Other clinical trials did not provide evidence for an increased risk of infectious complications either [238–240]. Because denosumab is a relatively recent treatment option, continued follow-up of any potential safety PF299 manufacturer signals will be required, as with other agents in osteoporosis. Denosumab and cardiovascular risks RANKL and OPG could also play a role in the regulation of vascular calcification. Mice knocked out for OPG developed extensive vascular calcifications [241]. OPG produced locally by endothelial cells could promote endothelial

survival and decrease atherotic plate mineralisation [228]. Several clinical studies have shown that circulating OPG was higher in patients with cardiovascular diseases, particularly in terminal renal failure [242, 243], an increase considered as a reaction to the inflammatory signal [244]. One human study has shown conversely an inverse relationship between OPG and echogenicity of carotid plaques, thus that individuals with more fibrous and calcified plates had a lower serum OPG concentration [245]. Inhibiting RANKL decreased vascular calcifications in human RANKL knocked-in mice

with glucocorticoid induced www.selleckchem.com/products/gsk3326595-epz015938.html osteoporosis [246]. Thus, one could expect that besides protecting bone, denosumab could decrease the risk of atherosclerosis. The clinical trials on bone efficacy click here in osteoporosis and osteopenia did not show differences in cardiovascular accidents in the denosumab-treated patients. However, these studies were not designed to study this end point, and the cardiovascular risk in the patients included was not high (6.8% of the patients in the placebo group of the FREEDOM study Cell press had a cardiovascular event, stroke, coronary heart disease or peripheral vascular disease). It would be interesting to look at high-risk subgroups and to include cardiovascular events as an end point in osteopenia or osteoporosis studies conducted in patients at increased risk of atheromatosis, like those with glucocorticoid induced osteoporosis. Teriparatide and parathyroid hormone(1–84) The biological activity of the intact human PTH, i.e. PTH(1–84), resides

in its N-terminal sequence. Within the PTH peptide family, teriparatide, the recombinant human PTH(1–34) fragment has been most extensively developed for clinical use in osteoporosis. Miscellaneous effects In clinical trials, commonly reported mild side effects have been headaches (8%), nausea (8%), dizziness (9%) and leg cramps (3%), with only for the latter two a significantly higher incidence compared to placebo. These side effects tend to occur within the first few hours following subcutaneous injection [247, 248]. Subcutaneous injection of 20 μg of teriparatide results in a limited increase (around 0.8 mg/dl) of serum calcium, peaking after 4 to 6 h, followed by a progressive return to baseline before the next injection.