Published: Oct 22, 2013 | Updated: Oct 22, 2013
By Nancy Walsh, Staff Writer, MedPage Today

Full Story:  http://www.medpagetoday.com/Rheumatology/Arthritis/42424

Early decline in bone mineral density (BMD) of the hands helped predict which patients with rheumatoid arthritis (RA) developed erosive and more severe disease by 1 year, Australian researchers found.

Compared with patients who had no bone loss, those whose dual energy x-ray absorptiometry (DXA) scores showed BMD loss at 6 months had higher erosion scores at 1 year (P=0.021), according to Susanna Proudman, MBBS, of Royal Adelaide Hospital in Adelaide, and colleagues.

Patients who already had BMD loss at 6 months also were rated as having greater increases in those scores, reflecting worsening disease, 12 months post diagnosis (P=0.033), the researchers reported online in Arthritis Care & Research.

Despite the current practice of early, aggressive treatment of RA in the first year “window of opportunity,” joint damage does occur during that time period in some patients.

However, traditional markers of disease haven’t been successful in identifying those patients.

“Safe and cost-effective measures are needed to guide decision-making with regard to dose-escalation of DMARDs and possible introduction of biologic therapy in these patients,” Proudman and colleagues wrote.

A specialized research technique known as digital x-ray radiogrammetry has shown efficacy in predicting long-term joint damage but isn’t widely available for routine clinical use.

To explore the possibility that DXA scans — using hardware available at most rheumatology centers — could be a useful alternative, the researchers enrolled 106 consecutive patients newly diagnosed with RA whose median symptom duration was 4 months.

Patients had not previously received disease-modifying anti-rheumatic drugs (DMARD), but at enrollment began treatment with methotrexate, sulfasalazine, and hydroxychloroquine in atreat-to-target dosing approach.

At baseline, disease markers such as erythrocyte sedimentation rate, C-reactive protein (CRP), rheumatoid factor, and anti-cyclic citrullinated peptide (CCP) antibodies were measured.

Disease activity scores in 28 joints (DAS28) were calculated at baseline and then at 6 and 12 months. DXA scans were performed at baseline and repeated at 6 months.

Patients who didn’t develop erosions between baseline and 6 months were categorized as the “no loss” group, while those who did so were classified as the “BMD loss” group.

In addition, radiographs of the hands and feet were obtained at baseline and 1 year and examined in a blinded fashion for the presence of erosions and narrowing of the joint space.

The statistical analysis included a Hurdle model looking at factors that could predict erosion scores at 1 year, including a “zero component” indicating the presence or absence of erosions and a “count component” reflecting erosion severity.

Three-quarters of the patients were women, and mean age at disease onset was 57.

A total of 58% were positive for rheumatoid factor, as were 62% for anti-CCP antibodies.

The no-loss group consisted of 53% of the patients while the remaining 47% represented the BMD loss group.

Among the no loss group, the change in BMD by 6 months was +0.006 g/cm², compared with -0.012 g/cm² in the loss group.

Loss of BMD was associated with typical risk factors in the general population for bone loss, including female sex (odds ratio 3.2, 95% CI 1.2-8.4, P=0.020), smoking (OR 2.4, 95% CI 1-5.6,P=0.041), and age (OR 1.04, 95% CI 1.01-1.07, P=0.013).

On a multiple regression analysis using the Hurdle model, factors that were predictive of erosion scores at 1 year (zero component) were:

• Age of onset 50 or later (beta=1.65, P=0.014)
• BMD loss at 6 months (beta=0.89, P=0.046)
• Baseline BMD (beta= -3.02, P=0.072)

Factors that independently predicted erosion severity (count component) were:

• Baseline erosions (beta=0.76, P=0.001)
• CCP positivity (beta=0.65, P=0.024)
• CRP at 6 months (beta=0.19, P=0.055)

Using the fitted model, the researchers then calculated that approximately 70% of patients diagnosed after age 50, and who had declines in hand BMD, could be expected to have erosions present within a year.

Their observations also confirmed that the development of radiographic erosions is influenced by various factors and differs according to whether or not erosive changes are already present at baseline.

“BMD loss, together with age, was associated with increased susceptibility to erosive disease, and therefore BMD loss may have the most utility in the identification of erosion-free patients at risk of developing erosive disease,” the researchers explained.

“In contrast, anti-CCP status and ongoing inflammation as measured by CRP levels at 6 months contribute to erosion scores and their progression in patients with erosions at baseline,” they added.

The finding that risk factors for severity of erosions were more specific to RA than were risk factors for susceptibility to erosions suggested that nonspecific factors, such as age and bone loss, may somehow be protective against the development of erosions, although this remains to be established.

Limitations of the study included its small number of patients and brief follow-up.

“Ultimately, the utility of hand DXA will need to be evaluated prospectively in a randomized controlled trial by incorporating it into a treatment algorithm whereby those with high BMD loss receive additional DMARD therapy at 6 months, irrespective of disease activity,” Proudman and colleagues concluded.