Background Receptor activator of nuclear factor kappa-B ligand (RANKL) is a key inducer of osteoclast differentiation and activation, which plays a crucial role in osteoporosis and bone erosion of rheumatic diseases. Denosumab (DSM) is an anti-RANKL antibody approved for the treatment of postmenopausal osteoporosis, while its effect in rheumatic diseases (especially in glucocorticoid-induced osteoporosis) still remains unknown.
Objectives The aim of this study is to clarify the effect of 12 months administration of DSM on patients with rheumatic diseases (RD).
Methods DSM was introduced in 145 RD patients (127 female, 61.5 years old, 95 RA, 28 SLE, 4 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 vertebral fracture 1.0, prior treatment; bisphosphonate 63.4%, teriparatide 18.6%, none 16.6%) and followed up for 12 months by monitoring bone mineral density (BMD) and bone turnover markers.
Results BMD increase from baseline to 6→12 months was as follows. LS; 3.0→5.4%, TH; 1.6→2.6%, FN; 2.0→3.1%. Baseline dose of oral PSL showed negative correlation with baseline value of bone turnover markers [Type I collagen N-terminal propeptide (P1NP) (r=-0.31, p=0.0004), Isoform 5b of tartrate-resistant acid phosphatase (TRACP-5b) (r=-0.32, p=0.0003), undercarboxylated osteocalcin (ucOC) (r=-0.42, p=0.000004)] and BMD increase of LS at 6 months (r=-0.27, p=0.002) and 12 months (r=-0.29, p=0.04), and also with TH at 12 months (r=-0.39, p=0.01). BMD increase of LS at 12 months (%) was positively correlated with baseline value of bone turnover markers [P1NP (r=0.51, p=0.001), TRACP-5b (r=0.50, p=0.001), ucOC (r=0.54, p=0.001)] and their decreasing rate at 6 months [TRACP-5b (r=0.37, p=0.02), ucOC (r=0.53, p=0.003)]. Multivariate logistic regression analysis with a forward stepwise procedure revealed that significant indicator of LS BMD change at 12 months was decreasing rate of ucOC at 6 months (β=0.50, 95%CI=-0.13 to -0.03, p=0.005).
Conclusions Our findings indicate that BMD increasing effects of 12 months DSM administration in patients with RD is significantly correlated with baseline bone metabolism turnover which is suppressed by baseline oral PSL dose-dependently. In addition, BMD increase of LS at 12 months is strongly predicted by decreasing rate of ucOC at 6 months.
Disclosure of Interest None declared
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