ORLANDO – A single infusion of zoledronic acid does not completely prevent bone mineral density (BMD) loss regardless of the timing of the infusion in patients with osteopenia who discontinued denosumab (Prolia), according to a speaker at the annual meeting of the American Society for Bone and Mineral Research.
“If you consider a treatment break in patients treated with [denosumab] for a long time, I suggest to aim for a higher BMD, allowing a smaller bone loss when transitioning via [zoledronic acid] to a treatment break, or maybe you need to give more than one infusion of [zoledronic acid],” said, of Aarhus (Denmark) University Hospital during her presentation.
Dr. Langdahl and her colleagues enrolled 60 patients with osteopenia in a 2-year, randomized, open-label interventionalof patients who discontinued denosumab after more than 2 years of use (average treatment, 4.6 years). One group of 20 patients received 5 mg of zoledronic acid at 6 months after their last denosumab injection. Another group of 20 patients underwent monthly monitoring starting at 6 months after their last denosumab injection and received zoledronic acid if their s-carboxy-terminal collagen crosslinks (s-CTX) increased more than 1.26 mcg/L or if they reached 9 months after their last denosumab injection. A third group underwent observation with monthly monitoring starting at 6 months after their last denosumab injection, and they received zoledronic acid if s-CTX increased more than 1.26 mcg/L, BMD loss was 5% or more at any site, they experienced a fragility vertebral or hip fracture, or they reached 12 months after their last denosumab injection. All patients received a readministration of zoledronic acid if their BMD decreased by greater than 5% or if their s-CTX increased more than 1.26 mcg/L after 6 months, 12 months, or 24 months.
The researchers included postmenopausal women and men older than 50 years (mean, 67.7 years), but the majority of patients were women (n = 53) distributed evenly between the 6-month, 9-month, and observation groups. Patients were excluded if they had a low-energy vertebral fracture, had any hip fracture within 12 months, had a T score of less than –2.5 at any site, had received alendronate more than 3 years prior to taking denosumab, used glucocorticoids, had metabolic bone disease, had received hormone replacement therapy, or had cancer.
The observational group patients who met criteria to receive zoledronic acid because of increased s-CTX included one at 1 month after stopping denosumab, two at 2 months, six at 3 months, and one at 4 months. Of six patients who met BMD criteria for treatment at 3 months, one received retreatment 6 months after their first administration of zoledronic acid, and four patients received retreatment at 12 months.
At 2 months, two patients in the 9-month group met s-CTX criteria for treatment, four patients underwent retreatment under BMD criteria 6 months after the first administration of zoledronic acid, and one patient underwent retreatment at 12 months under BMD criteria. In the 6-month group, one patient met s-CTX criteria for retreatment at 6 months, and one patient at 12 months, with five patients meeting BMD criteria for retreatment at 6 months and at 12 months.
Overall, the average bone loss was 4.6% at the lumbar spine and 3.2% for total hip with no clinically significant between-group differences for either site. At 12 months, lumbar spine bone loss was 4.8% in the 6-month group, 4.2% in the 9-month group, and 4.9% in the observational group (P less than or equal to .006), and total hip bone loss was 2.6% in the 6-month group, 3.3% in the 9-month group, and 3.8% in the observational group (P less than or equal to .001).
Although the study followed patients for 2 years after the first zoledronic acid injection, data were available for the first year only, and the study is ongoing, Dr. Langdahl said.
This study was funded in part by Amgen, the Foundation of Vilhelm Pedersen and wife, Aarhus University, the Danish Osteoporosis Society Research Foundation, the P. Carl Petersens Foundation, and the Torkil Steenbeck Foundation. Dr. Langdahl reported receiving research funding from Amgen and Novo Nordisk and is on the advisory board for Amgen, Eli Lilly, and UCB.
SOURCE: Sølling A. ASBMR 2019.