Use of proton pump inhibitors and risk of fragility hip fracture in a Mediterranean region
OBJECTIVE: To determine whether there is an increased risk of hip fracture associated with the use of proton pump inhibitors in a Mediterranean area after adjusting for other potential risk factors. METHODS: Retrospective multicenter case-control study carried out in 6 primary health care centers in Catalonia, Spain. Cases were patients aged 50years and over with a fragility hip fracture registered between January 2007 and December 2010, matched with 2 controls by sex and age. Data collected: use of proton pump inhibitors (type, dosage) in the 5years previous to the hip fracture, socio-demographic data, body mass index, alcohol and tobacco consumption as well as health conditions and drugs associated with an increase risk of fragility hip fracture. RESULTS: 358 cases were matched with 698 controls. The mean age was 82years old in both groups. Women represented 77.1% in the case group and 76.9% in the control group. Crude association between proton pump inhibitors and hip fracture was 1.44 (95% CI, 1.09-1.89) and adjusted OR was 1.24 (95% CI, 0.93-1.65). No association was found with the continuous or discontinuous use of proton pump inhibitors, OR 1.17 (95% CI, 0.77-1.79), and OR of 1.16 (95% CI, 0.85-1.60) respectively. No association was found when restricting the analysis by sex, OR of 1.19 (95% CI, 0.27-5.14) or by age, younger or older than 80years, OR of 0.72 (95% CI, 0.24-2.15). CONCLUSION: The use of proton pump inhibitors was not associated with an increased risk of hip fracture after adjusting for other risk factors in a Mediterranean area. This result suggests the existence of protective environmental factors linked to this southern area of Europe that eventually could compensate for the potential harm produced by proton pump inhibitors.
[Show abstract] [Hide abstract] ABSTRACT: The increased rate of fractures associated with epilepsy has been long recognised but remains incompletely understood. Study quality and study results have varied, with some but not all studies showing bone diseases including osteoporosis and/or osteomalacia, and a high prevalence of vitamin D insufficiency and deficiency are also noted. Falls risk can also be higher in patients with epilepsy taking anti-epileptic medications, potentially leading to fracture. Larger research collaborations are recommended to further advance understanding in this field, particularly to examine underlying genetic and pharmacogenomic associations of epilepsy and anti-epileptic medication usage and its association with bone diseases and fractures, as well as further investigation into optimal management of bone health in epilepsy.
- "The adjusted conditional logistic regression gave an odds ratio for hip fractures in users of anti-epileptic medications of 3.36 (CI 1.13–9.96), although due to the limited numbers in this subgroup, the study was not well-powered to examine for effects of AEM and it was not a primary outcome measure ; this rate is similar to a Southern European study of men aged over 50 years where hip fracture relative risk with use of AEM was 3.16 , but higher than other studies such as a UK cohort study where the adjusted hazard ratio with use of inducer , and a Danish study of men over 50 years discharged from hospital with a fracture, where the "
[Show abstract] [Hide abstract] ABSTRACT: Opinion statement: There are 34 studies in almost 2 million participants that have reported on the association between proton pump inhibitor (PPI) therapy and risk of fracture. There is substantial variation between the results of each study but systematic reviews of the data suggest overall there is an association between PPI therapy and risk of fracture. The magnitude of the association is modest and is most likely due to confounding factors as patients prescribed PPI therapy tend to be more frail with more risk factors for fractures than those not given these drugs. There is no clear dose-response relationship and there is no association between PPI therapy and risk of fracture in those at highest risk. Finally, there is no clear mechanism through which PPI therapy increases the risk of fracture, as recent randomized trials show no impact of PPI therapy on calcium absorption and there is no association between PPI therapy and risk of osteoporosis. We therefore feel there is insufficient evidence to change PPI prescribing habits based on risk of fracture. Similarly, we do not recommend bone mineral density investigations for patients taking PPI therapy other than would be normally indicated. There is no evidence to support prescription of calcium and/or vitamin D in patients simply because they are taking PPI therapy. As with all medications, we only recommend prescribing PPI therapy when there is a clear indication that benefit will outweigh risk and at the lowest effective dose. Patients should be regularly assessed as to whether acid suppression is still required.
- "The literature search that was performed in May 2013 identified 25 relevant observational studies. A meta-analysis of the 13 case–control studies [11, 12,2122232425262728293031 that comprised 1,105,595 participants showed that PPI treatment was associated with hip fracture; the pooled odds ratio (OR) was 1.21; 95 % confidence interval (CI) 1.07– 1.38, with substantial heterogeneity that could not be explained by subgroup analyses. A meta-analysis of the 12 cohort studies323334353637383940414243 that included 834,442 participants (3,712,891 patient-years of follow up) also showed a statistically significant association between PPI treatment and hip fracture; the pooled relative risk [RR] was 1.30; 95 % CI 1.13–1.49, "
- [Show abstract] [Hide abstract] ABSTRACT: There have been numerous studies investigating the risk of fracture with PPI therapy since the CAG position statement in 2008. These data, however, do not change the conclusions of the original position statement. Current data would not support particular care in prescribing PPI therapy due to concerns about risk of fracture. The risk is extremely modest and there is no persuasive evidence that even this risk is causal and the association could be spurious. As with all medications, PPIs should only be given when there are clear indications that the benefit of therapy outweighs the risk.