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.”