Osteonecrosis of the jaw is a rare complication that has been associated with the use of bisphosphonates. A 77-year-old patient presented in April 2013 asking for a consultation. She reported that in May 2009, she underwent an implant rehabilitation with 8 implants and an immediately loaded fixed prosthesis in the maxilla. After a few months the patient started to report pain and purulent secretions that were neglected by the clinician for several years. She decided to refer to the Dental Clinic after another acute pain episode. Once the fixed prosthesis was removed, exposed necrotic bone was found in relation to the implants. The patient reported having taken oral alendronic acid to treat osteoporosis since before 2006. The patient underwent a functional endoscopic sinus surgery and a removal of necrotic bone blocks. Three years of follow-up showed healed tissues with no recurrence, although the alveolar crest appeared irregular on radiographs.

Introduction

As with any surgery, oral surgery needs careful assessment of the medical conditions of the patients, such as disease and drug consumption.1 

Bisphosphonates (BP) are potent inhibitors of bone resorption and are mainly used in the treatment of diseases affecting bone metabolism such as osteoporosis and Paget's disease, but also for the treatment of malignant tumors.2,3  BP suppressing the activity of osteoclasts prevent complications such as pathological fractures, pain, and malignant hypercalcemia. Numerous studies have clearly shown positive effects on bone mass and a significant reduction of the risk of fracture using antiremodeling agents currently approved for osteoporosis.3 

In the literature, incidence of BP-related osteonecrosis of the jaws (BRONJ) in patients receiving intravenous BPs is 0–10% compared to <1% of incidence in patients treated with oral somministration.4  Most of BRONJ reported cases are associated with invasive dental procedures. However, a recent systematic review5  reveals a low rate of BRONJ after implant surgery.

Patients affected by BRONJ may suffer from a nonhealing extraction socket or exposed jaw bone, associated with swelling of oral and perioral tissues, pain, bleeding, persistent purulent discharge and draining fistulas, bone sequestrum formation, severe halitosis, lower lip paresthesia, mobility, and loosening of teeth.6  These lesions can evolve into an osteomyelitis with purulent material often containing Actinomyces. Radiographic examination may show regions of mottled bone.3 

The treatment for this condition is usually a combination of antibiotic therapy and surgical intervention to remove the necrotic bone.

The present article present a case of extensive BRONJ following implant placement in a patient undergoing oral BP therapy for osteoporosis.

Case Presentation

Patient history

In April 2013, a 77-year-old Caucasian female presented to the Dental Clinic of the University of Milan, Ospedale Santi Paolo e Carlo in Milan asking for a medical opinion about long-lasting problems on her fixed implant rehabilitation. The patient was not a smoker.

The patient presented a fixed Toronto bridge prosthesis that was inserted the day after the surgery with an immediate loading protocol in 2009. The patient reported that no computerized tomography (CT) scan was performed prior to the surgery and that all treatment was planned and provided on the basis of an orthopantomogram (OPG).

Three months after the surgery (Figure 1), the patient started to report occasional acute pain, manifested purulent secretions from the tissues around the implants, and repeated sinusitis episodes. The clinician kept denying that there were some problems with the implants and the rehabilitation. After 4 years, the patient, displeased with the clinician's response, sought a consultation.

Figures 1–3

Figure 1. Orthopantomogram of the patient immediately after the implant placement and the immediate loading in 2009. Figure 2. Intraoral frontal photograph of the patient at the time of the first consultation at S. Paolo Hospital, Milan in 2013. Figure 3. Intraoral radiographic status of the patient during the consultations in 2013.

Figures 1–3

Figure 1. Orthopantomogram of the patient immediately after the implant placement and the immediate loading in 2009. Figure 2. Intraoral frontal photograph of the patient at the time of the first consultation at S. Paolo Hospital, Milan in 2013. Figure 3. Intraoral radiographic status of the patient during the consultations in 2013.

Patient medical history

The patient's medical history includes various diseases: atrial fibrillation, hypothyroidism, hypercholesterolemia, hypertension, and osteoporosis treated respectively with levothyroxine, 50 mg once a day; simvastatin, 20 mg once a day; bisoprolol fumarate, 1.25 mg; and valsartan, 80 mg once a day. The patient remembered to have used alendronic acid (70 mg tablets) with the addition of vitamin D3 once a week. She started the BP approximately 3 years before implant therapy. In 2009–2010 her physician autonomously changed medication in favor of vitamin D only. It was not possible to contact the physician to have exact dates.

