Oral Virtual Presentation (Virtual only) ESA-SRB-ANZBMS 2021

Kinetic reconstruction of the cancellous (Cn) and endocortical (Ec) remodeling unit reveals a net positive bone balance after 12 months (M12) of treatment with romosozumab (Romo) (#9)

Erik F Eriksen 1 , Yifei Shi 2 , Jacques P Brown 3 , Stephane Horlait 4 , Cesar Libanati 5 , Pascale Chavassieux 6 , Rogely W Boyce 2
  1. Department of Endocrinology, Oslo University Hospital, Oslo, Norway
  2. Amgen Inc, Thousand Oaks, CA, USA
  3. CHU de Québec (CHUL) Research Centre, Laval University, Quebec City, Canada
  4. Amgen, Boulogne Billancourt, France
  5. UCB, Brusseles, Belgium
  6. Université de Lyon, Lyon, France

Purpose:

To assess the effect of Romo on bone formation and resorption at the level of the basic multicellular unit (BMU) and determine the integral effects on BMU bone balance (BB).

 

Methods:

Transiliac biopsy sections from FRAME (NCT01575834) were obtained after M12 of Romo or placebo (Pbo) treatment; histomorphometric parameters were measured on Cn and Ec envelopes. Erosion depth (E.De; classified by the predominate resorptive cell type), osteoid thickness (O.Th), and complete and incomplete wall thickness (W.Th) were based on counting of lamellae in polarized light. To assess the formative site at M12, O.Th/mineralized (Md) W.Th at osteoid surfaces were classified using a 4-sector system; the sector containing the nearly completed formative sites provided the reconstructed W.Th. Kinetics of remodeling phases were reconstructed according to Steiniche (Bone 1992).

 

Results:

On Cn envelope, Romo resulted in a net positive BB compared with Pbo primarily due to sustained reduction in resorptive cell activity throughout 12 months, resulting in a significant reduction in final (Pre-Ob) E.De. On Ec envelope, Romo also resulted in net positive BB, not due to effects on resorption but due to positive effects on the formative site. Consequently, Romo significantly increased W.Th in bone packets that had completed by M12. This effect was not sustained in actively forming packets at the end of treatment, suggesting these positive effects on bone formation at the BMU occurred earlier in treatment.

 

Conclusion:

After 12 months of Romo, a positive BB at the level of individual BMUs was evident on Cn and Ec envelopes, predominantly due to a net decrease in resorptive cell activity in Cn bone and a net increase in osteoblastic function in Ec bone. These effects likely contribute to the progressive increase in bone mass and microarchitectural improvements with Romo across 12 months of treatment.610a10f65553f-Eriksen+kinetics+abstract.png