-20% lower than normal


Doses between 5500 and 6500 cGy
     Individual patient factors such as fractionation, tissue responses,
      clinical findings, dental history etc. impact the decision. Success
      rates not well documented


Doses above 6500 cGy
     The risk of osteoradionecrosis becomes significant and implants
      should not placed unless HBO is given.
        In such patients the success rates have been in the 75-80%

         range with little osteoradionecrosis seen.
Implants in the irradiated edentulous mandible
At doses above 55 Gy
anchorage is probably primarily
mechanical as opposed to
biologic.
Without HBO long term
success rates may be
problematic (Granstrom, 2005; Yerit
et al, 2006)
Therefore if implants are used
we recommend:

      Four implants splinted together with a implant assisted
       overlay denture.
      In this design the “Hader” segment anteriorly serves as the
       axis of rotation. The resilient “ERA” attachments
       posteriorly allow the prosthesis to rotate around the Hader
       segment when posterior occlusal forces are applied.
Implants in the irradiated mandible




 Patient had hemiglossectomy and reconstruction
 of tongue with a free flap and received 55 Gy
 post operatively. Without implants use of a
 complete denture would have been problematic.
Implants irradiated maxillary sites
 Risk of osteoradionecrosis is negligible unless the doses are
  extremely high (above 7500 cGy)
 Success rate has generally been less than the mandible
  presumably because less bone density and depends on:
    Dose to bone
    Load biomechanics, etc.
    Quality and quantity of bone
    Implant length




  For maxillectomy patients
         Splint implants together with rigid frameworks
         Tissue bars should be implant assisted
Implants - Irradiated craniofacial sites
Floor of nose
   Little biomechanical stress
   Success rates will probably be
    60-80% depending on the dose
Mastoid
   Little biomechanical stress but
    implants are short
   Success rates will probably be
    60-80% depending on the dose
Supraorbital rim
   All cortical bone
   Success rates will be very low,
    long term, probably less that 25%
CRT - Implants in irradiated patients
         vs implants in the radiation field
  Check fields and dose
       Fields are often reduced in size as treatment progresses




Implants can be placed in the anterior mandible and anterior maxilla in such
patients and the success will be equivalent to normal non irradiated patients
CRT - Implants in irradiated patients vs
    implants in the radiation field




   These implants were positioned anterior to the field of
    radiation (note the pattern of hair loss).
Radiation delivery factors - IMRT
Check dosimetry
   Dose varies considerably and
   there may be hot spots in unusual
   areas




3 fields              5 fields         7 fields
Irradiation of Existing Implants - Backscatter




These implants
were irradiated 2
years following
placement. Note
the exposure of
the implant            Dose enhancement of about 15%
flanges.                within 1 mm of implant surface
                        (Schwartz et al, 1978:;Wang et al,1996).
Irradiation of existing implants- Backscatter




Implants were placed simultaneous with tumor
resection and reconstruction of this large body-
symphyseal defect with a fibula free flap. The
patient received 6000 cGy post operatively.
Irradiation of existing implants- Backscatter




Several months later and just after delivery of the
tissue bar, the tissues on the labial surfaces of the
implants dehisced and the bone overlying the implants
sequestrated leading to loss of the implants.
Irradiation of existing implants- Backscatter




Following loss of the implants, the mucosa
recovered the area. The graft remained viable and
mandibular continuity was maintained.
Irradiation of Existing Implants




Options
• Do nothing
• Remove the prosthesis and close the wound (Granstrom et al,
     1993)
• Remove the bridge and place healing abutments on the implants
      (No data is available but our experience has led us to favor   we
      favor this option)
Irradiation of Existing Implants




Remove    the prosthesis and close the wound (Granstrom et al,
       1993)
In this patient the fixed partial denture was removed and the
       implants surgically buried beneath the mucosa. However
       they soon became exposed to the oral cavity
Irradiation of Existing Implants
Remove the bridge and replace with healing abutments
   Minimizes backscatter

Following completion of radiation therapy should we
  replace the bridge, tissue bar etc.? Factors to consider
                                                  conside

   Dose to bone anchoring the implants
   Mandible vs maxilla
   Target volume/fields
   Chemoradiation or radiation alone
   Hygiene access - Beware of posterior ridge laps
   Patient compliance issues
Irradiation of Existing Implants
Remove the bridge and replace with healing abutments
   Minimizes backscatter

Following completion of radiation therapy should we
  replace the bridge, tissue bar etc.? Factors to consider
                                                  conside

  Dose to bone anchoring the implants

     If the implants are located in the mandible and the dose t
      the implant sites exceeds 65 Gy the risk of ORN is
      significant and replacing the prosthesis may predispose to
      a high level of risk.
Irradiation of Existing Implants
Remove the bridge and replace with healing abutments
   Minimizes backscatter

Following completion of radiation therapy should we
  replace the bridge, tissue bar etc.? Factors to consider

  Mandible vs maxilla

     Since the risk of ORN in the maxilla is very low and the
      morbidity is minimal reinserting an implant retained
      prostheses in the maxilla carries very low risk.
Irradiation of Existing Implants
Remove the bridge and replace with healing abutments
   Minimizes backscatter

Following completion of radiation therapy should we
  replace the bridge, tissue bar etc.? Factors to consider
                                                  conside

  Target volume/fields

     Implants sites out of the field of radiation when CRT is
      used receive virtually no radiation and implant sites
      beyond the clinical tumor volume when IMRT is used will
      receive lower dose. Therefore prostheses can be
      reinserted in these situations in both the mandible and
      maxilla with little or no risk of ORN.
Irradiation of Existing Implants
Remove the bridge and replace with healing abutments
   Minimizes backscatter

Following completion of radiation therapy should we
  replace the bridge, tissue bar etc.? Factors to consider
                                                  conside

  Chemoradiation or radiation alone

     ChemoRT raise the BED (biologically equivalent dose by
      700 – 1000 cGy. The implant sites are in the mandible
      and exposed to these dose levels replacement of the
      prosthesis may predispose to a high risk of developing an
      ORN
Irradiation of Existing Implants
Remove the bridge and replace with healing abutments
   Minimizes backscatter

Following completion of radiation therapy should we
  replace the bridge, tissue bar etc.? Factors to consider
                                                  conside

  Hygiene access and patient compliance issues
     Beware of posterior ridge laps of fixed implant supported
      prostheses in the mandible in the marginally compliant
      patient. These patient are at high risk for periimplantitis
      and ORN.
Irradiation of Existing Implants
Remove the bridge and replace with healing abutments
   Minimizes backscatter

Following completion of radiation therapy should we
  replace the bridge, tissue bar etc.? Factors to consider
                                                  conside

In summary in the mandible if the BED (biologically
equivalent dose) to the implant sites exceeds 6500 cGy we
do not recommend placing the prosthesis back into position in
most patients because compromised hygiene and the risk of
a peri-implant soft tissue infection may lead to an
osteoradionecrosis (see slide #56).
In the maxilla and craniofacial sites the prosthesis can be
reinserted with little risk to the patient.
Placement of implants in patients to
     receive postoperative radiation.
  Should the clinician place these implants at the
  time of tumor ablation or wait until after the
  radiation treatments have been completed?

