Hip fracture risk in patients with a diagnosis of pernicious anemia

Gastroenterology. 2010 Apr;138(4):1330-7. doi: 10.1053/j.gastro.2009.12.007. Epub 2009 Dec 21.


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.

Keywords: Pernicious anemia; hip fracture; osteoporosis; vitamin b12.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Achlorhydria / complications
  • Adult
  • Aged
  • Aged, 80 and over
  • Anemia, Pernicious / complications*
  • Anemia, Pernicious / drug therapy
  • Cohort Studies
  • Female
  • Hip Fractures / etiology*
  • Humans
  • Male
  • Middle Aged
  • Proportional Hazards Models
  • Retrospective Studies
  • Risk
  • Vitamin B 12 / therapeutic use


  • Vitamin B 12