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Presented by: R. Sailesh Kumar (PG Trainee)
Definition of Osteoradionecrosis
 ‘Irradiated bone becomes devitalised
and exposed through the overlying
skin or mucosa, persisting without
healing for 3 months in the absence
of tumor recurrence’
(Harris M. The conservative management of osteoradionecrosis of the mandible with ultrasound therapy.
Br J Oral Maxillofac Surg 1992;30:313e318)
Definition
 “When bone in the radiation field is exposed for at least 2 months in the absence of
local neoplastic disease”, (BEUMER)
 “An area greater than 1 cm of exposed bone in a field of irradiation that fails to show
any evidence of healing for at least 6 months” (MARX)
 “An area of exposed mandible present for longer than 2 months in a previously
irradiated field, in the absence of recurrent tumor” (HUTCHINSON)
 Ulceration of the mucous membrane with exposure of necrotic bone (EPSTEIN)
History
 Regaud published the first report on ORN of the jaw after radiotherapy
in 1922
 Ewing reported in 1926 on the bone changes associated with radiation
therapy and described this disease state as “radiation osteitis”
ORN has also been described as
Radiation osteitis,
Radio-osteonecrosis,
Radiation osteomyelitis,
Osteomyelitis of irradiated bone,
Osteonecrosis,
Radio-osteomyelitis,
Septic osteoradionecrosis,
Post-radiotherapy osteonecrosis
Clinical Features of ORN
Symptoms
• Pain
• Trismus
• Dysesthesia.
Clinical signs
• Ulceration and/or necrosis of the oral mucosa
• Exposure of underlying bone
• Malodor
• In advanced stages
• Ulceration of overlying skin
• Pathologic fracture
Hypotheses for the development of ORN
1. Watson and Scarboroughfirst described the sequence of radiation exposure, local injury, and infection as a
possible cause, and this hypothesis was further popularized by Meyer
2. Marx (1983)described the “Three-H” hypothesis: wherein the area shows a
Hypocellular, Hypoxic, and Hypovascular state
3. Suppression of osteoclast mediated bone turnover, wherein irradiation-induced loss of osteoclast
function results in the clinical features described earlier.
4. Delanian and Lefaix proposed a fourth hypothesis of fibroatrophic bone change in 2004
PATHOGENESIS
Classifications of ORN
MARX
(1983)
Staging ORN based on response to treatment
STAGE DESCRIPTION
I Exposed alveolar bone without pathologic fracture,
which responds to hyperbaric oxygen therapy
II Disease does not respond to HBOT, and requires
sequestrectomy and saucerization
III Full thickness bone damage or pathologic fracture, usually requires
complete resection and reconstruction with free tissue
Epstein et al
(1987)
NOTANI et al (2003)
Notani K, Yamazaki Y, Kitada H, Sakakibara N, Fukuda H, Omori K, Nakamura M. Management of mandibular osteroradionecrosis corresponding to
the severity of osteoradionecrosis and the method of radiotherapy. Head Neck 2003: 25: 181–186.
GRADE DESCRIPTION
I ORN confined to alveolar bone
II ORN limited to the alveolar bone and/or mandible above
the level of the inferior alveolar canal
III ORN involving the mandible below the level of the inferior
alveolar canal and/or skin fistula and/or pathological fracture
Characteristics:
• Irradiated bone becomes devitalized and
exposed through the overlying skin or
mucosa without healing for 3months,
without recurrence of tumor
• Most case happen in mandible
• 70-94% of cases developed within the
first 3 years after radiotherapy
Risk Factors
• Hyperfractionated irradiation regimen - High total
dose (6000-7000cGy)
• Recent reports have suggested that when
chemotherapy is added to radiotherapy the incidence
of ORN may be increased
• Pre-irradiation and post-irradiation dental extractions
• Poor oral hygien with periodontal disease
• Tobacco and alcohol use
Conservative Treatment:
• Improve Oral hygiene
• Minimal surgical debridement
• HBOT
• Use of Pentoxifyline and Tocopherol
Surgical Treatment:
• Sequestrectomy
• Saucerization
• Segmental resection
• Free flap reconstruction
Journal for Discussion
Objective
To evaluate the outcome of the surgical treatment of
osteonecrosis of the jaw (ONJ) with the additional use of
autologous membranes of platelet-rich fibrin (PRF).
