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Cyclic teriparatide, denosumab administration benefits cortical BMD in osteoporosis
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Postmenopausal women with osteoporosis who received a regimen of three separate, 6-month cycles of daily teriparatide followed by one subcutaneous injection of denosumab experienced a moderate gain in cortical bone mineral density at 18 months that was not observed among similar women who received the standard regimen of 18 months of teriparatide followed by 18 months of denosumab, according to findings published in the Journal of Bone and Mineral Research.
“In an effort to maximize BMD improvement with [teriparatide], we have previously tested a cyclic approach,” Felicia Cosman, MD, a professor of medicine at Columbia University in New York, and colleagues wrote in the study background. “In women who received short, cyclic courses of [teriparatide], BMD declined during the off-[teriparatide] periods, in the absence of an antiresorptive agent. We hypothesized that administration of cyclic [teriparatide] might be optimized by using an intervening antiresorptive agent during these off-[teriparatide] periods.”
In a randomized, parallel-design study, Cosman and colleagues analyzed data from 70 postmenopausal women with a diagnosis of osteoporosis who were not using an osteoporosis medication (mean age, 65 years; mean BMI, 23.2 kg/m²; mean lumbar spine T-score, –2.7). Researchers randomly assigned participants to 18 months of teriparatide (Forteo, Eli Lilly) followed by 18 months of denosumab (Prolia, Amgen; standard treatment) or three separate, 12-month cycles of 6 months of teriparatide followed by 6 months of denosumab (cyclic treatment). Women underwent DXA scans to assess BMD at the lumbar spine, total hip, femoral neck and radius every 6 months and total-body bone mineral (TBBM) density at 18 and 36 months.
At 36 months, women in the standard treatment group experienced mean BMD gains of 16% at the lumbar spine, 4% at the total hip and 3% at the femoral neck and a TBBM density gain of 4.8% when compared with baseline assessments (P < .001 for all).
Women in the cyclic group experienced similar BMD gains at 36 months, with mean increases of 12% at the lumbar spine, 4% at the total hip and 4% at the femoral neck and a 4.1% increase in TBBM density (P < .001 for all). However, at 18 months, women in the cyclic group did not experience a decline in BMD at the distal radius (P = .007) or in TBBM density (P < .001), whereas women in the standard group did.
The researchers speculated that gains at 18 months seen with cyclic administration are likely due to a reduction in teriparatide-mediated remodeling and cortical porosity as a result of the denosumab treatment given at 6 months.
“The BMD findings seen in this trial in the cyclic arm are superior to those seen in our prior study where women received cyclic [teriparatide] without any intervening antiresorptive therapy,” the researchers wrote. “This cyclic approach could potentially be appropriate for some patients who are at particularly high imminent risk of fracture, especially at cortical predominant nonvertebral skeletal sites.”
The researchers noted that the BMD increases seen with 18 months of denosumab after 18 months of teriparatide were “quite large,” especially at the spine and total hip, and were larger than those seen in other studies when alendronate is administered after teriparatide or abaloparatide (Tymlos, Radius Health).
“Several other studies suggest that [denosumab] treatment enhances BMD gain after [teriparatide] to a greater degree than bisphosphonates,” the researchers wrote. “The explanation is likely due to a more potent antiresorptive effect of [denosumab] compared to bisphosphonates.”
Researchers concluded that for most high-risk patients, standard monotherapy sequences should continue to be utilized, with anabolic treatment for 18 to 24 months, followed by potent antiresorptive therapy for several years to achieve expected BMD gains and expected fracture risk reductions. – by Regina Schaffer
Disclosures: Amgen funded this study. Amgen and Eli Lilly provided study medications. Roche supplied biochemical assays. Cosman reports she has received grants, consultant, advisory board and speaking fees from Amgen, Radius Health and RPharm and previously received grants, consultant, advisory board and speaking fees from Eli Lilly and Merck. Please see the study for all other authors’ relevant financial disclosures.
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