Zoledronic Acid after Treatment with Denosumab is Associated with Bone Loss within 1 Year

Bone mineral density (BMD) declines when zoledronic acid (ZA) is administered. This case series describes the patterns of change in BMD when 1 or 2 doses of ZA are administered after denosumab.

Twelve patients who received at least 2 doses of denosumab followed by at least 1 dose of ZA and who had a dual energy X-ray absorptiometry (DXA) scan at the end of denosumab and 1 year after the first dose of ZA were included. We excluded patients with bone cancer or conditions affecting bone metabolism, including hyperparathyroidism, rickets, osteogenesis imperfecta, rheumatologic disorders, fibrous dysplasia, Paget's disease of bone, untreated hyperthyroidism, chronic kidney disease, liver cirrhosis, malabsorption, ongoing corticosteroid therapy, and aromatase inhibitor use.

There was a significant decline in BMD at the femoral neck within 1 year of the first ZA dose and a non-significant downward trend in the hip and lumbar spine. This trend was more severe in patients with osteoporosis at the time of drug transition. No increase in clinical vertebral fractures was observed. BMD seemed to stabilize in a smaller number of patients who received a second dose of ZA and had a DXA scan 1 year later.

A single dose of ZA administered approximately 6 months after denosumab leads to some BMD loss, mostly within 1 year of ZA administration, particularly in patients with osteoporosis at the time of denosumab discontinuation.