 The study used leucocyte-rich and platelet-rich fibrin (L-PRF), which is prepared
without the addition of chemicals.
 It can be prepared in the form of membranes with physical properties that
allow it to be handled and layered to cover the bone
 This study was done to evaluate the outcome of surgical treatment of ONJ with
the use of L-PRF
Platelet rich fibrin (PRF)
Platelet rich fibrin (PRF) is a fibrin
matrix in which platelet cytokines,
growth factors, and cells are trapped
and may be released after a certain
time and that can serve as a
resorbable membrane
PDGF, TGF-B1, VEGF, EGF, IGF-1 are
growth factors released from PRF (in 5
hours of placement)
• Promote wound healing,
• Bone regeneration,
• Graft stabilization,
• Wound sealing,
• Hemostasis.
Uses of
PRF
Advantages of PRF
 It is an autogenous material with an inherent strength to support growth
factors for timely and optimum release.
 It is user-friendly and economical, and has huge potential to be used
routinely to reduce postoperative discomfort.
Advantages of PRF
 It may also be used to hasten natural healing in immuno-compromised
patients, those taking drugs that interfere with natural healing, and those
with a history of radiotherapy.
 As minimal cost is involved, it can be used for all types of patients.
Diagnosis of ONJ and planning of treatment
 Patient’s history and physical and oral examinations, as well as the
necessary radiological examination (OPG, CBCT)
 Detailed information was obtained on the patients’ medical history
including anti-resorptive drug treatment and any concomitant
medications.
Treatment Plan
 Oral or IV antibiotics were administered based on LA / GA administration,
the day before the surgery
 The standard antibiotic regime was
 2 MIU(Million International Units) / 1200mg penicillin and 1 g metronidazole
preoperatively,
 Followed by 1 MIU/ 600mg penicillin four times a day for 4 weeks and 0.5 g
metronidazole twice a day for 5 days.
 Clindamycin 600 mg three times a day was used in the case of an allergy to penicillin.
PRF collection method
The L-PRF was prepared from blood samples collected before
surgery from the cubital vein in 10-ml tubes with no
anticoagulants
 The samples were centrifuged at 1300 rpm for 14 min using
the L-PRF
Centrifuge immediately - avoids the natural coagulation
process.
 When using eight tubes, centrifugation was started once the first four
tubes had been filled and was restarted after the last four tubes had
been obtained.
 After centrifugation, the tubes were placed vertically in a rack to
allowing the blood to clot for 10–15 min.
Lastly, the fibrin clots in the middle of the tubes were
transferred to the surgical table to be put under gentle
pressure for a few minutes, after which they were ready for
use as membranes with a size of approximately 10 mm x 20
mm x 2 mm
Surgical Procedure
 The surgical procedure included elevation of a mucoperiosteal flap mobilized
to facilitate tension-free closure.
 Necrotic bone was removed with a piezoelectric device or with rotating burs
and the bone surface was smoothened to remove any sharp edges.
 The extent of the resection was based on the preoperative radiological findings
and perioperative appearance of the bone at the resected surface.
Sequestration
Exposure of the necrosed bone
Mucoperiosteal flap closure
Saucerisation
Post OP
PRF membrane placement
 Multiple layers of the PRF membranes - used to cover the bony surfaces.
 A buccal fat pad was mobilized to help cover the bony defect in five patients.
 The mucoperiosteal flap was adapted and a tension-free closure with 5–0
resorbable sutures was performed.
 Postoperatively, the use of any dentures was not allowed for the first 2
weeks
 A soft diet was prescribed for 2 weeks and mouth rinse with 0.12%
chlorhexidine was used for 2 weeks.
 Follow up to be done for - 6 months postoperatively
 Outcome - complete mucosal healing and no symptoms from the jaw
Discussion
 The use of PRF membranes seemed to work as an adjunct measure in
the present study, providing multilayered coverage of the bone surface
and strengthening the efforts made to obtain an intact mucosa.
