Zoledronic Acid May Not Prevent Bone Loss After Denosumab Monotherapy

The loss of bone mineral density (BMD) that individuals with osteopenia can experience after discontinuing treatment with denosumab may not be preventable with zoledronic acid infusion, according to initial findings from an ongoing study presented at the American Society for Bone and Mineral Research 2019 Annual Meeting.

To reach this conclusion, Anne Sophie Sølling, MD, from the Department of Endocrinology and Internal Medicine at Aarhus University Hospital in Denmark, and colleagues studied data on 60 postmenopausal women and men with osteopenia who had received treatment with denosumab for an average of 4.6 years.

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Of the participants, 20 had received a zoledronic acid infusion 6 months after their last denosumab injection, 20 had received a zoledronic acid infusion 9 months after their last denosumab injection, and 20 had received a zoledronic acid infusion when bone turnover was increased.

On a monthly basis, the researchers monitored the participants who had received their infusion at 9 months and those who had bone turnover. The researchers administered zoledronic acid to participants if their serum carboxy-terminal collagen crosslinks (s-CTX) increased more than 1.26 µg/L (50% above the normal range for postmenopausal women and elderly men) or if they had a fragility vertebral or hip fracture. At 2 months, 2 participants had fulfilled the CTX requirement.

After 3 months, the researchers performed bone densitometry among participants in the bone turnover group. Zoledronic acid was administered if the participants’ BMD decreased by more than 5.0%. By 5 months, 10 participants had fulfilled the CTX or BMD criteria. 

Bone densitometry was monitored at 6, 12, and 24 months. Zoledronic acid was re-administered if BMD decreased by more than 5.0% or if s-CTX increased more than 1.26 µg/L.

In all, 19 participants fulfilled the criteria for re-retreatment during the follow-up.

BMD decreased at the lumbar spine by 4.8 ± 0.7% in the 6-month group, by 4.2 ± 1.1% in the 9-month group, and by 4.9 ± 1.4% in the bone turnover group, 1 year after the initial zoledronic acid infusion. Total hip BMD decreased by 2.6 ± 0.5% in the 6-month group, by 3.3 ± 0.8% in the 9-month group, and by 3.8 ± 0.9% in the bone turnover group.

Among all 3 groups, mean CTX was within the postmenopausal reference range 6 and 12 months after the initial treatment.

“Treatment with [zoledronic acid] irrespective of the timing did not fully prevent loss of BMD in patients with osteopenia,” the authors concluded.

—Colleen Murphy

Reference:

Sølling AS, Harsløf T, Lomholt L. Treatment with zoledronic acid subsequent to treatment with denosumab [Abstract #LB-1169]. Presented at: American Society for Bone and Mineral Research 2019 Annual Meeting; September 23, 2019; Orlando, FL.