Use of Proton Pump Inhibitors and Risk of Osteoporosis-Related Fractures

Abstract

O steoporosis is a common condition throughout the developed world, affecting up to 16% of women and 7% of men aged 50 years and older. 1 The presence of underlying osteoporosis is a major risk factor for the development of fractures of the hip, proximal femur, spinal vertebra and forearm. In 2000, the estimated number of people with fractures worldwide was 56 million, and about 9 million new osteoporotic fractures occur each year.2 In 1993/94, the number of hip fractures in Canada was 23 375.3 This number is predicted to increase to 88 124 by the year 2041, with a parallel increase in the number of days in hospital (465 000 patientdays in 1993/94 to 1.8 million in 2041).3 Moreover, the casefatality rate for hip fractures can exceed 20%, 4 and all osteoporosis-related fractures can lead to substantial long-term disability and decreased quality of life. 5Many risk factors for the development of osteoporosis-related fracture have been identified, including white ethnic background, low body mass index, physical inactivity and female sex. [6][7][8] There are also a number of medication classes, including corticosteroids and serotonin selective reuptake inhibitors, whose use has been linked to higher rates of osteoporosis.9-11 Furthermore, any condition or drug that increases the risk of falls and injury also increases the risk of an osteoporosis-related fracture. 12,13One medication class that may affect bone mineral metabolism is proton pump inhibitors. This class of drugs inhibits the production and intragastric secretion of hydrochloric acid, which is believed to be an important mediator of calcium absorption in the small intestine.14 Recent studies have suggested that the use of proton pump inhibitors for 1 or more years is associated with hip fracture and other osteoporotic fractures; however, there is limited data on additional risk beyond 4 years exposure. 15,16 Because proton pump inhibitors are commonly prescribed to control and prevent symptoms of chronic unrelenting conditions, it is likely that many patients will use these medications for more than 4 years. Therefore, we used an adminstrative database to examine the effects of longer durations of proton pump inhibitor use on the development of osteoporosis-related fractures. Methods Data sourcesWe performed a retrospective, matched cohort study using the Population Health Research Data Repository, which contains comprehensive health care utilization data for nearly all CMAJ ResearchBackground: The use of proton pump inhibitors has been associated with an increased risk of hip fracture. We sought to further explore the relation between duration of exposure to proton pump inhibitors and osteoporosis-related fractures. Methods:We used administrative claims data to identify patients with a fracture of the hip, vertebra or wrist between April 1996 and March 2004. Cases were each matched with 3 controls based on age, sex and comorbidities. We calculated adjusted odds ratios (OR) for the risk of hip fracture and all osteoporosis-related fractures for durations...

Fracture risk in patients receiving acid-suppressant medication alone and in combination with bisphosphonates

“…As with Yang et al [10], a significant increase in the risk of hip fracture and trends with dose for both PPI and H 2 RA use were observed. However, the magnitude of effect was smaller in this study, and it did not demonstrate the same pattern of effects with cumulative use over time, as reported by Yang et al and Targownik et al, who conducted a case-control study within a Canadian administrative claims database [10,15]. Other than the study designs, the major difference between these studies was the choice of comparison group.…”

“…Other than the study designs, the major difference between these studies was the choice of comparison group. Both case-control studies [10,15] compared patients who had used acid-suppressive medication with those who had never used such drugs; whilst here, a time-dependent approach was used along with a comparison of current to past use in the acid-suppressant cohort. This allows the recency of exposure as well as intermittent use to be taken into account and reduces the likelihood of confounding by indication.…”

Post hoc analysis of a single IV infusion of zoledronic acid versus daily oral risedronate on lumbar spine bone mineral density in different subgroups with glucocorticoid-induced osteoporosis

“…However, the long-term use of PPIs significantly increases the risk of osteoporosisrelated fracture [30,31]. In our study, zoledronic acid showed significant increases in LS BMD versus risedronate in patients with history of PPI use at baseline in the prevention subpopulation with no differences in anti-TNF and SSRI patient subgroups, which were relatively small.…”

The effect of proton pump inhibitors on fracture risk: report from the Canadian Multicenter Osteoporosis Study

“…Although not all studies have supported an increased risk of fracture with ongoing PPI use [27], the strength of the association between hip fracture and PPI use has been shown previously to increase with the duration of PPI therapy over a 4-year period [28]. Similarly, a Canadian study showed that hip fracture risk progressively increased in PPI users after 5 years of therapy, and all osteoporotic fractures increased after 7 years of PPI therapy [29]. Our study shows a similar trend and extends this observation to a 10-year period.…”