Risk of Severe Upper Gastrointestinal Complications among Oral Bisphosphonate Users

Abstract

BackgroundOral bisphosphonates (BPs) are the primary agents for the treatment of osteoporosis. Although BPs are generally well tolerated, serious gastrointestinal adverse events have been observed.AimTo assess the risk of severe upper gastrointestinal complications (UGIC) among BP users by means of a large study based on a network of Italian healthcare utilization databases.MethodsA nested case-control study was carried out by including 110,220 patients aged 45 years or older who, from 2003 until 2005, were treated with oral BPs. Cases were the 862 patients who experienced the outcome (hospitalization for UGIC) until 2007. Up to 20 controls were randomly selected for each case. Conditional logistic regression model was used to estimate odds ratio (OR) associated with current use of BPs after adjusting for several covariates. A set of sensitivity analyses was performed in order to account for sources of systematic uncertainty.ResultsThe adjusted OR for current use of BPs with respect to past use was 0.94 (95% CI 0.81 to 1.08). There was no evidence that this risk changed either with BP type and regimen, or concurrent use of other drugs or previous hospitalizations.ConclusionsNo evidence was found that current use of BPs increases the risk of severe upper gastrointestinal complications compared to past use.

Stem cells in Osteoporosis: From Biology to New Therapeutic Approaches

“…Bisphosphonates, which are nonhydrolysable pyrophosphate analogs, inhibit the absorption of bone mass by disrupting the function of osteoclasts and affecting their survival via a disorder of the subcellular localization and the normal function of certain signaling proteins which leads to accumulation of toxic nucleotide metabolites [27]. Although bisphosphonates are the most common treatment of osteoporosis, generally well tolerated and reduce the risk of osteoporotic-related fractures, a number of serious adverse events have been observed to occur [28], such as osteonecrosis of the jaw, gastrointestinal upsets, renal complications, and atypical femoral fractures [29–33]. Another agent that reduces bone loss and minimizes the risk of bone fracture is calcitonin, which is a hormone produced and secreted by the C cells of the thyroid gland.…”

Immeasurable time bias due to hospitalization in medico‐administrative databases: which impact for pharmacoepidemiological studies?

“…From a causality point of view, some of the deaths occurring during unobservable time could also be attributed to BZD exposure (through an indirect pathway exposed → hospitalized → death). Possibility of early deaths after hospital discharge has also to be considered (exposed → hospitalized → discharge → death), and some studies have discussed the choice of this post‐discharge period …”

“…Some other authors censored patients' follow‐up during hospitalization and up to discharge for a fixed number of days. In Ghirardi's study, patients were temporarily censored at the date of hospital admission and re‐established 10 days after hospital discharge . Cook et al .…”

Treatment with once‐weekly alendronate oral jelly compared with once‐weekly alendronate oral tablet for Japanese patients with primary osteoporosis: An open‐label, prospective, observational study

“…Although previous studies reported that patients taking oral bisphosphonates develop upper gastrointestinal symptoms, recent studies have failed to find a relationship between the use of oral bisphosphonates and upper gastrointestinal symptoms . Conversely, upper gastrointestinal symptoms were not associated with the administration of oral bisphosphonates . The poor reported adherence to oral bisphosphonates is attributable to adverse drug reactions and the complexity of dosage, and around 50% of patients discontinue within a year of initiating treatment .…”

“…[17][18][19][20] Conversely, upper gastrointestinal symptoms were not associated with the administration of oral bisphosphonates. [21][22][23][24][25] The poor reported adherence to oral bisphosphonates is attributable to adverse drug reactions and the complexity of dosage, and around 50% of patients discontinue within a year of initiating treatment. [26][27][28][29][30] Previous reports indicate that fracture prevention effects can only be achieved with good treatment adherence or an approximate medication possession ratio of >80%.…”