Article

Effects of denosumab on bone mineral density and bone turnover in patients with rheumatoid arthritis receiving concurrent glucocorticoids or bisphosphonates

Robin K Dore Inc, Tustin, CA, USA.
Annals of the rheumatic diseases (Impact Factor: 10.38). 10/2009; 69(5):872-5. DOI: 10.1136/ard.2009.112920
Source: PubMed

ABSTRACT To report results of subgroup analyses of bone mineral density (BMD) and bone turnover markers from a randomised, double-blind, placebo-controlled, phase II study of denosumab, an investigational RANKL inhibitor, in patients with rheumatoid arthritis (RA) concurrently receiving treatment with bisphosphonates or glucocorticoids.
Patients received subcutaneous placebo (n=75), denosumab 60 mg (n=71) or denosumab 180 mg (n=72) at baseline and 6 months. Assessments included dual x-ray absorptiometry scans of the lumbar spine and hip, and determination of levels of serum type I C-telopeptide (sCTx-I) and serum procollagen 1N-terminal peptide (P1NP).
Denosumab treatment increased mean lumbar spine and hip BMD and reduced sCTx-I and P1NP compared with placebo through 12 months, regardless of baseline BMD or marker levels or concomitant bisphosphonate or glucocorticoid use.
This study extends evidence that denosumab increases BMD and reduces bone turnover in patients with RA and may provide a new therapeutic option for reducing systemic bone loss in patients with RA.

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    • "In contrast, RANKL is not influenced by the treatment, showing that the ratio RANKL/OPG is of major importance in regulating bone resorption rather than each of the markers taken alone [15]. Then, it is not surprising that deleterious effects of RANKL on BMD can be prevented by denosumab which is an anti-RANKL monoclonal antibody, increasing BMD and reducing bone turnover in RA patients [16]. Bone formation is also decreased during inflammation as shown in mice. "
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    • "Like MIP-1c, targeting these factors could inhibit the osteoclastogenesis and the following bone sorption (Dimitrova et al., 2012; Park et al., 2012). Using antibodies that specifically targeted to RANKL, clinical trials were conducted to treat osteoporosis and rheumatism arthritis , and showed promising results (Cohen et al., 2008; Cummings et al., 2009; Dore et al., 2010). Okamatsu et al. (2004) reported that among all the mediators screened, MIP- 1c was the most strongly upregulated cytokines in osteoclasts derived from RANKL-stimulated monocytes/macrophages. "
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    • "The ability of these agents to promote healing of bone in PsA has not been evaluated. Another molecule with potent effects on bone is anti-RANKL antibody (denosumab), currently approved for the treatment of osteoporosis [48–50]. This agent blocks bone degradation but can also promote new bone formation, as shown by the increased bone density in osteoporotic patients treated with this agent and in preclinical models. "
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