Modeling-and remodeling-based bone formation in the anabolic vs. antire-sorptive (ava) study in postmeno-pausal women with osteoporosis
Dempster DW, Zhou H, Recker RR, Brown JP, Recknor CP, Lewiecki EM, Miller PD, Rao SD, Kendler DL, Lindsay R, Krege JH, Alam J, Taylor KA, and Ruff VA. Modeling-and remodeling-based bone formation in the anabolic vs. antire-sorptive (ava) study in postmeno-pausal women with osteoporosis. Osteoporosis Int 2017; 28:S191-S192
Objective: To compare early effects of an established anabolic (teriparatide: TPTD) vs. a prototypical antiresorptive (denosumab: DMAb) agent on modeling-and remodeling-based bone formation (MBF and RBF). Materials and Methods: Postmenopausal women with osteo-porosis were randomized to open-label TPTD (20 mcg/day) or DMAb (60 mg once) for 6 months. Double fluorochrome labeling was performed at baseline (BL) and prior to transiliac biopsy at month 3, when any effects of a transient rise in endogenous PTH with DMAb should be observable. Bone formation was expressed as a proportion of bone surface (BS), and was considered RBF if the underlying cement line was scalloped, MBF if it was smooth, and overflow MBF (oMBF) if over a smooth cement line adjacent to RBF. Mean changes from BL were compared between treatment groups using ANCOVA; within group differences were tested by paired T-tests. Results: At BL, mean RBF/BS, MBF/BS, and oMBF/BS were similar between the TPTD and DMAb groups in the cancellous, endocortical, and periosteal envelopes. At 3 months, with TPTD, all types of formation increased significantly in the cancellous and endocortical envelopes (range: 3-22-fold; all differences p<0. 001), as did MBF/BS in the peri-osteal envelope (4-fold, difference p<0. 001). Response to TPTD was especially robust in the endocortical envelope (Figure). In contrast, with DMAb all types of formation were decreased or unchanged except MBF, which increased 2-fold in cancellous envelope (BL=0. 1%, 3 month=0. 2%, difference p=0. 048). All types of bone formation were significantly greater with TPTD vs. DMAb, excepting oMBF in periosteal envelope. Conclusions: A short course of TPTD generally increased RBF, MBF, and oMBF in the 3 bone envelopes, while these were mostly reduced or unchanged with DMAb, reflecting the marked difference in mechanism of action of the 2 drugs. The results also provide the clearest evidence to date that TPTD stimulates MBF on the periosteal surface. [Graph Presented].