Sclerostin neutralizing antibodies are being tested in ongoing clinical trials to target osteoporosis and osteogenesis imperfecta but their interaction with mechanical stimuli on bone formation remains unclear.
For example, in metabolic bone diseases like osteoporosis (OP) and renal osteodystrophy (ROD), the association with a worse cardiovascular outcome can be tentatively explained by the possible derangements of three recently discovered bone hormones (osteocalcin, fibroblast growth factor 23 and sclerostin) and a bone-specific enzyme (alkaline phosphatase).
Ordinal logistic regression analysis suggested that the levels of serum sclerostin were independently associated with the presence of osteopenia and osteoporosis after adjusting for age, gender and 25OHD<sub>3</sub> (sclerostin: OR = 1.02, p = 0.001).
Increased expression of the osteocyte-derived bone inhibitor sclerostin has been linked to estrogen deficiency-induced osteoporosis and is therefore a promising target for osteoporosis management.
The role of sclerostin/dickkopf-1 and receptor activator of nuclear factor kB ligand/osteoprotegerin signalling pathways in the development of osteoporosis in patients with haemophilia A and B: A cross-sectional study.
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.
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).
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.
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.
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.
A highly specific expression pattern and the exclusive bone phenotype have made Sclerostin an attractive target for therapeutic intervention in treating metabolic bone diseases such as osteoporosis and in facilitating fracture repair.
Together, these results demonstrate that inhibition of sclerostin by Scl-Ab increased bone formation, and decreased bone resorption, leading to improved bone structure, bone mass and bone strength while maintaining bone quality in multiple animal models of osteoporosis.
Furthermore, novel bone-forming strategies for the treatment of osteoporosis that resulted from these discoveries, such as antibodies against sclerostin, are discussed as well.
Three of these genes, RANKL, ADAMTS and SOST, were known to be associated with osteoporosis in humans, which makes them good candidate genes for osteoporosis in chickens.
In cartilage, TG2 expression was faint in control and OP and significantly less than in OA and OP + OA chondrocytes; the opposite was found for Osteocalcin, whereas Osteopontin and Sclerostin expression was similar.
Thus, sclerostin has quickly become a promising molecular target for the treatment of osteoporosis and other skeletal diseases, and beneficial skeletal outcomes are observed in animal studies and clinical trials using neutralizing antibodies against sclerostin.
Collectively, these findings suggest that bone loss associated with steroid-induced osteoporosis is a consequence of sclerostin-mediated restriction of Wnt signaling, which may mechanistically facilitate glucocorticoid toxicity in bone.