Effects of alendronate and pamidronate on apoptosis and cell proliferation in cultured primary human gingival fibroblasts

Soydan, Sıdıka Sinem; Araz, Kenan; Şenel, Figen Çizmeci; Yurtçu, Erkan; Helvacıoğlu, Fatma; Dağdevıren, Attıla; Tekindal, Mustafa Agâh; Şahin, Feride İffet

doi:10.1177/0960327115569808

Cited by 23 publications

(21 citation statements)

References 33 publications

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“…One-way ANOVA analysis was applied to determine the statistical differences in rapport with control/DMSO followed by Dunnett's multiple comparisons posttest (** p<0.01 and **** p< 0.0001). alendronate -F on human primary gingival fibroblasts was also shown by other groups of research [21][22][23], data that are in agreement with these results. Stimulation of human stem cells derived from the gingiva with risedronate in the range of 1-10 µM led to changes in cells morphology and a reduced viability [24], findings that confirm our results.…”

Section: Bisphosphonates Impair Human Primar Y Gingival Fibroblasts -supporting

confidence: 91%

“…Another study conducted by Soydan et al [22] demonstrated the toxic effects of Alendronate (Fosamax) and PAM on human gingival fibroblasts, characterized by significant changes in the apoptotic and proliferative indices leading to an in vitro faulty epithelisation of the oral mucosa. The apoptotic index of the PAM group was significantly higher than the alendronate group for all concentrations, especially at 24 h of incubation (p <0.05).…”

Section: Bisphosphonates Impair Human Primar Y Gingival Fibroblasts -mentioning

confidence: 99%

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Comparative Effects of Oral and Injectable Bisphosphonates in Primary Human Gingival Fibroblasts

Bălean¹,

Floare²,

Focht³

et al. 2019

Rev. Chim.

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Bisphosphonates are effective antiresorptive agents frequently used in the treatment of different bone disorders, as osteoporosis, Paget�s disease and tumours that cause osteolysis. A major concern related to bisphosphonates therapy is represented by osteonecrosis of jaw, a serious, debilitating, and mostly, a therapy-resistant disease, reported as a frequent side effect of bisphosphonates. The present study was aimed to assess and compare the effect of four commercially available bisphosphonates, very frequently used as oral (Fosamax - F and Actonel - A) and injectable (Ossica - O and Zoledronic acid - Z) therapy on primary human gingival fibroblasts - HGF viability. Alamar blue cell viability assay was performed to assess the effect of test compounds (1.5; 2.5; 5 and 10 mM) on gingival fibroblasts viability after a 24 h interval. In these experimental conditions, injectable bisphosphonates (O and Z) proved to be safe for HGF cells, whereas oral compounds (F and A) were cytotoxic even at low concentrations.

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Section: Bisphosphonates Impair Human Primar Y Gingival Fibroblasts -supporting

confidence: 91%

Section: Bisphosphonates Impair Human Primar Y Gingival Fibroblasts -mentioning

confidence: 99%

Comparative Effects of Oral and Injectable Bisphosphonates in Primary Human Gingival Fibroblasts

Bălean¹,

Floare²,

Focht³

et al. 2019

Rev. Chim.

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show abstract

“…Our results showed that F and A become cytotoxic even at low concentrations as 1.5 µM (see Figure 1B) and also cells morphology was altered (see Figures 3 and 4), whereas O and Z had no cytotoxic effects at the concentrations tested (1.5; 2.5; 5 and 10 µM) (see Figure 1A). The cytotoxic effect of alendronate -F on human primary gingival fibroblasts was also shown by other groups of research [27,28,29], data that are in agreement with these results. Stimulation of human stem cells derived from the gingiva with risedronate in the range of 1-10 µM led to changes in cells morphology and a reduced viability [30], findings that confirm our results.…”

Section: Bisphosphonates Decrease Human Primary Gingival Fibroblasts supporting

confidence: 90%

Ozone saline solution counteracts bisphosphonates noxious effects in primary human gingival fibroblasts

