SAN DIEGO – Heart failure constitutes a previously unrecognized independent risk factor for major osteoporotic fractures, according to a Canadian cohort study.
"Patients with heart failure have double the 5-year risk of fracture," compared with those without heart failure. And "patients with heart failure have lower bone mineral density at every skeletal site at the time of their first test," compared with those without heart failure. "Finally, neither differences in bone mass nor shared risk factors [are enough] to explain the increased risk," said Dr. Sumit Majumdar at the annual meeting of the American Society for Bone and Mineral Research.
Dr. Sumit Majumdar
He presented a population-based cohort study that included all Manitobans older than age 50 years who had their first bone mineral density test in 1998-2009. The study earned him the 2011 ASBMR Most Outstanding Clinical Abstract Award.
Overall, 4% of the nearly 46,000 Manitobans who had an initial bone minteral density (BMD) test during the study years were identified as having recent-onset heart failure (that is, heart failure diagnosed within the previous 2 years). There were 2,703 new fractures in the study population during a median 5 years of follow-up. The recent heart failure group had a 10% incidence of major nontraumatic fractures of the upper extremities, vertebrae, and hip during the 5 years following the first BMD test, compared with a 5% incidence in subjects without heart failure.
The median time to first fracture in the heart failure group was 3.6 years. The curves describing fracture incidence started to diverge soon after the first BMD test and continued to widen throughout the maximum 10 years of follow-up, reported Dr. Majumdar, professor of general internal medicine at the University of Alberta, Edmonton.
Patients with heart failure had more of all the standard risk factors for osteoporosis (except weight) than did subjects without heart failure. They were significantly older (mean age, 74 vs. 66 years) and 21% of them had a prior major osteoporotic fracture, compared with 13% of those without heart failure. Some 12% of heart failure patients had been on systemic corticosteroids for longer than 90 days, compared with 4% of those without heart failure.
Moreover, 40% of heart failure patients had osteoporosis at the time of their first BMD measurement (defined as a T score less than –2.5 at any skeletal site), compared with 29% of individuals without heart failure. T scores were significantly lower in the heart failure group at all measured sites.
"A diagnosis of heart failure portends an increased risk of fracture greater than rheumatoid arthritis or prior fracture."
On the other hand, nearly every medication used in treating heart failure has previously been shown to increase BMD and to reduce fracture risk, with the exception of loop diuretics, which reduce BMD.
In addition, osteoporosis and heart failure are common, chronic conditions that share several etiologic risk factors, including older age, postmenopausal status, diabetes, and smoking, he continued.
The unadjusted risk of a major osteoporotic fracture was increased 2.45-fold in patients with heart failure. But upon adjustment in a multivariate analysis for nearly 30 potential confounders including age, sex, osteoporosis-related factors, medications, comorbidities, and total hip BMD, heart failure remained independently associated with a highly significant 28% increased risk of major osteoporotic fractures.
A disturbing finding of the study was that a mere 14% of heart failure patients who experienced an osteoporotic fracture were then placed on a bisphosphonate or other bone-protective therapy. Bisphosphonates had no association with mortality in the heart failure group.
"For clinicians, I think our study means we need to start understanding that a diagnosis of heart failure portends an increased risk of fracture greater than rheumatoid arthritis or prior fracture, in our data. And we need to learn that patients with heart failure are easily diagnosed and need much more attention to their bone health," Dr. Majumdar observed.
This study also opens up research opportunities for bench scientists, as the Manitoba database contains no information on patients’ aldosterone, parathyroid hormone, or vitamin D levels, or indeed on any other variables that might provide a mechanistic explanation for the link between heart failure and osteoporotic fractures.
"Ours is an example of bedside-to-bench research," he said.
In that vein, one audience member noted that increased adrenergic drive is a hallmark of heart failure. He wondered if heart failure patients on beta-blocker therapy had a lower fracture risk. Dr. Majumdar replied that he and his coinvestigators had had the same thought. However, when they specifically compared the nearly 35% of heart failure patients who were on a beta-blocker vs. those who weren’t, they found that fracture rates in the two groups weren’t significantly different.