Table 2.
Included literature
| Implant | ||||||||||
| Author Year Reference | Study type | Patients | Primary disease in BP patients (n) | BP BP-Th (years min- max) | BP-ONJ cases due to implants | Implants (n) | Implant insertion in all patients (patients [n]) Point of time | Comment | ||
| before BP therapy | during BP therapy | after BP therapy | ||||||||
| Al-Sabbagh 2015 [24] | RS CS | 203 patients with 515 implants; 20 out of those patients with osteoporosis and oral BP | Osteoporosis 20 | Oral BP > 3 | 0 | 46 | n.s. | n.s. | n.s. | All patients with implant therapy from 08/2000 until 05/2004 were contacted and data was collected by interview (in person/per telephone). 203 patients with 515 implants; in 20 patients (46 implants) with osteoporosis and oral BP no ONJ occurred no implant was lost. There is no data regarding the implant success in the patients without osteoporosis. |
| Nisi 2015 [20] | RS CS | 90 patients with established ONJ some of them with implants | Malignoma 90 | Z n.s. | 9 | n.s. | n.s. | n.s. | n.s. | All patients with BP-ONJ from 01/2004 until 12/2015 were retrospectively analyzed. 78% had an additional radiation. It is not clear if the head and neck region was affected and if the implant patients were affected. The study describes the cumulative BP dose, smoking, steroid intake and the maxillary location as risk factors for an increases BP-ONJ stage. |
| Holzinger 2014 [9] | RS CS | 13 patients with established ONJ due to dental implants | Osteoporosis 5 breast cancer 3 lung cancer 1 Langerhans cell histiocytosis 1 |
Z A P I- 0.5 – 9 0 – 15.6 |
13 | 47 | 3 | 7 | 3 | All patients with BP-ONJ from 04/2004 – 07/2012 were analyzed. Among those were 13 patients (47 implants) with implants as a trigger. 30 implants had to be removed. It takes longer for BP-ONJ development if implants are placed during or after BP treatment compared to implants being inserted before BP treatment. |
| Lopez-Cedrun 2013 [10] | RS CS | 9 Patients with established ONJ due to dental implants | Osteoporosis Polymyalgia rheumatica | A I R 0.5 - 10 |
9 | 57 | - | 9 | - | Retrospective multicenter study analyzing all patients with BP-ONJ due to dental implants from 01/2009 – 06/2012. The authors state that the ONJ was more common in the mandible (8/9) and more often in the premolar and molar region. 28 implants maxilla → 1 BP-ONJ 29 implants mandible →8 BP-ONJ |
| Tam 2013 [16] | RS CS | 6 patients with established BP-ONJ due to dental implants | Osteoporosis 4 breast cancer 1 multiple myeloma 1 | A Z 1.5-6 |
6 | - | 6 | - | All patients with BP-ONJ due to dental implants from 2009 – 2011 were analyzed; 3 patients with BP-ONJ in the posterior maxilla 3 patients with BP-ONJ in the mandible (2 distal, 1 anterior) | |
| Kwon 2014 [17] | RS CS | 19 patients with established BP-ONJ due to dental implants | Osteoporosis 18 multiple myeloma 1 | A I P R Z 1 - 5 | 19 | n.s. | 3 | 16 | - | All patients with BP-ONJ due to dental implants from 06/2008 – 12/2011 were analyzed. 8 patients with BP-ONJ in the maxilla, 9 patients with BP-ONJ in the mandible, 2 patients with BP-ONJ in mandible and maxilla |
| Jacobsen 2013 [18] | RS CS | 14 patients with established BP-ONJ due to dental implants | Osteoporosis 5 Breast cancer 5 multiple myeloma 2 prostate cancer 1 lung cancer 1 |
A I P Z Average BP duration 3.2 osteoporosis; 4.2 malignant disease |
14 | n.s. | n.s. | n.s. | n.s. | The authors state that implants placed posterior are of higher risk than implants in the anterior region. 4 patients had implants in the posterior maxilla, 5 in the posterior mandible and 3 in the anterior mandible. In one patient implants were removed and new implants were inserted at the same site with continuing problems. In one patient a sinus lift was performed |
| Famili 2011 [25] | RS CS | 211 female patients with 592 dental implants, out of those 120 older than 50 y with 347 implants out of those 22 with BP and 75 implants | Osteoporosis 21 osteoarthritis 1 | A I <1 - > 5 |
0 | 75 | n.s. | At least 20 | n.s. | All female patients with implant therapy from 01/2008 – 06/2010 were analyzed. Among those 22 with oral BP therapy. One implant did not heal and was successfully replaced |
| Kwon 2011 [21] | RS CCS but not focused on dental implants → RS CS |
