Romosozumab in Postmenopausal Women with Low Bone Mineral Density

Abstract

In postmenopausal women with low bone mass, romosozumab was associated with increased bone mineral density and bone formation and with decreased bone resorption. (Funded by Amgen and UCB Pharma; ClinicalTrials.gov number, NCT00896532.).

Targeting Wnts at the Source—New Mechanisms, New Biomarkers, New Drugs

“…2). SOST and LRP4 loss-offunction mutations cause increased bone mass, a finding that can be mimicked therapeutically for the treatment of osteoporosis by SOST or LRP4 neutralizing antibodies (16,17).…”

CORR Insights®: Does Sclerostin Depletion Stimulate Fracture Healing in a Mouse Model?

“…Does this benefit persist beyond a year? The wrist is a common site of fracture but limited changes were observed after 1 year of romosozumab injections and for unknown reasons [6]. Lastly, SclAb injections in clinical trials are both anabolic and antiresorptive [6,10], whereas anabolic in lower-order species [8].…”

“…Researchers would then note the progression of the healing. In particular, the bone mass at the wrist does not improve demonstrably with romosozumab injections [6]. It is possible that since the site does not sustain the same level and variety of mechanical loads as the hip or spine and since bone is a highly load-sensitive tissue, a clinical trial may include a group where the wrist is subjected to a mechanical stimulus, such as resistive exercise, during Scl-Ab injections to increase bone mass.…”

“…While most pharmacologic approaches exclusively target osteoclast activity (bisphosphonates and denosumab), sclerostinneutralizing monoclonal-antibody (SclAb) injections are gaining traction as a potential anabolic treatment to improve bone-healing and increase bone mass [5,6,8,10]. Deficiency of sclerostin, which is secreted by osteocytes to target the Wnt pathway in osteoblasts, augments bone formation and strength in rodents and monkeys [4,9].…”

“…Deficiency of sclerostin, which is secreted by osteocytes to target the Wnt pathway in osteoblasts, augments bone formation and strength in rodents and monkeys [4,9]. In Phase I and II clinical trials, Scl-Ab treatment (romosozumab [Amgen/UCB, Thousand Oaks, CA, USA] and blosozumab [Eli Lily & Co, Indianapolis, IA, USA)]) [1,6,10] also increases bone formation with minimal side-effects, other than mild reactions at the injection site. However, as stated by Alzahrani et al [1], ''Fracture healing has been reported to be improved with the Scl-Ab, but the degree of sclerostin depletion with this modality has yet to be determined.…”