The association of vasomotor symptoms with fracture risk and bone mineral density in postmenopausal women: a systematic review and meta-analysis of observational studies.

BACKGROUND/AIMS: Vasomotor symptoms (VMS) adversely affect postmenopausal quality of life. However, their association with bone health has not been elucidated. This study aimed to systematically review and meta-analyze the evidence regarding the association of VMS with fracture risk and bone mineral density (BMD) in peri- and postmenopausal women. METHODS: A literature search was conducted in PubMed, Scopus and Cochrane databases until 31 August 2023. Fracture, low BMD (osteoporosis/osteopenia) and mean change in lumbar spine (LS) and femoral neck (FN) BMD were assessed. The results are presented as odds ratio (OR) and mean difference (MD), respectively, with a 95% confidence interval (95% CI). The I2 index quantified heterogeneity. RESULTS: Twenty studies were included in the qualitative and 12 in the quantitative analysis (n=49,659). No difference in fractures between women with and without VMS was found (n=5, OR 1.04, 95% CI 0.93-1.16, I2 16%). However, VMS were associated with low BMD (n=5, OR 1.54, 95% CI 1.42-1.67, I2 0%). This difference was evident for LS (MD -0.019 g/cm2, 95% CI -0.03 to -0.008, I2 85.2%), but not for FN BMD (MD -0.010 g/cm2, 95% CI -0.021 to 0.001, I2 78.2%). These results were independent of VMS severity, age and study design. When the analysis was confined to studies that excluded menopausal hormone therapy use, the association with BMD remained significant. CONCLUSIONS: The presence of VMS is associated with low BMD in postmenopausal women, although it does not seem to increase fracture risk.

Physical function trajectory after wrist or lower arm fracture in postmenopausal women: results from the Women's Health Initiative Study.

Long-term physical functioning trajectories following distal forearm fracture are unknown. We found that women with versus those without distal forearm fracture were more likely to experience a 5-year decline in physical functioning, independent of initial physical functioning level. This association was most evident among women 80 years and older. INTRODUCTION: Physical functioning trajectory following lower arm or wrist fracture is not well understood. PURPOSE: This study is to evaluate physical functioning trajectory before vs. after lower arm or wrist fracture, stratified by age. METHODS: We performed a nested case-control study of prospective data from the Women's Health Initiative Study (n = 2097 cases with lower arm or wrist fracture, 20,970 controls). Self-reported fractures and the physical functioning subscale of the RAND 36-item Short-Form Health Survey were assessed annually. We examined three physical functioning trajectory groups: stable, improving, and declining. RESULTS: Mean (SD) number of physical functioning measurements was 5.2 (1.5) for cases and 5.0 (1.4) for controls. Declining physical functioning was observed among 20.4% of cases and 16.0% of controls. Compared to women without lower arm or wrist fracture, women with lower arm or wrist fracture were 33% more likely to experience declining physical functioning (adjusted odds ratio [aOR] 1.33 95% confidence interval [CI] 1.19-1.49, reference group stable or improving physical functioning trajectory). Associations varied by age: age ≥ 80 years aOR 1.56 (95% CI 1.29-1.88); age 70-79 years aOR 1.29 (95% CI 1.09-1.52); age < 70 years aOR 1.15 (95% CI 0.86-1.53) (pinteraction = 0.06). Associations between lower arm or wrist fracture and odds of declining physical functioning did not vary by baseline physical functioning or physical activity level. CONCLUSIONS: Women with lower arm or wrist fracture, particularly those aged 80 and older, were more likely to experience declines in physical functioning than women without such fractures, independent of baseline physical functioning level.

Low-dose glucocorticoid increase the risk of fracture in postmenopausal women with low bone mass: a retrospective cohort study.

