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Biologic Antiresorptive: Denosumab

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Abstract

Background:

Osteoporosis is an age-related common bone disorder characterized by low bone mineral density and increased fragility fracture risk. Various Antiresorptive medications are being used to target osteoclast mediated bone resorption to prevent bone loss and reduce fracture risk.

About Denosumab:

Denosumab is a novel biological antiresorptive drug that belongs to the class of monoclonal antibodies. It binds to and inhibits the cytokine receptor activator of nuclear factor kappa-B ligand (RANKL), which is requisite for osteoclast differentiation, function and survival.

Effectiveness:

Denosumab has been shown to be a potent and effective therapy for osteoporosis, with clinical trial data demonstrating significant improvement in bone mineral density (BMD) and reductions in fracture risk at various skeletal sites for more than 10 years of treatment.

Safety Profile:

Denosumab has a favourable benefit/risk profile, with low rates of complications such as infection, atypical femoral fracture and osteonecrosis of the jawbone.

Challenges:

However, denosumab treatment requires continuous administration, as discontinuation leads to rapid bone mineral loss and increased risk of multiple vertebral fractures due to rebound of bone turnover. Therefore, modification to another anti-osteoporosis drug therapy after denosumab discontinuation is required to maintain bone health.

Conclusion:

Denosumab is a promising biological antiresorptive therapy for osteoporosis that offers high efficacy and safety, but also poses challenges for long-term management.

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Abbreviations

AFF:

Atypical femur fracture

BMD:

Bone mineral density

BRC:

Bone remodeling compartment

BTMs:

Bone turnover markers

CMP:

Common myeloid progenitors

CTX:

C-telopeptide

DAPS:

Denosumab adherence preference satisfactions

DEFEND:

Denosumab fortifies bone density

FREEDOM:

Fracture reduction evaluation of denosumab in osteoporosis every 6 Months

GMP:

Granulocyte/macrophage progenitors

GM-CSF:

Granulocyte/macrophage colony stimulating factor

HALT:

Hormone ablation bone loss trial

HSC:

Hematopoietic Stem Cells

IGF-I:

Insulin-like growth factor-I

IL:

Interleukin and IL-6

MVF:

Multiple vertebral fractures

ONJ:

Osteonecrosis of jaw

OPG:

Osteoprotegerin

OPGL:

Osteoprotegerin ligand

P1NP:

Procollagen type 1 N-terminal peptide

PTH:

Human recombinant parathyroid hormone,

PTHrP:

Synthetic PTH-related peptide

RANK:

Receptor activator of nuclear factor kappa beta (NKfB)

RANKL:

Receptor activator of nuclear factor kappa beta (NKfB) ligand

SCF:

Stem cell factor

SERMs:

Selective estrogen receptor modulators

SC:

Subcutaneous

TGF-β:

Transforming growth factor beta

TRANCE:

TNF related activation induced cytokine

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  1. Marengo Asia Hospital, Gurugram, Haryana, India

    Lalit Kumar, Mohit Kumar Arora & Sunil Marwah

  2. Gurugram, India

    Mohit Kumar Arora & Sunil Marwah

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Kumar, L., Arora, M.K. & Marwah, S. Biologic Antiresorptive: Denosumab. JOIO 57 (Suppl 1), 127–134 (2023). https://doi.org/10.1007/s43465-023-01064-5

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