 In addition to the physical properties of the membranes, PRF has been
shown to contain growth factors and leukocytes, which tend to stimulate
the healing process.
 The buccal fat pad is an attractive pedicled flap for use in covering
defects in the posterior part of the maxilla or mandible.
 However, the use of this flap is not always applicable, and other
techniques including mobilization of the soft tissue, local flaps, and tissue
transfer to ensure a complete soft tissue cover have been described
Result of the Study
 TOTAL sample : 15 patients (11 females and 4 males)
 Mean age - 68.5 years (range 54–83 years).
 Follow-up - 7 to 20 months.
 Site : Maxilla- 11 patients
Mandible- 3, both- 1
 The development of ONJ –
 Dental extraction in 11 patients,
 Pressure from a prosthesis in 3 patients, and
 Spontaneous in 1 patient.
 A buccal fat pad was mobilized to add a layer in the coverage of the
bony lesion in five patients; three of these lesions were in the maxilla and
two in the posterior mandible.
 Eight patients had malignant disease and were treated with high-dose
anti-resorptive drugs; seven patients with osteoporosis were treated with
low-dose anti-resorptive drugs.
 The mean duration of high-dose anti-resorptive drug treatment was 34
months (range 15–73 months); for low-dose treatment, the mean duration
was 126 months (range 48–240 months).
Outcome of treatment
 The outcome of the surgical treatment was successful in 14 of the 15 patients (93%).
 One patient had recurrence of the exposed bone.
 This patient had been treated with high-dose anti-resorptive drugs and had bilateral
involvement of the mandible.
 At the latest follow-up, the bone was exposed but without signs of infection.
 The patient had cancer and died 14 months after the jaw resection.
Merits
 Benefits of this approach are
The relief from symptoms such as pain, sharp edges, odour, swelling, etc.,
 The avoidance of recurrent infections, and the prevention of a more
extensive osteonecrotic lesion
 Usage of L-PRF is economical , can be taken from patient.
Critical Analysis
 The design of the present study does not allow for conclusive statements
regarding the association between the use of PRF membranes and a successful
outcome;
 A study with a randomized design is required to elucidate this further.
 Comparitive study analysis with other modes of management of ORN would
provide details of which treatment is better
Conclusion of the Study
 The surgical treatment of ONJ with the use of PRF membranes provides
multilayered closure.
 Availability of PRF is easy and economical.
 Benefits the patient with reduced post operative complications and
better healing
Radiation therapy and Dental Extractions
 Atraumatic extraction is preferred in irradiated patients; its done by limited
mucoperiosteal disruption and minimal bone injury.
 If one has to consider dental extraction after R/T,
 An extraction time less than 6 months after R/T or during the period of head and neck R/T
and
 Extraction tooth number fewer than 5 teeth
 These considerations would significantly lower the ORNJ prevalence.