Bălean¹,

Floare²,

Focht³

et al. 2019

Preprint

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Background Bisphosphonates are effective antiresorptive agents frequently used in the treatment of different bone disorders, as osteoporosis, Paget’s disease and tumours that cause osteolysis. A major concern related to bisphosphonates therapy is represented by osteonecrosis of jaw, a serious, debilitating, and mostly, a therapy-resistant disease, reported as a frequent side effect of bisphosphonates. In the present study were proposed two approaches: 1) to verify the impact of four commercially available bisphosphonates, very frequently used as oral (Fosamax - F and Actonel - A) and injectable (Ossica - O and Zoledronic acid - Z) therapy on primary human gingival fibroblasts - HGF viability and 2) to evaluate the protective effect of an ozone saline solution on HGF cells pretreated with bisphosphonates. Methods Alamar blue cell viability assay was performed to assess the effect of test compounds (1.5; 2.5; 5 and 10 μM) on gingival fibroblasts viability after a 24 h interval. An ozone - O3 saline solution – 80 µg/mL was added to bisphosphonates pretreated fibroblasts for 24 h and cell viability and cell morphology changes were determined by the means of Alamar blue test and microscopic images. Results Fosamax and Actonel induced a significant reduction of HGF cells viability even at concentrations as low as 2.5 μM (82 and 79.33%) and changes in cells morphology (round and floating cells), effects that were reversed by O3 saline solution administration: an increased cell viability after F and A at 2.5 μM: 147.54 and 120.11%), no changes in cells morphology and an improved confluence. Ossica and Zoledronic acid exerted no cytotoxic effect. Conclusions In conclusion, in these experimental conditions, injectable bisphosphonates (O and Z) proved to be safe for HGF cells, whereas oral compounds (F and A) were cytotoxic even at low concentrations, effects that were counteracted by O3 saline solution administration. Based on these data, ozone saline solution might represent a therapeutic alternative for bisphosphonates noxious effects on oral mucosa cells.

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“…e drug accumulating e ect on di erent sites of skeletal bones might play a part in the site-speci c e ect of MRONJ. Studies showed that BPs exerted direct toxic e ects on oral epithelial cells and broblasts when accumulated at su cient concentrations in bone tissue [19][20][21][22]. is toxic e ect further led to delayed so tissue healing and secondary infection and resulted in necrosis of the underlying bone.…”

Section: Discussionmentioning

confidence: 99%

Skeletal Site-Specific Response of Jawbones and Long Bones to Surgical Interventions in Rats Treated with Zoledronic Acid

Wang

Huo

et al. 2019

BioMed Research International

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Bisphosphonates (BPs) have been extensively used for management of bone diseases with pathologically high resorption. Despite the great clinical benefits, a severe complication known as medication-related osteonecrosis of the jaw (MRONJ) has been reported. It is found that most of the reported MRONJ cases were limited in the jawbones/craniofacial bones instead of long bones. The present study aims to investigate the differential bone response to surgical procedures between jawbones and long bones exposed to BPs. Forty-eight skeletal mature Sprague Dawley female rats were administered oncologic dose of zoledronic acid (ZA) or normal saline for 4 weeks and then subjected to tooth extraction on the mandible and maxilla, and a bone defect creation on the femur. After surgical procedures, ZA or saline treatment were continued until sacrifice at week 2, week 4, and week 8, post-operatively. The samples were subjected to micro-computerized tomography (micro-CT) and histological assessment. Osteonecrosis was only found in jawbones in ZA-treated rats. ZA-treated rats showed significantly higher bone mineral density with greater bone volume in all surgical sites than that in the controls. The length of exposure of ZA did not seem to affect trabecular microstructure, and it only showed higher bone volume and BMD with longer healing time which is expected in the healing process.

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Effects of alendronate and pamidronate on apoptosis and cell proliferation in cultured primary human gingival fibroblasts

Cited by 23 publications

References 33 publications

Comparative Effects of Oral and Injectable Bisphosphonates in Primary Human Gingival Fibroblasts

Comparative Effects of Oral and Injectable Bisphosphonates in Primary Human Gingival Fibroblasts

Ozone saline solution counteracts bisphosphonates noxious effects in primary human gingival fibroblasts

Skeletal Site-Specific Response of Jawbones and Long Bones to Surgical Interventions in Rats Treated with Zoledronic Acid

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