Long-term glucocorticoids (GCs) treatment is associated with osteoporosis and fractures. We investigated whether low-dose GC treatment also increased the risk of osteoporotic fractures, and the results showed that even low-dose GC treatment increased the risk of osteoporotic fractures, especially spine fractures. PURPOSE: The effect of low-dose glucocorticoid (GC) therapy on the fracture risk in postmenopausal women with low bone mass was investigated. METHODS: 119,790 66-year-old postmenopausal women with low bone mass based on bone mineral density (BMD) results were included. GC group consisted of patients who had been prescribed oral GCs within 6 months of BMD testing. In GC group, GCs dosage was calculated by a defined daily dose (DDD), and divided into five groups according to GC usage (Group 1[G1]; < 11.25 DDDs, G2; ≥ 11.25, < 22.5 DDDs, G3; ≥ 22.5, < 45 DDDs, G4; ≥ 45, < 90 DDDs, G5; ≥ 90 DDDs). The risk of major osteoporotic fractures (MOF) and non-MOF was analyzed and compared with that of the control group during the 1-year follow-up. RESULTS: The risk of total fracture was higher in G3-G5 than in the control group (G3, hazard ratio (HR) 1.25, 95% confidence interval [CI] 1.07-1.46; G4, 1.37 [1.13-1.66]; G5 1.45 [1.08-1.94]). The risk of MOF was higher in all groups except G2 than in the control group (G1, 1.23 [1.05-1.45]; G3, 1.37 [1.11-1.68]; G4, 1.41 [1.09-1.83]; G5, 1.66 [1.14-2.42]). The risk of spine fracture was significantly higher in all GC groups except G2 than in the control group. The risk of non-MOF was higher only in G4 than in the control group (G4, 1.48 [1.13-1.94]). CONCLUSION: Low-dose GC therapy can increase the risk of osteoporotic fractures, particularly spine fractures, in postmenopausal women with low bone mass.

Romosozumab in patients who experienced an on-study fracture: post hoc analyses of the FRAME and ARCH phase 3 trials.

Post hoc analysis of FRAME and ARCH revealed that on-study nonvertebral and vertebral fractures by Month 12 were less common in women initially treated with romosozumab versus placebo or alendronate. Recurrent fracture risk was also lower in romosozumab­treated patients, and there were no fracture­related complications. Results support continuing romosozumab treatment post­fracture. PURPOSE: Post hoc analysis evaluating efficacy and safety of romosozumab, administered in the immediate post­fracture period, in the FRAME and ARCH phase 3 trials. METHODS: In FRAME (NCT01575834) and ARCH (NCT01631214), postmenopausal women with osteoporosis were randomized 1:1 to romosozumab 210 mg monthly or comparator (FRAME, placebo; ARCH, alendronate 70 mg weekly) for 12 months, followed by antiresorptive therapy (FRAME, denosumab; ARCH, alendronate). In patients who experienced on-study nonvertebral or new/worsening vertebral fracture by Month 12, we report the following: fracture and treatment­emergent adverse event (TEAE) incidence through 36 months, bone mineral density changes (BMD), and romosozumab timing. Due to the sample sizes employed, meaningful statistical comparisons between treatments were not possible. RESULTS: Incidence of on-study nonvertebral and vertebral fractures by Month 12 was numerically lower in romosozumab- versus comparator-treated patients (FRAME, 1.6% and 0.5% versus 2.1% and 1.6%; ARCH, 3.4% and 3.3% versus 4.6% and 4.9%, respectively). In those who experienced on-study nonvertebral fracture by Month 12, recurrent nonvertebral and subsequent vertebral fracture incidences were numerically lower in patients initially treated with romosozumab versus comparator (FRAME, 3.6% [2/56] and 1.8% [1/56] versus 9.2% [7/76] and 3.9% [3/76]; ARCH, 10.0% [7/70] and 5.7% [4/70] versus 12.6% [12/95] and 8.4% [8/95], respectively). Among those with on-study vertebral fracture by Month 12, recurrent vertebral and subsequent nonvertebral fracture incidences were numerically lower with romosozumab versus comparator (FRAME, 0.0% [0/17] and 0.0% [0/17] versus 11.9% [7/59] and 8.5% [5/59]; ARCH, 9.0% [6/67] and 7.5% [5/67] versus 15.0% [15/100] and 16.0% [16/100], respectively). In patients with fracture by Month 12, no fracture­related complications were reported in romosozumab-treated patients. BMD gains were numerically greater with romosozumab than comparators. CONCLUSION: Data suggest support for the efficacy and safety of continuing romosozumab treatment following fracture. TRIAL REGISTRATIONS: NCT01575834; NCT01631214.

