Bone metabolism appears to change before patients show clinical signs of rheumatoid arthritis and could ultimately serve as an early marker of disease, based on a study of 79 patients with the disease.

"There appears to be an alteration in bone metabolism parallel to inflammation and autoimmunity in the asymptomatic preclinical phase of RA, which may reflect the beginning of joint destruction," Dr. Dirkjan van Schaardenburg and his coinvestigators wrote in an article in the Annals of the Rheumatic Diseases, published online on Oct. 18, 2010.

They found significantly increased average levels of only P1NP (procollagen type I intact N-terminal propeptide) and osteoprotegerin in the group of preclinical RA patients, compared with a control group of healthy individuals. Specifically, P1NP increased by 5 ng/mL and osteoprotegerin increased by 4 pmol/L (Ann. Rheum. Dis. 2010 Oct. 18 [doi:10.1136/ard.2010.135723]). P1NP promotes bone growth, and osteoprotegerin inhibits bone resorption.

Three blood samples taken 1, 2, and 5 years prior to the onset of symptoms were identified for 47 patients with RA; two samples were collected from 18 patients and one sample was collected from 14 patients. The individuals had been blood donors prior to developing the disease.

Control samples from healthy individuals who were matched for sex, age, and time of blood donation were also obtained. Osteocalcin, P1NP, beta-CTX, osteoprotegerin, and RANKL (receptor-activated nuclear factor–kappaB ligand) were measured and compared between preclinical RA patients and control individuals.

Models were corrected for age, sex, time of donation, autoantibodies (IgM rheumatoid factor and antibodies against cyclic citrullinated peptides) and markers of inflammation (C-reactive protein and secretory phospholipase A2).

Interestingly, after adjustment for age, sex, and autoantibodies, the researchers found negative associations between preclinical levels of both P1NP and osteoprotegerin and Sharp/van der Heijde scores on x-ray, although these differences were not significant.

Dr. van Schaardenburg is a rheumatologist at Jan van Breemen Institute in Amsterdam.

The study was funded by the Dutch Arthritis Association. The authors reported that they had no competing interests.

10/29/10