Bonacina (2011) Canada; Prospective cohort. |
7/65 (10.7%) NR |
Zoledronate (7) |
Zoledronate (55) Zoledronate and sunitinib (3) |
Cancer (7); Corticoids (0) |
Cancer (7); Corticoids (7) |
Extraction (1); NR; NR |
Extraction (3); NR; NR |
NR; 0 |
NR; 13 |
Among the evaluated patients, there was a correlation between the number of zoledronate infusions and MRONJ. In addition, all these patients presented previous exposure to bisphosphonates. |
Calvo-Villas (2016) Spain; Retrospective cohort. |
7/64 (10.9%) 75 yo |
Zoledronate (3) Pamidronate and zoledronate (4) |
Zoledronate (57) Pamidronate and zoledronate (43) |
Multiple myeloma (7); Corticoids (7) Thalidomide (3) |
Multiple myeloma (57); Corticoids (35) Thalidomide (14) |
Extraction (5); NR; Oral infection (6) |
Extraction (1); NR; Oral infection (44) |
NR; 2 |
NR; 18 |
Occurrence of MRONJ was directly related to duration of bisphosphonate therapy and presence of local factors, as oral infections. |
Carmagnola (2008) Italy; Retrospective cohort. |
20/39 (51.7%) 65 yo |
Zoledronate (19) Pamidronate and zoledronate (1) |
Zoledronate (18) Pamidronate (1) |
Cancer (14) Multiple myeloma (6); NR |
Cancer (12) Multiple myeloma (6) Lymphoma (1); NR |
Extraction (10); Dentures (7); NR |
Extraction (5); NR; NR |
NR; NR |
NR; NR |
The authors did not find an association between dental extractions and MRONJ. Increased doses of zoledronate were related to MRONJ. |
Gunaldi (2015) Turkey; Case-Control |
24/44 (54.4%) 60,5 yo |
Zoledronate (23) Zoledronate + Bevacizumab (1) |
Zoledronate (19) Zoledronate + Bevacizumab (1) |
Cancer (14) Multiple myeloma (8) Other (2); Corticoids (7) Thalidomide (5) |
Cancer (9) Multiple myeloma (7) Other (4); Corticoids (7) Thalidomide (4) |
Extraction (13); NR; NR |
Extraction (4); NR; NR |
1; 4 |
1; 4 |
Time of exposure to zoledronate and tooth extraction were factors related to MRONJ. |
Hoff (2008) USA Retrospective cohort. |
29/3965 (0.79%) 62yo |
Pamidronate (7) Zoledronate (9) Pamidronate + Zoledronate (13) |
Pamidronate (2281) Zoledronate (1171) Pamidronate + Zoledronate (513) |
Cancer (16) Multiple myeloma (13); Corticoids (23) |
Cancer (2392) Multiple myeloma (535) Osteoporosis (271) Paget’s disease (11); Corticoids (3272) |
Extraction (16); Dentures (3); Oral infection (14) |
Extraction (136); NR; NR |
NR; NR |
NR; NR |
Mean time of treatment and dental extractions were related to occurrence of MRONJ. Use of zoledronate increases risk of osteonecrosis. |
Ikesue (2021) Japan Retrospective cohort |
34/374 (9.09%) 70 yo |
Denosumab (27) Zoledronate (7) |
Denosumab (188) Zoledronate (152) |
Cancer (28) Multiple myeloma (4) Others (2) Oral bisphosphonate (1) Antiangiogenic agents (11) Corticoid (22) |
Cancer (246) Multiple myeloma (52) Others (40) Oral bisphosphonate (12) Antiangiogenic agent (62) Corticoid (181) |
Extraction (10); NR; NR |
Extraction (10); NR; NR |
3; NR |
67; NR |
Incidence of MRONJ was greater in the denosumab group than in zoledronate users. MRONJ occurrence was related to age > 65 years and tooth extraction before or after starting therapy. |
Ikesue (2021) Japan Retrospective cohort |
58/799 (7.3%) NR |
Denosumab (39) Zoledronate (19) |
Denosumab (367) Zoledronate (374) |
NR NR |
NR NR |
NR; NR; NR |
NR; NR; NR |
NR; NR |
NR;NR |
Risk of developing MRONJ was higher in denosumab users. Tooth extraction after starting therapy was a significant risk factor to develop MRONJ. |
Ikesue (2021) Japan Retrospective cohort |
65/795 (8.2%) NR |
Denosumab after Zoledronate (7) Zoledronate (19) Denosumab (39) |
Denosumab after Zoledronate (36) Zoledronate (331) Denosumab (363) |
NR NR |
NR NR |
NR; NR; NR |
NR;NR;NR |
NR;NR |
NR; NR |
MRONJ occurrence was associated with tooth extraction, concomitant use of antiangiogenics, denosumab therapy and switching zoledronate to denosumab. |
Jadu (2007) Canada Retrospective cohort |
21/655 (3.2%) NR |
Pamidronate (21) |
Pamidronate (634) |
Multiple myeloma (21) NR |
Multiple myeloma (634) NR |
NR; NR; NR |
NR;NR;NR |
NR;NR |
NR; NR |
