Arthritis Today

Understanding the Link Between RA and Bone Loss

Both inflammation and some inflammation-fighting drugs can leach bone mineral density. Find out what you can do.


At the onset of rheumatoid arthritis (RA), a rheumatologist takes immediate steps to control the inflammation that causes severe pain, swelling and destruction of cartilage. Cartilage is not the only tissue at risk, however. Your bones can also be destroyed by the effects of inflammation, as well as from many of the drugs used to control that inflammation.

“It’s been suggested that active, systemic inflammation – the production of inflammatory cytokines – has some negative action with bone remodeling,” says Seo Young Kim, MD, a rheumatologist and researcher at Brigham and Women’s Hospital in Boston, who has studied the connection among RA, common RA drugs to fight inflammation and the loss of bone mineral density that can increase the risk of fracture.

“The bottom line is that people with RA have a high risk of osteoporotic fracture at the typical sites: the hip, forearm, pelvis,” she says. Dr. Kim estimates that if you have RA, your risk of these fractures is 25 to 30 percent higher than the average population.

“We are all losing bone mass, but some things, like RA, speed up that process,” says Michael DiMuzio, PhD, executive director of the North Shore Osteoporosis Center in Highland Park, Ill.

RA’s inflammation contributes to the damage to bone, possibly by stimulating osteoclasts, bone cells that deplete bone minerals. Prednisone, a common, inexpensive corticosteroid drug used for decades to control inflammation, is one of the notorious culprits in bone mineral density loss.

“Prednisone stops the function of bone-forming cells. When that happens, the body still needs calcium, so it takes it out of the bone, but it’s not allowing the bone-forming cells to put it back,” he says. The result: Weakened bones that boost a person’s risk for falls and painful fractures.

Corticosteroid drugs like prednisone and even disease-modifying antirheumatic drugs like methotrexate can interfere with the body’s natural process of bone remodeling – the body’s way of  putting calcium back into bone to keep it strong. Newer inflammation-fighting drugs, like the biologic class of drugs that include TNF inhibitors etanercept and adalimumab, can control inflammation without interfering with bone remodeling.

Some early studies suggest that they may help reduce bone loss or boost bone mineral density build-up for RA patients. But experts are divided on whether the bone mineral density benefit of using these powerful – but expensive – new drugs is that they aggressively control inflammation early and, therefore, prevent bone loss, or whether the drugs themselves protect the bones apart from their inflammation-fighting power.

Bones Don’t Sit Still

Bones are active organs that change every day throughout our lives, says DiMuzio. At his suburban Chicago center, he measures bone density in a variety of patients, including many with active RA, who are either at risk for or who have developed osteoporosis, a common disease where bone mineral density is considerably reduced from normal, healthy levels.

Bone mineral density loss can occur over time due to various factors: chronic inflammation, long-term use of corticosteroid drugs, inadequate dietary intake of calcium, or lack of weight-bearing exercise that strengthens bones, DiMuzio explains.

“Our bones are a reservoir for this key mineral, calcium. Calcium is coming out of our bones all the time. It comes out through our kidneys, and we leave it in the toilet. So we have to find a way to put calcium back into our bones,” he says.

In addition to the bone-leaching potential of corticosteroids or even methotrexate, which was used at higher, more toxic doses in the past to treat RA inflammation, other factors common in people with RA can contribute to bone loss. RA pain, swelling or fatigue may keep you from daily weight-bearing activities like walking that can help strengthen bone.

Consumption of calcium in food or supplements can help replenish this lost mineral that is a building block of healthy bone. Yet drugs like proton pump inhibitors, used by some people with RA to protect the stomach from the effects of nonsteroidal anti-inflammatory drugs (NSAIDs), can interfere with calcium absorption.

As people age, they are also at increased risk of developing osteoporosis, as our bodies stop actively building bone mass at about age 30.

“A lot of our patients fit those risk factors, including age, medications and sedentary lifestyle,” says Carolyn Felton, MD, a rheumatologist at Piedmont Arthritis and Rheumatology in Atlanta. Dr. Felton was formerly on the staff of the United Osteoporosis Center in Gainesville, Fla.

