Benefits of the Phytoestrogen Resveratrol for Perimenopausal Women

Endometriosis, characterized by macroscopic lesions in the ovaries, is a serious problem for women who desire conception. Damage to the ovarian cortex is inevitable when lesions are removed via surgery, which finally decreases the ovarian reserve, thereby accelerating the transition to the menopausal state. Soon after cessation of ovarian function, in addition to climacteric symptoms, dyslipidemia and osteopenia are known to occur in women aged >50 years. Epidemiologically, there are sex-related differences in the frequencies of dyslipidemia, hypertension, and osteoporosis. Females are more susceptible to these diseases, prevention of which is important for healthy life expectancy. Dyslipidemia and hypertension are associated with the progression of arteriosclerosis, and arteriosclerotic changes in the large and middle blood vessels are one of the main causes of myocardial and cerebral infarctions. Osteoporosis is associated with aberrant fractures in the spine and hip, which may confine the patients to the bed for long durations. Bone resorption is accelerated by activated osteoclasts, and rapid bone remodeling reduces bone mineral density. Resveratrol, a plant-derived molecule that promotes the function and expression of the sirtuin, SIRT1, has been attracting attention, and many reports have shown that resveratrol might exert cardiovascular protective effects. Preclinical reports also indicate that it can prevent bone loss and endometriosis. In this review, I have described the possible protective effects of resveratrol against arteriosclerosis, osteoporosis, and endometriosis because of its wide-ranging functions, including anti-inflammatory and antioxidative stress functions. As ovarian function inevitably declines after 40 years, intake of resveratrol can be beneficial for women with endometriosis aged <40 years.

Magnesium Picolinate Improves Bone Formation by Regulation of RANK/RANKL/OPG and BMP-2/Runx2 Signaling Pathways in High-Fat Fed Rats

Magnesium (Mg) deficiency may affect bone metabolism by increasing osteoclasts, decreasing osteoblasts, promoting inflammation/oxidative stress, and result in subsequent bone loss. The objective of the present study was to identify the molecular mechanism underlying the bone protective effect of different forms of Mg (inorganic magnesium oxide (MgO) versus organic magnesium picolinate (MgPic) compound) in rats fed with a high-fat diet (HFD). Forty-two Wistar albino male rats were divided into six group (n = 7): (i) control, (ii) MgO, (iii) MgPic, (iv) HFD, (v) HFD + MgO, and (vi) HFD + MgPic. Bone mineral density (BMD) increased in the Mg supplemented groups, especially MgPic, as compared with the HFD group (p < 0.001). As compared with the HFD + MgO group, the HFD + MgPic group had higher bone P (p < 0.05) and Mg levels (p < 0.001). In addition, as compared to MgO, MgPic improved bone formation by increasing the levels of osteogenetic proteins (COL1A1 (p < 0.001), BMP2 (p < 0.001), Runx2 (p < 0.001), OPG (p < 0.05), and OCN (p < 0.001), IGF-1 (p < 0.001)), while prevented bone resorption by reducing the levels of RANK and RANKL (p < 0.001). In conclusion, the present data showed that the MgPic could increase osteogenic protein levels in bone more effectively than MgO, prevent bone loss, and contribute to bone formation in HFD rats.

The duration of denosumab treatment and the efficacy of zoledronate to preserve bone mineral density after its discontinuation

Context Zoledronate is used to prevent bone loss following denosumab discontinuation but its efficacy differs among studies. Objective To test if the duration of denosumab treatment affects the efficacy of subsequent zoledronate infusion. Design Multicenter, prospective cohort study. Setting Two Greek and one Dutch bone centers. Patients Postmenopausal women (n=47) who received a single zoledronate infusion 6 months after the last denosumab injection and were followed for 1 year. Twenty-seven women received ≤ 6 denosumab injections (≤ 6 Group) and twenty received &gt; 6 denosumab injections (&gt; 6 Group). Main outcome measure Changes in lumbar spine (LS) BMD. Results At 12 months LS- BMD values were maintained in the ≤6 Group (0.98±0.10 to 0.99±0.9/ g/cm 2 p=0.409) but decreased significantly in the &gt;6 Group (1.0 ± 0.11 to 0.93 ± 0.12 g/cm 2, p &lt;0.001). The percent change of LS-BMD of the ≤ 6 Group (+1.0%) was significantly different (p&lt;0.001) from the change of the &gt; 6 Group (-7.0%). In the whole cohort the duration of denosumab treatment was negatively correlated with the percentage change of LS-BMD (rs:-0.669, p&lt;0.001) but not with the change of FN-BMD. Bone turnover markers increased in all patients 6 months following zoledronate administration with no difference between the two groups Conclusions The duration of denosumab treatment significantly affects the efficacy of subsequent zoledronate infusion to maintain BMD gains. Frequent follow-up of patients treated with denosumab longer than 3 years is advisable as additional therapeutic interventions may be needed.

