Postmenopausal Osteoporotic Women Research Articles

More potent antiresorptive effect of denosumab versus zoledronate in osteoporotic postmenopausal women with primary hyperparathyroidism

More potent antiresorptive effect of denosumab versus zoledronate in osteoporotic postmenopausal women with primary hyperparathyroidism

Cost-effectiveness of romosozumab for the treatment of postmenopausal women with osteoporosis at high risk of fracture in Belgium.

This study aimed to evaluate the cost-effectiveness of sequential treatment with romosozumab followed by alendronate compared to alendronate monotherapy and teriparatide followed by alendronate, in postmenopausal osteoporotic women at high risk of fracture, from a Belgian healthcare perspective. Romosozumab is reimbursed in Belgium since December 2021. A Markov microsimulation model was used to evaluate the cost-effectiveness of romosozumab-to-alendronate compared to alendronate monotherapy and to teriparatide-to-alendronate over a lifetime horizon. Patients transition between five different health states every 6 months based on fracture risks or death. The model was populated with Belgium-specific epidemiological and cost data, where available. The fracture risk reduction of romosozumab treatment was collated from the ARCH study, and from a published network meta-analysis. Costs were included from a healthcare perspective (NIHDI). Cost-effectiveness was reported in terms of costs per quality-adjusted life year (QALY), reported in Euro (€) 2022. Deterministic (DSA) and probabilistic sensitivity analyses (PSA) were performed. Romosozumab-to-alendronate was associated with 0.12 additional QALYs at an additional cost of €2314 compared to alendronate monotherapy, resulting in an ICER of €19,978. Compared to teriparatide-to-alendronate, romosozumab-to-alendronate was found to be dominant, with higherQALYs and lower costs. The base-case results were robust to uncertainty in the input parameters when conducting the sensitivity analysis. Sequential treatment with romosozumab followed by alendronate was found to be cost-effective compared to alendronate monotherapy and dominant compared to teriparatide followed by alendronate for postmenopausal women with osteoporosis at high risk of fracture in Belgium.

Safety and effects of calcifediol 0.266 milligrams soft capsules monthly and cholecalciferol 25000 international units monthly in osteoporotic women undergoing therapy with alendronate: a cross-sectional study.

The role of vitamin D in human physiology is a topic of great interest for the scientific community in the last decades. The common target for all clinicians is to improve its status in order to prevent several pathological conditions. The aim of our study was to evaluate the safety and the efficacy of both calcifediol and cholecalciferol in combination with alendronate in osteoporotic women. A homogeneous population of 300 postmenopausal osteoporotic women was selected for this study. 150 women were administered with alendronate 70 mg combined with clacifediol 0.266 mg soft capsules monthly. The other half (other 150 women) were administered with alendronate 70 mg combined with cholecalciferol 25000 IU monthly. First follow up was after 4 months and second follow-up after 12 months. No case of toxicity was detected throughout the study in any patient. In regards to increase of vitamin D serum level, after four months supplementation calcifediol is 1.29 fold more effective than cholecalciferol while after 12 months of supplementation calcifediol is 2.32 fold more effective compared to cholecalciferol. In our study calcifediol showed to be as safe as cholecalciferol and more effective than cholecalciferol in order to increase vitamin D serum level after four and 12 months of supplementation when supplementation is combined with alendronate 70 mg in osteoporotic women.

Plasma microRNA signature associated with skeletal muscle wasting in post-menopausal osteoporotic women.

