An essential source of information for preparing and testing new treatments is the study of the regulatory mechanisms of metabolic turnover.
In this area, to which also belongs the discovery of the RANK-RANKL-OPG system, biochemical studies are being extended on a glycoprotein, sclerostin, which belongs to a family of proteins that share the ability to express activity antagonistic to that of bone morphogenetic proteins, leading to a reduction in osteoblastic activity. It has been demonstrated that the expression of mRNA encoding for this protein is inhibited by parathormone (PTH) both in vivo and in vitro; moreover, recent studies have shown that the administration of monoclonal antibodies that block the activity of sclerostin results in an increase in bone mineral density, associated with an increase in circulating biochemical markers of neoformation and a significant decrease in those of resorption.
Since sclerostin is an excreted soluble factor, it has been possible to develop commercially available immunometric methods to measure its circulating concentration, but the results obtained so far seem somewhat conflicting. In particular, studies on healthy subjects show that the concentrations of sclerostin increase with age in both sexes but are modestly associated with bone mineral density and the con centration of biochemical markers of metabolic turnover. Addionally, they decrease in postmenopausal women treated with estrogen replacement therapy or PTH. Finally, they are not significantly affected by therapy with teriparatide. In studies evaluating the risk of fracture, which represents a critical clinical parameter in the evaluation of patients with osteoporosis, the associations between basal concentrations of sclerostin and incidence or prevalence of fracture risk do not seem to be statistically significant, highlighting the low effectiveness of the biochemical marker concerning this specific clinical information.
On the other hand, a significant positive correlation between protein concentration and bone mineral density has been demonstrated in all studies conducted in postmenopausal women, suggesting that circulating sclerostin mainly reflects the number of osteocytes. Thus, the concentration of sclerostin is proportional to the level of bone mass and not to the activity of individual cells or bone remodeling units. Also, a negative, statistically significant correlation with bio chemical markers of bone remodeling (PINP and CTX) has been shown.
Before introducing sclerostin in clinical practice as a new and promising biochemical marker for the study of bone turnover, further studies are mandatory.
