New data suggest that women with knee osteoarthritis (OA) treated with raloxifene (RLX) may have a statistically significant decrease in type II collagen (CTX-II) and cartilage-specific C-terminal tetrapeptide of type II collagen (CTX-II/Cr) excretion with a simultaneous significant lowering of WOMAC index compared to placebo, according to research presented at the 10th OARSI World Congress on Osteoarthritis.¹

Researchers in Poland conducted a study with 65 women, aged 52 to 79 (mean age 65.4 years) with diagnosed knee OA according to ACR criteria. All the women were rated on a 3-point Kellgren-Lawrence scale, with low bone mass. The women were randomly assigned to either placebo or 12 months of treatment with RLX 60 mg/day. All the women received up to 1200 mg of calcium, 800 IU of vitamin D, and tramadol 50 mg once or twice daily as needed for pain.

The researchers measured the effects of RLX based on an analysis of urine specimens of CTX-II/Cr and cartilage oligometric matrix protein (COMP) with the ELISA method. The researchers also monitored bone turnover with bone-specific alkaline phosphatase (b-ALP), osteoprotegerin (OP), bone-specific C-terminal tetrapeptide of type I collagen (CTC-I), and soluble NF-kappa-B receptor activator with the ELISA method. The markers were monitored before the study and after 3, 6, and 12 months of treatment with RLX.

The investigators found statistically significant decreases in OP, CTX-II, and CTX-II/CR in those women treated with RLX, and no changes in the control group. At the end of 12 weeks, the women treated with RLX showed a 30% decrease in CTX-II and a 40% decrease in CTX-II/Cr. There was also a simultaneous significant lowering of WOMAC index in the RLX treated group compared to the control group. No differences were noted between the two groups for markers of bone metabolism and their correlation with markers of cartilage degeneration or COMP changes.

"[It] seems that raloxifene has a curative effect on cartilage degradation with improvement in clinical outcomes," the researchers conclude. "There was no evidence of interaction between cartilage and bone metabolism except a decrease in OP."

New findings are promising but very preliminary

These markers "are blood markers and not direct markers from the joint fluid; while they are commonly used, they are still somewhat questionable in terms of what they really show," cautions Robert Willkens, MD, clinical professor of medicine and rheumatology at the University of Washington in Seattle. "[Researchers] need to show radiologically an increase in cartilage. If we can demonstrate that the cartilage is regrown or [show] an increase in cartilage thickness with radiographic images, then that would be more clinically significant than just showing improvement in bone markers."

Rheumatologist Richard Brasington, MD, associate professor of medicine at Washington University School of Medicine in St. Louis, Missouri, agrees. He says that these types of biomarkers have not been definitively validated and that the authors of the study did not address the mechanism of action of RLX.

"I certainly wouldn't use the word ‘curative,'" Dr. Brasington says. "This kind of trial is state of the art. It uses the kind of markers we have right now, but we need to have better biomarkers and better correlations with biomarkers. One year is a long time to do a study, but it is a very short time in terms of OA, because people have OA for decades."

However, Dr. Brasington continues, "there aren't any other medicines out there that can make this claim. To reduce the rate of progression is the holy grail. Right now in OA all we can do now is make people feel better. We need to be able to shut down the disease process. So these are promising results and this good news."
 

Reference

1.  Daniluk S, Badurski JE, Dobrenko A, et al. The inhibition of cartilage degradation markers excretion after treatment with raloxifene in women with knee osteoarthritis. Presented at: 10th World Congress of the Osteoarthritis Research Society International; December 8–11, 2005; Boston, Mass. Abstract P67.