Dental extractions were associated with MRONJ onset. Other factors were duration of pamidronate therapy, advanced age, and concomitant use of some drugs, such as corticoids. |
Kim (2021) South Korea Retrospective cohort |
166/164,926 (0,1%) NR |
Bisphosphonate not specified (166) |
Bisphosphonate not specified (164,760) |
Osteoporosis (166) NR |
Osteoporosis (164,760) NR |
NR; NR; NR |
NR;NR;NR |
NR;NR |
NR; NR |
Dental extraction, gingivitis and periodontitis were strongly associated with MRONJ onset. |
Kyrgidis (2008) Greece Case-Control |
20/60 (NA) 59.5 |
Zoledronate (20) |
Zoledronate (40) |
Cancer (20); NR |
Cancer (40); NR |
Extraction (10); 8; NR |
Extraction (3); 7; NR |
NR; 16 |
NR; 23 |
Odds of MRONJ occurrence increased towards use of dentures and dental extraction. |
McGowan (2019) Australia Case-control |
44/159 (NA) 67.8 |
Alendronate (10) Zoledronate (17) Pamidronate (5) Risedronate (5) Denosumab (7) |
Alendronate (28) Zoledronate (38) Pamidronate (14) Risedronate (15) Denosumab (18) |
Osteoporosis (16) Multiple myeloma (13) Cancer (12) Rheumatoid arthritis (3) |
Osteoporosis (49) Multiple myeloma (31) Cancer (26) Rheumatoid arthritis (7) |
Extraction (28) Periodontal treatment (3) Periodontal acute infection (4) Dental prosthesis (24) |
Periodontal treatment (3) Periodontal acute infection (3) Dental prosthesis (60) |
13; 11 |
19; 14 |
Non-surgical therapy and tooth extraction were associated with MRONJ occurrence. |
Matsui (2015) Japan Retrospective cohort |
23/106 (21.6%) 74.8 |
Zoledronate (7) Minodronate (3) Risedronate (2) Alendronate (5) Denosumab (5) Unknown (1) |
Risedronate (34) Alendronate (26) Minodronate (14) Unknown (7) Etidronate (1) |
Osteoporosis (10) Cancer (11) Others (1) Unknown (1) |
Osteoporosis (72) Cancer (4) Others (5) Unknown (2) |
Tooth extraction (9) Dental prosthesis (2) Periodontal disease (3) |
Tooth extraction (79) Cystectomy (3) Biopsy (1) |
NR; NR |
NR; NR |
Tooth extraction was the main cause related to MRONJ onset. Most patients with MRONJ had a history of zoledronate use. |
Soutome (2021) Japan Retrospective cohort |
33 jaws/359 jaws NA 65.9 |
Bisphosphonate not specified (12 jaws) Denosumab (20 jaws) |
Bisphosphonate not specified (149 jaws) Denosumab (169 jaws) Bisphosphonate to denosumab |
Cancer (33 jaws) Corticosteroid (3 jaws) |
Cancer (326 jaws) Corticosteroid (38 jaws) |
Tooth extraction (5 jaws) Oral infection (13 jaws) |
Tooth extraction (22 jaws) Oral infection (17) jaws |
4; 3 |
34; 54 |
Presence of local symptoms of infections or infected teeth were independent risk factors to MRONJ occurrence, such as duration of antiresorptive therapy. Dental extraction was not a risk factor to MRONJ onset. |
Ueda (2021) Japan Retrospective cohort |
43/745 NA NR |
NR |
NR |
Cancer (43) |
Cancer (702) |
Tooth extraction (6) |
Tooth extraction (13) |
NR;NR |
NR;NR |
Tooth extractions were associated with MRONJ occurrence. Radiographic findings as osteosclerotic areas at the first exam were related with future MRONJ occurrence. |
Ueda (2021) Japan Retrospective cohort |
42/398 (10.6%) 70.5 |
Bisphosphonate not specified (11) Denosumab (26) Bisphosphonate not specified plus denosumab (5) |
Bisphosphonate not specified (136) Denosumab (179) Bisphosphonate not specified plus denosumab (41) |
Cancer (42) Multiple myeloma (3) Corticoid (1) |
Cancer (310) Multiple myeloma (46) Corticoid (13) |
Tooth extraction (5) |
Tooth extraction (7) |
4;14 |
51; 68 |
Alveolar bone loss involving more than half the root on panoramic radiographs and torus mandibularis carry a high risk of MRONJ development. tooth extraction was not associated with MRONJ onset. |
Vahtsevanos (2009) Greece Retrospective cohort |
80/1621 (4.93%) 63.6 |
Bisphosphonate not specified (80) |
Bisphosphonate not specified (1541) |
Cancer (34) Multiple myeloma (46) |
Cancer (1048) Multiple myeloma (493) |
Tooth extraction (46) Dentures (24) |
Tooth extraction (69) Dentures (199) |
NR;42 |
NR;826 |
Tooth extractions and use of dentures were risk factors for MRONJ development. |