Rationale: Growing evidence indicates that intracellular reactive oxygen species (ROS) accumulation is a critical factor in the development of osteoporosis by triggering osteoclast formation and function. Pseurotin A (Pse) is a secondary metabolite isolated from Aspergillus fumigatus with antioxidant properties, recently shown to exhibit a wide range of potential therapeutic applications. However, its effects on osteoporosis remain unknown. This study aimed to explore whether Pse, by suppressing ROS level, is able to inhibit osteoclastogenesis and prevent the bone loss induced by estrogen-deficiency in ovariectomized (OVX) mice. Methods: The effects of Pse on receptor activator of nuclear factor-κB (NF-κB) ligand (RANKL)-induced osteoclastogenesis and bone resorptive function were examined by tartrate resistant acid phosphatase (TRAcP) staining and hydroxyapatite resorption assay. 2',7'-dichlorodihydrofluorescein diacetate (H 2 DCFDA) was used to detect intracellular ROS production in vitro . Western blot assay was used to identify proteins associated with ROS generation and scavenging as well as ROS-mediated signaling cascades including mitogen-activated protein kinases (MAPKs), NF-κB pathways, and nuclear factor of activated T cells 1 (NFATc1) signaling. The expression of osteoclast-specific genes was assessed by qPCR. The in vivo potential of Pse was determined using an OVX mouse model administered with Pse or vehicle for 6 weeks. In vivo ROS production was assessed by intravenous injection of dihydroethidium (DHE) into OVX mice 24h prior to killing. After sacrifice, the bone samples were analyzed using micro-CT and histomorphometry to determine bone volume, osteoclast activity, and ROS level ex vivo . Results: Pse was demonstrated to inhibit osteoclastogenesis and bone resorptive function in vitro , as well as the downregulation of osteoclast-specific genes including Acp5 (encoding TRAcP), Ctsk (encoding cathepsin K), and Mmp9 (encoding matrix metalloproteinase 9). Mechanistically, Pse suppressed intracellular ROS level by inhibiting RANKL-induced ROS production and enhancing ROS scavenging enzymes, subsequently suppressing MAPK pathway (ERK, P38, and JNK) and NF-κB pathways, leading to the inhibition of NFATc1 signaling. Micro-CT and histological data indicated that OVX procedure resulted in a significant bone loss, with dramatically increased the number of osteoclasts on the bone surface as well as increased ROS level in the bone marrow microenvironment; whereas Pse supplementation was capable of effectively preventing these OVX-induced changes. Conclusion: Pse was demonstrated for the first time as a novel alternative therapy for osteoclast-related bone diseases such as osteoporosis through suppressing ROS level. ...

The present study describes for the first time, a metabolic profile reflecting the osteoporosis progression in 364 pre- and postmenopausal Chinese women using GC-MS. In order to accurately evaluate the dynamic changes of metabolites along with estrogen deficiency and osteoporosis progression, we divided these subjects into the following four groups: premenopausal women with normal bone mass density (BMD, group I), postmenopausal women with normal BMD (group II), postmenopausal women with osteopenia (group III) and postmenopausal women with osteoporosis (group IV), according to their menopause or low BMD status. Principal component analysis (PCA) and Partial least squares-discriminant analysis (PLS-DA) were used to evaluate the associations of metabolic changes with low BMD or estrogen deficiency. Twelve metabolites identified by the PLS-DA model were found to be able to differentiate low BMD groups from normal BMD groups. Of the 12 metabolites, five free fatty acids (LA, oleic acid, AA and 11,14-eicosadienoic acid) have the most potential to be used as osteoporosis biomarkers due to their better correlations with BMD, and high sensitivity and specificity in distinguishing the low BMD groups from the normal BMD groups calculated by the receiver operating characteristic curve (ROC). The lipid profile may be useful for osteoporosis prediction and diagnosis.

Compared with open surgery retroperitoneoscopic lateral adrenalectomy for pheochromocytoma is a safe, minimally invasive and effective procedure.