Eurycoma longifolia, a promising suppressor of RANKL-induced differentiation and activation of osteoclasts: An in vitro mechanistic evaluation

Background: Eurycoma longifolia (E. longifolia) has gained remarkable recognition due to its promisingefficacy of stimulating bone formation in androgen-deficient osteoporosis. Numerous in vivo studies haveexplored the effects of E. longifolia on osteoporosis; however, the in vitro cellular mechanism was notdiscovered yet.Objectives: The present study was aimed to investigate the effect of E. longifolia on the proliferation,differentiation and maturation of osteoclasts and the translational mechanism of inhibition of osteoclastogenesis using RAW 264.7 cells as an in vitro osteoclastic model.Materials and methods: Having assessed cytotoxicity, the cell viability, cell proliferation rate and osteoclastic differentiation capacity of E. longifolia was investigated by evaluating the tartrate-resistant acidphosphatase (TRAP) activity in receptor activator of nuclear factor-kB (NF-kB) ligand (RANKL)-inducedosteoclasts. Taken together, the time-mannered expression of osteoclast-related protein biomarkers suchas matrix metallopeptidase-9 (MMP-9), cathepsin-K, TRAP, nuclear factor of activated T-cells cytoplasmic1 (NFATc1), superoxide (free radicals) generation and superoxide dismutase activity were also measuredto comprehend the mechanism of osteoclastogenesis.Results: E. longifolia did not show significant effects on cytotoxicity and cell proliferation of RAW 264.7cells; however, a significant inhibition of cells differentiation and maturation of osteoclasts was observed.Moreover, a significant down-regulation of RANKL-induced TRAP activity and expression of MMP-9,cathepsin-K, TRAP, NFATc1 and generation of superoxide and enhanced superoxide dismutase activitywas observed in E. longifolia treated cell cultures.Conclusion: We anticipated that E. longifolia that enhances bone regeneration on the one hand andsuppresses osteoclast’s maturation on the other hand may have great therapeutic value in treatingosteoporosis and other bone-erosive diseases such as rheumatoid arthritis and metastasis associatedwith bone loss.© 2017 Transdisciplinary University, Bangalore and World Ayurveda Foundation. Publishing Services byElsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Sex hormones in Malay and Chinese men in Malaysia: are there age and race differences?

OBJECTIVES: Variations in the prevalence of sex-hormone-related diseases have been observed between Asian ethnic groups living in the same country; however, available data concerning their sex hormone levels are limited. The present study aimed to determine the influence of ethnicity and age on the sex hormone levels of Malay and Chinese men in Malaysia. METHODS: A total of 547 males of Malay and Chinese ethnicity residing in the Klang Valley Malaysia underwent a detailed screening, and their blood was collected for sex hormones analyses. RESULTS: Testosterone levels were normally distributed in the men (total, free and non-sex hormone-binding globulin (SHBG) bound fractions), and significant ethnic differences were observed (p<0.05); however, the effect size was small. In general, testosterone levels in males began to decline significantly after age 50. Significant ethnic differences in total, free and non-SHBG bound fraction estradiol levels were observed in the 20-29 and 50-59 age groups (p<0.05). The estradiol levels of Malay men decreased as they aged, but they increased for Chinese men starting at age 40. CONCLUSIONS: Small but significant differences in testosterone levels existed between Malay and Chinese males. Significant age and race differences existed in estradiol levels. These differences might contribute to the ethnic group differences in diseases related to sex hormones, which other studies have found in Malaysia.

Serum testosterone, sex hormone-binding globulin and total calcium levels predict the calcaneal speed of sound in men

OBJECTIVES: Variations in sex hormones and the calcium balance can influence bone health in men. The present study aimed to examine the relationship between the calcaneal speed of sound and biochemical determinants of bone mass, such as sex hormones, parathyroid hormones and serum calcium. METHODS: Data from 549 subjects from the Malaysian Aging Male Study, which included Malay and Chinese men aged 20 years and older residing in the Klang Valley, were used for analysis. The subjects' calcaneal speed of sound was measured, and their blood was collected for biochemical analysis. Two sets of multiple regression models were generated for the total/bioavailable testosterone and estradiol to avoid multicollinearity. RESULTS: The multiple regression results revealed that bioavailable testosterone and serum total calcium were significant predictors of the calcaneal speed of sound in the adjusted model. After adjustment for ethnicity and body mass index, only bioavailable testosterone remained significant; the total serum calcium was marginally insignificant. In a separate model, the total testosterone and sex hormone-binding globulin were significant predictors, whereas the total serum calcium was marginally insignificant. After adjustment for ethnicity and body mass index (BMI), the significance persisted for total testosterone and SHBG. After further adjustment for age, none of the serum biochemical determinants was a significant predictor of the calcaneal speed of sound. CONCLUSION: There is a significant age-dependent relationship between the calcaneal speed of sound and total testosterone, bioavailable testosterone and sex hormone-binding globulin in Chinese and Malay men in Malaysia. The relationship between total serum calcium and calcaneal speed of sound is ethnicity-dependent.