Biochemical bone markers were evaluated in 23 osteoporosis patients with established BP-ONJ | Osteoporosis | A 2.5 - 5 |
2 | n.s. | n.s. | n.s. | n.s. | It is not clear, when and how the 23 BP-ONJ patients were recruited. 61 BP control patients. 2 patients developed BP-ONJ due to implants CTX was evaluated at the time of ONJ diagnosis and not at the time point of any possible BP-ONJ triggering intervention. |
| Koka 2010 [22] | RS CS | 370 patients over 50 years old with 818 implants. 233 patients could not be reached so that the phone interview was conducted with remaining 137 patients: 55 BP patients and 82 non-BP patients | Osteoporosis | A & n.s. <3 - > 5 |
0 | 121 | - | 55 | - | All patients from 11/2006 – 05/2009 that had not denied access to data for research purposes. None of the BP patients had a drug holiday. 121 implants were inserted, one did not survive. The patients were not examined only a phone interview was conducted. The control group consisted of 82 non-BP users with 166 implants (163 survived, 2 losses in 1 patient). 233 patients could not be reached by phone and were excluded. |
| Lazarovici 2010 [19] | RS CS | 27 patients with established ONJ due to dental implants | Osteoporosis 11 multiple myeloma 7 breast cancer 7 prostate cancer 2 |
A P Z average BP duration A 5.7 Z 1.4 P 4.2 |
27 | n.s. | 2 | 25 | - | All patients from 04/2003 – 01/2009 with BP-ONJ and dental implants. 15 patients had implants in the posterior mandible, 5 in the anterior mandible, 4 in the posterior maxilla, 3 in the anterior maxilla |
| Goss 2010 [26] | RS CS | Questionnaire to 46 dentists placing either > 50 implants/y or treat BP-ONJ in South Australia | Osteoporosis in the 7 patients with implant loss | A R in the 7 patients with implant loss | 7 | ≥9 | 4 | 3 | - | 46 dentists placed approximately 28,000 implants in 16,000 patients. There is no number given how many patients received BP. 7 implants were lost in patients with BP |
| Lo 2009 [27] | RS CS questionnaire | Questionnaire to 13,496 patients with oral BP therapy, 8,572 answered, 2,159 reported dental symptoms, 1005 were examined, 9 BP-ONJ | n.s. | A I R ≥1 |
1 | n.s. | n.s. | n.s. | n.s. | 13,946 questionnaires were sent, 5,374 did not participate, 9 ONJ were identified and 1 was associated with an implant loss and a tooth extraction. The bisphosphonates had been administered before implant insertion |
| Bell 2008 [28] | RS CS | 42 patients with BP therapy and oral bone grafting or implant placement | n.s. | A R I | 0 | 100 or 101 both numbers are given in the paper | - | 42 | - | All patients from ??/1990 - ??/???? (paper published in 2008) with BP treatment prior to implant therapy were analyzed. 5 implants failed, no patient with more the 1 implant loss, all implants successfully replaced. 30 patients received an additional bone augmentation (socket graft, sinus lift, closed sinus lift, guided tissue regeneration, or tunnel graft). |
| Grant 2008 [29] | RS CS | Questionnaire to all 1,319 female patients over 40 y and with implants, 458 patients responded, 115 out of those had oral BP, 72 patients came to a follow-up |
n.s. | A I R Mean 3.2 |
0 | 456 in the 115 patients | 26 out of the 115 |
89 out of the 115 |
- | All 1,319 patients over 40 y of age with implant therapy between 01/1998 – 12/2006 were contacted. |
| Fugazotto 2007 [30] |
RS CS | 61 patients out of two private practices with oral BP | n.s. | A R Mean 3.3 |
0 | 169 | - | 61 | - | All 61 patients with oral bisphosphonates with implant therapy between 01/2005 – 12/2005 were analyzed. 43 immediate implants 1 Pat had exposed bone at a different location that was treated by debridement. At the next control there was granulated soft tissue. |
| Jeffcoat 2006 [31] | PS | 50 patients with 210 implants 25 patients with oral BP 102 implants 25 patients without BP 108 implants |
Osteoporosis 25 | A R 1 - 4 |
0 | 102 | - | 102 | - | Longitudinal single-blind controlled study Two-stage osseointegrated implants in all patients, no BP-ONJ |
| Marx 2005 [23] | RS CS | 119 patients with BP-ONJ | n.s. for the patients with implants | n.s. for the patients with implants, in 1 case Z & P |
4 | n.s. | n.s. | n.s. | n.s. | RS with 119 ONJ patients, 4 due to dental implants |
| Denture | ||||||||||
| Author Year Reference | Study type | Patients | Primary Disease in BP-ONJ | BP/Denosumab | BP-ONJ Cases | Comment | ||||