Associations between ultra-distal forearm bone mineral density and incident fracture in women.

Bone mineral density measured at the ultra-distal forearm site was associated with any fracture, as well as distal radius fracture in women from a longitudinal cohort study. PURPOSE: Femoral neck (BMDhip) and lumbar spine (BMDspine) bone mineral density (BMD) are routinely used to assess fracture risk. More data are needed to understand how ultra-distal forearm BMD (BMDUDforearm) may assist fracture prediction. METHODS: Using a Lunar DPX-L, Geelong Osteoporosis Study women (n = 1026), aged 40-90 years, had BMD measured. Incident low-trauma fractures were radiologically verified. Using Cox proportional hazard models, hazard ratios (HR) were calculated for BMDUDforearm as a continuous variable (expressed as a one-unit decrease in T-score) and a categorical variable (normal/osteopenia/osteoporosis). Areas under receiver operating characteristics (AUROC) curves were calculated. Analyses were conducted for any fracture and distal radius fractures. RESULTS: During 14,270 person-years of follow-up, there were 318 fractures (85 distal radius). In adjusted models, continuous BMDUDforearm was associated with any (HR 1.26;95%CI 1.15-1.39) and distal radius fractures (HR 1.59;95%CI 1.38-1.83). AUROCs for continuous BMDUDforearm, 33% forearm(BMD33%forearm), BMDhip, BMDspine, and FRAX without BMD were similar for any fracture (p > 0.05). For distal radius fracture, the AUROC for BMDUDforearm was higher than other sites and FRAX (p < 0.05). In adjusted models, those with osteoporosis had a higher likelihood of any fracture (HR 2.12; 95%CI 1.50-2.98). For distal radius fractures, both osteopenia and osteoporosis had a higher risk (HR 4.31; 95%CI 2.59-7.15 and 4.81; 95%CI 2.70-8.58). AUROCs for any fracture were similar for categorical BMD at all sites but lower for FRAX (p < 0.05). For distal radius fractures, the AUROC for BMDUDforearm, was higher than other sites and FRAX (p < 0.05). CONCLUSION: Ultra-distal forearm BMD may aid risk assessments for any distal radius fractures.

The relationship of body composition with bone mineral density and 10-year probability of hip fracture in postmenopausal women.

INTRODUCTION: Postmenopausal osteoporosis and fractures are widely prevalent. However, the relationship of body composition with bone health in this population remains unclear. The aim of this study was to investigate the association of body composition with bone mineral density (BMD) and 10-year probability of hip fracture in postmenopausal women. MATERIALS AND METHODS: This is a cross-sectional study. A total of 1285 subjects were included in our study. Body composition and BMD were assessed using dual-energy X-ray densitometry. The 10-year probability of hip fracture of participants was calculated. All participants were categorized into four groups: sarcopenic-obese (SO) group, sarcopenic-nonobese (S) group, nonsarcopenic-obese (O) group, or nonsarcopenic-nonobese control (C) group. Multivariate analyses and binary logistic regression were conducted to explore the relationship of body composition with BMD and 10-year probability of hip fracture. RESULTS: Participants in S group were 2.8, 4.7 and 4.8 times more likely to develop osteoporosis in the lumbar spine, the total hip and femoral neck sites, respectively. Lean mass was positively correlated with BMD, wherein lumbar spine BMD was significantly affected by appendicular lean mass, while total hip BMD and femoral neck BMD were mainly influenced by trunk lean mass. Total fat mass was positively associated with total hip and femoral neck BMD, but not with lumbar spine BMD. A significant correlation was observed between lean mass and 10-year probability of hip fracture. CONCLUSION: Changes in body composition in postmenopausal women could affect bone health. A decrease in regional lean mass may be associated with an increased risk of osteoporosis and fractures.