Patient status

At the time of our visit, there were signs of generalized inflammation of the soft tissues (Figure 2). The peri-implant tissues were inflamed and there was bleeding on probing in several sites (Table). The patient presented with normal body temperature that remained stable during the whole treatment process. The radiographic examination showed a bone resorption <2 mm around the implants. No clear signs of peri-implant radiolucency nor bone anomalies were visible (Figure 3).

Table

Probing depth, bleeding on probing, purulent secretions and mobility of dental implant before the surgery, and removal torque of the implant during the surgery*

Probing depth, bleeding on probing, purulent secretions and mobility of dental implant before the surgery, and removal torque of the implant during the surgery*
Probing depth, bleeding on probing, purulent secretions and mobility of dental implant before the surgery, and removal torque of the implant during the surgery*

The patient underwent a cone-beam CT scan, which showed that the apex of 3 implants were positioned into the maxillary sinus with a thickening of the internal mucosa (Figure 4a through c).

Figure 4

(a–c) CT scan images showing no bone alterations and the position of the apex of the posterior implants directly inside the maxillary sinus with bilateral sinusitis.

Figure 4

(a–c) CT scan images showing no bone alterations and the position of the apex of the posterior implants directly inside the maxillary sinus with bilateral sinusitis.

Once the fixed prosthesis was removed, purulent secretions and exposition of necrotic bone was detected between the implants in positions 25 and 26 (Figure 5). The implant in the upper left first molar showed a third-grade mobility and was immediately removed atraumatically without the need of local anesthesia.

Figures 5–13

Figure 5. Intraoral photo of the maxilla of the patient after removing the prosthesis. Around the implants there is erythematous tissue, purulent secretion, and exposed necrotic bone between implants 24 and 25. Figure 6. In area 24-25 implants appeared to be surrounded by necrotic bone. Full-thickness flaps were raised to expose the sequestered maxillary bone. Figure 7. The necrotic bone was isolated and separated by the maxillary bone using a burr. Figure 8. A portion of 2 × 1 cm of necrotic bone war removed from the left maxillae bone in area 24-25. Figure 9. Implants in the pre-maxilla were unscrewed with a specific instrument. Implant in position 12 fractured during removal. Figure 10. The 2 flaps were sutured and an antibiotic and analgesia therapy was prescribed. Figure 11. All implants were extracted from the maxillae bone of the patient and two blocks of 2 × 1 cm and 1 × 1 cm of necrotic bone were removed, as well as many other particles. Figure 12. Intraoral image of the healed crests at 3 year after the surgery. It is possible to acknowledge the amount of bone loss. Figure 13. OPG at 3 years showing the amount of bone loss faced by the patient.

Figures 5–13

Figure 5. Intraoral photo of the maxilla of the patient after removing the prosthesis. Around the implants there is erythematous tissue, purulent secretion, and exposed necrotic bone between implants 24 and 25. Figure 6. In area 24-25 implants appeared to be surrounded by necrotic bone. Full-thickness flaps were raised to expose the sequestered maxillary bone. Figure 7. The necrotic bone was isolated and separated by the maxillary bone using a burr. Figure 8. A portion of 2 × 1 cm of necrotic bone war removed from the left maxillae bone in area 24-25. Figure 9. Implants in the pre-maxilla were unscrewed with a specific instrument. Implant in position 12 fractured during removal. Figure 10. The 2 flaps were sutured and an antibiotic and analgesia therapy was prescribed. Figure 11. All implants were extracted from the maxillae bone of the patient and two blocks of 2 × 1 cm and 1 × 1 cm of necrotic bone were removed, as well as many other particles. Figure 12. Intraoral image of the healed crests at 3 year after the surgery. It is possible to acknowledge the amount of bone loss. Figure 13. OPG at 3 years showing the amount of bone loss faced by the patient.

After careful evaluation of the patient's medical history and consultation of an otolaryngologist, it was suggested to proceed with a functional endoscopic sinus surgery (FESS) and the removal of all hopeless implants under general anesthesia.

Surgical approach

The FESS procedure8  started with a partial bilateral middle turbinectomy and was followed by inferior uncinectomy and left anterior ethmoidectomy owing to the presence of hyperplastic mucosa. At the first inspection through the natural ostium, the sinus mucosa presented a hyperplastic and hypertrophic reaction with an abnormal yellowish color. The internal mucosa was removed and the sinus was rinsed with abundant saline solution.

Intraorally, necrotic sequestered bone blocks of 2 × 1 cm and 1 × 1 cm in size were removed respectively in area 14/16 and 25 (Figures 6 through 8). The necrotic bone in area 14/16 was not exposed but dimensionally larger than the exposed one in area 25. Subsequently the surrounding bone was scraped and widely washed with sterile saline solution followed by antibiotic solution (rifampicin, 90 mg).