Skeletal muscle mass wasting almost invariably accompanies bone loss in elderly, and the coexistence of these two conditions depends on the tight endocrine crosstalk existing between the two organs, other than the biomechanical coupling. Since the current diagnostics limitation in this field, and given the progressive population aging, more effective tools are needed. The aim of this study was to identify circulating microRNAs (miRNAs) as potential biomarkers for muscle mass wasting in post-menopausal osteoporotic women. One hundred seventy-nine miRNAs were assayed by quantitative real-time polymerase chain reaction in plasma samples from 28 otherwise healthy post-menopausal osteoporotic women (73.4±6.6years old). The cohort was divided in tertiles based on appendicular skeletal muscle mass index (ASMMI) to better highlight the differences on skeletal muscle mass (first tertile: n=9, ASMMI=4.88±0.40kg·m-2; second tertile: n=10, ASMMI=5.73±0.23kg·m-2; third tertile: n=9, ASMMI=6.40±0.22kg·m-2). Receiver operating characteristic (ROC) curves were calculated to estimate the diagnostic potential of miRNAs. miRNAs displaying a statistically significant fold change≥±1.5 and area under the curve (AUC)>0.800 (P<0.05) between the first and third tertiles were considered. A linear regression model was applied to estimate the association between miRNA expression and ASMMI in the whole population, adjusting for body mass index, age, total fat (measured by total-body dual-energy X-ray absorptiometry [DXA]) and bone mineral density (measured by femur DXA). Circulating levels of adipo-myokines were evaluated by bead-based immunofluorescent assays and enzyme-linked immunosorbent assays. Five miRNAs (hsa-miR-221-3p, hsa-miR-374b-5p, hsa-miR-146a-5p, hsa-miR-126-5p and hsa-miR-425-5p) resulted down-regulated and two miRNAs (hsa-miR-145-5p and hsa-miR-25-3p) were up-regulated in the first tertile (relative-low ASMMI) compared with the third tertile (relative-high ASMMI) (fold change≥±1.5; P-value<0.05). All the corresponding ROC curves had AUC>0.8 (P<0.05). Two signatures hsa-miR-126-5p, hsa-miR-146a-5p and hsa-miR-425-5p; and hsa-miR-126-5p, hsa-miR-146a-5p, hsa-miR-145-5p and hsa-miR-25-3p showed the highest AUC, 0.914 (sensitivity=77.78%; specificity=100.00%) and 0.901 (sensitivity=88.89%; specificity=100.00%), respectively. In this study, we identified, for the first time, two miRNA signatures, hsa-miR-126-5p, hsa-miR-146a-5p and hsa-miR-425-5p; and hsa-miR-126-5p, hsa-miR-146a-5p, hsa-miR-145-5p and hsa-miR-25-3p, specifically associated with muscle mass wasting in post-menopausal osteoporotic women.

Role of rs2762934 and rs4809957 polymorphisms of CYP24A1 on outcomes of vitamin D treatment in postmenopausal osteoporotic women in Iraq

Osteoporosis is widely distributed condition characterized by bone weakness making it more fragile and easier to be fractured. Various elements enter in bone structure making it rigid to tolerate body weight and any accident. Many factors had a role in its progression, like age, gender, taking medications and genetic variations in enzymes responsible for vitamin D metabolism. The aim of our study is to evaluate role of polymorphism of metabolic enzyme CYP24A1 on responding to vitamin D in postmenopausal osteoporotic women. Method: 40 postmenopausal women were followed up for two months and took 50000IU/week of vitamin D during study period, and 30 postmenopausal women without osteoporosis as a control group. Blood sample were taken pre- and post-treatment to determine responder to vitamin D therapy. Results: regarding vitamin D level, there is a significant difference between responder and non-responder at pre-treatment level. GG genotype of rs2762934 was presented in higher percent in patients group (non-response one), and AA genotype of rs4809957 was the predominant one with a negative correlation to the responsiveness to vitamin D therapy. Conclusions: The homozygote wild GG genotype of rs2762934 predict vitamin D non-responsiveness in sample of osteoporotic postmenopausal women. The AA genotype of the same SNP substantially increases the responsiveness. While AA of rs4809957 associate with non-responsiveness. This study will implicate in correct choosing the desired dose of vitamin D for desired osteoporotic women to get better response and avoid any harmful effect of vitamin D overdose.

Utilization of Romosozumab in Primary Care.

