BOSTON, Mass. – A recent assessment of a cohort of patients with radiographic knee osteoarthritis (OA) uncovered substantial variations in the serum concentrations of key biomarkers of disease activity throughout the morning hours, changes that may affect clinical assessment of disease progression, according to research presented here at the 10th OARSI World Congress on Osteoarthritis.
The study of 20 patients with radiographic OA of at least one knee, undertaken by researchers at Duke University Medical Center in Durham, North Carolina, demonstrated statistically significant variations in the morning concentrations of 6 of 11 biomarkers of OA, findings that should be taken into consideration to more precisely assess the progression of the disease.
"The big surprise of the study was that blood drawn in the evening was most indicative of the state of the subjects' arthritis, as indicated by x-ray," principal investigator Virginia Kraus, MD, tells CIAOMed. If these results are confirmed by larger studies, clinical practice may need to change, as blood samples are typically drawn in the morning, says Dr. Kraus, an associate professor in the division of rheumatology, department of medicine at Duke.
Biomarkers replacing x-rays for measuring joint space in OA progression
Biomarkers are increasingly replacing x-ray measurements of joint space in the evaluation of OA progression. The rationale, according to Joyce Kong, a research associate in the division of rheumatology at Duke University Medical Center, who presented the research, is that "by the time osteoarthritis is detected on x-ray, significant collagen degradation has already taken place." Nonetheless, only a couple of studies have investigated diurnal variations.
Patients in the study were admitted to Duke University Medical Center for an overnight stay for sampling serial blood and urine. Blood was taken between 6:00 and 8:00 PM on the evening of arrival after a day of normal activity. The next morning, following at least five hours' sleep, more blood and urine samples were taken at three points in time: just prior to arising at 8:00 AM (T0), 1 hour later (T1), and then 4 hours after arising (T2), during which time subjects ate breakfast and performed other daily activities.
Serum concentrations of hyaluronan (HA), cartilage oligomeric matrix protein (COMP), keratin sulfate (KS 5D4), and transforming growth factor-ß1 (TGF-ß1) increased significantly from T0 to T1 (P <.01, .001, .001, and .01, respectively). CPII, as well as COMP, KS 5D4, and TGF- ß1, increased significantly from T0 to T2 (P <.01, .001, .05, and .01, respectively).
Urinary CTX-II decreased significantly (P = .04) from T0 to T2. COMP increased significantly from T0 to T3 (P <.01), while uCTX-II decreased (P = .01). The biomarkers in which variation was not significant were C-reactive protein, RP, osteocalcin, C2C, and C1,2C.
According to Kong, in 1999 "[Daniel-Henri] Manicourt demonstrated significant changes in serum hyaluronic acid during the first hour of physical activity [in patients with RA]. We used [this study] as a template for our own." In Manicourt's study, the variation occurred in both controls and in active RA patients, but not in inactive RA patients. A September 2005 study by Dr. Kraus and colleagues showed an increase in serum hyaluronan among patients with OA of the knee after 1 hour of daily morning activities.
The new research points up the need to "standardize sample collection within and across studies," Kong concludes. Bruce Caterson, PhD, a member of the Connective Tissue Biology Research Group and a professor in the Cardiff School of Biosciences at the University of Cardiff in Cardiff, Wales, UK, agrees with this assessment. "This is an excellent piece of work that many of us in the biomarker field will copy to try to improve and standardize our results," he says.
One limitation of the study, however, is that "we don't differentiate eating from activity," Dr. Kraus tells CIAOMed. "A follow-up study is getting underway to do that."
Reference
- Kong SY, Stabler TV, Criscione LG, et al. Diurnal variation of biomarkers in patients with radiographic knee osteoarthritis. Presented at: 10th World Congress of the Osteoarthritis Research Society International (OARSI); December 8–11, 2005; Boston, Mass. Abstract A8.