09.26.2015
Anti-TNF and NSAID therapies have protective effects
by Diana Swift
Contributing Writer
More than four in 10 patients having inflammatory back pain suggestive of early axial spondyloarthritis (SpA) and followed for 2 years experienced bone loss in the lumbar spine and hip, according to findings published in Rheumatology.
Furthermore, even a short duration of anti-tumor necrosis factor (TNF) therapy had a positive effect on bone mineral density (BMD) in the lumbar spine and hip, while baseline use of nonsteroidal anti-inflammatory drugs (NSAIDs) and an increase in BMI were associated with protection at the hip.
French researchers studied 265 patients from DESIR (Devenir des spondyloarthrites indifferenciees recentes), a longitudinal prospective study at 25 French centers. Participants (46% female, mean age 34.4 years) had BMD measurements at baseline and at 2 years.
About one in seven patients (n=39, 14.7%) had low BMD at baseline, whereas the expected prevalence in young adults is just 2.2%. Notably, 112 patients (42.3%) had significant bone loss over the 2 years. “This could be worrisome if such bone loss is continuous in long-standing disease,” wrote researchers led by rheumatologist Karine Briot, MD, PhD, of Cochin Hospital in Paris, France, adding that the relationship between BMD and fracture risk is less well established in secondary osteoporosis than in postmenopausal osteoporosis.
Overall, small but significant changes in BMD were measured from baseline over 2 years at the lumbar spine: +1.3% (SD 6.4, P=0.033); and also in the total hip: –0.3% (SD 4.0,P=0.020). At 2 years, the prevalence of low BMD (Z score <–2 at least one site) was 11.2%. Notable bone loss (BMD >0.03 g/cm2) was observed at the lumbar spine alone in 22.4% (n=59) and at total hip alone in 18.0% (n=46).
At baseline, 187 (70.6%) used NSAIDs and 89 (33.6%) received anti-TNF therapy over 2 years. In anti-TNF patients, lumbar spine BMD significantly increased from baseline (3.2%, SD 8.0, P=0.001).
No significant change occurred in patients without anti-TNF (0.3%, SD 5.3, P=0.70,P=0.008 for comparison between groups). Total hip BMD did not significantly change in patients on anti-TNF (0.6%, SD 4.1, P=0.236), whereas it decreased in patients without (0.8%, SD 3.9, P=0.0001) and the difference between the two groups was significant (P=0.003).
“Since the BMD increase was observed at the lumbar spine, and not at the hip, this increase could be an artifact related to spinal ossifications (syndesmophytes) or periosteal bone formation (vertebral squaring),” the authors wrote.
At the hip, baseline use of NSAIDs had a protective effect on bone loss, with an odds ratio of 0.38 (P=0.006). In patients not using anti-TNF therapy, both baseline NSAIDs and 2-year increase in BMI had protective effects on hip bone loss.
The main risk factor associated with low BMD was MRI-imaged inflammation and systemic inflammation, but the prospective analysis could not confirm that baseline inflammation parameters were determinants of bone loss.
While BMI did not change markedly over 2 years, total fat mass significantly increased from baseline (+6.2%, SD 31.0, P=0.001). Interestingly, a 2-year percentage increase in fat mass was associated with hip bone loss (OR 1.18, P=0.046). “Whether this relationship could be related to an indirect effect of inflammation on fat mass and/or the secretion by fat tissue of adipokines cannot be elucidated with our available data,” the authors wrote.
At 2 years, disease activity scores were significantly lower than at baseline. The mean Ankylosing Spondylitis Disease Activity Score was 2, mean C-reactive protein was 4.6 mg/mL, and mean Bath Ankylosing Spondylitis Disease Activity Index was 3.4 (P<0.0001 for all).
An unexpected finding was the role of a low Z score on bone loss risk: a Z score ≤2 at any site was protective of lumbar spine bone loss. “This may indicate that bone loss occurred early in some patients, before the occurrence of symptoms, as reported in Crohn’s disease, suggesting a deleterious systemic effect of preclinical inflammation,” the investigators wrote.
Study limitations include the reduced number of patients with BMD measurements at 2 years compared with baseline (67 had only baseline measurements), and the lack of centralized quality control in BMD measurements across the study centres (e.g., use of different devices, absence of cross-calibration).
One co-author has received financial support from Alexion, Amgen, Bongrain, Lilly, and MSD.
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