Zoledronic acid maintains BMD gains after overlapping teriparatide, denosumab treatment
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A single dose of zoledronic acid effectively maintains large and rapid gains in spine and hip bone mineral density after 15 months of overlapping teriparatide and denosumab therapy, according to a speaker.
The cessation of denosumab (Prolia, Amgen) leads to prompt bone loss, loss of antifracture efficacy and increased risk for multiple vertebral fractures, Sabashini K. Ramchand, MD, research fellow in medicine in the department of endocrinology at Massachusetts General Hospital, said during an online presentation at the virtual American Society for Bone and Mineral Research Annual Meeting. Expert recommendation is to transition to a bisphosphonate when denosumab is discontinued; however, the optimal drug, dose and schedule remain unidentified, Ramchand said. In the DATA-HD extension study, Ramchand and colleagues assessed whether a single, 5 mg dose of zoledronic acid would maintain the large and rapid increases in BMD induced by 15 months of overlapping therapy.
“This is the first prospective trial evaluating the efficacy of a single dose of zoledronic acid in maintaining large and rapid gains in BMD achieved with short-term overlapping treatment with teriparatide and denosumab,” Ramchand told Healio. “Zoledronic acid shows promising results and may be an effective strategy in the management of women at high fracture risk.”
Ramchand and colleagues analyzed data from postmenopausal women aged at least 45 years who have not received oral bisphosphonates or denosumab within 6 months. For the main DATA-HD study (n = 69; mean age, 66 years; 58% previous oral bisphosphonate users; 57% with history of fragility fracture), women received 20 µg or 40 µg teriparatide (Forteo, Eli Lilly; Bonsity, Alvogen) daily and 60 mg denosumab once every 6 months for 15 months. For the extension study (n = 53; mean age, 66 years; 53% previous oral bisphosphonate users; 49% with history of fragility fracture), women received one dose of zoledronic acid 24 to 35 weeks after the last denosumab dose and were followed an additional 27 months.
At the end of the main DATA-HD study, researchers observed large and rapid BMD gains at the spine and hip; DXA data showed areal BMD gains of 13.6% at the lumbar spine, 5.1% at the total hip and 5.6% at the femoral neck at 15 months.
After receiving one dose of zoledronic acid, mean total hip and femoral neck BMD was maintained for at least 27 months, Ramchand said, with areal BMD remaining at 4.8% above baseline at the total hip and 6.4% above baseline at the femoral neck at month 42. Lumbar spine BMD was fully maintained for 12 months and partially maintained 27 months after the transition, with mean areal BMD remaining at 10.1% above baseline values at month 42.
Additionally, concentrations of the bone turnover markers propeptide of type 1 procollagen, osteocalcin and C-terminal telopeptide gradually increased during the extension phase, but remained at or below pretreatment baseline values, Ramchand said.
“The rise in serum bone turnover markers and loss of BMD after 12 months, particularly at the spine, suggests more frequent re-dosing of zoledronic acid is required,” Ramchand said.
Ramchand noted that the treatment duration in this study was short — 9 months of treatment with teriparatide and two doses of denosumab — and that the findings may not apply to women who received longer courses of therapy.
“These data suggest that short-term overlapping treatment with teriparatide and denosumab followed by a single dose of zoledronic acid may be a particularly effective strategy in the long-term management of patients at high risk of osteoporotic fractures,” Ramchand said.
In a second study assessing the effect of zoledronic acid on volumetric BMD and microarchitecture after denosumab, the researchers found that zoledronic acid partially maintains bone density and microarchitecture for at least 12 months after the transition from overlapping therapy. The observed increase in cortical porosity after 27 months, as well as ongoing bone loss and microstructural deterioration, further suggests that more frequent re-dosing of zoledronic acid is required, Ramchand said.
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Ramchand, S, et al. Abstract #1037 and #1038. Presented at: American Society for Bone and Mineral Research Annual Meeting; Sept. 11-15, 2020 (virtual meeting).
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