The association between serious upper gastrointestinal bleeding and incident bisphosphonate use: a population-based nested cohort study

Abstract

BackgroundOral bisphosphonates are commonly used to prevent / treat osteoporosis. However, bisphosphonate treatment is not without risk and serious adverse effects, including upper gastrointestinal bleeding (UGIB) have been described. We sought to determine if new users of bisphosphonate drugs were more likely to suffer a serious UGIB within 120 days of drug initiation.MethodsThis was a population-based nested cohort study utilizing administrative healthcare data in British Columbia, Canada. Community based individuals ≥ 65 years with a new prescription for a bisphosphonate between 1991 and 2007 were included. A multivariate logistic regression model was used to examine the relationship between older age and the development of a serious UGIB within 120 days of new exposure to oral bisphosphonate drugs.ResultsWithin the exposure cohort (n = 26,223), 117 individuals had suffered a serious UGIB within 120 days of incident bisphosphonate use. Cases tended to be > 80 years old, and were significantly more likely to have had a past history of gastric ulcer disease, a remote history of serious UGIB, and had been dispensed proton pump inhibitor (PPI) medications (p < 0.001 for all comparisons). After adjustment for confounding covariates, those > 80 years were more than twice as likely to suffer a UGIB when compared to those ≤ 80 years (adjusted OR = 2.03; 95% CI 1.40–2.94). A past history of serious UGIB was the strongest predictor of UGIB within 120 days of incident bisphosphonate use (adjusted OR = 2.28; 95% CI = 1.29–4.03) followed by PPI use (adjusted OR = 2.04; 95% CI = 1.35–3.07). Males were 70% more likely to suffer an UGIB compared to females (adjusted OR = 1.69; 95% CI = 1.05–2.72).ConclusionsUpper GIB is a rare, but serious, side effect of bisphosphonate therapy more often afflicting older individuals. At the same time, concern about potential rare adverse events should not discourage clinicians from prescribing bisphosphonate drugs, particularly in older patients who have already sustained a fragility fracture. Clinicians must remain cognizant of potential adverse events associated with bisphosphonate use and should routinely ask about pre-existing GI disorders and concurrent medication history prior to prescribing these drugs.

A Guide to Improving the Care of Patients with Fragility Fractures, Edition 2

“…Oral bisphosphonates can cause gastroesophageal side effects in patients. 377 Oral agents should not be used in patients with Barrett esophagitis, as these patients are at increased risk of esophageal cancer and any additional esophageal irritation should be avoided. Intravenous bisphosphonates are generally used when patients experience GI intolerance to oral agents or when patients have difficulty maintaining compliance with medication regimens (dementia and polypharmacy) and a notation of these reasons may be needed when applying for insurance approval.…”

Melatonin supports alendronate in preserving bone matrix and prevents gastric inflammation in ovariectomized rats

“…When OVX rats were injected weekly with alendronate, gastric injury has become evident, while antioxidant GSH levels were depleted. Despite the well-established side effects of the oral form on the upper gastrointestinal tract, 4 the injurious effect of parenteral alendronate was not documented before. Our findings also demonstrated that melatonin reduced gastric inflammation by depressing neutrophil infiltration and lipid peroxidation, and these receptor-independent effects of melatonin possibly depend on its radical scavenging actions.…”

“…1 Primary target in the treatment of osteoporosis is to reduce pain, to reduce the risk of fracture, and to improve impaired functions. 2 Since the anticatabolic bisphosphonate alendronate maintains bone mass via the inhibition of osteoclastic activity, it is the first-line medical treatment in post-menopausal osteoporosis 3,4 , during which disrupted bone remodelling with an accelerated bone resorption occurs due to the absence of oestrogen. 5 Despite its considerably safe and tolerable use, some side effects associated with its long-term or parenteral use, including gastrointestinal adverse events, [6][7][8] acute phase reaction, hypocalcaemia, osteonecrosis, and atypical fractures of jaw 9,10 were reported.…”

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, [14][15][16] recent studies have failed to find a relationship between the use of oral bisphosphonates and upper gastrointestinal symptoms. [17][18][19][20] Conversely, upper gastrointestinal symptoms were not associated with the administration of oral bisphosphonates.…”