A single dose of zoledronic acid (Reclast) given after 15 months of combination therapy with teriparatide (Forteo) and denosumab (Prolia) largely maintained the bone mineral density (BMD) positive aspects in postmenopausal females with osteoporosis, a researcher reported.
In the originate-impress segment IV DATA-HD trial, 76 females purchased either 20 or 40 µg of teriparatide subcutaneously day after day for 9 months, and at 3 and 9 months, all of them purchased subcutaneous denosumab, 60 mg. Girls who executed the mix segment of the peep procure been then invited to participate in an extension segment; 53 did so and acquired a single dose of 5 mg intravenous zoledronic acid 24 to 35 weeks after the final dose of denosumab. Their mean age became once 66.
“In postmenopausal females with osteoporosis, combination therapy with teriparatide and denosumab produces hastily and extensive positive aspects in bone mineral density when in comparison with monotherapy,” acknowledged Sabashini Okay. Ramchand, MBBS, of Harvard College in Boston, in a presentation on the virtual American Society for Bone and Mineral Research meeting.
“Alternatively, conclude of denosumab ends in suggested bone loss, lack of antifracture efficacy, and elevated possibility of multiple vertebral fractures. The most up-to-date expert advice is to transition to a bisphosphonate when denosumab is discontinued, however the optimum drug, dose, and time desk remains undefined,” she acknowledged.
“We hypothesized that a single dose of zoledronic acid, 5 mg, would protect the extensive and hastily increases in bone density triggered by 15 months of overlapping teriparatide and denosumab in females at excessive possibility of crash,” she acknowledged.
Excessive possibility of crash became once defined at a BMD T-receive ? -2.5 at any anatomic design; or a T-receive ?2 with one or more clinical possibility elements; or a T-receive ? -1 plus a history of fragility crash.
At month 15 in DATA-HD, the moderate contain in BMD became once 13.6% on the lumbar spine and 5.1% and 5.6% on the total hip and femoral neck, respectively. At month 27, 12 months after the one dose of zoledronic acid, these positive aspects procure been maintained in any respect three web sites, with adjustments since baseline of 13.8%, 5.1%, and 5.5%, respectively.
At month 42, which became once 27 months after the one dose of zoledronic acid, bone density became once most productive partly maintained on the lumbar spine, remaining 10.1% above baseline, but became once maintained on the total hip and femoral neck, with adjustments of 4.8% and 6.4% from baseline.
She and her colleagues also regarded at adjustments in serum biomarkers of bone turnover. At 15 months, osteocalcin, amino-terminal propeptide of fashion 1 collagen (P1NP), and C-telopeptide of fashion 1 collagen (CTx) all procure been suppressed, as expected with denosumab therapy. After the transition to zoledronic acid, a unhurried return of the biomarkers in the direction of baseline became once observed. At 42 months, osteocalcin and P1NP concentrations procure been equivalent to baseline, whereas CTx focus remained suppressed at 32% under pretreatment baseline.
“It has also been hypothesized that administering a bisphosphonate whereas denosumab suppression of bone reworking is silent maximal would be less efficient than if it became once delayed till modeling has resumed,” Ramchand acknowledged.
They in consequence of this truth analyzed responses in step with when the zoledronic acid became once given: early, now now not as a lot as 26 weeks after the final dose of denosumab; on time, at 26 to 30 weeks; or unhurried, previous 30 weeks.
At 27 months on the hip web sites there perceived to be a precious raise out on bond density of unhurried, fairly than early, administration of zoledronic acid, and at 42 months a identical pattern became once observed however the outcomes procure been now now now not statistically indispensable.
“Our peep became once now now not designed to assess this endpoint, on the opposite hand, and became once in all probability underpowered for this,” she cautioned.
Whereas the findings expose that the one dose of zoledronic acid became once efficient for declaring the positive aspects in spine and hip BMD for 12 months after administration, the following return to baseline concentrations of bone turnover markers and the shortcoming of some BMD on the spine “counsel that more frequent dosing of zoledronic acid is required,” she concluded.
Disclosures
The DATA-HD trial became once funded by the NIH and the Hotfoot Foundation.
Ramchand disclosed no related relationships with industry.