Jaw osteoradionecrosis and dental extraction after head and neck radiotherapy: A nationwide population-based retrospective study in
Taiwan , Tsu-Jen Kuo et al, Oral Oncology 56 (2016) 71–77
References
 Nørholt SE, Hartlev J. Surgical treatment of osteonecrosis of the jaw with the use of platelet-rich
fibrin: a prospective study of 15 patients, Int J Oral Maxillofac Surg (2016)
 Brad.W. Neville, Carl M.Allen et al Textbook of Oral & maxillofacial pathology 2nd edition (2002)
 Pharmacologic Modalities in the Treatment of Osteoradionecrosis of the Jaw James Anthony
McCaul, PhD, FRCS(OMFS), FRCS, FDSRCPS. Oral Maxillofacial Surg Clin N Am 26 (2014) 247–252
 Kumar YR, et al. Platelet-rich fibrin: the benefits. Br J Oral Maxillofac Surg (2015),
 Jaw osteoradionecrosis and dental extraction after head and neck radiotherapy: A nationwide
population-based retrospective study in Taiwan , Tsu-Jen Kuo et al, Oral Oncology 56 (2016) 71–
77
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Osteoradionecrosis

  • 1. Presented by: R. Sailesh Kumar (PG Trainee)
  • 2. Definition of Osteoradionecrosis  ‘Irradiated bone becomes devitalised and exposed through the overlying skin or mucosa, persisting without healing for 3 months in the absence of tumor recurrence’ (Harris M. The conservative management of osteoradionecrosis of the mandible with ultrasound therapy. Br J Oral Maxillofac Surg 1992;30:313e318)
  • 3. Definition  “When bone in the radiation field is exposed for at least 2 months in the absence of local neoplastic disease”, (BEUMER)  “An area greater than 1 cm of exposed bone in a field of irradiation that fails to show any evidence of healing for at least 6 months” (MARX)  “An area of exposed mandible present for longer than 2 months in a previously irradiated field, in the absence of recurrent tumor” (HUTCHINSON)  Ulceration of the mucous membrane with exposure of necrotic bone (EPSTEIN)
  • 4. History  Regaud published the first report on ORN of the jaw after radiotherapy in 1922  Ewing reported in 1926 on the bone changes associated with radiation therapy and described this disease state as “radiation osteitis”
  • 5. ORN has also been described as Radiation osteitis, Radio-osteonecrosis, Radiation osteomyelitis, Osteomyelitis of irradiated bone, Osteonecrosis, Radio-osteomyelitis, Septic osteoradionecrosis, Post-radiotherapy osteonecrosis
  • 6. Clinical Features of ORN Symptoms • Pain • Trismus • Dysesthesia. Clinical signs • Ulceration and/or necrosis of the oral mucosa • Exposure of underlying bone • Malodor • In advanced stages • Ulceration of overlying skin • Pathologic fracture
  • 7. Hypotheses for the development of ORN 1. Watson and Scarboroughfirst described the sequence of radiation exposure, local injury, and infection as a possible cause, and this hypothesis was further popularized by Meyer 2. Marx (1983)described the “Three-H” hypothesis: wherein the area shows a Hypocellular, Hypoxic, and Hypovascular state 3. Suppression of osteoclast mediated bone turnover, wherein irradiation-induced loss of osteoclast function results in the clinical features described earlier. 4. Delanian and Lefaix proposed a fourth hypothesis of fibroatrophic bone change in 2004
  • 10. MARX (1983) Staging ORN based on response to treatment STAGE DESCRIPTION I Exposed alveolar bone without pathologic fracture, which responds to hyperbaric oxygen therapy II Disease does not respond to HBOT, and requires sequestrectomy and saucerization III Full thickness bone damage or pathologic fracture, usually requires complete resection and reconstruction with free tissue
  • 12. NOTANI et al (2003) Notani K, Yamazaki Y, Kitada H, Sakakibara N, Fukuda H, Omori K, Nakamura M. Management of mandibular osteroradionecrosis corresponding to the severity of osteoradionecrosis and the method of radiotherapy. Head Neck 2003: 25: 181–186. GRADE DESCRIPTION I ORN confined to alveolar bone II ORN limited to the alveolar bone and/or mandible above the level of the inferior alveolar canal III ORN involving the mandible below the level of the inferior alveolar canal and/or skin fistula and/or pathological fracture
  • 13. Characteristics: • Irradiated bone becomes devitalized and exposed through the overlying skin or mucosa without healing for 3months, without recurrence of tumor • Most case happen in mandible • 70-94% of cases developed within the first 3 years after radiotherapy
  • 14. Risk Factors • Hyperfractionated irradiation regimen - High total dose (6000-7000cGy) • Recent reports have suggested that when chemotherapy is added to radiotherapy the incidence of ORN may be increased • Pre-irradiation and post-irradiation dental extractions • Poor oral hygien with periodontal disease • Tobacco and alcohol use
  • 15. Conservative Treatment: • Improve Oral hygiene • Minimal surgical debridement • HBOT • Use of Pentoxifyline and Tocopherol Surgical Treatment: • Sequestrectomy • Saucerization • Segmental resection • Free flap reconstruction
  • 17. Objective To evaluate the outcome of the surgical treatment of osteonecrosis of the jaw (ONJ) with the additional use of autologous membranes of platelet-rich fibrin (PRF).
