January 8, 2010 — Patients with pernicious anemia have significantly higher risks for hip fracture, research shows.
Compared to age- and sex-matched controls, patients with pernicious anemia had a 73% greater risk of hip fracture (3.4 vs. 2.0 hip fractures/1000 person-years of follow-up). The elevated risk was even greater with newly diagnosed pernicious anemia (HR, 2.63).
"These data suggest that physicians need to carefully follow the bone health of patients with pernicious anemia," senior author Dr. Yu-Xiao Yang of the University of Pennsylvania School of Medicine in Philadelphia noted in an email to Reuters Health.
Additionally, Dr. Yang and colleagues found that the increased risk of hip fracture persisted for many years even after vitamin B12 repletion therapy was started.
"Physicians should recognize that correction of their vitamin B12 deficiency alone is probably insufficient in reducing the risk of fractures in these patients. The persistent nature of the elevated fracture risk in these patients suggests the presence of underlying mechanisms independent of vitamin B12 deficiency," Dr. Yang said.
There are physiologic reasons to suspect that patients with pernicious anemia (who are by definition achlorhydric) may have impaired bone strength and increased fall risk (i.e., due to vitamin B12 deficiency), but there have been no definitive epidemiologic data to confirm an increased fracture risk in these patients, the researcher explained.
The new findings stem from an analysis of data from the United Kingdom's General Practice Research Database. Included were 9506 adults with pernicious anemia who received vitamin B12 therapy for at least 1 year. Each case patient was matched with four controls without pernicious anemia (n = 38,024). The average follow-up time in both groups was slightly more than 5 years.
As reported online December 18 in Gastroenterology, the increased risk of hip fracture appeared to persist well beyond 5 years after the diagnosis of pernicious anemia and initiation of vitamin B12 therapy. Pernicious anemia was associated with a threefold increased risk of hip fracture when follow-up years 3 through 10 were combined in the analysis.
"One potential mechanism," Dr. Yang said, "may be related to the achlorhydria-induced hypergastrinemia in these patients that could lead to parathyroid hyperplasia, which could result in increased parathyroid hormone secretion or altered parathyroid hormone secretion pattern."
Another possibility is that their lack of gastric acid may compromise calcium absorption in the intestine. "Therefore," Dr. Yang advised, "physicians should at least ensure that these patients maintain daily recommended calcium intake appropriate for their age, and preferably by taking water-soluble calcium supplements (e.g., calcium citrate) or through dairy products. If they must take water-insoluble calcium supplements (e.g., calcium carbonate), they should take them with a meal."
Both of these potential mechanisms, Dr. Yang noted, may also be relevant to the reported association between acid suppressive therapy and increased risk of fractures.
"Further research is urgently needed to investigate these potential mechanisms so that effective preventive measures can be developed both for patients with pernicious anemia and for the large population of patients who require chronic acid suppressive therapy," he concluded.
Gastroenterology. Published online December 18, 2009. Abstract
Reuters Health Information 2010. © 2010 Reuters Ltd.
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