Pharmacoepidemiology and clinical characteristics of medication-related osteonecrosis of the jaw

Son, Hyo-Jeong; Kim, Jin-Woo; Kim, Sun‐Jong

doi:10.1186/s40902-019-0210-8

Cited by 16 publications

(18 citation statements)

References 45 publications

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“…Bisphosphonates, despite their long-established use as the first line of treatment for osteoporosis, have concerning relationships to osteonecrosis of the jaw and atypical fracture of the femur [10][11][12][13]. Although bisphosphonates are known to suppress bone turnover, the effect of this action on soft tissues has not been completely evaluated.…”

Section: Introductionmentioning

confidence: 99%

In vitro effects of alendronate on fibroblasts of the human rotator cuff tendon

Sung

Kim

Hah

et al. 2020

BMC Musculoskelet Disord

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Background: Bone mineral density of the humeral head is an independent determining factor for postoperative rotator cuff tendon healing. Bisphosphonates, which are commonly used to treat osteoporosis, have raised concerns regarding their relationships to osteonecrosis of the jaw and to atypical fracture of the femur. In view of the prevalence of rotator cuff tear in osteoporotic elderly people, it is important to determine whether bisphosphonates affect rotator cuff tendon healing. However, no studies have investigated bisphosphonates' cytotoxicity to human rotator cuff tendon fibroblasts (HRFs) or bisphosphonates' effects on rotator cuff tendon healing. The purpose of this study was to evaluate the cytotoxicity of alendronate (Ald), a bisphosphonate, and its effects on HRF wound healing. Methods: HRFs were obtained from human supraspinatus tendons, using primary cell cultures. The experimental groups were control, 0.1 μM Ald, 1 μM Ald, 10 μM Ald, and 100 μM Ald. Alendronate exposure was for 48 h, except during a cell viability analysis with durations from 1 day to 6 days. The experimental groups were evaluated for cell viability, cell cycle and cell proliferation, type of cell death, caspase activity, and wound-healing ability. Results: The following findings regarding the 100 μM Ald group contrasted with those for all the other experimental groups: a significantly lower rate of live cells (p < 0.01), a higher rate of subG1 population, a lower rate of Ki-67 positive cells, higher rates of apoptosis and necrosis, a higher number of cells with DNA fragmentation, higher caspase-3/7 activity (p < 0.001), and a higher number of caspase-3 positive staining cells. In scratch-wound healing analyses of all the experimental groups, all the wounds healed within 48 h, except in the 100 μM Ald group (p < 0.001). Conclusions: Low concentrations of alendronate appear to have little effect on HRF viability, proliferation, migration, and wound healing. However, high concentrations are significantly cytotoxic, impairing cellular proliferation, cellular migration, and wound healing in vitro.

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Section: Introductionmentioning

confidence: 99%

In vitro effects of alendronate on fibroblasts of the human rotator cuff tendon

Sung

Kim

Hah

et al. 2020

BMC Musculoskelet Disord

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“…In this case, bisphosphonate therapy was signi cantly associated with the general refusal of treatment. Because bisphosphonate therapy has a considerable in uence on bone metabolism, it can lead to bisphosphonate-induced bone necrosis (14). Serious complications are therefore possible under bisphosphonate therapy in the course of implantological treatment (15, 16), and special measures must be taken to minimize risks (17).…”

Section: Discussionmentioning

confidence: 99%

How Do Specialist Surgeons Treat the Atrophic Tooth Gap? - A Vignette-based Study Among Maxillofacial and Oral Surgeons

