Averting arthritis

INDIANAPOLIS -- A study led by Indiana University scientists found that a common antibiotic appears to reduce cartilage loss and pain in women whose knees show early signs of the crippling effects of osteoarthritis.

The results suggest that doxycycline, a prescription medicine used to treat infections and acne, suppresses enzymes that damage cartilage and may protect cartilage not yet affected by the degenerative disease, said the scientist who led the study.

Kenneth D. Brandt, a professor of medicine and of orthopedic surgery at the Indiana University School of Medicine, said the study is the first to convincingly demonstrate a pharmacological effect in slowing cartilage damage in patients with osteoarthritis.

He said the findings do not necessarily mean doxycycline could be a treatment for osteoarthritis, but instead suggest a relatively fast method for testing a wide range of drugs on a condition common among older Americans, especially women.

"Up until this point there has been a general inhibition of doing this type of research," Brandt said. "The question has been, 'Could it demonstrate a drug effect in people in a study that didn't cost the moon and take 20 years to show?"'

Brandt, who was the principal investigator for the National Institutes of Health-funded study, hopes the findings encourage other scientists and the pharmaceutical industry to develop a variety of agents that can be similarly tested.

Osteoarthritis is the leading cause of disability among elderly Americans, afflicting about 70 percent of people over the age of 60.

The study was conducted over a 30-month period at six sites across the nation on overweight women ranging in age from 45 to 64 years.

Study participants had standard X-ray evidence of osteoarthritis in only one knee at the start of the trial but were at very high risk for the development of osteoarthritis in the good knee in the near future, Brandt said.

Half of the 431 participants were randomly assigned to receive a placebo, and the other half received doxycycline. Both the placebo and the 100 milligrams of the antibiotic were administered twice daily to each participant.

At the end of the 30 months, X-rays showed that the women who received doxycycline had an average 33 percent less cartilage loss -- about 0.15 of a millimeter less -- in their affected knee, compared with the group that received the placebo.

There was also preliminary evidence that doxycycline had a beneficial effect on the participants' unaffected knees.

Less increase in knee pain

In addition, Brandt said the results showed that women taking doxycycline were less likely to report "clinically significant increases" in knee pain compared with those in the placebo group. And participants with the most frequent increases in joint pain exhibited the most rapid loss of cartilage, he said.

Brandt said further study is needed to determine whether cartilage loss causes pain or whether other factors may be to blame.

He said the study's most important contribution was using fluoroscopy -- a technique for obtaining "live" X-ray images of a living patient -- to place each subject's knees in the same position for the series of X-rays that tracked changes in knee cartilage.

The study's initial results were released in November at the annual scientific meeting of the American College of Rheumatology.

Marc C. Hochberg, a professor of medicine at the University of Maryland in Baltimore who was not involved in the study, said the findings are compelling and add to evidence that certain enzymes produced by the body destroy cartilage.

Similar results with doxycycline had already been shown in animal studies, and the next step will be to replicate Brandt's findings, he said.

"It would be nice to see a second study to replicate the results before we go out with this recommendation that our patients take doxycycline," Hochberg said.

He said some researchers are already trying to chemically modify some tetracyclines -- a family of antibiotics of which doxycycline is a member -- to remove their antibacterial qualities but preserve their ability to suppress the damaging enzymes.

The goal would be a drug that provides a therapy for osteoarthritis without the common side effects of antibiotics, including nausea, vomiting and light sensitivity.