Mechanical and Mechanosensing Properties of Tumor Affected Bone Cells Were Inhibited via PI3K/Akt Pathway

BACKGROUND: Osteolytic metastasis is a common destructive form of metastasis, in which there is an increased bone resorption but impaired bone formation. It is hypothesized that the changed mechanical properties of tumor affected bone cells could inhibit its mechanosensing, thus contributing to differences in bone remodeling. METHODS: Here, atomic force microscopy indentation on primary bone cells exposed to 50% conditioned medium from Walker 256 (W) carcinoma cell line or its adaptive tumor (T) cells was carried out. Nitric oxide levels of bone cells were monitored in response to low-magnitude, high-frequency (LMHF) vibrations. RESULTS: A stronger sustained inhibitive effect on bone cell viability and differentiation by T cells as compared to that of its cell line was demonstrated. This could be attributed to the higher levels of transforming growth factor-β1 (TGF-β1) in the T-conditioned medium as compared to W-conditioned medium. Bone cell elastic moduli in W and T-groups were found to decrease significantly by 61.0% and 69.6%, respectively compared to control and corresponded to filamentous actin changes. Nitric oxide responses were significantly inhibited in T-conditioned group but not in W-conditioned group. CONCLUSIONS: It implied that a change in cell mechanical properties is not sufficient as an indicator of change in mechanosensing ability. Moreover, inhibition of phosphoinositide 3-kinase/Akt downstream signaling pathway of TGF-β1 alleviated the inhibition effects on mechanosensing in T-conditioned cells, further suggesting that growth factors such as TGF-β could be good therapeutic targets for osteoblast treatment.

The correlation between bone mineral density/trabecular bone score and body mass index, height, and weight

OBJECTIVES: This study investigated the correlation between bone mineral density (BMD)/trabecular bone score (TBS) and body mass index (BMI), height and weight in Korean adults. METHODS: We enrolled 2555 female participants in their 20s–80s and 1631 male participants in their 20s–70s. Participants with history of previous vertebral surgeries or current vertebral diseases were excluded. Female and male participants were divided into osteoporosis group (n = 136 and n = 31, respectively), osteopenia group (n = 822 and n = 460, respectively), and normal group (n = 1596 and n = 1140, respectively) based on their BMD T-score. Dual-energy X-ray absorptiometry image analysis and linear regression analysis were conducted on each participant in each group to determine the P-value and the correlation between BMD T-score/TBS T-score and BMI, weight, and height. RESULTS: We found a significant correlation between BMI and TBS in both male and female participants. In the male participants, the correlation coefficient increased progressively from the normal group to the osteoporosis group. In the female group, we observed a significant positive correlation between height and TBS, and in the male group a significant negative correlation between weight and TBS was observed. CONCLUSIONS: BMI and weight are closely correlated to body fat content. BMD was positively correlated to BMI and weight, while TBS was negatively correlated to BMI and weight. Therefore, although BMI causes an increase in BMD, it appears to be negatively affecting bone quality.

Comparative Effects of Ibandronate and Paclitaxel on Immunocompetent Bone Metastasis Model

PURPOSE: Bone metastasis invariably increases morbidity and mortality. This study compares the effects of ibandronate and paclitaxel on bone structure and its mechanical properties and biochemical turnover in resorption markers using an immunocompetent Walker 256-Sprague-Dawley model, which was subjected to tumor-induced osteolysis. MATERIALS AND METHODS: Seventy rats were divided equally into 4 groups: 1) sham group (SHAM), 2) tumor group (CANC), 3) ibandronate treated group (IBAN), and 4) paclitaxel treated group (PAC). Morphological indices [bone volume fraction (BV/TV), trabecular number (Tb.N), trabecular thickness (Tb.Th), trabecular separation (Tb.Sp)] and mechanical properties (failure load, stiffness) were evaluated after thirty days of treatment period. Bone resorption rate was analysed using serum deoxypyridinoline (Dpd) concentrations. RESULTS: Morphological indices showed that ibandronate (anti-resorptive drug) had a better effect in treating tumor-induced architectural changes in bone than paclitaxel (chemotherapeutic drug). The deterioration in bone architecture was reflected in the biomechanical properties of bone as studied with decreased failure load (F(x)) and stiffness (S) of the bone on the 30th day postsurgery. Dpd concentrations were significantly lower in the IBAN group, indicating successful inhibition of bone resorption and destruction. CONCLUSION: Ibandronate was found to be as effective as higher doses of paclitaxel in maintaining stiffness of bone. Paclitaxel treatment did not appear to inhibit osteoclast resorption, which is contrary to earlier in-vitro literature. Emphasis should be placed on the use of immunocompetent models for examining drug efficacy since it adequately reflects bone metastasis in clinical scenarios.

Effect of Ibandronate and hPTH on the Viscoelastic Response of Ovariectomized Rat Femur / 대한골다공증학회지

PTH and ibandronate are proven to be effective in reversing negative effects of postmenopausal osteoporosis in terms of bone architecture and density. However, the changes of viscoelastic properties of the bone during the pathogenesis of osteoporosis and its treatment were seldom studied. Thus, this study aimed at studying the viscoelastic changes in PTH and ibandronate treated ovariectomized rat to assess the efficacy of the treatments. In this study, distal femurs of twenty-two female rats from four different groups (SHM, OVX, PTH and IBN) were evaluated using CT, pQCT and nanoindentation tests. While density parameters were well preserved in ibandronate treated group, elastic modulus and hardness were found to be better in PTH treated group. Thus, cortical and trabecular bone could be differentially affected by these two categories of drug, due to their difference in the action of mechanism. Moreover, viscosity of the cortical bone showed a positive correlation (R(2)=0.72) with bone strength predictor SSIy, which would possibly correlate with fracture risk.

Morphological and Mechanical Changes in Ovariectomized Rat Tibia with Treatments of Ibandronate and Parathyroid Hormone / 대한골다공증학회지

Osteoporosis is a debilitating disease affecting the elderly population, associated with compromised stability and reduced mobility of the bone. Osteoporosis is diagnosed as a condition when the measured bone mineral density (BMD) falls below 2.5 standard deviations of peak mass. However, BMD alone might not be enough to define the osteoporotic condition because it does not accounts on the micro-architectural changes in the bone trabeculae. Thus, this study aimed at studying the micro-architecural changes in trabeculae rich bone metaphysis of ovariectomized rat models in comparison with the conventional BMD measurements and the mechanical parameters. In this study, proximal tibiae of twenty-five female rats from four different groups (SHAM, OVX, IBAN and PTH) were evaluated using micro-CT, pQCT and three point bending tests. The micro-CT analysis showed that the deterioration of trabecular bone was significant during the first 6 weeks after OVX surgery. During the early stage of osteoporosis, the trabecular density decreased more rapidly than the cortical density. Morphological analysis showed that early administration of both ibandronate and parathyroid hormone has a beneficial effect on restoring the trabecular structures. Bone mechanical properties of treatment groups did not show significant difference, but followed the overall trend as morphological indices. The results suggest that early administration of either ibandronate or PTH is effective in restoring the trabecular bone loss caused by osteoporosis. However, larger-scale studies should be conducted to better understand the effect of both anti-resorptive and anabolic treatments in terms of morphological and mechanical properties.