Modeling-and remodeling-based bone formation in the anabolic vs. antire-sorptive (ava) study in postmeno-pausal women with osteoporosis

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Conference Proceeding

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Osteoporosis Int


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].



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