We consider this issue from two perspectives:
  Quality of implant anchorage and prospects for
     long term success
  Risk of osteoradionecrosis
Quality of implant anchorage and prospects
 for long term success
This issue is debatable but from this perspective it is probably best to place
implants at the time of tumor ablation. Given the bio-reactivity of the micro-
rough or nano-enhanced surfaces the implants will become very well
anchored in bone by 6 weeks – the period of time usually employed to allow
the surgical wounds to heal prior to commencing postoperative radiation
treatments. Admittedly the dose enhancement effect will render this bone
nonvital and the implant anchorage becomes primarily mechanical.

If one delays implant placement until radiation treatments are completed
the postoperative doses used today (usually 60 Gy and above) will also
render the anchoring bone relatively nonvital and the implant anchorage will
also be primarily mechanical as opposed to biologic.

The implant anchorage of the former will be considerably better than the
later approach.
Risk of osteoradionecrosis
 In  the mandible the risk of ORN
  secondary to dose enhancement may be
  significant
 If there is the chance that the postop BED
  to mandibular implant sites will exceed
  6500 cGy it is probably best to defer.
Nano-enhanced and genetically
      engineered implant surfaces
   Will these phenomenon be clinically
   significant in the irradiated patient?
  Probably not. Anchorage is mechanical as
  opposed to biologic. The macro-surface
  topography, the quality of bone and the skill
  of the surgeon are the most critical factors.
  The major problem in the irradiated patient is
loss of vasculature and fibrosis and with it the loss
of osteoprogenitor cells (mesenchymal stem cells)
in the marrow.
Dental development
   Levels as low as 2500 cGy effect tooth development
    (Gorlin and Meskin, 1963; Pietrokovski and Menczel,
    1966; Dahllof et al, 1994; Kaste et al, 1994)
   Changes reflect a variety of defects that indicate the
    several stages of development existing during the
    course of radiotherapy




 This patient is 16 years of age. He received 3600 cGy of radiation
 when he was 4 years of age for treatment of a rhabdomyosarcoma.
Dental development
   Levels as low as 2500 cGy effect tooth development
    (Gorlin and Meskin, 1963; Pietrokovski and Menczel,
    1966; Dahllof et al, 1994; Kaste et al, 1994)
   Changes reflect a variety of defects that indicate the
    several stages of development existing during the course
    of radiotherapy




Are these patients candidates for implants?
         Yes! If t dose is below 4000 cGy.
Early Radiation to the Enamel Organ
           Implant supported fixed partial denture




This patient was irradiated as a young child for
a rhabdomyosarcoma. She received slightly less
than 40 Gy along with several courses of
chemotherapy which arrested the development
of her permanent dentition.
Eventually all her teeth were lost or extracted
and several implants were placed in the maxilla
and mandible
PFM fixed prostheses were then fabricated
 Visit ffofr.org for hundreds of additional lectures
  on Complete Dentures, Implant Dentistry,
  Removable Partial Dentures, Esthetic Dentistry
  and Maxillofacial Prosthetics.
 The lectures are free.
 Our objective is to create the best and most
  comprehensive online programs of instruction in
  Prosthodontics
Coming soon
Implant Biomechanics and Treatment
 Planning in partially Edentulous Patients
Abutment selection in partially edentulous
 patients
Early and Immediate loading
References
   Garrett N. (2008) Outcomes of Maxillectomies with conventional and implant
    restorations. Presented at International Congress on Maxillofacial Rehabilitation
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   Garrett NR, Kapur K, Hamada M, et al. (1998) A randomized clinical trial
    comparing the efficacy of mandibular implant supported overdentures and
    conventional dentures in diabetic patients. Part II. Comparisons of masticatory
    performance. J Prosthet Dent 79:632-40.
   Geertmen M, Slagter A, van Waas M et al. (1994) Comminution of food with
    mandibular implant-retained overdentures. J Dent Res 73:1858-64.
   Geertmen M, Marinus A, van Waas M et al. (1996) Denture satisfaction in a
    comparative study of implant-retained mandibular overdentures: A randomized
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   Chang T, Garrett N, Roumanas E, et al. (2005) Treatment satisfaction with
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   Jacobsson M, Tjellstrom A, Thomson P, et al. (1988) Integration of titanium
    implants in irradiated bone. Histologic and clinical study. Ann. Otol. Rhinol.
    Laryngol. 97:337-40.
   Hum S, Larsen P. (1992) The effect of radiation at the titanium/bone interface.
    In: Tissue integration in oral, orthopedic and maxillofacial reconstruction. ed. by
    Laney, W. and Tolman, D. Quintessence Publishing Co. Chicago. pp.234-9.
References
   Nishimura R, Roumanas E, Sugai, T et al. (1996) Nasal defects and
    osseointegrated implants: UCLA experience. J Prosthet Dent 76:597-602.
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References
   Roumanas E, Nishimura R, Davis B, et al. (1997) Clinical evaluation of
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   Esser E, Wagner W. (1997) Dental implants following radical oral cancer
    surgery and adjuvant radiotherapy. Int J Maxillofac Implants 12:552-57.
   Nimi A, Ueda M, Kaneda T. (1993) Maxillary obturator supported by
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    Maxillofac Surg 51:804-9.
   Nimi A, Ueda M, Kaneda T. (1998) Maxillary obturator supported by
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   Visch L, van Waas M, Schmitz P, et al. (2002) A clinical evaluation of implants
    in irradiated oral cancer patients. J Dent Res 81:856-59.
   Roumanas E, Freymiller E, Chang T, et al. (2002) Implant retained
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   Granstrom G. (2005) Osseointegration in irradiated cancer patiens: An
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References
   Yerit K, Posch M, Seemann S, et al. (2006) Implant survival in mandibles or
    irradiated oral cancer patients. Clin Oral Impl Res 17:337-44.
   Visser A. (2007) Aftercare of implant-retained facial prostheses. In
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   Salinas TJ, Valmont PD, Katsnelson A, et al. (2010) Clinical evaluation of
    implants in radiated fibula free flaps. J Oral Maxillofac Surg 68:524-9.
   Flood T, Downie I, Ethunandan M. (2009) Prosthetic reconstruction after
    rhinectomy-evolution of bone anchored epistheses and adjunctive surgical
    techniques in nasal reconstruction from one unit. (Presentation at the 2nd
    International Symposium. Bone Conduction Hearing-Craniofacial
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   Proops D, Worrollo S, Jeynes P et al. (2009) Head and neck reconstruction in
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   Marx R. (1993) Preprosthetic surgery in a radiated cancer patient. (abstract #
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   Dudziak M, Saadeh P, Mehara B et al. (2000) The effect of ionizing radiation on
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   Donoff RB. (2006) Treatment of the irradiated patient with dental implants: The
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   Nishimura R, Roumanas E, Sugai T, et al. (1995) Auricular prostheses and
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   Nishimura R, Roumanas, E, Sugai T, et al. (1998) Osseointegrated implants
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   Schwartz H, Wollin M, Leake D, et al. (1979) Interface radiation dosimetry in
    mandibular reconstruction. Arch. Otolaryngol. 105:293-5.
   Miam TA, Van Putten MC, Kramer DC et al. (1987) Backscatter radiation at
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    Biol Phys 13:1943-47.
   Granstrom G, Tjellstrom A, Albrektsson T: (1995) Post implant irradiation of
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The End
Thank you for your kind attention