The Association of Systemic and Mandibular Bone Mineral Density in Postmenopausal Females with Osteoporosis.

Background/Objectives: Osteoporosis is a common general disease that mostly affects the skeletal system, including the jawbone. There is a link between systemic and mandibular osteoporosis. This study aimed at assessing the association between systemic (lumbar spine L1-L4, femoral neck, total hip) bone mineral density (BMD) and mandible BMD sites in Romanian postmenopausal females. Methods: A total of 97 menopausal patients were studied, 62 with osteoporosis and 35 females with no osteoporosis. For each patient, dual-energy X-ray absorptiometry (DXA) assessments of BMD in the mandible, proximal femur, total hip, and lumbar spine (L1-L4) were performed. Mandibular measurements were performed using the distal forearm software, followed by manual analysis after the bone contour was defined in each case. Results: Comparing the osteoporosis and control groups, there were significant differences in BMD at each examined location. The mandibular BMD (1.125 ± 0.181506 g/cm2) in the osteoporosis group was considerably smaller than in the control group (1.35497 ± 0.244397 g/cm2). Correlations between the BMD at different sites were significant: lumbar spine and femoral neck (r = 0.738, p < 0.0001), lumbar spine and total hip (r = 0.735, p < 0.0001), lumbar spine and mandible (r = 0.506, p < 0.0001), femoral neck and total hip (r = 0.891, p < 0.0001), femoral neck and mandible (r = 0.482, p < 0.0001), and total hip and mandible (r = 0.466, p < 0.0001). Conclusions: There were correlations between mandible BMD and lumbar spine, femoral neck, and total hip BMD, suggesting that osteoporosis affects mandibular bone density. BMD assessments at common locations may help predict mandibular BMD and the probability of osteoporosis.

[Bone mineral density in women with rheumatoid arthritis: A link between immune and biochemical markers].

AIM: To study the association of bone mineral density (BMD) with serum biochemical and immunological markers in postmenopausal women with rheumatoid arthritis (RA). MATERIALS AND METHODS: The study included 173 women with RA (age 61.0 [56.0; 66.0] years). A survey, dual-energy X-ray absorptiometry to measure the BMD of the lumbar spine (LI-LIV), femoral neck (FN) and total hip (TH), routine blood chemistry, measurement of C-reactive protein (CRP), rheumatoid factor, cyclic citrullinated peptide antibodies (CCPA), parathyroid hormone (PTH), vitamin D3, myostatin, follistatin, interleukin-6 (IL-6), IL-6 receptors, insulin-like growth factor 1, adiponectin, leptin, fibroblast growth factor 23, and tumor necrosis factor SF12 were performed. RESULTS: PTH (ß=-0.22, -0.35 and -0.30 for LI-LIV, FN and TH, respectively), CRP (ß=-0.18, 0.23 and -0.22 for LI-LIV, FN and TH, respectively) and leptin (ß=0.35, 0.32 and 0.42 for LI-LIV, FN and TH, respectively) were shown a significant association with BMD in all sites of measurement. It was independent of age, body mass index and postmenopause duration. Associations were also found between adiponectin and BMD of LI-LIV and TH (ß=-0.36 and -0.28, respectively), CCPA and BMD of FN and TH (ß=-0.21, -0.24, respectively) and IL-6 and BMD of FN (ß=0.37). CONCLUSION: The study of biochemical and immunological markers in women with RA demonstrated that CRP, CCPA, PTH, IL-6, adiponectin, and leptin influenced BMD.

