Some evidence shows the combination of teriparatide and denosumab, followed by a single dose of zoledronate, may be an effective strategy in the long-term management of high-risk fragility fractures.
In postmenopausal women with osteoporosis, a single dose of zoledronate (Reclast, Novartis) maintains the increases in femoral neck and total hip bone mineral density achieved with combination teriparatide/denosumab for at least 27 months, according to a study presented at the American Society for Bone and Mineral Research (ASBMR) annual meeting being held virtually this week.
“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,” according to study author Sabashini Ramchand, MBBS, of Massachusetts General Hospital, Boston.
The optimal way to prevent the high-turnover bone loss caused by stopping denosumab has not been defined. The DATA-HD trial reported that teriparatide combined with denosumab greatly increased bone mineral density at all anatomic sites. In the DATA-HD Extension trial, Dr. Ramchand and colleagues tested the hypothesis that a single dose of zoledronate, given 24 to 35 weeks after denosumab, could preserve these bone mineral density gains for an additional 27 months in 53 postmenopausal women with osteoporosis.
At the femoral neck and total hip, the mean 5.6 percent and 5.1 percent gains in bone mineral density achieved by month 15 were maintained both 12 and 27 months after zoledronate administration. At the spine, the mean 13.5 percent gain in bone mineral density achieved by month 15 was maintained for the first 12 months but decreased thereafter resulting in a 3 percent reduction 27 months after zoledronate administration. Still, spine bone mineral density remained 10.1 percent higher than the original DATA-HD baseline.
Further, the pattern of bone mineral density changes between months 15 and 42 were similarin participants who has received 20-µg or 40-µgof teriparatide in DATA-HD. Between months 15 and 27, femoral neck bone mineral density decreased more in patients who received zoledronate early (<26 weeks) versus those who received it late (>30 weeks) but this difference did not persist to month 42.
“A single dose of zoledronic acid 5 mg effectively maintains the large and rapid gains in hip and spine bone mineral density achieved after 15 months of overlapping treatment with teriparatide and denosumab,” Dr. Ramchand said. “Hip BMD was maintained for at least 27 months and spine BMD was fully maintained for 12 months and partially maintained 27 months after the transition.”
Meanwhile, a further follow up trial, DATA-HD Extension HR-pQCT, presented by Dr. Ramchand found that a single dose of zoledronate effectively maintained trabecular, but not cortical, volumetric bone miner density and microarchitecture at peripheral anatomic sites after treatment with combination teriparatide/denosumab.
“The increase in cortical porosity after 12 months from the transition, and the ongoing microstructural deterioration observed, would suggest more frequent re-dosing of zoledronic acid is required,” Dr. Ramchand said.
 Zoledronic Acid Maintains Areal Bone Density after Denosumab Administration (DATA-HD Extension). Sabashini K. Ramchand. September 12. ASMBR 2020 Annual Meeting Virtual Event.
 Effect of Zoledronic Acid on Volumetric Bone Density and Microarchitecture after Denosumab Administration (DATA-HD Extension HR-pQCT Study). Sabashini K. Ramchand. September 12. ASMBR 2020 Annual Meeting Virtual Event.