Abstract
Sickle cell anaemia is a congenital disease characterized by painful vaso-occlusive crises. It is associated with vitamin D deficiency, osteoporosis and recurrent attacks of micro-infarctions lead to bone osteonecrosis. The most common sites of osteonecrosis in sickle cell disease are the femoral and humeral heads which could lead to severe pain and extensive physical disability. Denosumab is a new human monoclonal antibody product; it is a receptor activator of nuclear factor kappa B ligand RANKL. That decreases osteoclastic bone restoration. It is Food and Drug Administration FDA approved for osteoporosis for women with high risk of fracture; and it is also being used for the treatment and prevention of bone loss in patients undergoing hormone ablation therapy for breast and prostate cancer. Denosumab is not restricted for sickle cell disease patients within its approved indications. It has less nephrotoxicity effect than the bisphosphonates which is a big advantage for sickle cell patients. It also used as an adjuvant agent to reduce metastatic bone pain in solid tumors. The extension of Denosumab use for sickle cell patients’ osteoporosis and osteonecrosis deserve a randomized multi central trail aiming to improve bone integrity and possible reduction of the devastating pain in sickle cell disease patients.
Highlights
Denosumab Role in Bone IntegrityDenosumab is a human monoclonal IgG2 antibody [24]
N Reviewed & Approved by: Dr Raul H
The vaso-occlusive crises (VOC) in SCD is the prominent devastating phenomena; it causes impaired nourishment of critical structures in the big joints, Sickle cell disease (SCD) is the most common inherited blood lead to bony lesions with loss of trabeculae resulting in osteonecrosis disorder, with a worldwide distribution
Summary
Denosumab is a human monoclonal IgG2 antibody [24] It is the newest bone antiresorptive agent, with a novel mechanism of action [25]. Binding of denosumab to RANKL inhibits its actions; so osteoclast recruitment, maturation and action are inhibited, and bone resorption slows [30] It prevents the interaction of the receptor activator of nuclear factor kappa B ligand (RANK-L) with the receptor activator of nuclear factor kappa (RANK) and, inhibits bone resorption [31]. Denosumab Recently approved for unresectable giant cell tumor of bone in adults It increase bone mass in patients at high risk for fracture including androgen deprivation therapy, prostate cancer, in breast cancer, and prevention of skeletal-related events in patients with bone metastases from solid tumors [32]
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