Olive oil effectively mitigates ovariectomy-induced marrow adiposity assessed by MR spectroscopy in estrogen-deficient rabbits.

BACKGROUND: Polyphenols in extra virgin olive oil (EVOO) have been found to reduce the expression of PPARγ2, inhibit adipocyte differentiation, and enhance the formation of osteoblasts from bone marrow stem cells. However, the underlying mechanisms of their action remain unknown. PURPOSE: To determine the sequential effects of EVOO on marrow fat expansion induced by estrogen deprivation using 3.0-T proton magnetic resonance (MR) spectroscopy in an ovariectomy (OVX) rabbit model of postmenopausal bone loss over a six-month period. MATERIAL AND METHODS: A total of 45 female New Zealand rabbits were equally divided into sham-operation, OVX controls, and OVX treated with EVOO for six months. Marrow fat fraction was measured by MR spectroscopy at baseline conditions, and three and six months postoperatively, respectively. Serum bone biomarkers, lumbar and femoral bone mineral density, microtomographic parameters, biomechanical properties, and quantitative parameters of marrow adipocytes were studied. RESULTS: OVX was associated with marrow adiposity in a time-dependent manner, accompanied with increased bone turnover and impaired bone mass and trabecular microarchitecture. In OVX rabbits, EVOO markedly alleviated trabecular bone loss and reduced the accumulation of lipid droplets including adipocyte size, density, and areas of fat deposits in the bone marrow. EVOO prevented such changes in terms of both marrow adiposity and bone remodeling. CONCLUSION: Early EVOO treatment may exert beneficial effects on bone by modulating marrow adiposity, which would support their protective effect against bone pathologies.

Tributyltin protects against ovariectomy-induced trabecular bone loss in C57BL/6J mice with an attenuated effect in high fat fed mice.

Risk factors for poor bone quality include estrogen loss at menopause, a high fat diet and exposures to drugs/chemicals that activate peroxisome proliferator activated receptor gamma (PPARγ). We previously reported that the PPARγ and retinoid X receptor dual ligand, tributyltin (TBT), repressed periosteal bone formation but enhanced trabecular bone formation in vivo. Here, we examined the interaction of diet, ovariectomy (OVX) and TBT exposure on bone structure. C57BL/6J mice underwent either sham surgery or OVX at 10 weeks of age. At 12 weeks of age, they were placed on a low (10% kcal) or high (45% kcal) fat, sucrose-matched diet and treated with vehicle or TBT (1 or 5 mg/kg) for 14 weeks. OVX increased body weight gain in mice on either diet. TBT enhanced body weight gain in intact mice fed a high fat diet, but decreased weight gain in OVX mice. Elemental tin concentrations increased dose-dependently in bone. TBT had marginal effects on cortical and trabecular bone in intact mice fed either diet. OVX caused a reduction in cortical and trabecular bone, regardless of diet. In high fat fed OVX mice, TBT further reduced cortical thickness, bone area and total area. Interestingly, TBT protected against OVX-induced trabecular bone loss in low fat fed mice. The protective effect of TBT was nullified by the high fat. These results show that TBT protects against trabecular bone loss, even in the presence of a strongly resorptive environment, at an even lower level of exposure than we showed repressed homeostatic resorption.

Plasma periostin as a biomarker of osteoporosis in postmenopausal women with type 2 diabetes.