Korsch¹,

Walther

Robra

et al. 2020

Preprint

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BackgroundThere is little information available regarding the decision-making process of clinicians, especially in the choice of therapy for a severely atrophic tooth gap. The aim of this research was to use case vignettes to determine the influence of possible factors on the decision making of maxillofacial and oral surgeons.MethodsA total of 250 maxillofacial (MFS) and oral (OS) surgeons in southern Germany were surveyed for atrophic single- or multiple-tooth gap with the help of case vignettes. The influence of different determinants on the therapy decision was investigated. Two case vignettes were designed for this purpose: vignette 1 with determinants “patient age” and “endocarditis prophylaxis” and vignette 2 with determinants “anxiety” and “bisphosphonate therapy”. Furthermore, the specialist designation was assessed for both. The options available to achieve a sufficient implant site were "bone split", "bone block", "augmentation with bone substitute material" and "bone resection". Therapy was either recommended or rejected based on principle.ResultsA total of 117 participants returned the questionnaire: 68 (58%) were OS and 49 (42%) MFS. “Patient age” and “patient anxiety” were not significantly associated with any therapy decision. However, required “endocarditis prophylaxis” led to significantly higher refusal rates for "bone split", "bone block" and "bone replacement material" and to higher rates of general refusal of a therapy. “Bisphosphonate therapy” was significantly associated with general refusal of therapy, but with no significant correlation with different therapy options. In vignette 1, OS refused therapy significantly more often than MFS, though there was no association with the specialist designation for other therapy modalities. In vignette 2, specialty was not significantly associated with the therapy decision.Conclusion“Patient age” as well as “patient anxiety” appear to have no or little influence on the treatment decision for severely atrophic single- or multiple-tooth gap by specialist surgeons. Surgeons more often refuse treatment for patients with endocarditis prophylaxis and bisphosphonate therapy.

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“…Besides, drug holidays of the same period were recommended for patients who were administered bisphosphonate for less than four years and were also administered corticosteroids or antiangiogenic agents. Since it has been reported that a high total accumulation dose of bisphosphonate is associated with a significantly poor prognosis in the treatment of MRONJ [ 125 ], a drug holiday is considered to be necessary as the duration of bisphosphonate administration increases. However, there is no data on a drug holiday for denosumab and antiangiogenic agents, so, in this case, the clinician faces a difficult situation.…”

Section: Various Therapeutic Methods For Mronjmentioning

confidence: 99%

Various Therapeutic Methods for the Treatment of Medication-Related Osteonecrosis of the Jaw (MRONJ) and Their Limitations: A Narrative Review on New Molecular and Cellular Therapeutic Approaches

Cho

Byun

et al. 2021

Antioxidants

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Medication-related osteonecrosis of the jaw (MRONJ) is one of the most interesting diseases in the field of maxillofacial surgery. In addition to bisphosphonates, the use of antiresorptive and antiangiogenic agents is known to be the leading cause. However, the exact pathogenesis of MRONJ has not been established, and various hypotheses have been proposed, such as oxidative stress-related theory. As a result, a definitive treatment protocol for MRONJ has not been identified, while various therapeutic approaches are applied to manage patients with MRONJ. Although the surgical approach to treat osteomyelitis of the jaw has been proven to be most effective, there are limitations, such as recurrence and delayed healing. Many studies and clinical trials are being conducted to develop another effective therapeutic modality. The use of some materials, including platelet concentrates and bone morphogenetic proteins, showed a positive effect on MRONJ. Among them, teriparatide is currently the most promising material, and it has shown encouraging results when applied to patients with MRONJ. Furthermore, cell therapy using mesenchymal stem cells showed promising results, and it can be the new therapeutic approach for the treatment of MRONJ. This review presents various treatment methods for MRONJ and their limitations while investigating newly developed and researched molecular and cellular therapeutic approaches along with a literature review.

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Pharmacoepidemiology and clinical characteristics of medication-related osteonecrosis of the jaw

Cited by 16 publications

References 45 publications

In vitro effects of alendronate on fibroblasts of the human rotator cuff tendon

In vitro effects of alendronate on fibroblasts of the human rotator cuff tendon

How Do Specialist Surgeons Treat the Atrophic Tooth Gap? - A Vignette-based Study Among Maxillofacial and Oral Surgeons

Various Therapeutic Methods for the Treatment of Medication-Related Osteonecrosis of the Jaw (MRONJ) and Their Limitations: A Narrative Review on New Molecular and Cellular Therapeutic Approaches

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