Abstract
SummaryResearch into the drug romosozumab began with the investigation of patients with excess bone formation. The understanding of the wingless-type mouse mammary tumor virus integration site (Wnt) signaling pathway in bone metabolism identified the negative regulator of bone mass sclerostin as a potential target for the treatment of osteoporosis. Preclinical studies confirmed this idea because they showed that sclerostin antibodies have the potential to increase bone formation. Biochemical analyses of clinical studies showed a significant increase in bone formation markers, which then slowly decreased within a year. This was accompanied by a particularly initially pronounced decrease in bone resorption. This dual mechanism of action led to an increase in bone mineral density and a significant reduction in fracture risk. Clinical vertebral fractures decreased by between 28 and 36%, nonvertebral fractures shown in a post hoc analysis by 42%. Romosozumab is administered once a month in the form of two injections. At the puncture site, reactions occur in about 5%. The most significant side effects are cardiovascular. In phase III studies, the number of serious cardiovascular complications was not significantly, albeit numerically, higher than in the control group. In Japan, South Korea, Canada, Australia, and the USA, osteoporosis patients at a high risk of fracture may already be treated with romosozumab (Evenity). Approval in the European Union was granted by 2019-12-12.
Highlights
SOS speed of soundTeosis, the thought that high sclerostin levels lead to loss of bone mass and bone strength with an increased fracture risk is obvious
Studies of patients with rare bone diseases and the understanding of the Wnt signaling pathway in bone metabolism identified the negative regulator of bone mass sclerostin as a potential target for the treatment of osteoporosis
Serum sclerostin levels are supposed to give a good impression of sclerostin levels in bone
Summary
Teosis, the thought that high sclerostin levels lead to loss of bone mass and bone strength with an increased fracture risk is obvious. Several studies [16, 17, 26,27,28,29] evaluated the association between serum sclerostin level on one hand and bone mineral density (BMD), bone turnover markers (BTMs), and risk of fracture on the other hand (Table 1). Low BMD is expected in subjects with high sclerostin levels, all studies so far have found a positive association between serum sclerostin and BMD. According to Arasu et al [26] and Ardawi et al [16], fracture risk is amplified in subjects with high serum sclerostin levels and low BMD. Fracture healing has been shown to be accelerated in SOST knockout mice as well as after sclerostin antibody treatment in wildtype rats [43, 44]
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