Chromatin immunoprecipitation showed that higher methylation was associated with reduced SP7, RUNX2, and ERα binding to the <i>SOST</i> promoter in patients with osteoporosis.
This finding suggests that the production and/or activity of sclerostin can be titrated in vivo, leading to variable increases in bone mass without any unwanted skeletal effects, a hypothesis of obvious significance for the development of new therapeutics for osteoporosis.
Together with the fact that focal radiation increases sclerostin amount in bone, we sought to determine whether weekly treatment with Scl-Ab would prevent focal radiotherapy-induced osteoporosis in mice.
We review here current knowledge of the regulation of the expression and formation of sclerostin, its mechanism of action, and its potential as a bone-building treatment for patients with osteoporosis.
The most promising new drugs in the treatment of osteoporosis include the antibody that neutralizes RANKL (denosumab, DMAb), monoclonal antibodies against sclerostin and parathyroid hormone-related protein analogue.
There was a positive, high-level relationship between sclerostin levels and BMI in the osteoporosis group and it was found to be statistically significant (p < 0.001, r = 0.786).
Sclerostin, an antagonist of the Wnt/β-catenin signaling pathway, was discovered as a potential therapeutic target for stimulating bone formation in osteoporosis.
The present study was conducted to determine whether individuals with SCI present alterations in serum periostin and sclerostin and to assess their relationships with bone mineral density, bone turnover markers, fracture status, time since injury, densitometric osteoporosis and paraplegic vs. tetraplegic status.
Therefore, the common variation of SOST gene contribute to the therapeutic response to alendronate treatment in Chinese women with osteoporosis or osteopenia.
Romosozumab, a humanized monoclonal sclerostin antibody under development for the treatment of osteoporosis, has a unique mechanism of action on bone-increasing bone formation and decreasing bone resorption.
Among the most distinctly expressed genes were Wnt antagonists DKK1 and SOST, the transcription factor SOX4, and the bone matrix proteins MMP13 and MEPE, all reduced in osteoporosis versus control groups.
We also describe the available preclinical and clinical studies and discuss the benefits and risks of using sclerostin inhibitors for the management of patients with osteoporosis.
Antibodies directed against sclerostin stimulate bone formation and represent a new therapeutic option in the treatment of diseases with increased bone resorption, such as osteoporosis and inflammatory diseases where there is generalized bone loss, periarticular osteoporosis, and cartilage damage, such as rheumatoid arthritis (RA), ankylosing spondylitis (AS), and glucocorticoid-induced osteoporosis (GIO).
In this article we review the demographic, clinical, biochemical, radiological, and histological characteristics of patients with sclerosteosis and van Buchem disease that led to a better understanding of the role of sclerostin in bone metabolism in humans and we discuss the relevance of these findings for the development of new therapeutics for the treatment of patients with osteoporosis.
Our findings uncover the biological consequences of four independent genetic variants in the SOST region and their important roles in SOST expression via diverse mechanisms, providing new insights into the genetics and molecular pathogenesis of osteoporosis.
Therefore, as anti-sclerostin antibodies are being developed for the treatment of osteoporosis, it is important to understand the functions of sclerostin beyond the regulation of bone formation.
By enhancing the osteogenic potential of the context in which individual therapies such as sclerostin antibodies act it may become possible to both prevent and reverse the age-related skeletal structural deterioration characteristic of osteoporosis.
Sclerostin, an antagonist of the Wingless-type mouse mammary tumor virus integration site (Wnt) pathway that regulates bone metabolism, is a potential contributor of chronic kidney disease (CKD)-mineral and bone disorder (MBD), which has various forms of presentation, from osteoporosis to vascular calcification.
The SOST gene promoter region showed increased CpG methylation in OP patients (n = 4) compared to age and body mass index (BMI) balanced controls (n = 4) (80.5% versus 63.2%, p = 0.0001) with replication in independent cohorts (n = 27 and n = 36, respectively).