Systematic Analysis of mRNAs and ncRNAs in BMSCs of Senile Osteoporosis Patients

Senile osteoporosis (SOP) is a worldwide age-related disease characterized by the loss of bone mass and decrease in bone strength. Bone mesenchymal stem cells (BMSCs) play an important role in the pathology of senile osteoporosis. Abnormal expression and regulation of non-coding RNA (ncRNA) are involved in a variety of human diseases. In the present study, we aimed to identify differentially expressed mRNAs and ncRNAs in senile osteoporosis patient-derived BMSCs via high-throughput transcriptome sequencing in combination with bioinformatics analysis. As a result, 415 mRNAs, 30 lncRNAs, 6 circRNAs and 27 miRNAs were found to be significantly changed in the senile osteoporosis group. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were applied to analyze the function of differentially expressed mRNAs and ncRNAs. The circRNA–miRNA–mRNA regulatory network was constructed using the cytoHubba plugin based on the Cytoscape software. Interestingly, circRNA008876-miR-150-5p-mRNA was the sole predicted circRNA-miRNA-mRNA network. The differential expression profile of this ceRNA network was further verified by qRT-PCR. The biological function of this network was validated by overexpression and knockdown experiments. In conclusion, circRNA008876-miR-150-5p-mRNA could be an important ceRNA network involved in senile osteoporosis, which provides potential biomarkers and therapeutic targets for senile osteoporosis.

The role of Bacillus acidophilus in osteoporosis and its roles in osteocyte proliferation and differentiation

The microbes play an important role to physiological activities of human. Osteoporosis is one of the most closely relationship diseases with the elderly. In recent years, the studies found that gut microbiota can cause osteoporosis. These microbes may affect activity of osteoclasts and osteoblasts to affect bone metabolism. We selected 5 health people and 10 osteoporosis patients and found that the diversity of gut microbiota in osteoporosis patients are decreased and imbalance with lower abundance of lactobacillus and butylic acid bacteria, meanwhile, 25-hydroxyitamin D and procollagen type I N-terminal peptide (PINP) of osteoporosis patient was significantly lower than the normal group. The proliferation, differentiation and maturity of osteoblasts MC3T3-E1 cells was stimulated, the activity of alkaline phosphatase, concentration of osteocalcin and the expression of RUNX2, WNT2 and CTNNB1 was improved by supernatant of lactobacillus acidophilus and butanoic acids, however, the proliferation, differentiation and maturity, the expression of RANK,WNT2 and CTNNB1 in osteoclasts RAW 264.7 cells was suppressed. There is not a similar significant effect by lactobacillus rhamnosus treatment.

Pharmacological Management of Osteoporosis in Postmenopausal Women: An Endocrine Society* Clinical Practice Guideline

Objective The objective is to formulate clinical practice guidelines for the pharmacological management of osteoporosis in postmenopausal women. Conclusions Evidence from clinical trials and insights from clinical experience with pharmacologic therapies for osteoporosis were critically evaluated in formulating this guideline for the management of postmenopausal osteoporosis. Patient preferences, data on adherence and persistence, and risks and benefits from the patient and provider perspectives were also considered in writing committee deliberations. A consensus by the Writing Committee members was achieved for four management principles: (i) The risk of future fractures in postmenopausal women should be determined using country-specific assessment tools to guide decision-making. (ii) Patient preferences should be incorporated into treatment planning. (iii) Nutritional and lifestyle interventions and fall prevention should accompany all pharmacologic regimens to reduce fracture risk. (iv) Multiple pharmacologic therapies are capable of reducing fracture rates in postmenopausal women at risk with acceptable risk-benefit and safety profiles.

Antiresorptives: Safety Concerns—Clinical Perspective

Antiresorptive drugs, such as amino-bisphosphonates and denosumab (Dmab), have dominated osteoporosis therapies for over 20 years. Since osteoporosis is a chronic disease, antifracture therapy could continue for the rest of a patient’s life. Phase III clinical trials for antiresorptive drugs assessed relatively small patient populations for short durations and excluded up to 80% of patients who might seek osteoporosis therapy in clinical practice. Postmarketing reports based upon millions of patient-years and long-term (>5 years) clinical administration have associated some previously unknown, rare adverse events with antiresorptive use including osteonecrosis of the jaw (ONJ) and atypical femur fractures (AFFs). In the osteoporosis patient population, who receive much lower doses of bisphosphonate (BP) or Dmab, the incidence of ONJ is estimated at 0.001% to 0.01%, which is only slightly higher than that seen in the general population. AFFs are insufficiency or fissure transverse fractures originating on the lateral cortex of the subtrochanteric or diaphyseal region of the femur becoming oblique as they progress medially when complete. Incidence rates of AFF range from 1.8/100,000 per year with a 2-year BP exposure to 113/100,000 per year with BP exposure from 8 to 9.9 years. Most recent pathogenic hypotheses of these rare events will be discussed.

Correlation between estrogen and alkaline phosphatase expression in osteoporotic rat model

Background: Osteoporosis is a systemic disease that can decrease bone density as a result of imbalance bone remodeling and bone resorption. Estrogen reduction due to menopause can increase osteoclast activity and furthermore decrease bone density. Estrogen can stimulate alkaline phosphatase (ALP) expression, collagen type I and osteocalcin in bone remodelling process. Ovariectomized rat is a common animal for studying patofisiology, diagnosis and treatment osteoporosis patient. Purpose: To evaluate correlation between estrogen and ALP expression in osteoporotic rat model mandible. Methode: 18 female wistar rats, 2 months old, 200 grams were divided into 2 groups, ovariectomized group and sham surgery as control group. Surgery was done under intra muskular anesthesia using combination 2% xylazine 1cc and 10% ketamine 1cc. After 12 weeks, mandible was taken for ALP examination and blood from heart was taken to evaluate the amount of estrogen. Result: There was significant correlation between estrogen and ALP expression in osteoporotic rat model mandible. Conclusion: The amount of estrogen can influence ALP expression activity.