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8.implant in irradiated patients

  • 1. 8. Implants in Irradiated Tissues John Beumer III, DDS, MS Division of Advanced Prosthodontics, Biomaterials and Hospital Dentistry UCLA School of Dentistry All rights reserved. This program of instruction is covered by copyright ©. No part of this program of instruction may be reproduced, recorded, or transmitted, by any means, electronic, digital, photographic, mechanical, etc., or by any information storage or retrieval system, without prior permission of the authors.
  • 2. Implants in Irradiated Tissues Table of Contents  Radiation effects and impact on osseointegration  Changing methods of radiation delivery and the impact of chemoradiation  Patient selection criteria  Animal studies  Human data  Osteoradionecrosis  Role of HBO  Timing of implant placement  Irradiation of existing implants
  • 3. Osseointegration Success requires primary implant anchorage and immobilization, the formation of a clot between the surface of the implant and the osteotomy site, release of growth factors, angiogenesis and migration of osteoprogenitor cells to and deposition of bone on the surface of the implant and in the osteotomy site. Osteoblasts Mineral deposition Non-collagenous matrix Collagen matrix
  • 4. Osseointegrated Implants  These biologic processes may be compromised or absent in patients exposed to high dose radiation and as a result anchorage of implants in bone is probably mechanical as opposed to biological.  In addition, long term function of osseointegrated implants is dependent on the presence of viable bone that is capable of remodeling and turnover as the implant is subjected to stresses associated with supporting, retaining, and stabilizing prosthetic restorations. These processes are compromised or perhaps entirely lacking in heavily irradiated bone.
  • 5. Radiation effects  Reduced vasculature Lamellar bone  Loss of osteoprogenitor • Loss of central artery in Haversian systems cells • Death of osteocytes  Marrow undergoes fatty and fibrous degeneration  Periosteum becomes acellular and loss of vasculature Trabecular bone Root surface Marrow
  • 6. Radiation effects These tissue changes lead to: Lamellar bone • Loss of central artery in  Compromised remodeling Haversian systems • Death of osteocytes  Response to infection is compromised ie osteoradionecrosis  Continuing osteolytic activity Root Trabecular bone surface Marrow
  • 7. Why are these changes important?  Anchorage may be mechanical as opposed to biologic  Response to infection is compromised  Remodeling apparatus is not fully functional  Response to occlusal forces is compromised  Osteolytic activity continues and compromises the density of the bone Root Trabecular bone surface Marrow
  • 8. Continued osteolytic activity  The density of bone is diminished because bone resorption continues secondary to the presence of isolated osteoclasts making it more difficult to achieve primary stability of the implant.
  • 9. Remodeling apparatus – Osteolytic Activity This patient received 70 Gy to the mandible for an anterior floor of mouth Sq Ca. Note the dramatic change in the prominence of the cortical Preradiationplates (arrows) and the differences in trabecular patterns between preradiaton and postradiation radiographs. Osteolytic activity seems more prominent in patients treated with chemoRT Postradiation
  • 10. Remodeling apparatus – Osteolytic Activity Postradiation Hence in irradiated sites initial stabilization of the implants is more difficult to achieve In edentulous patients the irradiated mandible is more susceptible to fracture
  • 11. Remodeling apparatus – Osteolytic Activity  Patient received 60 Gy. The mandible fractured through the left posterior implant site (arrow) two weeks following implant placement. It was reduced and repaired as shown with eventual healing. An implant assisted overlay denture was later fabricated and used successfully by the patient.
  • 12. The tissue changes are dose dependent and the dose depends in part upon: Mode of therapy  CRT (Conventional radiation therapy)  IMRT (Intensely modulated radiation therapy)  Brachytherapy In edentulous patients the preferred implant sites are: Symphyseal region of the mandible Premaxilla The mode of therapy will determine the dose delivered to these regions and dose is the best predictor of long term success and the risk of ORN.
  • 13. Changing methods of radiation delivery Conventional radiation therapy (CRT)  200 cGy per fraction  Bilateral opposed equally weighted fields  Total doses Source: www.beaumonthospital.com  7000 cGy definitive dose  5000-6000 cGy post op Intensity modulated radiation therapy (IMRT) This technique uses multiple radiation beams of non-uniform intensities. The beams are modulated to the required intensity maps for delivering highly conformal doses of radiation to the treatment targets, while limiting dose normal tissue structures. Source: www.beaumonthospital.com
  • 14. IMRT dosimetry diagrams Note the hot spot on anterior mandible (oval).  With IMRT the dose distribution is not uniform.
  • 15. (CRT) Chemoradiation (IMRT) Source: www.beaumonthospital.com Source: www.beaumonthospital.com • Used in combination with CRT or IMRT • Full course of concomitant chemoradiation is theoretically equivalent to an additional 7-10 Gy (Kashibhatla, 2006; Fowler, 2008). Consequences (particularly with CRT): The biologically equivalent dose (BED) is raised leading to more short term and long term side effects (mucositis, fibrosis, trismus, velopharyngeal incompetence, osteoradionecrosis etc).
  • 16. Implants in Irradiated Tissues Issues to consider  Potential benefit to the patient  What are the objectives and wishes of the patient?  Risk – reward ratio?  Risk of osteoradionecrosis?  Morbidity?  Short term success rates?  Long term success rates?
  • 17. Risk vs Reward Edentulous Maxillectomy Patients  As indicated by the following data, without implants to help retain and stabilize the complete denture-obturator prosthesis, mastication is not restored  With the retention provided by the implants mastication levels are restored to presurgical levels of function (Garrett et al, 2008).  The risk of osteoradionecrosis secondary to implant placement is very low.  Since the risk is minimal and the rewards are significant we do not hesitate to recommend the use of implants in patients with palatal defects that have been irradiated.
  • 18. Masticatory Performance Maxillectomy N=5 (‘0’ score if not able to chew) 50 46.2 45 40.5 % performance 40 35 30 Defect 25 Intact 20 15.6 15 8.2 8.8 10 6.2 6.6 8.1 5 0 Entry Post-Surgery Post-CP Post-IP Garret et al, 2008 *p<0.01