  • 18.  The study used leucocyte-rich and platelet-rich fibrin (L-PRF), which is prepared without the addition of chemicals.  It can be prepared in the form of membranes with physical properties that allow it to be handled and layered to cover the bone  This study was done to evaluate the outcome of surgical treatment of ONJ with the use of L-PRF
  • 19. Platelet rich fibrin (PRF) Platelet rich fibrin (PRF) is a fibrin matrix in which platelet cytokines, growth factors, and cells are trapped and may be released after a certain time and that can serve as a resorbable membrane PDGF, TGF-B1, VEGF, EGF, IGF-1 are growth factors released from PRF (in 5 hours of placement)
  • 20. • Promote wound healing, • Bone regeneration, • Graft stabilization, • Wound sealing, • Hemostasis. Uses of PRF
  • 21. Advantages of PRF  It is an autogenous material with an inherent strength to support growth factors for timely and optimum release.  It is user-friendly and economical, and has huge potential to be used routinely to reduce postoperative discomfort.
  • 22. Advantages of PRF  It may also be used to hasten natural healing in immuno-compromised patients, those taking drugs that interfere with natural healing, and those with a history of radiotherapy.  As minimal cost is involved, it can be used for all types of patients.
  • 23. Diagnosis of ONJ and planning of treatment  Patient’s history and physical and oral examinations, as well as the necessary radiological examination (OPG, CBCT)  Detailed information was obtained on the patients’ medical history including anti-resorptive drug treatment and any concomitant medications.
  • 24. Treatment Plan  Oral or IV antibiotics were administered based on LA / GA administration, the day before the surgery  The standard antibiotic regime was  2 MIU(Million International Units) / 1200mg penicillin and 1 g metronidazole preoperatively,  Followed by 1 MIU/ 600mg penicillin four times a day for 4 weeks and 0.5 g metronidazole twice a day for 5 days.  Clindamycin 600 mg three times a day was used in the case of an allergy to penicillin.
  • 25. PRF collection method The L-PRF was prepared from blood samples collected before surgery from the cubital vein in 10-ml tubes with no anticoagulants  The samples were centrifuged at 1300 rpm for 14 min using the L-PRF Centrifuge immediately - avoids the natural coagulation process.
  • 26.  When using eight tubes, centrifugation was started once the first four tubes had been filled and was restarted after the last four tubes had been obtained.  After centrifugation, the tubes were placed vertically in a rack to allowing the blood to clot for 10–15 min.
  • 27. Lastly, the fibrin clots in the middle of the tubes were transferred to the surgical table to be put under gentle pressure for a few minutes, after which they were ready for use as membranes with a size of approximately 10 mm x 20 mm x 2 mm
  • 28. Surgical Procedure  The surgical procedure included elevation of a mucoperiosteal flap mobilized to facilitate tension-free closure.  Necrotic bone was removed with a piezoelectric device or with rotating burs and the bone surface was smoothened to remove any sharp edges.  The extent of the resection was based on the preoperative radiological findings and perioperative appearance of the bone at the resected surface.
  • 31.  Multiple layers of the PRF membranes - used to cover the bony surfaces.  A buccal fat pad was mobilized to help cover the bony defect in five patients.  The mucoperiosteal flap was adapted and a tension-free closure with 5–0 resorbable sutures was performed.
  • 32.  Postoperatively, the use of any dentures was not allowed for the first 2 weeks  A soft diet was prescribed for 2 weeks and mouth rinse with 0.12% chlorhexidine was used for 2 weeks.  Follow up to be done for - 6 months postoperatively  Outcome - complete mucosal healing and no symptoms from the jaw
  • 33. Discussion  The use of PRF membranes seemed to work as an adjunct measure in the present study, providing multilayered coverage of the bone surface and strengthening the efforts made to obtain an intact mucosa.  In addition to the physical properties of the membranes, PRF has been shown to contain growth factors and leukocytes, which tend to stimulate the healing process.