Objective: The objective of the study is to highlight the role and safety of romosozumab in patients at high risk of fractures in primary care. Data Sources: A systemic database search of PubMed/MEDLINE, ClinicalTrials.gov, and Cochrane Library was conducted for articles with keywords romosozumab, osteoporosis, and safety between inception and July 2022. Study Selection and Data Extraction: Phase 3 trials in patients with osteoporosis were included. Data results from these trials were utilized for assessment. Data Synthesis: Romosozumab decreased vertebral fracture incidence by 73% at 12 months (P < 0.001) in osteoporotic postmenopausal women compared with placebo. In an active-controlled fracture study in postmenopausal women with osteoporosis at high risk of fracture, a 48% lower risk of new vertebral fracture was observed at 24 months in the romosozumab-alendronate group (P < 0.001) compared with alendronate group. In a study comparing romosozumab with teriparatide in postmenopausal women with osteoporosis at high risk of fracture, 2.6% of the mean percentage change from baseline in the total hip (TH) areal bone mineral density (BMD) was observed with romosozumab, while teriparatide led -0.6% of change (P < 0.0001). Romosozumab significantly increased the mean percentage change from baseline in the lumbar spine (LS) and total hip (TH) BMD than placebo in men with osteoporosis (LS, 12.1% vs 1.2%; TH, 2.5% vs -0.5%; P < 0.001). Serious cardiovascular events were observed in the romosozumab compared with alendronate (2.5% vs 1.9%; odds ratio [OR] = 1.31; 95% confidence interval [CI] = 0.85-2.00) in postmenopausal women, and placebo (4.9% vs 2.5%) in men with osteoporosis. Relevance to Patient Care and Clinical Practice: This review discusses the role of romosozumab in patients with high fracture risk and its safety in primary care. Conclusions: Primary care physicians should consider romosozumab for patients at high fracture risk who are intolerant or have not responded to other pharmacological treatment. Further studies are needed to clarify the safety of cardiovascular events.

Effect of denosumab on glucose metabolism in postmenopausal osteoporotic women with prediabetes: a study protocol for a 12-month multicenter, open-label, randomized controlled trial

BackgroundParticipants with prediabetes are at a high risk of developing type 2 diabetes (T2D). Recent studies have suggested that blocking the receptor activator of nuclear factor-κB ligand (RANKL) may improve glucose metabolism and delay the development of T2D. However, the effect of denosumab, a fully human monoclonal antibody that inhibits RANKL, on glycemic parameters in the prediabetes population is uncertain. We aim to examine the effect of denosumab on glucose metabolism in postmenopausal women with osteoporosis and prediabetes.MethodsThis is a 12-month multicenter, open-label, randomized controlled trial involving postmenopausal women who have been diagnosed with both osteoporosis and prediabetes. Osteoporosis is defined by the World Health Organization (WHO) as a bone mineral density T score of ≤ − 2.5, as measured by dual-energy X-ray absorptiometry (DXA). Prediabetes is defined as (i) a fasting plasma glucose level of 100–125 mg/dL, (ii) a 2-hour plasma glucose level of 140–199 mg/dL, or (iii) a glycosylated hemoglobin A1c (HbA1c) level of 5.7–6.4%. A total of 346 eligible subjects will be randomly assigned in a 1:1 ratio to receive either subcutaneous denosumab 60 mg every 6 months or oral alendronate 70 mg every week for 12 months. The primary outcome is the change in HbA1c levels from baseline to 12 months. Secondary outcomes include changes in fasting and 2-hour blood glucose levels, serum insulin levels, C-peptide levels, and insulin sensitivity from baseline to 12 months, and the incidence of T2D at the end of the study. Follow-up visits will be scheduled at 3, 6, 9, and 12 months.DiscussionThis study aims to provide evidence on the efficacy of denosumab on glucose metabolism in postmenopausal women with osteoporosis and prediabetes. The results derived from this clinical trial may provide insight into the potential of denosumab in preventing T2D in high-risk populations.Trial registrationThis study had been registered in the Chinese Clinical Trials Registry. Registration number: ChiCTR2300070789 on April 23, 2023. https://www.chictr.org.cn.

Hair and Serum Trace Element and Mineral Levels Profiles in Women with Premenopausal and Postmenopausal Osteoporosis.