INTRODUCTION: Periostin, as an emerging biomarker, is involved in multiple steps in bone metabolism. This study aimed to investigate the correlation between periostin levels and bone mineral density as well as bone turnover markers in postmenopausal women with type 2 diabetes (T2DM). MATERIALS AND METHODS: This study was a cross-sectional study that included 164 postmenopausal women with T2DM as study subjects and 32 age-matched nondiabetic postmenopausal women with normal bone mineral density (BMD) as healthy control subjects. A total of 164 subjects with T2DM were then divided into three groups according to BMD: the normal BMD group (n = 29), the osteopenia group (n = 70), and the osteoporosis group (n = 65). The clinical data of all subjects along with the relevant biochemical parameter data were collected. Plasma periostin was detected using an enzyme-linked immunosorbent assay (ELISA). RESULTS: Plasma periostin levels were significantly increased in T2DM patients with normal BMD compared with healthy controls (p < 0.05). In the diabetic group, plasma periostin levels were significantly elevated with decreased BMD, were positively correlated with osteocalcin levels (r = 0.162, p = 0.039) and were inversely associated with femoral neck BMD (r = - 0.308, p < 0.001) and total femur BMD (r = - 0.295, p < 0.001). In the case of chronic complications, periostin levels were slightly increased in individuals with complications of diabetic retinopathy, diabetic nephropathy and fracture (p > 0.05). CONCLUSIONS: The current study demonstrated that plasma periostin levels were significantly associated with BMD in patients with T2DM, and periostin might act as a novel biochemical marker of osteoporosis in postmenopausal women with type 2 diabetes.

Osteocytes and Estrogen Deficiency.

PURPOSE OF REVIEW: Postmenopausal osteoporosis reduces circulating estrogen levels, which leads to osteoclast resorption, bone loss, and fracture. This review addresses emerging evidence that osteoporosis is not simply a disease of bone loss but that mechanosensitive osteocytes that regulate both osteoclasts and osteoblasts are also impacted by estrogen deficiency. RECENT FINDINGS: At the onset of estrogen deficiency, the osteocyte mechanical environment is altered, which coincides with temporal changes in bone tissue composition. The osteocyte microenvironment is also altered, apoptosis is more prevalent, and hypermineralization occurs. The mechanobiological responses of osteocytes are impaired under estrogen deficiency, which exacerbates osteocyte paracrine regulation of osteoclasts. Recent research reveals changes in osteocytes during estrogen deficiency that may play a critical role in the etiology of the disease. A paradigm change for osteoporosis therapy requires an advanced understanding of such changes to establish the efficacy of osteocyte-targeted therapies to inhibit resorption and secondary mineralization.

Comparison of the Characteristics of Back Pain in Women with Postmenopausal Osteoporosis with and without Vertebral Compression Fracture: A Retrospective Study at a Single Osteoporosis Center in Poland.

BACKGROUND The incidence of unspecific back pain and osteoporotic vertebral compression fractures increases significantly with age. Considering the difficulties in the diagnosis of spontaneous osteoporotic vertebral fractures, this retrospective study aimed to compare the characteristics of back pain in women with postmenopausal osteoporosis with and without vertebral compression fractures. MATERIAL AND METHODS This study enrolled 334 women with postmenopausal osteoporosis; 150 had vertebral fractures, and 184 had no vertebral fractures. Densitometric vertebral fracture assessment and bone mineral density measurements in the central skeleton were performed for each patient. The participants completed a survey about features of their back pain. RESULTS Patients with vertebral fractures had more severe back pain based on the numeric rating scale: 6.14 vs. 4.33 (P<0.001, odds ratio [OR]=1.43, 95% confidence interval [CI]: 1.29-1.59). Among these individuals, back pain caused reduction in normal activity during the day (P<0.001, OR=4.68, 95% CI: 2.86-7.68), and pain occurred more often (P<0.001, OR=1.77, 95% CI: 1.47-2.13), lasted longer (P<0.001, OR=2.01, 95% CI: 1.65-2.46), predominantly occurred in the lumbar spine (P<0.001, OR=4.70, 95% CI: 1.96-11.29), and intensified during normal everyday activities (P<0.001). Based on these results, a new survey was created. It demonstrated a sensitivity of 70.67% and a specificity of 67.37% in predicting a current compression fracture. CONCLUSIONS Patients with vertebral compression fractures experience higher pain intensity and exhibit specific features of back pain. The new survey can be considered a supportive tool in assessing the possibility of vertebral compression fractures.

