Hemochromatosis – a genetic disorder that affects roughly a million Americans – is a condition in which too much iron is absorbed into the blood and stored in the tissues and organs of the body. Not only can it cause joint pain and damage, but according to new research, it also triples the risk for needing hip replacement surgery, and more than doubles the risk of needing knee replacement surgery.

“The joint changes seen in GH [genetic hemochromatosis] are similar to that in osteoarthritis and may result in limited joint function requiring joint replacement surgery,” says study co-author Maria Elmberg, MD, PhD, director of studies at the research school in epidemiology at the Karolinska Institute, Sweden.

“Previous studies suggest an elevated prevalence of clinical and radiographic signs of [diseased joints] significantly affecting quality of life in patients with GH, but our study compared the results to the general population,” she says.

The study also sought to answer an important question: given that hemochromatosis is a genetic disorder, are close family members of those diagnosed with GH at higher risk for joint problems?

Typically, hemochromatosis occurs when there are defects (mutations) in the HFE gene, which controls the amount of iron a person’s body absorbs from food. A person inherits two copies of the HFE gene – one from the mother and one from the father. When one copy of the gene has a mutation, the person is considered a carrier, but doesn’t generally develop symptoms of hemochromatosis (although they may absorb more iron than someone with no mutation). When a person inherits two mutated copies of the HFE gene, he or she may develop hemochromatosis – which, besides joint pain and damage, can lead to life-threatening complications involving major organs such as the liver and heart.

It is estimated that between 6 and 20 percent of people of northern and western European descent carry a mutation in one copy of the HFE gene. First-degree relatives (parents, siblings and offspring) of a hemochromatosis patient are assumed to carry one copy of the mutation.

The study, recently published online in Arthritis Care & Research, culled data from a variety of Swedish government sources to identify more than 3,500 hemochromatosis patients. The researchers also analyzed data from nearly 12,000 first-degree relatives of the patients to see whether having a single copy of the gene mutation also increases the risk for arthritis problems.

The study subjects were then matched against a large, “control” sample of the general population.

The study found not only a connection between hemochromatosis and arthritis, but also an increased risk of serious damage to the joints, necessitating hip, knee and even ankle replacement surgeries. But, there appeared to be no increased risk for diseased joints among the first-degree relatives.

James Haddow, MD, professor of pathology and laboratory medicine at the Warren Alpert Medical School at Brown University in Providence, RI, says this latter finding is important.  

“That is a very big finding,” says Dr. Haddow. “There was uncertainty about this until now. This was a strong study … thanks to the use of a highly reliable national health register.”

Dr. Haddow, past vice-president and medical director for the Foundation for Blood Research in Scarborough, Maine, says it’s well known that hemochromatosis affects the joints – especially in the hand. “One of the areas in the hand, the metacarpophalangeal [MCP] joint, acts as a target for the iron,” he says. So much so that the American College of Rheumatology considers the degeneration of the MCP joints characteristic of hemochromatosis.  

The study authors point out that while a connection between hemochromatosis and arthritis symptoms has been known for nearly 50 years, this research adds to the modest but growing body of evidence that hemochromatosis raises the risk for serious joint damage.

Another recent study also zeroed in on hemochromatosis as a risk factor for arthritis complications. Earlier this year, researchers in Melbourne, Australia linked having two copies of the genetic mutation that causes hemochromatosis with a six-times higher risk for total hip replacement surgery in both hips, compared to people without the genetic mutation.

Treatment of hemochromatosis involves reducing the total load of iron in the body, by periodic phlebotomy – the removing or drawing of blood. “It varies, but initially over a period of a month or two, you have to take out several units of blood,” says Dr. Haddow. “Maintenance phlebotomy follows, perhaps once every month or two depending on the patient.”

But while this treatment reduces overall iron load in the body, the study authors point out that it appears to do nothing to iron stores in the joints.

That said, exactly how iron causes joint destruction is unknown. The authors say it may be that iron ages and causes degeneration of the cartilage – or it may promote chemical crystallizations. On a cellular level, they say that whatever’s going on in the joints of those with hemochromatosis, it is different than what’s seen with osteoarthritis or rheumatoid arthritis.

The study raises the question of whether, among those with arthritis, there is a potential pool of undiagnosed hemochromatosis. Dr. Haddow says this is unlikely. The genetic mutation that causes hemochromatosis is most common in northern and western Europeans, where the rate is about 1 in 200 testing positive for mutations on both copies of the HFE gene.

“To further complicate matters, the current thinking is that only about 1 in 10 individuals with the genetic predisposition [those with two copies of the genetic mutation] become symptomatic,” Dr. Haddow says, “suggesting that the contribution of hemochromatosis to the arthritis pool is very small.”