The objective of the present study was to evaluate serum and hair trace element and mineral levels in women with osteoporosis, as well as to estimate the impact of menopausal status on the profile of trace element and mineral status in women with osteoporosis. 207 women with diagnosed osteoporosis 22-85 years-of-age, and 197 healthy women of the respective age participated in the present study. Analysis of the levels of mineral and trace element in hair and serum samples was performed by inductively-coupled plasma mass-spectrometry (ICP-MS). Women with osteoporosis were characterized by significantly lower hair Ca, Mg, Co, I, Li, and Mn levels, as well as serum Ca, Mg, Co, Fe, V, and Zn concentrations compared to women in the control group. After additional grouping according to menopausal status, the lowest hair Ca and Mg content was observed in postmenopausal osteoporotic women, whereas serum Ca and Mg concentrations were the lowest in premenopausal osteoporotic women. Hair Co, Mn, and Zn levels in postmenopausal osteoporotic women were lower than in healthy postmenopausal women. The lowest circulating Zn levels were observed in osteoporotic postmenopausal women. Taken together, decreased hair and serum levels in osteoporotic women are indicative of increased risk of Ca, Mg, Co, and Zn deficiency in women with osteoporosis. In turn, alterations in hair trace element and mineral levels in osteoporosis are more profound in postmenopausal women. Hypothetically, improvement in trace element and mineral metabolism especially in postmenopausal women may be considered as a potential strategy for mitigating osteoporosis.

Relation between Postmenopausal Osteoporosis and IL-17 Serum Level

Background Osteoporosis is a bone condition that makes bones thinner and more fragile because of reduced bone density, and it puts people at risk of fractures, especially of the hip, spinal vertebrae and wrist. Aim of the Work to study possible relation between serum level of IL-17 and postmenopausal osteoporosis. Patient and Methods This was a cross sectional study that was conducted at Physical Medicine, Rheumatology and Rehabilitation department at Ain Shams University hospital including thirty postmenopausal females’ study were diagnosed as having primary post-menopausal“ type I”. Then they were further subdivided into 15 post-menopausal non-osteoporotic women with normal BMD and 15 Postmenopausal osteoporotic women with reduced bone mineral density BMD diagnosed as having Primary Post menopausal Osteoporosis According to the World Health Organization (WHO) definition of osteoporosis for post-menopausal women. The duration of the study ranged from 6-12 months. Results There was high statistically significant difference between with and without osteoporosis groups regarding DEXA Score and FRAX and IL-17 serum level. There was a significant negative correlation between IL-17 serum level and each of age and menopause duration, while there was highly significant positive correlation between FRAX and each of age and duration of menopause. ROC curve in our study showed that: IL-17 serum level can be used to diagnose osteoporosis at a cutoff level of &amp;gt; 80, AUC of 1.0, with 100% sensitivity, 100% specificity, 100% PPV and 100% NPV. DEXA Score can be used to diagnose osteoporosis at a cutoff level of ≤ -2.6, AUC of 1.0, with 100% sensitivity, 100% specificity, 100% PPV and 100% NPV. FRAX can be used to diagnose osteoporosis at a cutoff level of &amp;gt; 0.4, AUC of 0.92, with 93.33% sensitivity, 80% specificity, 82.4% PPV and 92.3% NPV. Conclusion Serum IL-17 is significantly elevated in postmenopausal osteoporosis which may indicate its role in bone-resorptive processes.

Economic evaluation of four treatment strategies for postmenopausal patients with osteoporosis and a recent fracture in mainland China: a cost-effectiveness analysis.

To evaluate the cost-effectiveness of four anti-osteoporosis medications (denosumab, zoledronate, teriparatide, and alendronate) for postmenopausal osteoporotic women in mainland China, using a stratified treatment strategy recommended by the American Association of Clinical Endocrinologists and the American College of Endocrinology (AACE/ACE). A microsimulation Markov model was used to compare the cost-effectiveness of the four treatments in postmenopausal osteoporotic patients of different ages (65, 70, 75, and 80 years), with a recent fracture from the Chinese healthcare perspective. The primary outcome was the incremental cost-effectiveness ratio (ICER), which represent the incremental cost per quality-adjusted life-year (QALY) obtained. One-way deterministic sensitivity analysis (DSA) and probabilistic sensitivity analysis (PSA) were performed to assess the robustness of model findings. Alendronate was dominated by denosumab-to-alendronate and zoledronate at all ages examined, indicating that the costs of the two drugs were lower, but QALYs was greater. However, teriparatide-to-alendronate yielded an ICER of $76,432.07/ QALY, compared with alendronate at age 65, which exceeded the pre-determined willingness-to-pay threshold of $37,653/ QALY. The results were similar at other ages. The DSA showed that the most sensitive parameters were drug efficacy for vertebral and wrist fractures, the relative risk of vertebral fractures, and the persistence of the drugs. The PSA showed that zoledronate had a 100% probability of being the most cost-effective treatment, with a willingness-to-pay threshold of $37,653/ QALY. Stratified treatment based on very high fracture risk is more cost-effective than conventional pills in mainland China. Among the stratified treatments, zoledronate is the optimal option.