Schistosome infection promotes osteoclast-mediated bone loss

Infection with schistosome results in immunological changes that might influence the skeletal system by inducing immunological states affecting bone metabolism. We investigated the relationships between chronic schistosome infection and bone metabolism by using a mouse model of chronic schistosomiasis, affecting millions of humans worldwide. Results showed that schistosome infection resulted in aberrant osteoclast-mediated bone loss, which was accompanied with an increased level of receptor activator of nuclear factor-κB (NF-κB) Ligand (RANKL) and decreased level of osteoprotegerin (OPG). The blockade of RANKL by the anti-RANKL antibody could prevent bone loss in the context of schistosome infection. Meanwhile, both B cells and CD4+ T cells, particularly follicular helper T (Tfh) cell subset, were the important cellular sources of RANKL during schistosome infection. These results highlight the risk of bone loss in schistosome-infected patients and the potential benefit of coupling bone therapy with anti-schistosome treatment.

Morroniside promotes the osteogenesis by activating PI3K/Akt/mTOR signaling

ABSTRACT Morroniside exerts a proosteogenic effect, which can prevent bone loss. However, the detailed mechanism underlying Morroniside-regulated bone formation is unclear. Morroniside can maintain cell homeostasis by promoting PI3K/Akt/mTOR signaling. The purpose of this study is to explore the significance of PI3K/Akt/mTOR signaling in Morroniside-regulated osteogenesis. The results showed that Morroniside promoted the activities of PI3K, Akt, and mTOR in osteoblast precursor MC3T3-E1. The differentiation of MC3T3-E1 to mature osteoblasts promoted by Morroniside can be reversed by the pharmacological inhibition of PI3K or mTOR. Importantly, in the presence of Morroniside, the osteoblast differentiation suppressed by PI3K inhibitor was reversed by mTOR overexpression. In vivo assays showed that in bone tissue of ovariectomized mice, Morroniside-enhanced osteoblast formation was reversed by the pharmacological inhibition of PI3K or mTOR. In conclusion, Morroniside can promote the osteogenesis through PI3K/Akt/mTOR signaling, which provides a novel clue for the strategy of Morroniside in treating osteoporosis.

The Effect of Bisphosphonates on Managing Osteoporosis After Spinal Cord Injury: A Meta-Analysis

Background: The increased bone loss after spinal cord injury (SCI) is associated with an increase in the morbidity and mortality of fragility fractures, which can constitute a substantial cost to health care systems. Bisphosphonates (BPs) are now the principal class of medications used for osteoporosis. Objective: To demonstrate the effect of BPs on treating osteoporosis after SCI. Methods: A comprehensive search in PubMed, EMBASE, Web of Science and Cochrane Central databases was undertaken for randomized controlled trials (RCTs), exploring the effect of BPs on osteoporosis after SCI. The primary outcome measures were the BMD of different locations, serum bone turnover marker levels, serum biochemistry marker levels and adverse effect (AE) risks. The final search was performed in September 2019. Reporting was carried out according to PRISMA Guidelines. Results: Six RCTs were included. A total of 147 patients met the inclusion criteria. BPs were found to statistically prevent bone loss in the total hip, femoral neck and trochanter at the 6- and 12-month follow-up points and to increase the BMD of the lumbar spine at the 12-month follow-up time point. BPs had no clear effect on serum PINP or serum calcium levels at the 12-month follow-up time point. Conclusion: BP therapy may prevent bone loss in the lumbar spine and hip when administered early after SCI and has relatively high safety.

Pure gonadal dysgenesis misdiagnosed as Mayer Rokitansky Kuster Hauser Syndrome: a case report

Gonadal dysgenesis is a group of heterogeneous disorders with very rare presentation. The spectrum of disease not only includes primary amenorrhoea but also secondary amenorrhoea. Herein, we are reporting a case of 16-year-old phenotypic female who presented with amenorrhoea with 46, XX karyotype with hypoplastic uterus with absent ovaries (on imaging), with high gonadotropins level and low estradiol. Suspecting Mayer–Rokitansky–Küster–Hauser syndrome (due to hypoplastic uterus) with gonadal dysgenesis she was started on cyclic hormones for development of secondary sexual characters and to prevent bone loss. But, during follow up, after giving estrogen for 8 months, her hypoplastic uterus again starts reappearing with attainment of cyclic menses on estrogen and progesterone withdrawal. We concluded that, in the presence of rudimentary or hypoplastic uterus, straightforward diagnosis of MRKH is to be avoided without seeing peripheral estrogenisation, hormone profile and karyotype analysis.