  • 19. Masticatory Performance Maxillectomy N=5 (‘0’ score if not able to chew) * * 50 46.2 45 % performance 40.5 40 35 30 Defect 25 Intact 20 15.6 15 8.2 8.8 10 6.2 6.6 8.1 5 0 Entry Post-Surgery Post-CP Post-IP Garret et al, 2008; Garrett et al, 2009 *p<0.01
  • 20. Tongue-Mandible Defects Reconstructed with Free Flaps Patients with dentition on the unresected side  As indicated from the following data you can see that patients retain their ability to masticate effectively on the nonresected side after mandibular reconstruction.  Implant placement on the fibula side does not add substantially to their mastication efficiency.  In addition if the tongue is restored with the flap the patient lacks the sensory and motor innervation to control the food bolus on the resected side.  The risk reward ratio is not as favorable and therefore in most such situations we therefore recommend a conventional RPD when the implant sites have been heavily irradiated.
  • 21. Masticatory Performance Fibula free flaps - Mandible (dentate patients) (“0” if unable to attempt test; n=15) % performance 45 Defect 40 Intact 41.6 36 35 34.5 30 32.7 25 21.1 24.9 20 20.3 15 10 5 7.3 0 Entry Post-Surgery Post-CP Post-IP Garrett et al, 2005
  • 22. Tongue-Mandible Defects Reconstructed with Free Flaps - Edentulous Patients The functional benefit derived from implant placement in irradiated edentulous patients depends on several factors, the most important being the status of tongue function.  If the tongue and/or mandible has been resected and reconstructed and the bulk, mobility and control of the reconstructed tongue results in reasonable tongue function, the placement of implants may significantly improve mastication performance particularly if the denture bearing surface has been compromised or is not ideal.
  • 23. Tongue-Mandible Defects Reconstructed with Free Flaps - Edentulous Patients  Patient had hemiglossectomy and reconstruction of tongue with a free flap and received 55 Gy post operatively.  Tongue bulk is restored and tongue mobility is excellent  Without implants use of a lower complete denture would have been problematic.  The dose is low. The risk reward ratio is favorable and therefore in such patients implants were placed to stabilize and retain the denture. Note: The patient must masticate on the sensate unresected side.
  • 24. Facial Prostheses – Quality of retention Quality of life When patients present with facial defects implant retention improves patient satisfaction and frequency of use (Chang et al, 2005). With large combination facial defects adhesive retention is ineffective and implant retention is required for most patients Although the implant loss rates are high the benefits are great particularly in patients with large facial defects such as this one. Therefore, we recommend the placement of implants in most patients with large facial defects even though the implant sites have been irradiated.
  • 25. Facial Prostheses - Retention During Daily Activities * Adhesive Implant * 95 * 100 89 90 84 85 79 80 70 63 57 60 % 'Excellent' 50 44 44 38 40 30 20 10 0 Chang et al, 2005 Home Eating Exercise Perspire Sneeze/Cough
  • 26. Frequency of Wear Facial Prostheses Chang et al, 2005 Adhesive Implant 120 95 100 100 89 88 80 *63 % Wearing 60 44 40 20 3 0 0 Home Work Social Never
  • 27. Implants in Irradiated Tissues Biologic viability (animal studies)  Hum and Larsen, (1990)  Weinlander et al, (2006)  Nishimura et al, (1996)  Asikainen et al, (1993)  Ohrnell et al, (1997)  Jacobsson et al, (1988)
  • 28. Implants in Irradiated Tissues Biologic viability (animal studies) Asikainen, 1998  Dogs received either 4000, 5000, or 6000 cGy  Two months later TPS screw type implants were inserted  Four months later the implants were loaded  Success rates:  4000 cGy group – 100%  5000 cGy group – 20%  6000 cGy group – 0 %
  • 29. Implants in Irradiated Tissues Weinlander et al, (2006)  Dogs were partially edentulated  Following a suitable healing period three implants were placed on each side  All seven dogs received radiation therapy, starting three weeks post implantation on one side of the mandible, consisting of a dose equivalent to 5000 cGy delivered in 4 fractions during a 2 week period
  • 30. Methods – Histomorphometric Calculations  A scanning electron microscope was used to image the background electron density of the three elements – bone, soft tissue and implant. The histometry calculation yielded volume and boundary fractions for the implant, bone and soft tissue components. Weinlander et al, 2006
  • 31. Bone contact area in control specimens 80 70 60 50 40 Bone 30 Appositional Index % 20 10 0 Machined Plasma HA Surface Spray Coated Weinlander et al,
  • 32. Bone contact area in irradiated tissue 70 60 50 40 Bone 30 Appositional 20 Index % 10 0 Machined Plasma HA Surface Spray Coated Weinlander et al, 2006
  • 33. Nishimura et al,1996 Dosage of Radiation Therapy Administered A rabbit tibia model was used in this study. The rat tibia were exposed to equivalents of the following doses and implants were placed 3 months following completion of radiation treatments. Polyfluorochrome labeling was performed three months after implant placement and the animals sacrificed 2 days later, (cGy) 4000 5800 4600 6400 5200 7000
  • 34. Nishimura et al, 1996 Results Normal 5200 cGy 5800 cGy Three months after implant placement the tissue samples were harvested and were evaluated with light and fluorescent microscopy. Fluorochrome labeling documented a steady decrease in biologic activity at the higher doses.
  • 35. Nishimura et al, 1996 Results Normal bone Irradiated bone At lower doses irradiated specimens had more woven bone at the bone implant interface than did the normal specimens at the time of sacrifice.
  • 36. Additional animal studies (summaries)  Jacobsson et al (1988) - Reduction in bone formation capacity, an increase in bone resorption and a reduction in the number of capillaries.  Ohrnell et al (1997) - Fibrosis of the bone marrow, bone resorption, less bone adjacent to the implants and an overall reduction in the remodeling capacity of bone.  Hum and Larsen (1990) - The bone contact area for irradiated specimens was significantly less than nonirradiated specimens
  • 37. Summary of tissue changes affecting osseointegration based on animal studies  At higher doses (70 Gy) virtually little or no bone will be deposited on the implant surface. Anchorage is primarily mechanical as opposed to biologically driven.  At lower doses a greater component of woven bone is seen in the interface. Compromise of the remodeling apparatus may preclude this woven bone from being replaced with lamellar bone  Death of osteocytes, loss of osteoprogenitor cells and the basic multi-cellular unit of the remodeling apparatus (BMU) compromises the remodeling of bone at the bone implant interface and compromises the bone’s response to occlusal load.