Effect of a single dose of zoledronic acid on bone mineral density and trabecular bone score in Indian postmenopausal osteoporotic women with and without type 2 diabetes mellitus - A prospective cohort pilot study.

The objectives were to study the effect of a single dose of intravenous (IV) zoledronic acid (ZA) on changes in bone mineral density (BMD) (lumbar spine (LS), hip, & distal forearm), trabecular bone score (TBS) and bone turnover markers (BTMs) in postmenopausal osteoporotic women with and without diabetes over 12 months. Patients were divided into two groups: type 2 diabetes mellitus (T2DM) (n = 40) and non-DM (n = 40). Both groups received a single dose of 4 mg IV ZA at baseline. The BMD with TBS and BTMs (β-CTX, sclerostin, P1NP) were measured at baseline, six months, and 12 months. At baseline, BMD in all three sites was similar in both groups. T2DM patients were older and had lower BTMs than non-DM patients. The mean increase in LS-BMD (gram/cm2) at 12 months in T2DM and the non-DM group was 3.6 ± 4.7% and 6.2 ± 4.7 %, respectively (P = 0.01). However, the age adjusted mean difference in LS BMD increment between two groups at one year was - 2.86 % (-5.02% to -0.69%), P = 0.01. There was a comparable change in BMD at other two sites, BTMs, and TBS in both the groups over one year follow-up. The gain in the LS-BMD was significantly lower in T2DM group compared to non-DM subjects over 12 months after a single IV infusion of 4 mg ZA. The explanation for this could be low bone turnover in diabetes subjects at baseline.

METTL14 represses osteoclast formation to ameliorate osteoporosis via enhancing GPX4 mRNA stability.

Excessive bone resorption by osteoclasts results in the development of multiple bone disorders including osteoporosis. This study aimed to explore the biological function of methyltransferase-like14 (METTL14) in osteoclast formation, as well as its related mechanisms. Expression levels of METTL14, GPX4 and osteoclast-related proteins TRAP, NFATc1, c-Fos were detected by qRT-PCR and Western blotting. The osteoporosis model was established in mice by bilateral ovariectomy (OVX). Bone histomorphology was determined by micro-CT and H&E staining. NFATc1 expression in bone tissues was determined by immunohistochemical staining. Proliferation of primary bone marrow macrophages cells (BMMs) was assessed by MTT assay. Osteoclast formation was observed by TRAP staining. The regulatory mechanism was evaluated by RNA methylation quantification assay, MeRIP-qPCR, dual luciferase reporter assay, and RIP, respectively. METTL14 was down-regulated in the serum samples of postmenopausal osteoporotic women, which was positively associated with bone mineral density (BMD). Osteoclast formation was promoted in OVX-treated METTL14+/- mice as compared with wild-type littermates. Conversely, METTL14 overexpression repressed RANKL-induced osteoclast differentiation of BMMs. Mechanistically, METTL14-mediated m6A modification post-transcriptionally stabilized glutathione peroxidase 4 (GPX4), with the assistance of Hu-Antigen R (HuR). Finally, GPX4 depletion-mediated osteoclast formation in BMMs could be counteracted by METTL14 or HuR overexpression. Collectively, METTL14 inhibits osteoclastogenesis and bone resorption via enhancing GPX4 stability through an m6A-HuR dependent mechanism. Therefore, targeting METTL14 might be a novel promising treatment strategy for osteoporosis.

Interrelations between clinical-psychological features and bone mineral density changes in post-menopausal women undergoing anti-osteoporotic treatment: a two-year follow-up.