The 7 remaining implants were unscrewed and removed with a dedicated instrument (Implant Removal Kit, Biomet 3i, Palm Beach, Fla) (Figure 9) . The removal torque was around 10 Ncm for implants in position 16, 14, 23, 25, and 25 Ncm for implant in position 22. The implant in position 12 had a torque >55 Ncm and fractured during removal. The flaps were sutured for primary closure using a monofilament nylon suture 4/0 (Figures 10 and 11).

An antibiotic therapy was prescribed (amoxicillin + clavulanic acid 1g 1×2×6 in association with metronidazole and mouth rinse with chlorhexidine mouth rinse 0.2% 1×2×15). The postoperative healing was normal and the sutures were removed 7 days later. After another 20 days the patient was rehabilitated with a removable complete prosthesis that needed extensive soft relining due to the great amount of removed bone. After 3 years, the patient is still rehabilitated with a removable complete denture and presented with completely healed tissues (Figures 12 and 13).

Discussion

Since the start of dental implant use, the patient's medical history was taken into strong consideration. Drugs like BPs have risen the attention of the international community since 2003, when cases of BRONJ started to be reported.1 

Intravenous administration of these medications have been associated with an higher incidence of ONJ (0.88%–1.15%) rather than oral administration (0.01%–0.04%).4,5,9 

Hansen et al11  reported that the incidence of BRONJ in patients in therapy with oral BP was calculated to be about 2.27%, but that the prevalence was more than half of those taking intravenous BP.

BRONJ is more frequent in the mandible (about 65%); involvement of the maxilla has been reported in about 26% of the cases, while in about 9% of cases, both the mandible and maxilla are involved.12  Radiographic images of advanced stages of BRONJ often reveal severe osteolysis, sequestra, and fractures.12  The literature considers the placement of an implant a safe procedure in patients taking oral BPs for <5 years. Current guidelines contraindicate the placement of dental implants in cancer patients treated with intravenous BPs.13 

Current American Association of Oral and Maxillofacial Surgeons (AAOMS) guidelines recommend 3 to 6 months of drug cessation before dental implant placement in patients with a history of oral BP use longer than 3 years, but there are no studies proving its efficacy.5,14 

Although failure of similar implant rehabilitations has been documented in the literature, such a dramatic outcome could be more easily referred to BRONJ rather than other causes (ie, primary implant failure, overload, overtorque, and so forth). The treatment applied to the patient is described in the literature as a possibile solution in edentulous patients.15  It must be pointed out that the surgeon who treated the patient with implants did not consider BP as a risk factor in implant placement. Also, he did not recognize that the patient was developing such an advanced osteonecrosis: He underestimated the problem, telling the patient that everything was going well and treating the patient with only systemic antibiotics. At the time of our visit, the patient, by contrast, experienced a Stage 3 BRONJ (AAOMS revised staging system),7  which comprised the presence of exposed necrotic bone.

It must be said that such a dramatic picture was not visible on radiographic exams; no bone lesion was visible on intraoral X ray or on the CT scan. The CT scan showed that 3 implants were partially inserted in the sinus. The sinus pathology could be related to the presence of the implants.

In conclusion, despite the documented low incidence of BRONJ after implant surgery in oral BP users, the fate of dental implants placed in these patients remains uncertain. Therefore, all patients treated with oral BPs must be given a full explanation of the potential risks of implant failure and eventual BRONJ development in the short and long term.7  Clinicians should provide treatment with low incidence of biological and prosthetic complications.16  Further studies are needed to establish a specific role of BPs and investigate the infectious origin of the BRONJ after implant placement.

Conclusions

Although BRONJ is a rare complication, clinicians need to be very careful when treating patients with BP medications. The complications that can occur are very severe for the patient and quite often require complex surgical intervention. Oral and implant surgery should be limited to well-trained clinicians, as an underestimated risk factor could cause harsh complications for the patients.

Abbreviations

    Abbreviations
     
  • AAOMS

    American Association of Oral and Maxillofacial Surgeons

  •  
  • BP

    bisphosphonate

  •  
  • BRONJ

    bisphosphonate-related osteonecrosis of the jaws

  •  
  • CT

    computerized tomography

  •  
  • FESS

    functional endoscopic sinus surgery

  •  
  • ONJ

    osteonecrosis of the jaws

  •  
  • OPG

    orthopantomogram

Note

The authors declare no conflicts of interest and no funding or financial support.

