Date: Sunday, November 8, 2015
Session Type: ACR Poster Session A
Session Time: 9:00AM-11:00AM
In patients with rheumatic diseases (RD), pro-inflammatory cytokines induce receptor activator of nuclear factor kappa-B ligand (RANKL), which plays a crucial role in inducing osteoclasts differentiation and consequent osteoporosis and bone erosion. Glucocorticoid (GC) is often used to treat RD, while strongly inhibits bone formation and increases fracture risk. Denosumab (DMAb) is an anti-RANKL antibody which strongly inhibits bone resorption, while its effect in RD (especially in GC-induced osteoporosis) remains unknown.
DMAb was introduced in 181 RD patients (160 female, 61.6 years old, 127 RA, 31 SLE, 5 dermatomyositis, 4 sarcoidosis, 14 other diseases, 77.2% taking prednisolone (PSL) with average dose 4.3mg/day, 21.4% taking biologics, lumbar spine (LS) T-score -1.7, femoral neck (FN) T-score -2.2, total hip (TH) T-score -1.9, prior treatment; bisphosphonate (BP) 63.4%, teriparatide (TPTD) 18.6%, naïve 16.6%) and followed up for 12 months by monitoring bone mineral density (BMD) and bone turnover markers.
Baseline FN T-score showed negative correlation with baseline serum CRP levels (r=-0.24, P<0.01) and bone resorption marker Isoform 5b of tartrate-resistant acid phosphatase (TRACP-5b; r=-0.44, P<0.001）, suggesting high inflammation levels and increased bone resorption is associated with low bone mass in RD patients. BMD increase from baseline→6→12 months was as follows. LS; 0→2.8→4.7％, TH; 0→1.5→2.9％, FN; 0→1.7→2.7％. There was no significant difference in BMD increase between the difference of prior osteoporosis treatment (BP, TPTD, and naïve) or the presence or absence of combined oral GC [without PSL (n=41); LS 0→3.2→4.4％; FN 0→2.2→2.5％, with PSL (5.6mg/day; n=140); LS 0→2.9→4.8％; FN 0→1.7→2.9％] or the dose of combined PSL [PSL<5mg/day (n=108); LS 0→3.4→4.9％; FN 0→2.3→2.9％, with PSL≧5mg/day (n=73); LS 0→2.3→4.6％; FN 0→1.2→2.4％]. In addition, there was no significant difference in baseline levels of bone turnover markers, which converged to constant levels regardless of the presence or absence of combined oral GC [TRACP-5b; without PSL; 267→238→126 mU/dl, with PSL; 298→151→113 mU/dl] . On the other hand, patients with high dose of combined oral GC (PSL≧5mg/day; n=73), compared to low dose users (PSL<5mg/day; n=108), was associated with lower TRACP-5b (94 vs 133 mU/dl; P<0.01) and undercarboxylated osteocalcin (ucOC; 0.9 vs 1.5 ng/ml; P<0.05) levels, but not with bone formation marker Type I collagen N-terminal propeptide (P1NP; 18.2 vs 18.2 ug/l) at 12 months. BMD increase (%) of LS at 12 months was positively correlated with baseline value of bone turnover markers［TRACP-5b（r=0.34, P<0.001）, ucOC（r=0.29, P<0.01）］and their decreasing rate at 6 months [TRACP-5b（r=0.31, P<0.01）, ucOC（r=0.30, P<0.01）].
Our findings indicate that DMAb increased BMD regardless of prior osteoporosis treatment and combined oral GC dose. High dose of combined oral GC (PSL≧5mg/day) significantly decreased serum TRACP-5b and ucOC levels, while sustained serum P1NP levels compared to that of low dose GC users (PSL<5mg/day). Sustained bone formation and greater bone resorption inhibition induced by DMAb in high dose GC users may contribute to sustained BMD increase.
To cite this abstract in AMA style:Ebina K, Hirao M, Hashimoto J, Hagihara K, Yoshikawa H, Noguchi T. Assessment of the Effect of 12 Months Administration of Denosumab in Patients with Rheumatic Diseases [abstract]. Arthritis Rheumatol. 2015; 67 (suppl 10). https://acrabstracts.org/abstract/assessment-of-the-effect-of-12-months-administration-of-denosumab-in-patients-with-rheumatic-diseases/. Accessed September 18, 2020.
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