Psychological features have been bidirectionally associated with osteoporosis, but it is still unclear whether patient's anxiety fluctuations during the anti-osteoporotic treatment can have an impact on bone mineral density (BMD) variation. The aim of this study was to investigate the interrelations between psychological distress features, such as anxiety, depression, health-related QoL (HRQoL) and bone health in women receiving anti-osteoporotic treatment. 192 post-menopausal osteoporotic women were treated with alendronate or risedronate according to the standard procedure. The levels of anxiety, depression, and perceived HRQoL, along with BMD, were assessed at baseline and at a 2-year follow-up. At the end of the study, the patients showed a statistically significant increase of both psychic and somatic anxiety (p<0.0001) and exhibited a worsening of depressive symptoms (p<0.0001), whereas HRQoL showed no change. BMD improved and no incident fractures occurred. BMD variation (ΔBMD) at lumbar spine was significantly associated with anxiety levels (r=0.23, p=0.021). Multiple regression analysis showed that both patients' worsening anxiety levels (β = -0.1283, SE=0.06142, p=0.04) and their treatment adherence (β=0.09, SE=0.02, p=0.0006) were independently associated with ΔBMD. The findings of the current follow-up study suggest that BMD in post-menopausal women undergoing anti-osteoporotic treatment was predicted by treatment adherence and anxiety change over time.

Impact of Zoledronate or Denosumab on Bone-related Biochemical Parameters in Osteoporotic Postmenopausal Women with Primary Hyperparathyroidism

Searchable abstracts of presentations at key conferences in endocrinology ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Factors associated with bone response to teriparatide in young postmenopausal women with osteoporosis.

To investigate the factors associated with changes in vertebral bone mineral density during teriparatide treatment. Single centre, longitudinal study involving 145 osteoporotic postmenopausal women treated with teriparatide. Clinical evaluation, bone mineral density (BMD) measurements assessment and laboratory analyses were performed at baseline then after 12 and 18months of treatment. Bone non-response to treatment was defined as no significant increase in BMD at 18months as compared to baseline. Of the 145 women initially included, 109 completed the 18-month course of the treatment. 75% of them had a history of prior osteoporotic treatment. Baseline mean age was 60 ± 8years. Mean baseline vertebral T-score was -3.7 ± 0.7 and 83 (76%) women had suffered at least one vertebral fracture. At the end of treatment, 18 women (17%) were classified as non-responders. In the responder group (n = 91), vertebral BMD increased by 0.091 ± 0.04g/cm2 (12.2 ± 5.3%). Clinical characteristics, baseline BMDs and the percentage of women previously treated with bisphosphonates as well as the duration of prior treatment did not significantly differ between the two groups of responders and non-responders. At baseline, non-responders had significant mean lower C-terminal fragment of type 1 collagen (CTX) values than responders (p < 0.01). Only baseline CTX values (r = 0.30 p < 0.01) were independently correlated to vertebral BMD changes during teriparatide treatment. A minority of treated women had no vertebral densitometric gain after 18months of teriparatide therapy. Low levels of baseline bone remodeling were the main factor associated with poor response to treatment.

Vitamin D receptor gene polymorphisms influence on clinical profile and bone mineral density at different skeletal sites in postmenopausal osteoporotic women.

Bone remodeling is marked by bone synthesis and absorption balance, and any altered dynamic in this process leads to osteoporosis (OP). The interaction of hormonal, environmental and genetic factors regulate bone metabolism. Since vitamin D displays a classic role in bone metabolism regulation, acting through vitamin D receptor (VDR), the genetic variants within VDR were the first ones associated with bone density and remodelling. Therefore, we investigated whether three single nucleotide polymorphisms (SNPs) within VDR were associated with OP differential susceptibility and clinical profile from postmenopausal versus healthy women from Northeast Brazil. Genetic association study enrolling 146 postmenopausal osteoporotic women as the patient group and 95 healthy age-matched women as the control group. We assessed three SNPs within VDR (rs11168268, rs1540339 and rs3890733), considering the clinical profile of all patients. Our results showed an association of rs11168268 G/G genotype with higher bone mineral density (BMD) mean for the total hip (A/A=0.828±0.09; A/G=0.081±0.13; G/G=0.876±0.12, p=.039), and the rs3890733 T/T genotype was associated with increased OP risk in patients below 60 years old (odds ratio [OR]=5.12, 95% confidence interval [CI]=1.13-23.27, p=.012). The rs1540339 T/T genotype was associated with protection for individuals with low melanin deposition when compared to the high melanin deposition group (OR=0.24, 95%CI=0.06-0.94, p=.029). Additionally, 61% of patients presented deficient vitamin D serum levels. The SNP rs11168268 G/G was associated with a significantly increased mean total hip BMD in patients OP, highlighting this SNP and its relationship with BMD.