  • 38. Summary of tissue changes affecting osseointegration based on animal studies • Poor blood supply in the marrow predisposes to infection and implant loss • At lower doses radiation induced tissue effects significantly reduced the bone appositional index as compared to controls and probably compromise implants load bearing capacity.
  • 39. Disclaimer  No animal model truly reflects human biology. Lower form vertebrates are more tissue and vascular tolerant of radiation damage than humans. Using the mathematical biologic equivalent of human doses in a single administration or using fewer fractions with large doses, serves a mathematical purpose but does not guarantee biologically equivalent outcomes. Animal studies have yet to be reported assessing the impact of chemoradiation on osseointegration.
  • 40. Anticipated outcomes in humans based on animal studies  Because anchorage is essentially mechanical as opposed to biologic, the load carrying capabilities of osseointegrated implants in irradiated bone will be less than seen in nonirradiated bone.  The success rates of osseointegrated implants in irradiated bone should be less than that seen in nonirradiated bone. The higher the dose, the more profound the tissue changes and the lower the success rates.
  • 41. Anticipated outcomes in humans based on animal studies  In the mandible at higher doses (above 6500 cGy with conventional fractionation) the risk of osteoradionecrosis is most likely quite significant.  Because of essentially mechanical anchorage and compromise of the remodeling apparatus of bone, late implant failures should be expected, even in good quality bone sites such as the anterior mandible
  • 42. Anticipated outcomes in humans based on animal studies  Persistent osteoclastic activity secondary to residual functioning osteoclasts leads to bone which is less dense, and therefore initial anchorage and stabilization may be difficult to achieve in irradiated sites.  Because of the compromised remodeling apparatus and impaired anchorage, long term clinical observations will be needed to properly assess the success-failure rates of implants in irradiated tissues
  • 43. Human studies  Yerit et al, 2006  Roumanas et al, 1997 (Maxilla)  Roumanas et al, 2002 (Craniofacial sites)  Nimi et al, 1998 (Maxilla)  Esser et al, 1997 (Mandible, maxilla)  Granstrom et al, 1994 (Craniofacial sites)  Granstrom, 2005 (All sites)
  • 44. Implants in irradiated mandible Yerit et al, 2006 (Pt base 1990-2003)*  Patients – 71  Dose 5000 cGY  Number of implants - 316  Implant survival • Nonirradiated – 95% • Irradiated sites – 72% *HBO was not used
  • 45. Implants in irradiated mandible Yerit et al, 2006 (Pt base 1990-2003)* Success rates – Irradiated sites -154 implants)  93% at 1 year  90% at 2 years  84% at 5 years  72% at 8 years followup. The survival rates for the 84 implants placed Success rates - nonirradiated residual mandibular sites (84 implants)  99% at one year  99% at 2 years  99% at 5 years  95% at 8 years followup
  • 46. Implants in irradiated mandible Esser and Wagner, 1997 Post op dose (CRT) – up to 6000 cGy Opposed mandibular fields – Symphysis? Pts - 58 (from 1985-1995) Implants placed – 221 Implants lost – 32 Before loading - 18 After loading -17 Success rate 84.2% Granstrom, 2005 63% survival rate for 15 implants placed in the mandible *HBO was not used
  • 47. Implants in the irradiated maxilla Predictability-Maxilla %  Roumanas et al, 1997* 55  Nimi et al, 1998* 63 *Without HBO
  • 48. Implants in edentulous maxillectomy patients Patients Number of implants Success Treated placed uncovered buried failed % Irradiated 13 50 29 3 10 55.2 Non- Irradiated 10 35 25 3 2 80.0 Totals 23 85 54 6 12 66.7 Roumanas et al, 1997 Failures in the irradiated group tend to be late, after the implants have been loaded.
  • 49. Implants in nonirradiated tissues Craniofacial sites* Implant Pts Implants Implants Implants Implants Survival sites placed uncovered buried failed rates (%) Auricular 35 111 97 8 5 94 Nasal 16 Piriform 27 25 0 5 80 Glabella 2 2 0 2 0 Orbital 9 28 25 2 7 70 Overall 60 172 153 10 21 85 *Roumanas et al, 2002
  • 50. *Roumanas et al, 2002 Implants in irradiated tissues Craniofacial sites* Implant Pts Implants Implants Implants Implants Survival sites placed uncovered buried failed rates (%) Auricular 2 6 6 0 0 100 Nasal 4 Piriform 8 6 0 1 83 Glabella 2 2 0 2 0 Orbital 6 19 15 0 11 27 Overall 12 35 29 0 14 52 Failures in the irradiated group tend to be late, after the implants have been loaded. loaded
  • 51. Implants in the Irradiated Supraorbital Rim Success is poor and failures are late because:  Mostly cortical bone • Blood supply from periosteum and is compromised • Anchorage is primarily mechanical  More radiation absorption  Compromised remodeling
  • 52. Implant failures -Irradiated sites Case report Flange exposure Eventually led to loss of implants This patient received more than 6000 cGy to the implant sites
  • 53. Implant failures – Irradiated sites Auricular defects  Flange exposure led to loss of implants three years post insertion  Noteexposed bone (ORN) (arrows)
  • 54. Risk of osteoradionecrosis Esser et al, 1997. In this retrospective analysis, 2 patients out 60 (3.4%), developed osteoradionecrosis, both in the mandible. All patients received 6000 cGy with CRT postoperatively via opposed mandibular fields.
  • 55. Risk of osteoradionecrosis Granstrom (2009)  10 out of 116 patients – 8.6%  Dose • Mean 79 Gy • 4 had two courses of radiation • 23- 145 Gy  Sites • Mandible • Orbit • Mastoid • Frontal bone
  • 56. Osteoradionecrosis Case report This patient received 6600 cGy for a squamous carcinoma of the lateral tongue. Three years later implants were placed. Three years after implant placement the patient developed an infection associated with left posterior implant. Eventually, the patient developed an osteoradionecrosis, a pathologic fracture of the mandible and subsequently the mandible was resected.
  • 57. Osteoradionecrosis - Mastoid  Note exposed bone (ORN) (arrows)  The necrosis eventually resolved with conservative measures and the two inferiorly positioned implants failed.
  • 58. Implants in irradiated mandible Role of hyperbaric oxygen The data is all retrospective, but based on the reports of Granstrom et al (1993, 2005), there appears to be an advantage. Success rates appear to be higher and the risk of osteoradionecrosis may be reduced depending upon the dosage to the implant sites. • 63% survival rate for 15 implants placed in the mandible without HBO • 100% survival rate for 30 implants placed in the mandible with pre-operative HBO therapy.
  • 59. Impact of HBO Granstrom 2005 -- All sites – 25 years Implants placed Implants lost ORN Without HBO 291 117 5 With HBO 340 29 0
