Table 4.
Drug holiday recommendations from the retrospective studies.
| Study | Primary disease | Drug holiday (patients)∗ | Duration of drug holiday (months) | Healing of MRONJ (patients with drug holidays) | Authors' conclusions on drug holidays |
|---|---|---|---|---|---|
| Dimitrakopoulos et al., 2006 [36] | Breast cancer (1/11), Prostate cancer (2/11), Multiple myeloma (5/11), Neuroendocrine cancer (1/11), Lung cancer (1/11), Fibrous dysplasia (1/11) | 10/11 | 2–8 | 5/10 | Discontinuation of BP, combined with surgical debridement, is the treatment of choice. More than 3 months of cessation appears to be necessary |
| Wilde et al., 2011 [27] | Breast cancer (6/24), Prostate cancer (7/24), Multiple myeloma (7/24), Thyroid cancer (1/24), Hodgkin's lymphoma (1/24), Non-Hodgkin's lymphoma (1/24), Kidney cancer (1/24) | 10/24 | - | 10/10 | Treatment results were not significantly affected, whether BP therapy was continued or discontinued. The results of this study indicate that there is no reason to interrupt AR therapy for surgery |
| Jabbour et al., 2012 [29] | Osteoporosis (4/14), Breast cancer (5/14), Prostate cancer (2/14), Multiple myeloma (1/14), Kidney cancer (2/14), | 9/14 (7 with cancer) | - | 10/14 | There was no standard protocol for a drug holiday in this study. None of the patients died or had their health status changed due to discontinuation of BP therapy |
| Voss et al., 2012 [30] | Osteoporosis (4/20), Breast cancer (9/20), Prostate cancer (1/20), Thyroid cancer (1/20), Plasmacytoma (3/20), Vulva cancer (1/20), Kidney cancer (1/20) | 20/20 | 1–1.5 (4 weeks before, 6 weeks after) | 19/20 | An individual approach in consultation with the prescribing oncologist is recommended |
| Wutzl et al., 2012 [26] | Osteoporosis (5/41), Breast cancer (9/41), Prostate cancer (3/41), Multiple myeloma (20/41), Histiocytosis X (1/41), Lung cancer (2/41), Anal cancer (1/41) | 28/41 | ?–6 (6 post-operatively) | - | Discontinuation of BPs before surgery favored significantly better treatment outcomes |
| Kim et al., 2014 [31] | Osteoporosis (47/54), Breast cancer (1/54), Multiple myeloma (5/54), Malignant lymphoma (1/54) | 54/54 | Surgical treatment group: 6.9 Conservative treatment group: 7.2 | 11/20 | A correlation was found between drug holidays and prognoses in the surgical treatment group. Drug holiday durations should be at least 4 months to prevent a poor prognosis after surgical management |
| Lopes et al., 2015 [32] | Osteoporosis (2/33), Breast cancer (18/33), Prostate cancer (4/33), Multiple myeloma (4/33), Lung cancer (4/33), Kidney cancer (1/33) | 31/33 | 6.8 ± 9.2 | - | A total of 40/46 sites (87%) healed. No conclusions can be drawn from this study |
| Bodem et al., 2016 [33] | Malignant disease (39/39) | 15/39 | - | 9/15 showed complete healing, 4/15 showed relative healing 2/15 showed no healing | No statistically significant differences were observed between patients who were still receiving their i.v. BPs at the time of surgery and those on a drug holiday |
| Hoefert et al., 2017 [34] | Osteoporosis (1/17), Breast cancer (9/17), Prostate cancer (6/17), Lung cancer (1/17) | 10/17 | - | 5/10 | Cessation of denosumab treatment had no apparent effect on healing outcomes |
| Aljohani et al., 2018 [35] | Osteoporosis (9/63), Breast cancer (27/63), Prostate cancer (17/63), Multiple myeloma (2/63), Lung cancer (1/63), Melanoma (1/63), Thyroid cancer (2/63), Kidney cancer (4/63) | 42/63 | 6 ± 3.4 | Healing (5/42), Partial healing (3/42), No healing (5/42), Missing data (9/42) | No associations were observed between denosumab drug holidays and healing outcomes |
| Jung et al., 2018 [28] | Cancer (317/1569), Other (1252/1569) | 836/1569 | 1 day to >4 years | - | Among all the cases of ONJ that occurred during the study, 53.3% occurred after BP therapy was suspended. Most ONJ cases occurred within 2–3 years of BP therapy being discontinued. Different approaches are needed to determine whether drug holidays are likely to be beneficial. The benefits of continuing therapy may outweight the risks of suspending it |
AR: Antiresorptive; BP: Bisphosphonate; MRONJ: Medication-related osteonecrosis of the jaw; i.v.: Intravenous.
∗
If no information is provided, then it was unclear whether the patients with drug holidays had a cancer diagnosis in the original studies; -: Not described in the article.