This article is more than 5 years old. Information may no longer be current.
Bone biopsies show early effects on bone formation with romosozumab
Click Here to Manage Email Alerts
A cohort of postmenopausal women with osteoporosis assigned the human monoclonal antibody romosozumab showed marked increases in dynamic parameters of bone formation just 2 months after initiating treatment when compared with women assigned placebo, according to findings published in the Journal of Bone and Mineral Research.
“The purpose of the present study was to characterize the effects of romosozumab on bone tissue by bone histomorphometry early in treatment at 2 months and to evaluate in another patient cohort the evolution of these effects after 12 months of romosozumab administration in postmenopausal women with osteoporosis,” Pascale Chavassieux, MD, of the University of Lyon in France, and colleagues wrote in the study background. “Bone histomorphometry allows the study of bone at the tissue or cell level to assess the intermediary levels of organization of bone (ie, the osteon or basic structural unit in cortical and cancellous bone). The use of fluorochrome labeling allows the measurement of dynamic parameters and adds a time dimension to the quantitative analysis.”
Chavassieux and colleagues analyzed data from 107 postmenopausal women with osteoporosis enrolled in the Fracture Study in Postmenopausal Women with Osteoporosis (FRAME), a randomized, double-blind, placebo-controlled, parallel-group study designed to assess the effects of monthly, subcutaneous romosozumab (210 mg; Evenity, Amgen) vs. placebo for 12 months, followed by 12 months of open-label denosumab (Prolia, Amgen) every 6 months (60 mg). Researchers performed transiliac bone biopsies at 2 months (n = 34) or 12 months (n = 73) in two different cohorts. For biopsies obtained at 2 months, the quadruple fluorochrome labeling procedure was used to compare dynamic bone formation parameters at baseline and after 2 months of romosozumab.
“This technique, when performed over a short period, such as 2 months, allows the evaluation of longitudinal data with only one biopsy, each serving as her own pretreatment control,” the researchers wrote.
Researchers performed histomorphometry measurements on whole tissue at month 2, including the cancellous, endocortical, intracortical and periosteal envelopes, and on cancellous, endocortical and intracortical envelopes at month 12.
The analysis showed that, at the tissue level, romosozumab produced an early and transient increase in bone formation and a persistent decrease in bone resorption.
At 2 months, researchers observed an increase in the ratio of mineralizing surface to bone surface for women assigned romosozumab (median at baseline and month 2, 1.51% and 5.64%, respectively) vs. placebo (median at baseline and month 2, 1.6% and 2.31%, respectively), which was associated with a decrease compared with placebo in parameters of resorption in cancellous bone (P = .002) and endocortical bone (P = .003), according to researchers.
At 12 months, cancellous bone formation was lower in women assigned romosozumab vs. placebo (P < .05 to P < .001) and the lower values for resorption endpoints observed at month 2 persisted (P < .001), signaling a decrease in bone turnover (P = .006). No significant change was observed in periosteal and endocortical bone, according to researchers.
“This resulted in an increase in bone mass and trabecular thickness with improved trabecular connectivity, without significant modification of cortical porosity at month 12,” the researchers wrote.
In a press release, the researchers noted that the observed effects contribute to the reduced fracture risk previously reported in postmenopausal women with osteoporosis treated with romosozumab.
“Romosozumab is the first osteoporosis therapy with a dual effect on bone tissue, increasing bone formation and decreasing resorption,” Chavassieux said in the release. – by Regina Schaffer
Disclosures: Chavassieux reports he has received a travel grant from Amgen and UCB, grants and research support from Amgen, Chugai-Roche and Merck, consultant fees from Amgen, Janssen, Radius, Sandoz and UCB, and speaking fees from AbbVie, Amgen, Bristol-Myers Squibb, Eli Lilly, MSD and Pfizer. Please see the study for all other authors’ relevant financial disclosures.
Click Here to Manage Email Alerts