Gastroenterology

Gastroenterology

Volume 138, Issue 4, April 2010, Pages 1330-1337
Gastroenterology

Clinical—Alimentary Tract
Hip Fracture Risk in Patients With a Diagnosis of Pernicious Anemia

https://doi.org/10.1053/j.gastro.2009.12.007Get rights and content

Background & Aims

Pernicious anemia (PA) is characterized by vitamin B-12 deficiency and achlorhydria, both of which have a detrimental effect on bone strength. The principle aim of this study was to determine the risk of hip fracture in patients with PA.

Methods

This is a retrospective cohort study using the General Practice Research Database (GPRD) from the United Kingdom. GPRD data from May 1987 until April 2002 were utilized to identify patients between 40 and 90 years of age at the time of GPRD enrollment. The exposed group contained patients with a diagnosis of PA being treated with vitamin B-12 therapy. We matched each patient having a diagnosis of PA with 4 randomly selected non-PA patients with respect to age (±1 year) and sex. Cox regression analysis was used to determine the hazard ratio (HR) for hip fracture associated with PA.

Results

Nine thousand five hundred six patients with a diagnosis of PA receiving vitamin B-12 injection therapy were identified and compared to 38,024 controls. Patients with PA had a greater risk of hip fracture than the controls (HR = 1.74; 95% CI: 1.45−2.08). The increase in hip fracture risk was even more pronounced among those patients newly diagnosed with PA during GPRD follow-up (HR = 2.63; 95% CI: 2.03−3.41).

Conclusions

Patients with a diagnosis of PA have an elevated risk of hip fracture. The increased hip fracture risk was persistent even years after vitamin B-12 therapy. Chronic achlorhydria could be the mechanism contributing to the persistently elevated hip fracture risk.

Section snippets

Study Design

We conducted a retrospective cohort study utilizing the General Practice Research Database (GPRD). The protocol for this study was approved by the University of Pennsylvania Institutional Review Board and the GPRD Independent Scientific Advisory Committee.

Data Source

The GPRD is a computerized medical record database system for general practitioners in the United Kingdom that was first established in May 1987.23 The database contains prospective information from >700 general practices in the United

Results

We identified 9544 patients with a diagnosis of PA who had received vitamin B-12 therapy for at least 1 year within GPRD. All but 38 (0.4%) of the 9544 patients with a diagnosis of PA were each matched with 4 sex- and age-comparable non-PA patients (n = 38,024). The 38 PA patients for whom no matched controls could be found were excluded from further analysis (Figure 1). The mean follow-up time was comparable among the controls compared to the patients with a diagnosis of PA (5.31 vs 5.17

Discussion

Patients with a diagnosis of PA have an increased risk of hip fracture compared to a control group from the same general UK population within the GPRD even after accounting for potential confounders. This risk increase was even more pronounced when the analysis was restricted to those patients newly diagnosed with PA after 1 year of GPRD follow-up. In addition, the increased risk of hip fracture among patients with a diagnosis of PA persisted after B-12 repletion.

There has been only 1 previous

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    Conflicts of interest The authors disclose the following: Dr Metz reports serving as a consultant and receiving honoraria and/or grant support from AstraZeneca, TAP Pharmaceutical Products, Altana, Wyeth-Ayerst Laboratories, Santarus, and Eisai. Dr Yang reports having served as a consultant for AstraZeneca and received grant support from AstraZeneca and GlaxoSmithKline. The remaining auhors disclose no conflicts.

    Funding Dr Merriman was supported by a National Institutes of Health educational training grant during his gastroenterology and epidemiologic training at the University of Pennsylvania. Dr Yang was supported by a National Institutes of Health/National Institute of Diabetes and Digestive and Kidney Diseases Mentored Career Development Award (K08 DK062978), which also funded the access to the data in the General Practice Research Database. This study was supported by an academic development fund from the University of Pennsylvania to Dr Yang. The funding sponsors played no role in the study design in the collection, analysis, and interpretation of data.

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