Circulating miR-340-5p and miR-506-3p as Two Osteo-miRNAs for Predicting Osteoporosis in a Cohort of Postmenopausal Women.

An increasing risk of developing osteoporosis which is characterized by bone production weakness and microarchitectural deterioration is found among postmenopausal women. MicroRNAs (miRNAs) are secreted into the circulation from cells of various tissues in response to local disease severity including bone diseases. Herein, we set out to identify candidate miRNAs predictable for osteoporosis incidence in postmenopausal elderly women. The circulating miRNA expression profiles deposited in the dataset accessioned as GSE201543 were downloaded from the GEO database. The study included 176 postmenopausal women who underwent BMD testing, including 96 women reporting osteoporosis and 70 women reporting normal BMD. All subjects were submitted their serum samples for measurements of bone metabolism markers. The miRNA expression profiles of the GSE201543 dataset were differentially analyzed and found 97 miRNAs being upregulated concomitantly with 31 miRNAs being downregulated in the serum samples between osteoporotic postmenopausal women and postmenopausal women with normal BMD. Osteoporotic postmenopausal women were demonstrated with elevated serum levels of miR-340-5p and miR-506-3p when compared to normal postmenopausal women. Pearson correlation analysis demonstrated that circulating miR-340-5p and miR-506-3p expressions were increased as BAP, β-CTx, and PINP levels increased, but osteocalcin and 25-(OH)VitD levels are declined in osteoporotic postmenopausal women. Results of the receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) showed circulating miR-340-5p and miR-506-3p expressions alone or combined together produced 0.843 AUC, 0.851 AUC, and 0.935 AUC, respectively, when used to predict the incidence of osteoporosis in postmenopausal women. Our work suggested that circulating miR-340-5p and miR-506-3p function as osteo-miRNAs in postmenopausal women and may serve as potential noninvasive biomarkers for the incidence of osteoporosis in postmenopausal women.

Effect of Teriparatide on Bone Mineral Density and Bone Markers in Real-Life: Argentine Experience.

To evaluate the effect of teriparatide (TPTD) on bone mineral density (BMD) and bone markers under clinical practice conditions. To assess whether the results in real-life match those published in clinical trials. Cross-sectional study of postmenopausal women treated with TPTD for at least 12 months. 264 patients were included in the study. Main characteristics are as follows: age: 68.7 ± 10.2 years, previous fractures: 57.6%, and previously treated with antiresorptive (AR-prior): 79%. All bone turnover markers studied significantly increased after 6 months. CTX and BGP remained high up to 24 months, but total and bone alkaline phosphatase returned to basal values at month 18. There was a significant increase in lumbar spine (LS) BMD after 6 months (+6.2%), with a maximum peak at 24 months (+13%). Femoral neck (FN) and total hip (TH) BMD showed a significant increase later than LS (just at month 12), reaching a maximum peak at month 24 (FN + 7.9% and TH + 5.5%). A significant increase in LS BMD was found from month 6 to month 24 compared to basal in both AR-naïve, and AR-prior patients (+16.7% and +10.5%, respectively), without significant differences between the two groups. Comparable results were found in FN and TH BMD. Main conclusions. As reported in real-life clinical studies, treatment of osteoporotic postmenopausal women with TPTD induced a significant increase in bone turnover markers from month 6 onward and an increase in BMD from months 6-12 with continuous gain up to month 24. The real-life results of our study matched the results of randomized clinical trials. In addition, TPTD induced an increase in BMD, regardless of the previous use of AR.

Healthy plant-based diet index as a determinant of bone mineral density in osteoporotic postmenopausal women: A case-control study.

