Comparison of the efficacy of denosumab and bisphosphonates for treating secondary osteoporosis in patients with rheumatoid arthritis

Kinoshita, Hayato; Miyakoshi, Naohisa; Kashiwagura, Takeshi; Kasukawa, Yuji; Sugimura, Yusuke; Shimada, Yasuhiro

doi:10.1080/14397595.2016.1232776

Cited by 17 publications

(18 citation statements)

References 22 publications

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“…Interestingly, the use of denosumab seems neither related to a higher risk for inflammatory activity (relapse of IBD), nor for an increased risk for infectious diseases [79]. This has been subject of study in rheumatoid arthritis but not in IBD [80], and effects on bone formation more than on bone resorption have been proposed when observing elevated concentrations of bone-specific alkaline phosphatase [81]. In addition, denosumab use seems to be associated with a rebound effect following discontinuation of therapy which may be considered to be a major flaw when using this drug in the relative young IBD population [82].…”

Section: Denosumab and Other New Bone Health-improving Agentsmentioning

confidence: 99%

Perspective on skeletal health in inflammatory bowel disease

Bodegraven

Bravenboer

2019

Osteoporos Int

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Osteopenia and osteoporosis are common features in inflammatory bowel disease (IBD), comprising both Crohn's disease and ulcerative colitis. Moreover, Crohn's disease is associated with increased fracture risk. The etiology of bone loss in IBD is multifactorial. It includes insufficient intake or absorption of calcium, vitamin D, and potassium; smoking; a low peak bone mass; a low body mass index; and decreased physical activity. In several studies, it has been shown that elevated concentrations of systemic and local pro-inflammatory cytokines, including tumor necrosis factor alpha (TNF-α), interferon-γ (IFNγ), interleukin (IL)-1β, IL-4, IL-5, IL-6, IL-13, and IL-17, present in IBD patients are potentially detrimental for bone metabolism and may be responsible for bone loss and increased fracture risk. This perspective aims to review the current literature on the role of inflammatory factors in the pathophysiology of skeletal problems in IBD and to suggest potential treatment to improve bone health, based on a combination of evidence and clinical and pathophysiological reasoning.

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Section: Denosumab and Other New Bone Health-improving Agentsmentioning

confidence: 99%

Perspective on skeletal health in inflammatory bowel disease

Bodegraven

Bravenboer

2019

Osteoporos Int

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“…However, DMab, but not bisphosphonates, significantly suppressed bone metabolism in a cohort of Japanese RA patients not previously treated for osteoporosis. These findings suggest distinct cellular mechanisms underlying DMab- and bisphosphonate-based RA therapy (4, 58). DMab exerts its protective effects likely through the WNT/β-catenin signaling pathway via regulating DKK-1 (25, 59).…”

Section: Denosumab - Current Indicationsmentioning

confidence: 94%

“…Findings from these studies suggest that bisphosphonates accumulate in bone but the effect on resorption is not well understood (54). Distinct cellular distribution and action could explain the difference in the degree, speed and action of anti-resorptive effects between DMab and bisphosphonate (18, 31, 58). In contrast to bisphosphonate, DMab significantly reduced bone-specific alkaline phosphatase at 6 and 12 months compared with pretreatment, but had no effect on tartrate-resistant acid phosphatase 5b levels, emphasizing the effect of DMab more on bone formation than resorption rate(58).…”

Section: Denosumab - Current Indicationsmentioning

confidence: 99%

“…Distinct cellular distribution and action could explain the difference in the degree, speed and action of anti-resorptive effects between DMab and bisphosphonate (18, 31, 58). In contrast to bisphosphonate, DMab significantly reduced bone-specific alkaline phosphatase at 6 and 12 months compared with pretreatment, but had no effect on tartrate-resistant acid phosphatase 5b levels, emphasizing the effect of DMab more on bone formation than resorption rate(58). In addition, effects of DMab on the reduction of bone resorption are more reversible and profound than bisphosphonates (54).…”

Section: Denosumab - Current Indicationsmentioning

confidence: 99%

“…In addition, effects of DMab on the reduction of bone resorption are more reversible and profound than bisphosphonates (54). One recent study showed that neither DMab nor bisphosphonates suppress rheumatoid inflammation (58). However, DMab, but not bisphosphonates, significantly suppressed bone metabolism in a cohort of Japanese RA patients not previously treated for osteoporosis.…”

Section: Denosumab - Current Indicationsmentioning

confidence: 99%

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Denosumab: targeting the RANKL pathway to treat rheumatoid arthritis

Chiu

Ritchlin

2016

Expert Opinion on Biological Therapy

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Introduction Rheumatoid arthritis (RA) is a chronic inflammatory disorder characterized by focal pathologic bone resorption due to excessive activity of osteoclasts (OC). Receptor activator of nuclear factor kappa B ligand (RANKL) is essential for the proliferation, differentiation, and survival of OC. Denosumab (DMab) is a humanized monoclonal antibody that binds to RANKL with high affinity and blocks its subsequent association with its receptor RANK on the surface of OC precursors. Area Covered The authors review the molecular and cellular mechanisms underlying therapeutic applications of DMab, provide recent highlights on pharmacology, efficacy and safety of DMab, and discuss the potential of DMab as a novel therapeutic option for the treatment of rheumatoid arthritis. Expert opinion Clinical results suggest that DMab is efficient both in systemic and articular bone loss in RA with limited side effects. Diminished bone erosion activity was also noted in RA patients on corticosteroids and bisphosphonates. Combination of DMab with an anti-TNF agent was not associated with increased infection rates. Collectively, these data indicate that DMab, in combination with methotrexate and possibly other conventional synthetic Disease Modifying Anti-Rheumatic Drugs (csDMARDs), is an effective, safe and cost-effective option for the treatment of RA.

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Skeletal complications of rheumatoid arthritis

Heinlen

Humphrey

2017

Osteoporos Int

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Rheumatoid arthritis (RA) is associated with local and systemic inflammation that induces many changes in the skeletal health. Locally, periarticular bone loss and juxta-articular bone erosions may occur while joint ankylosis, generalized bone loss, osteoporosis, and fractures may develop secondary to inflammation. The aim of this narrative review is to summarize the clinical evidence for abnormal skeletal health in RA, the effects of disease modifying anti-rheumatic drugs (DMARDS) on bone health, and the effects of drugs for the prevention or treatment of osteoporosis in the RA population.

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Comparison of the efficacy of denosumab and bisphosphonates for treating secondary osteoporosis in patients with rheumatoid arthritis

Abstract: Neither denosumab nor bisphosphonates could suppress inflammation or RA disease activity, but denosumab significantly suppressed a marker of bone metabolism in Japanese RA patients never previously treated for osteoporosis.

Cited by 17 publications

References 22 publications

Perspective on skeletal health in inflammatory bowel disease

Perspective on skeletal health in inflammatory bowel disease

Denosumab: targeting the RANKL pathway to treat rheumatoid arthritis

Skeletal complications of rheumatoid arthritis

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