  • 60. Impact of HBO  Periosteal blood supply improvement vs revascularizing the marrow and repopulating it with stem cells?  It is not known which of these two phenomenon is most important  Success rates improved over the short term particularly in ideal sites such as the anterior mandible  Experience in the orbit  Late failures with short implants even with HBO
  • 61. Impact of HBO - Maxilla Implants can be inserted with little or no risk of osteoradionecrosis regardless of dose as long as the dosage is within customary therapeutic levels. The use of hyperbaric oxygen can be justified only on the basis of improving success rates.
  • 62. Time from irradiation Impact of time – After cancerocial doses of radiation do the tissues recover?  At cancericidal doses the irradiated tissues do not recover. With time the irradiated tissues continue to deteriorate and become less vascular, more fibrotic etc.  The longer the time from radiotherapy the poorer the results (Granstrom, 2005)
  • 63. Implants in Irradiated Tissues Recommendations  Patient selection Edentulous patients receive the most benefit Consider risk – reward ratio Determine tumor status – 80% of recurrences occur within the 1st year Check the dosimetry of the radiation
  • 64. Implants in Irradiated Tissues Recommendations  Longer implants are recommended  Use more implants than the usual number  Splint implants together with rigid frameworks  Implant assisted tissue bar designs are preferred with overlay dentures  No cantilevers  HBO or pentoxyfilline-tocopherol protocol recommended to improve success rates and reduce risk of ORN
  • 65. Implants in the irradiated mandible Doses 5500 cGy and below  Implants can be inserted with little or no risk of osteoradionecrosis  Success rates will be probably be 15-20% lower than normal Doses between 5500 and 6500 cGy  Individual patient factors such as fractionation, tissue responses, clinical findings, dental history etc. impact the decision. Success rates not well documented Doses above 6500 cGy  The risk of osteoradionecrosis becomes significant and implants should not placed unless HBO is given.  In such patients the success rates have been in the 75-80% range with little osteoradionecrosis seen.
  • 66. Implants in the irradiated edentulous mandible At doses above 55 Gy anchorage is probably primarily mechanical as opposed to biologic. Without HBO long term success rates may be problematic (Granstrom, 2005; Yerit et al, 2006) Therefore if implants are used we recommend:  Four implants splinted together with a implant assisted overlay denture.  In this design the “Hader” segment anteriorly serves as the axis of rotation. The resilient “ERA” attachments posteriorly allow the prosthesis to rotate around the Hader segment when posterior occlusal forces are applied.
  • 67. Implants in the irradiated mandible Patient had hemiglossectomy and reconstruction of tongue with a free flap and received 55 Gy post operatively. Without implants use of a complete denture would have been problematic.
  • 68. Implants irradiated maxillary sites  Risk of osteoradionecrosis is negligible unless the doses are extremely high (above 7500 cGy)  Success rate has generally been less than the mandible presumably because less bone density and depends on:  Dose to bone  Load biomechanics, etc.  Quality and quantity of bone  Implant length For maxillectomy patients Splint implants together with rigid frameworks Tissue bars should be implant assisted
  • 69. Implants - Irradiated craniofacial sites Floor of nose  Little biomechanical stress  Success rates will probably be 60-80% depending on the dose Mastoid  Little biomechanical stress but implants are short  Success rates will probably be 60-80% depending on the dose Supraorbital rim  All cortical bone  Success rates will be very low, long term, probably less that 25%
  • 70. CRT - Implants in irradiated patients vs implants in the radiation field Check fields and dose  Fields are often reduced in size as treatment progresses Implants can be placed in the anterior mandible and anterior maxilla in such patients and the success will be equivalent to normal non irradiated patients
  • 71. CRT - Implants in irradiated patients vs implants in the radiation field  These implants were positioned anterior to the field of radiation (note the pattern of hair loss).
  • 72. Radiation delivery factors - IMRT Check dosimetry Dose varies considerably and there may be hot spots in unusual areas 3 fields 5 fields 7 fields
  • 73. Irradiation of Existing Implants - Backscatter These implants were irradiated 2 years following placement. Note the exposure of the implant  Dose enhancement of about 15% flanges. within 1 mm of implant surface (Schwartz et al, 1978:;Wang et al,1996).
  • 74. Irradiation of existing implants- Backscatter Implants were placed simultaneous with tumor resection and reconstruction of this large body- symphyseal defect with a fibula free flap. The patient received 6000 cGy post operatively.
  • 75. Irradiation of existing implants- Backscatter Several months later and just after delivery of the tissue bar, the tissues on the labial surfaces of the implants dehisced and the bone overlying the implants sequestrated leading to loss of the implants.
  • 76. Irradiation of existing implants- Backscatter Following loss of the implants, the mucosa recovered the area. The graft remained viable and mandibular continuity was maintained.
  • 77. Irradiation of Existing Implants Options • Do nothing • Remove the prosthesis and close the wound (Granstrom et al, 1993) • Remove the bridge and place healing abutments on the implants (No data is available but our experience has led us to favor we favor this option)
  • 78. Irradiation of Existing Implants Remove the prosthesis and close the wound (Granstrom et al, 1993) In this patient the fixed partial denture was removed and the implants surgically buried beneath the mucosa. However they soon became exposed to the oral cavity
  • 79. Irradiation of Existing Implants Remove the bridge and replace with healing abutments  Minimizes backscatter Following completion of radiation therapy should we replace the bridge, tissue bar etc.? Factors to consider conside  Dose to bone anchoring the implants  Mandible vs maxilla  Target volume/fields  Chemoradiation or radiation alone  Hygiene access - Beware of posterior ridge laps  Patient compliance issues
  • 80. Irradiation of Existing Implants Remove the bridge and replace with healing abutments  Minimizes backscatter Following completion of radiation therapy should we replace the bridge, tissue bar etc.? Factors to consider conside Dose to bone anchoring the implants If the implants are located in the mandible and the dose t the implant sites exceeds 65 Gy the risk of ORN is significant and replacing the prosthesis may predispose to a high level of risk.
