Effects of Combination Denosumab and High-Dose Teriparatide Administration on Bone Microarchitecture and Estimated Strength: The DATA-HD HR-pQCT Study

Abstract

In postmenopausal women at high risk of fracture, we previously reported that combined denosumab and high‐dose (HD; 40 μg) teriparatide increased spine and hip bone mineral density (BMD) more than combination with standard‐dose teriparatide (SD; 20 μg). To assess the effects of these combinations on bone microarchitecture and estimated bone strength, we performed high‐resolution peripheral quantitative computed tomography (HR‐pQCT) at the distal radius and distal tibia in these women, who were randomized to receive either teriparatide 20 μg (n = 39) or 40 μg (n = 37) during months 0 to 9 overlapped with denosumab 60 mg s.c. given at months 3 and 9, for a 15‐month study duration. The 69 women who completed at least one study visit after baseline are included in this analysis. Over 15 months, increases in total BMD were higher in the HD‐group than the SD‐group at the distal tibia (5.3% versus 3.4%, p = 0.01) with a similar trend at the distal radius (2.6% versus 1.0%, p = 0.06). At 15 months, cortical porosity remained similar to baseline, with absolute differences of −0.1% and −0.7% at the distal tibia and −0.4% and −0.1% at the distal radius in the HD‐group and SD‐group, respectively; p = NS for all comparisons. Tibial cortical tissue mineral density increased similarly in both treatment groups (1.3% [p < 0.0001 versus baseline] and 1.5% [p < 0.0001 versus baseline] in the HD‐group and SD‐group, respectively; p = 0.75 for overall group difference). Improvements in trabecular microarchitecture at the distal tibia and estimated strength by micro‐finite element analysis at both sites were numerically greater in the HD‐group compared with SD‐group but not significantly so. Together, these findings suggest that short‐term treatment combining denosumab with either high‐ or standard‐dose teriparatide improves HR‐pQCT measures of bone density, microstructure, and estimated strength, with greater gains in total bone density observed in the HD‐group, which may be of benefit in postmenopausal women with severe osteoporosis. © 2020 American Society for Bone and Mineral Research (ASBMR).

The clinical application of high-resolution peripheral computed tomography (HR-pQCT) in adults: state of the art and future directions

“… 24 months Highest Tt.BMD, Ct.BMD and Tb. BMD and Ct.Th, stiffness and failure load in combination group TPTD + DMAB Tsai [ 81 ] Ramchand [ 82 ] TPTD and DMAB switch RCT 77PMW n.a. 2 × 24 months before and after switch Switching from DMAB to TPTD: reduction in Tt.BMD and Ct.BMD, Ct.Th and estimated strength Switching from TPTD to DMAB or combination therapy improved these parameters with greatest improvements with combined therapy followed by DMAB ALN alendronate, RIS risedronate, IBN ibandronate, ZOL zoledronate, SRN strontium ranelate, ODN odanacatib, DMAB denosumab, TPTD teriparatide, PTH 1-84 parathormone 1-84, PBO placebo, PMW postmenopausal women, PreMW premenopausal women, LS lumbar spine, FN femoral neck, TH total hip, BMD bone mineral density, n.a.…”

“…Switching after 2 years of denosumab treatment to teriparatide for 2 years resulted in a reduction in Tt.BMD, Ct.BMD, Ct.Th, and estimated strength. Switching from teriparatide to denosumab or combination therapy improved these parameters with greatest improvements with combined therapy followed by denosumab [ 81 , 82 ].…”

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

“…A randomized controlled phase 4 trial showed that spine and hip BMD was increased in combined treatment with teriparatide 40 μg and denosumab compared with standard combination therapy ( Tsai et al, 2019 ). Both short-term treatments combining denosumab with either high (40 μg) or standard (20 μg) dose teriparatide were identified to improves HR-pQCT measures of bone density, microarchitecture, and estimated bone strength ( Ramchand et al, 2020a ). 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 ).…”

Teriparatide Followed by Denosumab in Premenopausal Idiopathic Osteoporosis: Bone Microstructure and Strength by HR-pQCT

“…Newer data in postmenopausal women suggest that combination therapy with teriparatide and denosumab may prevent the increase in cortical porosity associated with teriparatide, with comparable benefits to cortical and trabecular microarchitecture and strength with a shorter treatment period. ( 52 ) Therefore, future studies on the combination of denosumab and teriparatide may be warranted in premenopausal women with IOP.…”