Denosumab in postmenopausal osteoporosis: what the clinician needs to know

Abstract

Denosumab is a subcutaneously (SC) administered investigational fully human monoclonal antibody to receptor activator of nuclear factor-kB ligand (RANKL), a cytokine member of the tumor necrosis factor family that is the principal mediator of osteoclastic bone resorption. RANKL stimulates the formation, activity, and survival of osteoclasts, and is implicated in the pathogenesis of postmenopausal osteoporosis and other skeletal disorders associated with increased bone remodeling. Denosumab binds RANKL, preventing it from binding to RANK, thereby reducing the formation, activity, and survival of osteoclasts and slowing the rate of bone resorption. Postmenopausal women with low bone mineral density (BMD) treated with denosumab have a reduction of bone turnover markers and an increase in BMD that is rapid, sustained, and reversible. In postmenopausal women with osteoporosis, denosumab reduces the risk of vertebral, hip, and nonvertebral fractures. In postmenopausal women with low BMD randomized to receive denosumab or alendronate, denosumab is associated with a significantly greater increase in BMD and further reduction in bone turnover markers compared with alendronate. In postmenopausal women with low BMD who were previously treated with alendronate, those who switched to denosumab have a significantly greater BMD increase and further reduction in bone turnover markers compared with those continuing alendronate. Denosumab is well tolerated with a favorable safety profile. It is a promising emerging drug for the prevention and treatment of osteoporosis, offering a long dosing interval of every 6 months and convenient SC dosing, with the potential of improving long-term adherence to therapy compared with current oral treatments.

New and emerging concepts in the use of denosumab for the treatment of osteoporosis

“…The pharmacokinetics and pharmacodynamics of denosumab, previously described in this journal, 16 were evaluated in a phase I, dose-escalation study Table 1. Noteworthy features of denosumab in the management of osteoporosis.…”

“…The pharmacokinetics and pharmacodynamics of denosumab, previously described in this journal, 16 were evaluated in a phase I, dose-escalation study with 49 healthy postmenopausal women who received a single dose of denosumab (0.01, 0.03, 0.3, or 1.0 mg/kg SC) or placebo and were then followed for 6–9 months. 17 Administration of denosumab was followed by a rapid, dose dependent, sustained (lasting as long as 6 months) decrease in urinary N-telopeptide (NTX), a marker of bone resorption.…”

Medication-Related Osteonecrosis of the Jaw (MRONJ): Are Antiresorptive Drugs the Main Culprits or Only Accomplices? The Triggering Role of Vitamin D Deficiency

“…It has been suggested that the fostering factors for MRONJ are: BPs potency, treatment duration, concomitant oral surgery [ 30 , 31 ]. In addition to BPs, other therapeutic molecules can inhibit osteoclasts like denosumab, an anti-RANKL monoclonal antibody is currently used for the treatment of osteoporosis, primary and metastatic bone cancer as well as rheumatoid arthritis [ 32 , 33 , 34 ]. However, cases of ONJ have been reported in patients receiving denosumab [ 35 , 36 ].…”

4‑Hexylresorcinol inhibits osteoclastogenesis by suppressing the NF‑κB signaling pathway and reverses bone loss in ovariectomized mice

“…Potential anti resorptive drugs include estrogens (with or without progesterone), bisphosphonates (alendronate, risedronate, ibandronate and zoledronic acid), the estrogen agonist/antagonis traloxifene and salmon calcitonin ( 16 ). However, thus far teriparatide and recombinant human parathyroid hormone are the only approved anabolic agents ( 17 ), Denosumab, a human monoclonal antibody for RANKL, has been found to inhibit osteoclastogenesis and was approved for treating osteoporosis ( 18 ).…”