  • 81. Irradiation of Existing Implants Remove the bridge and replace with healing abutments  Minimizes backscatter Following completion of radiation therapy should we replace the bridge, tissue bar etc.? Factors to consider Mandible vs maxilla Since the risk of ORN in the maxilla is very low and the morbidity is minimal reinserting an implant retained prostheses in the maxilla carries very low risk.
  • 82. Irradiation of Existing Implants Remove the bridge and replace with healing abutments  Minimizes backscatter Following completion of radiation therapy should we replace the bridge, tissue bar etc.? Factors to consider conside Target volume/fields Implants sites out of the field of radiation when CRT is used receive virtually no radiation and implant sites beyond the clinical tumor volume when IMRT is used will receive lower dose. Therefore prostheses can be reinserted in these situations in both the mandible and maxilla with little or no risk of ORN.
  • 83. Irradiation of Existing Implants Remove the bridge and replace with healing abutments  Minimizes backscatter Following completion of radiation therapy should we replace the bridge, tissue bar etc.? Factors to consider conside Chemoradiation or radiation alone ChemoRT raise the BED (biologically equivalent dose by 700 – 1000 cGy. The implant sites are in the mandible and exposed to these dose levels replacement of the prosthesis may predispose to a high risk of developing an ORN
  • 84. Irradiation of Existing Implants Remove the bridge and replace with healing abutments  Minimizes backscatter Following completion of radiation therapy should we replace the bridge, tissue bar etc.? Factors to consider conside Hygiene access and patient compliance issues Beware of posterior ridge laps of fixed implant supported prostheses in the mandible in the marginally compliant patient. These patient are at high risk for periimplantitis and ORN.
  • 85. Irradiation of Existing Implants Remove the bridge and replace with healing abutments  Minimizes backscatter Following completion of radiation therapy should we replace the bridge, tissue bar etc.? Factors to consider conside In summary in the mandible if the BED (biologically equivalent dose) to the implant sites exceeds 6500 cGy we do not recommend placing the prosthesis back into position in most patients because compromised hygiene and the risk of a peri-implant soft tissue infection may lead to an osteoradionecrosis (see slide #56). In the maxilla and craniofacial sites the prosthesis can be reinserted with little risk to the patient.
  • 86. Placement of implants in patients to receive postoperative radiation. Should the clinician place these implants at the time of tumor ablation or wait until after the radiation treatments have been completed? We consider this issue from two perspectives: Quality of implant anchorage and prospects for long term success Risk of osteoradionecrosis
  • 87. Quality of implant anchorage and prospects for long term success This issue is debatable but from this perspective it is probably best to place implants at the time of tumor ablation. Given the bio-reactivity of the micro- rough or nano-enhanced surfaces the implants will become very well anchored in bone by 6 weeks – the period of time usually employed to allow the surgical wounds to heal prior to commencing postoperative radiation treatments. Admittedly the dose enhancement effect will render this bone nonvital and the implant anchorage becomes primarily mechanical. If one delays implant placement until radiation treatments are completed the postoperative doses used today (usually 60 Gy and above) will also render the anchoring bone relatively nonvital and the implant anchorage will also be primarily mechanical as opposed to biologic. The implant anchorage of the former will be considerably better than the later approach.
  • 88. Risk of osteoradionecrosis  In the mandible the risk of ORN secondary to dose enhancement may be significant  If there is the chance that the postop BED to mandibular implant sites will exceed 6500 cGy it is probably best to defer.
  • 89. Nano-enhanced and genetically engineered implant surfaces Will these phenomenon be clinically significant in the irradiated patient? Probably not. Anchorage is mechanical as opposed to biologic. The macro-surface topography, the quality of bone and the skill of the surgeon are the most critical factors. The major problem in the irradiated patient is loss of vasculature and fibrosis and with it the loss of osteoprogenitor cells (mesenchymal stem cells) in the marrow.
  • 90. Dental development  Levels as low as 2500 cGy effect tooth development (Gorlin and Meskin, 1963; Pietrokovski and Menczel, 1966; Dahllof et al, 1994; Kaste et al, 1994)  Changes reflect a variety of defects that indicate the several stages of development existing during the course of radiotherapy This patient is 16 years of age. He received 3600 cGy of radiation when he was 4 years of age for treatment of a rhabdomyosarcoma.
  • 91. Dental development  Levels as low as 2500 cGy effect tooth development (Gorlin and Meskin, 1963; Pietrokovski and Menczel, 1966; Dahllof et al, 1994; Kaste et al, 1994)  Changes reflect a variety of defects that indicate the several stages of development existing during the course of radiotherapy Are these patients candidates for implants? Yes! If t dose is below 4000 cGy.
  • 92. Early Radiation to the Enamel Organ Implant supported fixed partial denture This patient was irradiated as a young child for a rhabdomyosarcoma. She received slightly less than 40 Gy along with several courses of chemotherapy which arrested the development of her permanent dentition. Eventually all her teeth were lost or extracted and several implants were placed in the maxilla and mandible PFM fixed prostheses were then fabricated
  • 93.  Visit ffofr.org for hundreds of additional lectures on Complete Dentures, Implant Dentistry, Removable Partial Dentures, Esthetic Dentistry and Maxillofacial Prosthetics.  The lectures are free.  Our objective is to create the best and most comprehensive online programs of instruction in Prosthodontics
  • 94. Coming soon Implant Biomechanics and Treatment Planning in partially Edentulous Patients Abutment selection in partially edentulous patients Early and Immediate loading
