The relationship between length of denosumab treatment for postmenopausal osteoporosis and serum TRAcP5b measured six months after the last injection

Article Endocrinology & Metabolism

Changes in RANKL and TRAcP 5b after discontinuation of denosumab suggest RANKL mediated formation of osteoclasts results in the increased bone resorption

Anne Sophie Solling et al.

Summary: In patients discontinuing long-term denosumab, RANKL levels are initially high and then decrease, while TRAcP 5b levels increase. This suggests that accumulated RANKL leads to increased activity of osteoclasts.

OSTEOPOROSIS INTERNATIONAL (2023)

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Article Rheumatology

Mechanisms underlying the long-term and withdrawal effects of denosumab therapy on bone

Serge Ferrari et al.

Summary: Denosumab, a human monoclonal antibody against RANKL, inhibits osteoclast differentiation and activity, leading to anti-resorptive properties and anti-fracture efficacy. Compared with bisphosphonates, denosumab results in continuous bone mineral density gain during long-term treatment and rapid bone loss upon withdrawal. The underlying mechanisms for these effects are not fully understood, but emerging data suggest that denosumab may affect both osteoclasts and osteoblasts, causing sustained bone gain and bone loss. Future studies and clinical implications are discussed in this Perspective.

NATURE REVIEWS RHEUMATOLOGY (2023)

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Review Endocrinology & Metabolism

Bone Turnover Markers: Basic Biology to Clinical Applications

Marian Schini et al.

Summary: Bone turnover markers (BTMs) are widely used in research and clinical practice to assess bone metabolism. They can be helpful in diagnosing and managing various diseases, such as osteoporosis and chronic kidney disease-mineral bone disorder. Measurement and interpretation of BTMs have accumulated much experience over the past two decades.

ENDOCRINE REVIEWS (2023)

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Editorial Material Endocrinology & Metabolism

Short or Long-term Osteoporosis Therapy With Denosumab?

Serge Ferrari

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM (2022)

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Review Endocrinology & Metabolism

Denosumab Discontinuation

Anne Sophie Solling et al.

Summary: In this review, the literature published in the past 1 to 3 years investigating the discontinuation of denosumab (DMAB) and the transition to other anti-osteoporosis therapies was evaluated. Additionally, the current recommendations of international guidelines were summarized.

CURRENT OSTEOPOROSIS REPORTS (2022)

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Review Endocrinology & Metabolism

Osteoclast Recycling and the Rebound Phenomenon Following Denosumab Discontinuation

Albert S. Kim et al.

Summary: The purpose of this review is to explore the rebound increase in bone resorption following denosumab discontinuation and the potential mechanisms behind it. Recent studies suggest that osteoclasts are longer lived cells capable of undergoing fission into a novel cell type (the osteomorph) and re-fusion in a process termed osteoclast recycling. This provides a new framework to examine changes in osteoclast biology in response to bone disease treatment and offers potential for personalized medicine.

CURRENT OSTEOPOROSIS REPORTS (2022)

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Article Biochemistry & Molecular Biology

Osteoclasts recycle via osteomorphs during RANKL-stimulated bone resorption

Michelle M. McDonald et al.

Summary: Research has shown that RANKL-stimulated osteoclasts can undergo fission to form osteomorphs, which are involved in the regulation of bone resorption and could be targeted for the treatment of skeletal diseases. Single-cell RNA sequencing revealed that osteomorphs are transcriptionally distinct from osteoclasts and macrophages, expressing non-canonical osteoclast genes associated with bone phenotypes when deleted in mice.

CELL (2021)

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Article Endocrinology & Metabolism

Treatment With Zoledronate Subsequent to Denosumab in Osteoporosis: A 2-Year Randomized Study

Anne Sophie Solling et al.

Summary: This study investigated the long-term efficacy of zoledronate (ZOL) in maintaining bone mineral density (BMD) after discontinuation of denosumab. Results showed that ZOL could maintain lumbar spine and hip BMD during the second year, but bone turnover still increased and bone loss occurred during the first year.

JOURNAL OF BONE AND MINERAL RESEARCH (2021)

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Article Endocrinology & Metabolism

The Duration of Denosumab Treatment and the Efficacy of Zoledronate to Preserve Bone Mineral Density After Its Discontinuation

Polyzois Makras et al.

Summary: The duration of denosumab treatment significantly influences the efficacy of subsequent zoledronate infusion in maintaining bone mineral density gains. Frequent follow-up of patients treated with denosumab for more than 3 years is advisable as additional therapeutic interventions may be necessary.

JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM (2021)

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Article Endocrinology & Metabolism