The association between plant-based diet indices and bone mineral density (BMD) of women with osteoporosis have not been studied in Iranian women. This study aimed to evaluate the association between plant-based diet indices and BMD in postmenopausal women with osteopenia/osteoporosis. The present research was a case-control study conducted on 131 postmenopausal women with osteoporosis/osteopenia and 131 healthy women. The BMD of the femoral neck and lumbar vertebrae was measured by the Dual-energy X-ray absorptiometry (DXEA) method. Participants were asked to complete a validated semi-quantitative food frequency questionnaire (FFQ). We used three versions of plant-based diet indices, including plant-based diet index (PDI), healthy plant-based diet index (hPDI), and unhealthy plant-based diet index (uPDI). Two different multivariable logistic regression was used for the crude and adjusted model to assess the relationship between PDI, hPDI, and uPDI with odds of femoral and lumbar BMD. There was a reverse association between last tertile of hPDI with femoral BMD abnormality in the both adjusted model [Model 1: odds ratio (OR): 0.33; 95% confidence interval (CI): 0.19-0.63 and Model 2: OR: 0.30; 95% CI: 0.15-0.58, respectively]. Furthermore, we found a reverse relationship between hPDI with lumbar BMD abnormality in the first adjusted model (OR: 0.36; 95% CI: 0.19-0.67). On the other hand, a negative association was observed in the second and last tertile of hPDI with lumbar BMD abnormality (OR: 0.47; 95% CI: 0.24-0.90 and OR: 0.34; 95% CI: 0.17-0.64, respectively). According to the results, the association of femoral BMD abnormality in the last tertile of uPDI compared to the first tertile in the both adjusted models (Model 1: OR: 2.85; 95% CI: 1.52-5.36 and Model 2: OR: 2.63; 95% CI: 1.37-5.06) were significant. Also, we observed a positive relationship between the last tertile of uPDI with lumbar BMD abnormality compared to the lowest tertile in the both adjusted models (Model 1; OR: 4.16; 95% CI: 2.20-7.85, Model 2; OR: 4.23; 95% CI: 2.19-8.19). Overall, the findings indicated that in postmenopausal women with osteoporosis, a healthy plant-based diet could prevent bone loss, and an unhealthy plant-based diet might have detrimental effects on BMD.

Denosumab biosimilar (LY06006) in Chinese postmenopausal osteoporotic women: A randomized, double-blind, placebo-controlled, multicenter phase III study.

This study assessed the efficacy, safety, pharmacokinetics (PK), and immunogenicity profiles of a denosumab biosimilar (LY06006) in Chinese postmenopausal osteoporotic women with a high risk of fracture. In this multicenter, randomized, double-blind, placebo-controlled, phase 3 trial, 448 postmenopausal women aged 50-85 years with osteoporosis were enrolled at 49 centers in China and were randomly assigned (3:1) to receive 60​mg of the denosumab biosimilar (LY06006) or placebo subcutaneously every 6 months for 1 year. Lumbar spine bone mineral density (BMD) change was the primary endpoint. Of the 448 randomized patients, 409 (LY06006, n​=​311; placebo, n​=​98) completed the study. All 448 (100.0%) subjects were included in the intent-to-treat (ITT) trial, 427 (95.3%) were included in the full analysis set (FAS), 408 (91.1%) were included in the per protocol set (PPS), 446 (99.6%) were included in the safety set (SS), and 336 (75.0%) were included in the pharmacokinetics concentration set (PKCs). For the primary endpoint, a 4.71% (95% CI, 3.81%, 5.60%) treatment difference in percent change in lumbar spine BMD from baseline to month 12 was observed in the LY06006 group compared with the placebo group (P​<​0.0001). For the secondary endpoints, LY06006 was associated with increased lumbar spine BMD levels measured at month 6, BMD levels at the femoral neck, total hip, and trochanter measured at months 6 and 12 and reduced serum C-terminal telopeptide of type 1 collagen (CTX) and procollagen type 1​N-peptide (P1NP) levels at months 1, 6, and 12. Safety analysis was based on the safety analysis set (SS), and 264 (78.6%) subjects in the LY06006 group and 83 (75.5%) in the placebo group experienced adverse events (AEs). Most events were mild or moderate and not related to the study drugs. In postmenopausal women with a high risk of fracture, LY06006 increased the BMD and decreased bone resorption; thus, LY06006 might be an effective treatment for osteoporosis. LY06006 was generally safe and well tolerated without unexpected adverse reactions, similar to the reference drug Prolia®. The characteristics of effectiveness and safety were similar to those reported in previous studies. In this multi-center, randomized, double-blind, placebo-controlled phase 3 study, LY06006 showed substantially efficacy to increase BMD and well tolerance without unexpected adverse reactions, which is comparable to the reference drug Prolia ®. The presented results are encouraging and can offer some valuable evidence for the clinical practice.