Denosumab

Key Trials

Denosumab

• FREEDOM - Denosumab for Prevention of Fractures in Postmenopausal Women with Osteoporosis - NEJM 2009

• FREEDOM extension (8 years) - The effect of 8 or 5 years of denosumab treatment in postmenopausal women with osteoporosis: results from the FREEDOM Extension study - Osteoporosis International 2015

• FREEDOM extension (10 years) - 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension - Lancet Endocrinology 2017

• Discontinuation of Denosumab therapy for osteoporosis: A systematic review and position statement by ECTS - Bone 2017

Mechanism

Human IgG2 monoclonal antibody with affinity and specificity for human RANK ligand (RANKL) 

Inhibits RANKL from activating its receptor, RANK, on the surface of osteoclasts and their precursors.

Prevention of RANKL-RANK interaction inhibits osteoclast formation, function and survival, thereby decreasing bone resorption.

Contraindications

• Hypocalcemia

• Pregnancy

• Precautions:

  • Adequate calcium & vitamin D intake

  • Hypocalcemia treated

  • If predisposed to hypocalcemia, check Ca within 2 weeks

Caution - Rebound Bone Loss and fractures

• BMD

  • Decreased all sites

  • Still higher than non-treated group

• BTM

  • Rebound increase in both bone resorption and formation prior to returning to baseline

• Key article: Effects of Denosumab Treatment and Discontinuation on Bone Mineral Density and Bone Turnover Markers in Postmenopausal Women with Low Bone Mass - JCEM 2011