References

1
Zadik
Y,
Abu-Tair
J,
Yarom
N,
Zaharia
B,
Elad
S.
The importance of a thorough medical and pharmacological history before dental implant placement
.
Aust Dent J
.
2012
;
57
:
388
392
.
2
Saldanha
S,
Shenoy
V,
Eachampati
P,
Uppal
N.
Dental implications of biphosphonate-related osteonecrosis
.
Gerodontology
.
2012
;
29
:
177
187
.
3
Allen
MR,
Ruggiero
SL.
A review of pharmaceutical agents and oral bone health: how osteonecrosis of the jaw has affected the field
.
Int J Oral Maxillofac Implants
.
2014
;
29
:
e45
e57
.
4
Crépin
S,
Laroche
ML,
Sarry
B,
Merle
L.
Osteonecrosis of the jaw induced by clodronate, an alkylbisphosphonate: case report and literature review
.
Eur J Clin Pharmacol
.
2010
;
66
:
547
554
.
5
Chadha
GK,
Ahmadieh
A,
Kumar
S,
Sedghizadeh
PP.
Osseointegration of dental implants and osteonecrosis of the jaw in patients treated with bisphosphonate therapy: a systematic review
.
J Oral Implantol
.
2013
;
39
:
510
520
.
6
Manfredi
M,
Merigo
E,
Guidotti
R,
Meletti
M,
Vescovi
P.
Biphosphonate-related osteonecrosis of the jaws: a case series of 25 patients affected by osteoporosis
.
Int J Oral Maxillofac Surg
.
2011
;
40
:
277
284
.
7
Ruggiero
SL,
Dodson
TB,
Assael
LA,
Landesberg
R,
Marx
RE,
Mehrotra
B;
Task Force on Bisphosphonate-Related Osteonecrosis of the Jaws, American Association of Oral and Maxillofacial Surgeons. American Association of Oral and Maxillofacial Surgeons: position paper on bisphosphonate-related osteonecrosis of the jaws—2009 update
.
J Oral Maxillofac Surg
.
2009
;
67
:
2
12
.
8
Khalil
H,
Nunez
DA.
Functional endoscopic sinus surgery for chronic rhinosinusitis
.
Cochrane Database Syst Rev
.
2006
;(
3
): CD004458.
9
Mavrokokki
T,
Cheng
A,
Stein
B,
Goss
A.
Nature and frequency of bisphosphonate-associated osteonecrosis of the jaws in Australia
.
J Oral Maxillofac Surg
.
2007
;
65
:
415
423
.
10
Cooper
C,
Steinbuch
M,
Stevenson
R,
Miday
R,
Watts
NB.
The epidemiology of osteonecrosis: findings from the GPRD and THIN databases in the UK
.
Osteoporos Int
.
2010
;
21
:
569
577
.
11
Hansen
PJ,
Knitschke
M,
Draenert
FG,
Irle
S,
Neff
A.
Incidence of bisphosphonate-related osteonecrosis of the jaws (BRONJ) in patients taking bisphosphonates for osteoporosis treatment - a grossly underestimated risk?
Clin Oral Investig
.
2013
;
17
:
1829
1837
.
12
Vescovi
P,
Merigo
E,
Meletti
M,
Manfredi
M,
Guidotti
R,
Nammour
S.
Biphosphonates-related osteonecrosis of the jaws: a concise review of the literature and a report of a single-centre experience with 151 patients
.
J Oral Pathol Med
.
2012
;
41
:
214
221
.
13
Bedogni
A,
Bettini
G,
Totola
A,
Saia
G,
Nocini
PF.
Osteonecrosis of jaw after implant surgery
.
J Oral Maxillofac Surg
.
2010
;
68
:
1662
1666
.
14
Kühl
S,
Walter
C,
Acham
S,
Pfeffer
R,
Lambrecht
JT.
Biphosphonate-related osteonecrosis of the jaw. a review
.
Oral Oncol
.
2012
;
48
:
938
947
.
15
Amorfini
L,
Storelli
S,
Romeo
E.
Rehabilitation of a dentate mandible requiring a full arch rehabilitation. Immediate loading of a fixed complete denture on 8 implants placed with a bone-supported surgical computer-planned guide: a case report
.
J Oral Implantol
.
2011
;
37
:
106
113
.
16
Storelli
S,
Scanferla
M,
Palandrani
G,
Mosca
D,
Romeo
E.
Stratification of prosthetic complications by manufacturer in implant-supported restorations with a 5 years' follow-up: systematic review of the literature
.
Minerva Stomatol
.
2017
;
66
:
178
191
.