| Nibbe 2015 [15] | RS | 424 patients with oral/IV BP or denosumab. 128 patients with IV BP or denosumab - further investigation of this group 68 patients with dentures |
n.s. in all cases | Oral/IV BP Denosumab |
16 | 424 patients with oral or IV BP were analyzed, 21 BP-ONJ, only IV BP patients for further analysis 34 removable dentures → 11 BP-ONJ 34 fixed partial denture → 5 BP-ONJ 60 patients without denture → 5 BP-ONJ ONJ only in patients with IV BP or denosumab |
||||
| Hasegawa 2012 [43] | RS | Questionnaire was sent to 248 medical institutions regarding BP-ONJ 250 patients 99 with dentures 151 without dentures |
n.s. | Oral/IV BP | 99 | 151 osteonecrosis patients without denture had a longer osteonecrosis free time. Most ONJ in the mandible with a focus on the premolar and molar region 154 patients with IV BP, 102 with oral BP, 7 both |
||||
| Jabbour 2012 [35] | RS | 14 patients with BP-ONJ 4 due to dentures |
Osteoporosis 2 kidney cancer 1 breast cancer 1 |
A P | 4 | RS analyzing the reason for osteonecroses | ||||
| Vahtsevanos 2009 [39] | RS | 1,621 patients with IV BP | n.s. | n.s. for the denture patients | 24 | 24 out of 80 BP-ONJ patients denture as triggering factor diseases and BP for the patients with dentures n.s. I P Z were used as BP in the BP-ONJ patients. | ||||
| Kos 2010 [36] | RS | 34 patients with BP-ONJ | n.s. | n.s. for denture patients | 3 | 34 patients with osteonecrosis. A I P R Z were used as BP it is not clear what the patients with the dentures received and which primary disease was present. BP-therapy for all patients 0.3 – 8 y |
||||
| Carmagnola 2008 [34] | RS | 39 oncologic patients with BP | Multiple myeloma 2 breast cancer 3 prostate cancer 1 kidney cancer 1 |
P Z | 7 | 7 out of 20 BP-ONJ patients had an osteonecrosis due to denture pressure sores BP given for 1.1 – 6.8 y |
||||
| Walter 2008 [40] | CSS | 43 patients with prostate cancer out of those 21 patients with denture out of those 6 with ONJ | Prostate cancer | Z | 1 | 1 denture induced ONJ | ||||
| Kyrigidis 2008 [38] | CCS | 20 breast cancer patients 40 matched controls | Breast Cancer | Z | 8 | 20 patients with breast cancer and osteonecrosis, 8 with dentures use of dentures associated with BP-ONJ | ||||
| Kumar 2008 [37] | RS CS | 13 patients with BP-ONJ | Osteoporosis 4 breast cancer 1 multiple myeloma 1 |
A Z | 6 | 6 out of 13 patients denture as the trigger factor | ||||
| Yarom 2007 [42] | RS CS | 11 patients with BP-ONJ | Osteoporosis | A | 2 | 2 out of 11 BP-ONJ triggered by denture Alendorante was given for 2 and 6 y 2 patients (1 osteoporosis, 1 rheumtoid arthritis) had an implant related BP-ONJ in the posterior mandible, BP was given for 5 and 7 years |
||||
| Walter 2007 [41] | RS CS | 163 patients with an osteonecrosis, 17 BP-ONJ | Multiple Myeloma | P | 1 | 1 BP-ONJ due to a denture pressure sore in the mandible P was given for 5 y |
||||
| Bamias 2005 [33] | PS | 252 patients with BP 17 with BP-ONJ |
Multiple Myeloma | n.s. | 2 | 2 BP-ONJ due to a denture pressure sore I P Z for all 252 patients |
||||
| Quality of life | ||||||||||
| Author Year Reference | Patients | Comment | ||||||||
| DeBaz 2015 [44] | 524 patients asked to fill out the survey 237 completed survey 3 groups: 64 dental implant supported prosthesis 47 non-implant supported fixed restoration 60 non-implant supported removable restoration 66 no restoration of missing teeth |
The quality of life assessment: occupational score health score emotional score sexual score The patients dental implant supported prosthesis had the overall best score regarding quality of life compard to the other groups In total 134 patients reported oral BP, 51 IV BP, 10 patients denosumab In the implant group 35 patients received oral BP, 12 IV BP, 3 denosumab no ONJ |
||||||||
| Persisting alveolar socket | ||||||||||
| Author Year Reference | Study type | Patients | Comment | |||||||
| Hutchinson 2010 [46] | CSS | 10 patients with stage 0 BP-ONJ | Consistent findings of regional or diffuse osteosclerosis, density confluence of cortical and cancellous bone, prominence of the inferior alveolar nerve canal, thickened sclerotic lamina dura, periradicular radiolucencies, cortical disruption, and persisting alveolar sockets. | |||||||
