Standard Versus Cyclic Teriparatide and Denosumab Treatment for Osteoporosis: A Randomized Trial

Abstract

In the absence of an intervening antiresorptive agent, cyclic administration of teriparatide does not increase bone mineral density (BMD) more than standard daily therapy. Because denosumab is a potent antiresorptive agent with a rapid off‐effect, we hypothesized that it might be the optimal agent to help maximize bone gains with cyclic teriparatide. In this 3‐year protocol, 70 postmenopausal women with osteoporosis were randomized to 18 months of teriparatide followed by 18 months of denosumab (standard) or three separate 12‐month cycles of 6 months of teriparatide followed by 6 months of denosumab (cyclic). BMD (dual‐energy X‐ray absorptiometry [DXA]) measurements of lumbar spine (LS), total hip (TH), femoral neck (FN), and 1/3 radius (RAD) were performed every 6 months and total body bone mineral (TBBM) at 18 and 36 months. Baseline descriptive characteristics did not differ between groups except for a minimal difference in LS BMD but not T‐score (mean age 65 years, mean LS T‐score − 2.7). In the standard group, BMD increments at 36 months were: LS 16%, TH 4%, FN 3%, and TBBM 4.8% (all p < 0.001 versus baseline). In the cyclic group, 36‐month BMD increments were similar: LS 12%, TH 4%, FN 4%, and TBBM 4.1% (all p < 0.001 versus baseline). At 36 months, the LS BMD increase with standard was slightly larger than with cyclic (p = 0.04), but at 18 months, in the cyclic group, there was no decline in RAD or TBBM (p = 0.007 and < 0.001, respectively, versus standard). Although the cyclic regimen did not improve BMD compared with standard at 36 months, there appeared to be a benefit at 18 months, especially in the highly cortical skeletal sites. This could be clinically relevant in patients at high imminent risk of fracture, particularly at nonvertebral sites. © 2019 American Society for Bone and Mineral Research. © 2019 American Society for Bone and Mineral Research.

Combination Therapy of PTH and Antiresorptive Drugs on Osteoporosis: A Review of Treatment Alternatives

“…Another study also indicated that treatment with the HD regimen (40 μg) showed clinically meaningful and rapid increase in hip and spine BMD compared with the SD regimen (20 μg) (Ramchand et al, 2020b). The cyclic regimen of teriparatide combined with denosumab appeared to be beneficial in improving BMD at 18 months, especially in the highly cortical skeletal sites, which was clinically relevant in patients at high imminent risk of fracture, particularly at nonvertebral sites (Cosman et al, 2020). Combination therapy with PTH and denosumab or ZOL seemed to achieve higher BMD gains compared to each agent alone (Leder, 2018;Kelly and Garapati, 2019;Anastasilakis et al, 2020).…”

Denosumab in the Treatment of Osteoporosis: 10 Years Later: A Narrative Review

“…Cyclical administration of 6 months of teriparatide followed by 6 months of denosumab for 36 months (3 cycles) versus 18 months of teriparatide followed by 18 months of denosumab produced hip and radius BMD benefits at 18 months but no significant differences at 36 months [ 70 ]. A comparison of subjects who transitioned from bisphosphonate to denosumab or teriparatide showed that hip BMD increased with denosumab over 2 years but was unchanged with teriparatide; anti-fracture efficacy data are not available [ 71 ].…”

<p>A Review on the Role of Denosumab in Fracture Prevention</p>

“…56 Moreover, the cyclic teriparatide treatment with three cycles of teriparatide (6 months) to denosumab (6 months) was similar to standard sequential teriparatide (18 months) to denosumab (18 months) treatment in increasing the BMDs at spine, total femur, femoral neck and 1/3 radius. 57 On the other hand, in DATA-Switch study, co-treatment of teriparatide and denosumab for 24 months, followed by 24-month denosumab alone was more potent in increasing the BMDs at total hip, femoral neck and radius bone (but not lumbar spine) than sequential treatments with teriparatide (24 months) to denosumab (24 months) or vice versa.- 58,59 Similar findings were obtained in the DATA and DATA extension study, whereby the co-treatment of teriparatide and denosumab induced a greater increase in BMDs. 52,53 A summary of the anti-fracture effects of denosumab is presented in Table 1.…”