Gastric damage in the rat with nitrogen‐containing bisphosphonates depends on pH

Ma, Ben; Gw, Gibson; Wr, Myers; Ta, Dierckman; Rj, Phipps; Pn, Smith

doi:10.1046/j.1365-2036.2000.00816.x

Cited by 22 publications

(17 citation statements)

References 19 publications

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“…Although bisphosphonatesinduced gastric damage has been reported in an animal model to be pH dependent with increased damage at increasing pH, ulcerogenic effects of bisphosphonate co-therapy in our clinical setting did not seem to aggravate antisecretory agents that neutralize luminal gastric pH. 48 The mechanisms are unclear, but bisphosphonates-related mucosal damage may change with the doses and types of bisphosphonates and co-therapies.…”

Section: Discussionmentioning

confidence: 92%

“…Experimental studies in animal models have indicated that bisphosphonates have the potential to produce gastric mucosal irritation. [18][19][20][21] A number of short-term endoscopy studies have been performed to investigate the association between bisphosphonate treatment and the development of mucosal erosive lesions of the upper gastrointestinal (GI) tract. [22][23][24][25][26][27][28][29] Although the two representative bisphosphonates, alendronate and resedronate, have been demonstrated to have upper gastrointestinal safety and tolerability profi les comparable to those of placebo in large clinical studies, [30][31][32][33][34][35] there have not previously been endoscopic studies in the clinical setting that comprise long-term concomitant use of ulcerogenic agents such as NSAID, corticosteroids, and bisphosphonates.…”

Section: Introductionmentioning

confidence: 99%

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Bisphosphonate increases risk of gastroduodenal ulcer in rheumatoid arthritis patients on long-term nonsteroidal antiinflammatory drug therapy

et al. 2009

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Section: Discussionmentioning

confidence: 92%

Section: Introductionmentioning

confidence: 99%

Bisphosphonate increases risk of gastroduodenal ulcer in rheumatoid arthritis patients on long-term nonsteroidal antiinflammatory drug therapy

et al. 2009

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“…Studies conducted in animal models investigated the physiopathological mechanisms underlying GI AE occurrence after bisphosphonate ingestion, suggesting a direct correlation with low gastric pH [41,42]. The correlation between GI AE with increased pH and inflammation has been confirmed in these models using gastro protective and anti-inflammatory agents, showing a decrease in the occurrence and magnitude of these AE [43][44][45][46][47][48].…”

Section: New Alendronate Formulationmentioning

confidence: 94%

The potential impact of new effervescent alendronate formulation on compliance and persistence in osteoporosis treatment

2014

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Osteoporotic fractures are a public health problem and their incidence and subsequent economic and social costs are expected to rise in the next future. Different drugs have been developed to reduce osteoporosis and the risk of osteoporotic fractures, and among them, antiresorptive agents, and in particular oral alendronate, are the most widely utilized. However, one of the most common problems with antiresorptive drugs is poor adherence to treatment, which is associated with a high fracture incidence and with an increase in hospitalization costs. One of the main reasons of poor adherence to these treatments is the occurrence of adverse events, mainly at gastrointestinal (GI) level, including dyspepsia, dysphagia, and esophageal ulcers. In light of these considerations the aim of this paper is to perform a literature review to show the pathophysiologic bases of GI alendronate-induced adverse events and how new bisphosphonate formulations like effervescent alendronate can improve compliance and persistence to treatment and decrease the fracture rate incidence in osteoporotic patients.

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“…Similarly, it is well established that GI irritation is a common side effect of BP treatment. An interesting finding regarding GI irritation with BP is that these effects are enhanced in alkaline environments (9). These findings indicate separate effects of BP on membrane transport as well as paracellular transport processes, especially in GI epithelia, in which a barrier function is dependent on an intact (high resistance) paracellular pathway (for review, see Ref.…”

mentioning

confidence: 98%

Bisphosphonates stimulate an endogenous nonselective cation channel in Xenopus oocytes: potential mechanism of action

Shao¹,

Orlando²,

Awayda³

2005

American Journal of Physiology-Cell Physiology

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The mechanisms of action of bisphosphonates (BPs) have been poorly determined. Besides their actions on osteoclasts, these agents exhibit gastrointestinal complications. They have also recently been described as affecting various preparations that express an epithelial Na(+) channel (ENaC). To understand the effects of BP on ion channels and the ENaC in particular, we used the Xenopus oocyte expression system. Alendronate, and similarly risedronate, two aminobisphosphonates, caused a large stimulation of an endogenous nonselective cation conductance (NSCC). This stimulation averaged 63 +/- 12 muS (n = 18) 60 min after the addition of 2 mM alendronate. The effects on the endogenous NSCC were blocked by extracellular acidification to pH 6.4. On the other hand, alendronate caused a small inhibition of ENaC conductance at pH 7.4 and 6.4, but the effects at pH 6.4 were more readily observed in the absence of changes of the endogenous conductance. The effects on membrane capacitance were also markedly different, with a clear decrease at pH 6.4 and no consistent changes at pH 7.4. The effects on the endogenous channel were further augmented by genistein and were inhibited by a tyrosine phosphatase inhibitor, indicating the involvement of the tyrosine kinase pathway. Stimulation of NSCC with BP is expected to cause membrane depolarization and may explain, in part, its mechanisms of action in inhibiting osteoclasts.

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Gastric damage in the rat with nitrogen‐containing bisphosphonates depends on pH

Abstract: Gastric damage potential did not correlate with bone anti-resorptive effects, and the more potent anti-resorptive N-BPs were not necessarily more damaging to the stomach.

Cited by 22 publications

References 19 publications

Bisphosphonate increases risk of gastroduodenal ulcer in rheumatoid arthritis patients on long-term nonsteroidal antiinflammatory drug therapy

Bisphosphonate increases risk of gastroduodenal ulcer in rheumatoid arthritis patients on long-term nonsteroidal antiinflammatory drug therapy

The potential impact of new effervescent alendronate formulation on compliance and persistence in osteoporosis treatment

Bisphosphonates stimulate an endogenous nonselective cation channel in Xenopus oocytes: potential mechanism of action

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