  • 34.  The buccal fat pad is an attractive pedicled flap for use in covering defects in the posterior part of the maxilla or mandible.  However, the use of this flap is not always applicable, and other techniques including mobilization of the soft tissue, local flaps, and tissue transfer to ensure a complete soft tissue cover have been described
  • 35. Result of the Study  TOTAL sample : 15 patients (11 females and 4 males)  Mean age - 68.5 years (range 54–83 years).  Follow-up - 7 to 20 months.  Site : Maxilla- 11 patients Mandible- 3, both- 1
  • 36.  The development of ONJ –  Dental extraction in 11 patients,  Pressure from a prosthesis in 3 patients, and  Spontaneous in 1 patient.  A buccal fat pad was mobilized to add a layer in the coverage of the bony lesion in five patients; three of these lesions were in the maxilla and two in the posterior mandible.
  • 37.  Eight patients had malignant disease and were treated with high-dose anti-resorptive drugs; seven patients with osteoporosis were treated with low-dose anti-resorptive drugs.  The mean duration of high-dose anti-resorptive drug treatment was 34 months (range 15–73 months); for low-dose treatment, the mean duration was 126 months (range 48–240 months).
  • 38. Outcome of treatment  The outcome of the surgical treatment was successful in 14 of the 15 patients (93%).  One patient had recurrence of the exposed bone.  This patient had been treated with high-dose anti-resorptive drugs and had bilateral involvement of the mandible.  At the latest follow-up, the bone was exposed but without signs of infection.  The patient had cancer and died 14 months after the jaw resection.
  • 39. Merits  Benefits of this approach are The relief from symptoms such as pain, sharp edges, odour, swelling, etc.,  The avoidance of recurrent infections, and the prevention of a more extensive osteonecrotic lesion  Usage of L-PRF is economical , can be taken from patient.
  • 40. Critical Analysis  The design of the present study does not allow for conclusive statements regarding the association between the use of PRF membranes and a successful outcome;  A study with a randomized design is required to elucidate this further.  Comparitive study analysis with other modes of management of ORN would provide details of which treatment is better
  • 41. Conclusion of the Study  The surgical treatment of ONJ with the use of PRF membranes provides multilayered closure.  Availability of PRF is easy and economical.  Benefits the patient with reduced post operative complications and better healing
  • 42. Radiation therapy and Dental Extractions  Atraumatic extraction is preferred in irradiated patients; its done by limited mucoperiosteal disruption and minimal bone injury.  If one has to consider dental extraction after R/T,  An extraction time less than 6 months after R/T or during the period of head and neck R/T and  Extraction tooth number fewer than 5 teeth  These considerations would significantly lower the ORNJ prevalence. Jaw osteoradionecrosis and dental extraction after head and neck radiotherapy: A nationwide population-based retrospective study in Taiwan , Tsu-Jen Kuo et al, Oral Oncology 56 (2016) 71–77
  • 43. References  Nørholt SE, Hartlev J. Surgical treatment of osteonecrosis of the jaw with the use of platelet-rich fibrin: a prospective study of 15 patients, Int J Oral Maxillofac Surg (2016)  Brad.W. Neville, Carl M.Allen et al Textbook of Oral & maxillofacial pathology 2nd edition (2002)  Pharmacologic Modalities in the Treatment of Osteoradionecrosis of the Jaw James Anthony McCaul, PhD, FRCS(OMFS), FRCS, FDSRCPS. Oral Maxillofacial Surg Clin N Am 26 (2014) 247–252  Kumar YR, et al. Platelet-rich fibrin: the benefits. Br J Oral Maxillofac Surg (2015),  Jaw osteoradionecrosis and dental extraction after head and neck radiotherapy: A nationwide population-based retrospective study in Taiwan , Tsu-Jen Kuo et al, Oral Oncology 56 (2016) 71– 77

Editor's Notes

  1. 1 IU = 0.6 microgram of penicillin 1 MIU = 600 mg of penicillin 2 MIU = 1200mg of penicillin