Osteoporosis is characterized by low bone mass, deterioration of bone tissue and architecture, compromised bone strength, and an increase in fracture risk.1
The World Health Organization (WHO) defines osteoporosis as a bone mineral density (BMD) at the hip or spine ≤2.5 standard deviations below the young normal mean reference population. It affects nearly 10 million Americans and nearly 34 million are at risk, according to the National Osteoporosis Foundation. Although there is a greater incidence in women, men can also be affected.1
Postmenopausal women require special attention due to the decrease in estrogen levels, with an increase in the rate of bone remodeling causing an imbalance between osteoblasts and osteoclasts. Several measures are key techniques in both the prevention and treatment of osteoporosis, including but not limited to adequate intake of calcium and vitamin D, weight-bearing exercises, fall prevention techniques, bisphosphonate administration, nasal calcitonin, estrogen/hormonal replacement therapies, and parathyroid hormone supplementation.
In patients with bone metastases secondary to malignancy, there is an imbalance between osteoclast and osteoblast activity that results in local bone destruction. It is estimated that approximately 80% of all patients with diagnoses of breast cancer, prostate cancer, or multiple myeloma will develop bone metastases at some time during the course of their disease. The goal of treating these patients is to reduce the risk of developing a skeletal-related event (SRE), which is defined as spinal cord compression, a pathologic fracture, and a need for radiation therapy for skeletal stabilization or hypercalcemia.
Denosumab is a human IgG2 monoclonal antibody that inhibits binding of the receptor activator of nuclear factor kappa-B ligand (RANKL, part of the tumor necrosis factor family) to RANK receptors located on the surface of osteoclasts and their precursors. This inactivation prevents the formation, function, and survival of osteoclasts, which then reduces bone resorption, allowing for growth in cortical and trabecular bone.2
Improvements in BMD have been demonstrated with the use of denosumab.
Serum type I C-telopeptide (CTx), a bone resorption marker, adequately reflects denosumab activity. Three days following a single injection, CTx levels were reduced by 83%. A maximum reduction was noted in 1 month, with ranges of 45% to 80% during the 6-month dosing interval. Bone formation markers such as osteocalcin and procollagen type I N-terminal peptide (PINP) were also observed to decrease, indicating the coupled action of bone remodeling.2
Unlike the bisphosphonates, dose reductions were not required in renal or hepatic impairment. Clearance occurred through the reticuloendothelial system, ending with renal filtration and excretion.3
Studies have shown that denosumab is not incorporated into bone; therefore, accumulation is not a factor.