| Grötz 2006 [45] | RS CS | 42 patients with BP-ONJ | Consistent findings of persisting alveolar sockets. | |||||||
| Hand search | ||||||||||
| Author Year Reference | Study type | Patients | Comment | |||||||
| Grötz 2012 [1] | Guideline | German guidelines on bisphosphonate-associated osteonecrosis of the jaws (BP-ONJ) and other medication-related necroses of the jaw | ||||||||
| Grötz [52] | Description on many important aspects on implant surgery in bisphosphonate patients or patients with other resorptive medications. | |||||||||
| Grötz 2013 [53] | Review | The authors state the necessity for an individual risk assessment. The evaluation of dentures vs. implants. It is suggested to not place immediate implants in patients with antiresorptive therapy, atraumatic surgery with perioperative antibiotics, the necessity of a recall and the avoidance of bone augmentations | ||||||||
| Grötz 2010 [54] | Review | The authors provide an algorithm how to proceed with patients receiving BP seeking implant therapy. The authors state the necessity for an individual risk assessment and avoidance of bone augmentations |
||||||||
| Krimmel 2014 [55] | RS | 50 patients with BP-ONJ | DMFT of all patients 20.5 ± 4.2 disease free interval for patients with DMFT < 20: 39.7 ± 1.1 months disease free interval for patients with DMFT > 20: 14.4 ± 2.8 months The DMFT had no influence on the overall healing rate of BP-ONJ |
|||||||
| Tsao 2013 [56] | CCS | 63 patients 22 BP-ONJ patients 41 matched controls |
Caries similar between groups Periodontal disease associated with BP-ONJ (pocket depth, IgG serum titer against Porphyromonas gingivalis, IL 1ß level in gingival cervical fluid) |
|||||||
| Thumbigere-Math 2013 [57] | CCS | 73 patients 25 BP-ONJ patients 48 matched controls |
BP infusions BP-ONJ 38.4 and control 18.8 BP-ONJ vs control: missing teeth: 7.8 vs 3.1 clinical attachment level: 2.18 vs 1.56 radiogic bone loss at teeth > 50%: 20% vs. 6% |
|||||||
| Martin 2010 [58] | CSS | 8,752 patients with oral BP returned dental survey (62% response rate) 589 patients with dental implants |
16 patients with 26 implant failures 8 patients with failure of 12 implants in the maxilla 9 had failure with 14 implants in the mandible |
|||||||
| Shabestari 2009 [59] | RS | 21 female osteoporotic women with oral BP and 46 implants | No BP-ONJ, no signs of peri-implantitis | |||||||
| Zahid 2011 [60] | RS | 362 patients with implants 26 BP patients with 51 implants |
3 implants failed Patients with BP had more thread exposure |
|||||||
| Memon 2012 [61] | RS | 200 patients BP: 100 women with 153 implants control: 100 women with 132 implants |
Success equal for both groups 93.5 (BP) vs. 95.5 (control) crestal bone change from implant insertion to stage two surgery: no difference between the groups |
|||||||
| Yip 2012 [62] | CCS | 337 patients 114 patients with implant failure 223 patients without implant failure |
% of patients using BP Implant failure group: 9.65% no implant failure: 4.04 |
|||||||
| Walter 2014 [3] | RS | 504 patients with osteonecrosis 227 with BP-ONJ |
7 out of 227 patients with BP-ONJ implant as trigger factor | |||||||
| Lopez-Jornet 2011 [63] | Animal study | 120 rats with pamidronate treatment and molar extraction 60 with penicillin 60 without penicillin |
Osteonecrosis rate Penicillin group: 18 → 34.6 % no penicillin group: 5 → 9.61% |
|||||||
| Montefusco 2008 [51] | RS | 178 patients with multiple myeloma und BP treatment 75 patients with dental procedures 32 with antibiotics 43 without antibiotics |
ONJ rate with antibiotics: 0 without antibiotics: 8 Antibiotic prophylaxis can reduce the incidence of BP-ONJ |
|||||||
| Kyrgidis 2012 [50] | PS | Group 1: BP-ONJ breast cancer 21 Group 2: breast cancer 21 Group 3: oral cancer 22 |
Quality of life assessment before surgery Group 1 is affected in many factors such as pain, swallowing, senses, social eating, social contacts |
|||||||
| Boquete-Catro 2015 [32] | Review | Analysis of patients with denosumab associated ONJ | No implant related ONJ reported | |||||||
A: Alendronate; CCS: Case control study, CS: Case series; CSS: Cross sectional study; D: Denosumab; I: Ibandronate; LSBCD: Longitudinal single-blind controlled study; n.s.: Not specified; P: Pamidronate; PS: Prospective Study; R: Risedronate; RS: Retrospective study, Z: Zoledronate