Background In treating rheumatoid arthritis (RA), T2T (treat-to-Target) is the most reliable treatment strategy. Recent reports have indicated that reaching normal levels of bone mineral density (BMD) might be important for the prevention of fractures in osteoporosis treatment (reference 1 and 2).From this fact, there might be a possibility that T2T targeting BMD might be feasible also in osteoporosis treatment. In doing so, medicines with the ability to sufficiently increase BMD at a fast speed should be needed. Denosumab (DMAb) specifically inhibits the receptor activator for nuclear factor-kappa B ligand (RANKL) improves BMD rapidly at lumbar or hip. Therefore, DMAb is one of candidate drugs for T2T practice, and it is very important to know risk factors that attenuate its effect in the treatment of osteoporosis.
Objectives The aim of this study was to identify risk factors for inadequate response to the treatment of osteoporosis by DMAb.
Methods Sixty-six patients treated with DMAb were observed retrospectively for one year. The mean age was 74 years, women were 91% and 36 patients with RA were included.We measured BMDs at lumbar and hip by dual-energy X-ray absorptiometry (Hologic Discovery) at baseline and one year later. We evaluated the effects of age, body mass index (BMI), use of glucocorticoide (GC), previous treatment for osteoporosis, BMD at baseline, bone metabolic markers (BAP; bone alkaline phosphatase, uNTx; urinary N-telopeptide), serum Ca and P levels and the previous vertebral fractures for inadequate response to DMAb.We defined the cases who could not gain the increase of BMD over 2% at the lumbar vertebrae and 4% at the hip as inadequate responders by taking the measurement error into account.
Results Dose of PSL was significantly high in non-responder at non-RA trochanter and RA lumbar BMD (p=0.028, 0.006). BAP was higher in non-responder at RA lumbar BMD (p=0.007). Urinary NTX was significantly low in non-responder at non-RA lumbar and RA trochanter BMD (p=0.026, 0.048). Previous treatment for osteoporosis was significantly high in non-responder at non-RA lumbar, total hip and trochanter BMD (p=0.026, 0.022, 0.003).Multivariate logistic analysis including age, BMI, dose of PSL, BMD at baseline, BAP, uNTX, Ca and P level as confounders revealed that dose of PSL was the significant risk factors for no-response at lumbar BMD (OR0.634, 95% CI 0.433–0.93, p=0.02).
Conclusions Patients receiving GC might not gain an adequate response to the treatment by DMAb for osteoporosis. Reducing dose of GC or altanative treatment regimen might be necessary.
Kuroda T. et al. J Clin Densitom 15: 392–8, 2012.
Bauer D.C. et al. JAMA 174: 1126–34, 2014.
Disclosure of Interest None declared