  • 95. References  Garrett N. (2008) Outcomes of Maxillectomies with conventional and implant restorations. Presented at International Congress on Maxillofacial Rehabilitation Bangkok, Thailand September 24-27.  Garrett NR, Kapur K, Hamada M, et al. (1998) A randomized clinical trial comparing the efficacy of mandibular implant supported overdentures and conventional dentures in diabetic patients. Part II. Comparisons of masticatory performance. J Prosthet Dent 79:632-40.  Geertmen M, Slagter A, van Waas M et al. (1994) Comminution of food with mandibular implant-retained overdentures. J Dent Res 73:1858-64.  Geertmen M, Marinus A, van Waas M et al. (1996) Denture satisfaction in a comparative study of implant-retained mandibular overdentures: A randomized clinical trial. J Oral Maxillofac Implants 11:194-200.  Chang T, Garrett N, Roumanas E, et al. (2005) Treatment satisfaction with facial prostheses. J Prosthet Dent 94:275-80.  Jacobsson M, Tjellstrom A, Thomson P, et al. (1988) Integration of titanium implants in irradiated bone. Histologic and clinical study. Ann. Otol. Rhinol. Laryngol. 97:337-40.  Hum S, Larsen P. (1992) The effect of radiation at the titanium/bone interface. In: Tissue integration in oral, orthopedic and maxillofacial reconstruction. ed. by Laney, W. and Tolman, D. Quintessence Publishing Co. Chicago. pp.234-9.
  • 96. References  Nishimura R, Roumanas E, Sugai, T et al. (1996) Nasal defects and osseointegrated implants: UCLA experience. J Prosthet Dent 76:597-602.  Asikainen P, Kotilianinen R, Vuillemin, et al. (1993) Osseointegration of dental implants in radiated mandibles: An experimental study with beagle dogs. J Oral Implant 17:48-54.  Weinlander M, Beumer J, Kenney B, et al. (2006) Histomorphometric and fluorescence microscopic evaluation of interfacial bone healing around 3 different dental implants before and after radiation therapy. Int J Oral Maxillofac Implants 21:212-24.  Parel S, Tjellstrom A. (1991) The United States and Swedish experience with osseointegration and facial prostheses. Int J Oral Maxillofac Implants 6:675-9.  Roumanas E, Nishimura, R, Beumer J. (1994) Craniofacial defects and osseointegrated implants: Six year follow-up report on the success rates of craniofacial implants at UCLA. Int J Oral Maxillofac Implants 9:579-85.  Granstrom, G., Jacobsson, M., Tjellstrom, A. (1992) Titanium implants in irradiated tissue: Benefits from hyperbaric oxygen. Int J Oral Maxillofac Implants 7:15-25.  Granstrom G, Bergstrom K, Tjellstrom. (1994) A detailed analysis of fixture losses in irradiated tissue. Int J Oral and Maxillofac Implant 9:653-62
  • 97. References  Roumanas E, Nishimura R, Davis B, et al. (1997) Clinical evaluation of implants retaining edentulous maxillary obturator prostheses. J Prosth Dent 77:184-90.  Esser E, Wagner W. (1997) Dental implants following radical oral cancer surgery and adjuvant radiotherapy. Int J Maxillofac Implants 12:552-57.  Nimi A, Ueda M, Kaneda T. (1993) Maxillary obturator supported by osseointegrated implants placed in irradiated bone. Report of cases. J Oral Maxillofac Surg 51:804-9.  Nimi A, Ueda M, Kaneda T. (1998) Maxillary obturator supported by osseointegrated implants placed in irradiated tissues: A preliminary report. Int J Oral Maxillofac Implants 13:407.  Visch L, van Waas M, Schmitz P, et al. (2002) A clinical evaluation of implants in irradiated oral cancer patients. J Dent Res 81:856-59.  Roumanas E, Freymiller E, Chang T, et al. (2002) Implant retained prostheses for facial defects: An up to 14 year followup report on the survival rates of implants at UCLA. Int J Prosth 15:325-32.  Granstrom G. (2005) Osseointegration in irradiated cancer patiens: An analysis with respect to implant failures. J Oral Maxillofac Surg 63:579-85.
  • 98. References  Yerit K, Posch M, Seemann S, et al. (2006) Implant survival in mandibles or irradiated oral cancer patients. Clin Oral Impl Res 17:337-44.  Visser A. (2007) Aftercare of implant-retained facial prostheses. In Proceedings of Maxillofacial Rehabilitation-New technologies improve quality of life? University Medical Center, Groningen. Abstract #11.  Salinas TJ, Valmont PD, Katsnelson A, et al. (2010) Clinical evaluation of implants in radiated fibula free flaps. J Oral Maxillofac Surg 68:524-9.  Flood T, Downie I, Ethunandan M. (2009) Prosthetic reconstruction after rhinectomy-evolution of bone anchored epistheses and adjunctive surgical techniques in nasal reconstruction from one unit. (Presentation at the 2nd International Symposium. Bone Conduction Hearing-Craniofacial Osseointegration. June 11-13, 2009, Gothenburg, Sweden (Abstract O-24. pp 32).  Proops D, Worrollo S, Jeynes P et al. (2009) Head and neck reconstruction in adults-The Birmingham experience. (Presentation at the 2nd International Symposium. Bone Conduction Hearing-Craniofacial Osseointegration. June 11-13, 2009, Gothenburg, Sweden (Abstract O-22 pp 31).  Marx R. (1993) Preprosthetic surgery in a radiated cancer patient. (abstract # 61) In: Proceedings of the 5th International Congress on Preprosthetic Surgery. 15-18 April, Vienna: 75.
  • 99. References  Granstrom G. (2006) Placement of dental implants in irradiated bone: The case for using hyperbaric oxygen. J Oral Maxillofac Surg 64:812-18.  Dudziak M, Saadeh P, Mehara B et al. (2000) The effect of ionizing radiation on osteoblast-like cells in vitro. Plast Reconstr Surg 106:1049-61.  Donoff RB. (2006) Treatment of the irradiated patient with dental implants: The case against hyperbaric oxygen treatment. J Oral Maxillofac Surg 64:819-22.  Nishimura R, Roumanas E, Sugai T, et al. (1995) Auricular prostheses and osseointegrated implants: UCLA experience. J Prosthet Dent 73:553-58.  Nishimura R, Roumanas, E, Sugai T, et al. (1998) Osseointegrated implants and orbital implants: UCLA experience. J Prosthet Dent 79:304-9.  Kirk I, Gray W, Watson E. (1971) Cumulative radiation effect. Clin Radiol 22:145-55.  Schwartz H, Wollin M, Leake D, et al. (1979) Interface radiation dosimetry in mandibular reconstruction. Arch. Otolaryngol. 105:293-5.  Miam TA, Van Putten MC, Kramer DC et al. (1987) Backscatter radiation at bone titanium interface from high energy X and gamma rays. Int J Radiol Oncol Biol Phys 13:1943-47.  Granstrom G, Tjellstrom A, Albrektsson T: (1995) Post implant irradiation of osseointegrated implants. In proceedings of the First International Congress on Maxillofacial Prosthetics. Eds Zlotolow I, Esposito S, Beumer J. pp 292-6.
  • 100. The End Thank you for your kind attention

Hinweis der Redaktion

  1. Dental Management of the Irradiated Patient
  2. Among the 46 subjects we had 14 subjects who complete all the treatment procedure and data collection. The mean masticatory performance prior the surgery on the defect side was 22.6% and 38.6% on the non-defect side, then decreased to 7.8% and 25.3% postsurgically. Restoration with the conventional prosthesis significantly improved performance to 20% on the defect side and 32% on the non-defect side. Following treatment with the implant-supported prosthesis masticatory performance improved significantly to 31.4% on the defect side and 39.5% on the non-defect side. At the entry level the MP was 22and38% very low