Gastric and Esophagus Events Before and During Treatment of Osteoporosis

Abstract

Prior studies have indicated an excess risk of gastroduodenal ulcers and esophagus perforations with the use of bisphosphonates. However, little is known about the contribution of comorbid conditions and concomitant drug use on this risk. We studied the risk of esophagus and gastric events in patients on a wide range of drugs against osteoporosis both before and after initiation of these drugs. We studied a nationwide register-based cohort from Denmark with all users of drugs against osteoporosis between 1996 and 2006 (n = 103,562) as cases and three age- and sex-matched controls from the general population (n = 310,683). In a crude analysis, most drugs were already associated with an increased risk of esophagitis, esophageal ulcerations, or esophageal perforations or gastroduodenal ulcers before initiation of the drugs. Upon adjustment, this excess risk disappeared for most drugs except parathyroid hormone and its analogues, etidronate and clodronate. Only for etidronate, alendronate, and raloxifene were sufficient data present for events after initiation of the drugs, and for these, an increased risk was present for all events except gastroduodenal ulcers with raloxifene. Several drugs against osteoporosis are associated with an increased risk of esophagitis, esophageal ulcers, esophageal perforation, and gastroduodenal ulcers. However, the increase was already present before initiation of the drug for several types of drugs against osteoporosis. This points at an effect of the underlying condition being treated or comorbid conditions and drugs being provided in patients with osteoporosis, such as nonsteroidal anti-inflammatory drugs and corticosteroids.

Oral bisphosphonates and risk of cancer of oesophagus, stomach, and colorectum: case-control analysis within a UK primary care cohort

“…The effect of previous gastrointestinal disease on bisphosphonate prescribing is, however, probably more complex than this. 12 All the cases in this study were diagnosed several years before the publication of a possible link between bisphosphonates and oesophageal cancer, so the association cannot to be due to selective surveillance after publication of recent reports.…”

Gastrointestinal Events Among Patients Initiating Osteoporosis Therapy: A Retrospective Administrative Claims Database Analysis

“…17 The US Upper Gastrointestinal Study (N ¼ 9076 women) found that 21% of adult women experienced heartburn on a monthly basis. 18 Vestergaard et al 19 reported that Danish patients who started various osteoporosis therapies were already at increased risk of GI events, such as esophagitis, esophageal ulceration/perforation, and gastroduodenal ulcers, before taking the medications. Similarly, several US observational studies that reported both pre-initiation and post-initiation GI event rates found that the rate in the pre-initiation period was similar to (or greater than) that in the period of bisphosphonate use.…”

New strategies for osteoporosis patients previously managed with strontium ranelate

“…The usual contraindications such as risk of ulcerations in the upper gastrointestinal tract [Vestergaard et al 2010c] should of course be observed along with the more rare risk of osteonecrosis of the jaw [Khosla et al 2007;Cartsos et al 2008;Vestergaard, 2012]. Thus, the potential side effects of the alternative drug also need to be taken into consideration.…”