Abstract
Male osteoporosis is associated with higher rates of disability and mortality. Hence the search for suitable intervention and treatment to prevent the degeneration of skeletal health in men is necessary. Eurycoma longifolia (EL), a traditional plant with aphrodisiac potential may be used to treat and prevent male osteoporosis. The skeletal protective effect of quassinoid-rich EL extract, which has a high content of eurycomanone, has not been studied. This study aimed to determine whether EL could prevent skeletal deteriorations in gonadal hormone-deficient male rats. Ninety-six male Sprague–Dawley rats were randomly assigned to baseline, sham-operated (Sham), orchidectomised or chemically castrated groups. Chemical castration was achieved via subcutaneous injection of degarelix at 2 mg/kg. The orchidectomised and degarelix-castrated rats were then divided into negative control groups (ORX, DGX), testosterone-treated groups (intramuscular injection at 7 mg/kg weekly) (ORX + TES, DGX + TES), and EL-supplemented groups receiving daily oral gavages at doses of 25 mg/kg (ORX + EL25, DGX + EL25), 50 mg/kg (ORX + EL50, DGX + EL50), and 100 mg/kg (ORX + EL100, DGX + EL100). Following 10 weeks of treatment, the rats were euthanized and their blood and femora were collected. Bone biochemical markers, serum testosterone, osteoprotegerin (OPG), and receptor activator of nuclear factor kappa β-ligand (RANKL) levels and histomorphometric indices were evaluated. Quassinoid-rich EL supplementation was found to reduce degenerative changes of trabecular structure by improving bone volume, trabecular number, and separation. A reduction in the percentage of osteoclast and increase in percentage of osteoblast on bone surface were also seen with EL supplementation. Dynamic histomorphometric analysis showed that the single-labeled surface was significantly decreased while the double-labeled surface was significantly increased with EL supplementations. There was a marginal but significant increase in serum testosterone levels in the ORX + EL25, DGX + EL50, and DGX + EL100 groups compared to their negative control groups. Quassinoid-rich EL extract was effective in reducing skeletal deteriorations in the androgen-deficient osteoporosis rat model.
Highlights
Sex steroids play a crucial role in the development and maintenance of the skeletal system in human and in experimental animals [1]
The serum osteocalcin level of ORX + EL100, degarelix-induced control (DGX), DGX + EL25, DGX + EL50, and DGX + EL100 groups were significantly higher than Sham group (p < 0.01)
It was found that testosterone deficiency due to orchidectomy or chemical castration by degarelix resulted in unfavorable changes of static, structural, and dynamic bone histomorphometry indices
Summary
Sex steroids play a crucial role in the development and maintenance of the skeletal system in human and in experimental animals [1]. Androgens modulate the bone remodeling cycle through. Nutrients 2018, 10, 799 direct androgenic activity via androgen receptors that are present on bone compartments or by indirect action through aromatization into estrogens [2]. It has been established that lack of estrogen in females causes rapid bone loss and lack of androgen in males induces osteopenia. Osteoporosis is less common in men compared to women, it has been recognized that the morbidity and mortality after osteoporotic fractures in men are a major public health issue. The major causes of osteoporosis reported in men have been mainly separated into primary (age-related and idiopathic osteoporosis) and secondary causes (alcohol abuse, glucocorticoid excess, and hypogonadism) [3]. Hypogonadism (i.e., reduction in circulating androgens level) has been associated with low bone mineral density (BMD) and an increased risk of fractures [4]
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