Isoimperatorin attenuates bone loss by inhibiting the binding of RANKL to RANK.

Osteoporosis, an immune disease characterized by bone mass loss and microstructure destruction, is often seen in postmenopausal women. Isoimperatorin (ISO), a bioactive, natural furanocoumarin isolated from many traditional Chinese herbal medicines, has therapeutic effects against various diseases; however, its effect on bone homeostasis remains unclear. In this study, we investigated the effect of ISO on the differentiation and activation of osteoclast and its molecular mechanism in vitro, and evaluated the effect of ISO on bone metabolism by ovariectomized (OVX) rat model. In vitro experiments showed that ISO affected RANKL-induced MAPK, NFAT, NFATc1 trafficking and expression, osteoclast F-actin banding, osteoclast-characteristic gene expression, ROS inhibitory activity, and calcium oscillations, NF-κB signaling pathway. In vivo experiments showed that oral administration of ISO effectively reduced bone loss caused by ovariectomy and retained bone mass.Collectively, ISO inhibits RANK/RANKL binding, thereby reducing the activity of NFATc1, calcium, and ROS and inhibiting osteoclast generation. In addition, ISO protects bone mass by slowing osteoclast production and downregulating NFATc1 gene and protein expression in the bone tissue microenvironment and inhibits OVX-induced bone loss in vivo.

Carnosol suppresses RANKL-induced osteoclastogenesis and attenuates titanium particles-induced osteolysis.

Osteolysis is a common medical condition characterized by excessive activity of osteoclasts and bone resorption, leading to severe poor quality of life. It is essential to identify the medications that can effectively suppress the excessive differentiation and function of osteoclasts to prevent and reduce the osteolytic conditions. It has been reported that Carnosol (Car), isolated from rosemary and salvia, has anti-inflammatory, antioxidative, and anticancer effects, but its activity on osteolysis has not been determined. In this study, we found that Car has a strong inhibitory effect on the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation dose-dependently without any observable cytotoxicity. Moreover, Car can inhibit the RANKL-induced osteoclastogenesis and resorptive function via suppressing NFATc1, which is a result of affecting MAPK, NF-κB and Ca2+ signaling pathways. Moreover, the particle-induced osteolysis mouse model confirmed that Car could be effective for the treatment of bone loss in vivo. Taken together, by suppressing the formation and function of RANKL-induced osteoclast, Car, may be a therapeutic supplementary in the prevention or the treatment of osteolysis.

The cement leakage in cement-augmented pedicle screw instrumentation in degenerative lumbosacral diseases: a retrospective analysis of 202 cases and 950 augmented pedicle screws.

PURPOSE: To evaluate the incidence, type and risk factors of cement leakage (CL) with cement-augmented pedicle screw instrumentation (CAPSI) in degenerative lumbosacral disease. METHODS: Two hundred and two patients using a total of 950 cement-augmented screws were enrolled. CL was classified into three types: type S: leakage via segmental veins; type B: leakage via basivertebral veins; and type I: leakage via pedicle screw instrumentation to paravertebral soft tissue. The age, gender, operation stage (primary or later stage), body mass index, bone mineral density, the number and type of augmented screw, the position of the tip of screw (lateral or internal part of vertebral body), the position of screw (left or right side), the volume of bone cement, location of the augmented vertebra (lumbar or sacrum), the type of CL and complications were recorded. Binary logistic regression correlation was used to analyze risk factors of veins leakage (type S and type B). RESULTS: The CL was observed in 165 patients (81.68%) and 335 screws (35.26%), leakage types of S, B and I were seen in 255 (76.12%), 77 (22.99%), and 30 (8.96%) of screws, respectively. Besides, double or multiple routes of leakage were seen in 27 screws. Number of augmented screw was a risk factor for vein leakage (OR 0.58; 95% CI 0.44-0.77; P = 0.000). Furthermore, the doses of cement (OR 0.79; 95% CI 0.61-0.99; P = 0.038) and the position of screw (OR 0.39; 95% CI 0.29-0.53; P = 0.000) were identified as risk factors for type S, and the doses of bone cement (OR 0.37; 95% CI 0.25-0.54; P = 0.000) and the position of the tip of screw (OR 0.07; 95% CI 0.04-0.13; P = 0.000) were risk factors for type B. CONCLUSIONS: CAPSI bears a high risk of asymptomatic CL, with a higher rate of leakage into segmental veins and basivertebral veins. As is known, more augmented screws and larger doses of cement are risk factors for veins leakage (type S and type B), while the tip of screw approaching to the midline of the vertebral body is another risk factor to type B. Thus, the CL could be reduced by the amelioration of operative techniques and procedures. These slides can be retrieved under Electronic Supplementary Material.