To prevent bone mineral density loss and increased fracture risk, people with RA should “modify any risk factors you can, because prevention is key. If you have RA, you could also start preventive measures at a younger age” than someone without RA might do, Dr. Felton suggests.

She says she discusses calcium and vitamin D intake and regular weight-bearing exercise with all of her RA patients to prevent bone mineral density loss and tries to use prednisone for no more than three months’ duration if possible for the same reason.

With any RA patient, aggressively treating inflammation early may prevent damage to bones, cartilage and other tissue, says Dr. Felton. “Treating the underlying inflammation is important in preventing bone loss. We have medications that are effective at treating the underlying inflammation which helps to prevent bone loss and loss of function. If there is the additional benefit that the TNF inhibitors help to build bone it may be an indication to start these medications earlier for those that do not have any contraindications.”

Do Biologics Boost Bone?

Studies on the positive effects of biologic drugs on bone mineral density are early, small and somewhat mixed. Dr. Kim led a population-based cohort study published last December using health care utilization data for the years 1996 to 2008 – the prime years when biologic drugs were coming onto the market – in both the U.S. and Canada that tracked non-vertebral fracture risk in more than 16,000 RA patients on one of three different treatments: methotrexate, a TNF-inhibitor biologic drug, or another non-biologic DMARD.

She and her colleagues looked at hospitalizations for fractures of the hip, wrist, humerus (forearm bone) or pelvis. They found only a slightly better outcome for RA patients using TNF inhibitors: 5.11 incidence rate of fracture versus 5.35 for methotrexate and 6.38 for other DMARDs.

“I didn’t see any significant increase or decrease in any of the three groups,” says Dr. Kim. Methotrexate, once believed to be harmful for bones, is no longer used at high doses as in the past, so its impact may be lessened, she notes. As for the purported benefit of biologics? “Whether TNF inhibitors can improve the risk of fracture is still up in the air,” she says.

She feels that the studies that show some bone-protecting benefits are relatively small – observing 100 to 200 patients – and more, larger studies are needed.

DiMuzio doesn’t believe that TNF inhibitors positively affect bone in addition to inhibiting inflammation. “I haven’t seen any evidence that these new drugs like Enbrel (etanercept) have any effect on bone. Their effect is on inflammation of the cartilage, and cartilage and bone are two very different things,” he says. “Cartilage doesn’t remodel.”

But Dr. Felton is encouraged by some of these small studies on the bone benefits of TNF inhibitors. “From what I’ve read, it looks like an independent effect” on bone mineral density, not just an outcome of controlled inflammation.”

One promising Norwegian study published in the journal BMC Musculoskeletal Disorders in 2011 looked at the benefits of combining the TNF inhibitor adalimumab with methotrexate versus using methotrexate alone for periarticular bone loss in 214 RA patients. These researchers found that those patients treated with methotrexate alone showed greater bone loss in digital X-ray radiography than those using the combination regimen, leading the researchers to conclude that the inflammatory cytokine TNF-alpha stimulates osteoclasts, bone cells that deplete bone tissue. Inhibiting TNF-alpha with drugs like adalimumab may reduce the amount of destructive osteoclasts produced, the study suggests.

Another Taiwan-based study published in 2011 also showed that inhibiting the inflammatory cytokine IL-20 could lessen the production of damaging osteoclasts.

Bone-Healthy Lifestyle

While these doctors disagree on the evidence of the bone building benefits of TNF inhibitors, they all strongly support the use of drugs to control inflammation as a way to protect bones as well as other tissue. In addition to medications, RA patients can protect their bones by committing to taking calcium and vitamin D, eating a healthy diet rich in those nutrients, and getting regular weight-bearing exercise can help reduce fracture risk if you have RA. 

“I always tell my patients that you have to be really religious about it,” DiMuzio says about bone-building lifestyle modifications. “You have to believe it will be useful, even though you won’t see or feel it. You’ll slow down bone loss – and that is what we all want to do every day.”