Change in kyphosis does not affect the risk of falling in postmenopausal osteopenic and osteoporotic women.

OBJECTIVES: To examine the influence of the annual change in kyphosis on the risk of falling in postmenopausal osteopenic and osteoporotic women. METHODS: This prospective observational study included 498 postmenopausal Greek women over the age of 50, suffering from either osteoporosis or osteopenia. Data on age, height, weight, and self-reported falls were collected. Additionally, we evaluated the degree of the kyphosis angle, the balance, the mobility, the functionality and the handgrip strength on both hands of each subject using the Debrunner kyphometer, the Berg Balance Scale, the Timed-Up-and-Go test, the 30 Seconds Sit-to-Stand test and the Jamar Hydraulic Hand Dynamometer, respectively. All the above data were recorded at the baseline visit and the 12-month follow-up visit for each participant. RESULTS: All examined variables presented a statistically significant change at the 12-month follow-up visit. Nevertheless, the annual change in kyphosis did not show any association with the risk of falling. CONCLUSION: No association was shown between the annual change in kyphosis and the risk of falling in postmenopausal osteopenic and osteoporotic women, nor bears any substantial prognostic value for future falls.

Isoflavone-enriched soybean leaves attenuate ovariectomy-induced osteoporosis in rats by anti-inflammatory activity.

BACKGROUND: With an increasing aging population, postmenopausal osteoporosis has become a global public health problem. Previous evidence has shown that postmenopausal osteoporosis is a skeletal disease mainly caused by estrogen deficiency, generally accompanied by inflammation, and dietary isoflavones may ameliorate postmenopausal osteoporosis by anti-inflammatory activity. We have generated isoflavone-enriched soybean leaves (IESLs), but their anti-inflammatory activity and effect on attenuating osteoporosis are still obscure. Here, we determined the isoflavone profiles of IESLs and evaluated their anti-inflammatory activity in lipopolysaccharide-stimulated RAW 264.7 cells and anti-osteoporotic effects on ovariectomy-induced osteoporosis in rats. RESULTS: IESLs had a high content of total isoflavone. Hydrolysate of IESLs (HIESLs) was rich with the aglycones daidzein and genistein, and HIESLs can significantly inhibit lipopolysaccharide-induced inflammation by reducing messenger RNA expression of iNOS, COX-2, IL6, and IL1ß. Moreover, ovariectomized rats receiving aqueous extracts of IESLs (HIESLs) orally maintained more bone mass than control rats did, which was attributed to inhibition of osteoclastogenesis by downregulating the messenger RNA expression of the bone-specific genes RANKL/OPG, OC, and cathepsin K, and the inflammation-related genes IL6, NFκB, and COX-2. CONCLUSION: IESLs may attenuate postmenopausal osteoporosis by suppressing osteoclastogenesis with anti-inflammatory activity and be a potential source of functional food ingredients for the prevention of osteoporosis. © 2020 Society of Chemical Industry.

PSMC6 promotes osteoblast apoptosis through inhibiting PI3K/AKT signaling pathway activation in ovariectomy-induced osteoporosis mouse model.

There is now increasing evidence which suggests a key role for osteoblast apoptosis in the pathogenesis of postmenopausal osteoporosis. Here, we evaluated the role and mechanism of proteasome 26S subunit, ATPase (PSMC) 6, a protein that is highly expressed in bone. Gene expression pattern had been extracted based on database of Gene Expression Omnibus (GEO). GEO2R was employed for analyses, while the DAVID database was adopted to further analyze the gene ontology (GO) as well as Kyoto Encyclopedia of Genomes pathway (KEGG) enrichment. Then, the Search Tool Retrieval of Interacting Genes (STRING) was utilized to carry out interaction regulatory network for the top 200 differentially expressed genes (DEGs). A key gene, called PSMC6, was identified by Cytoscape 3.6.0. The OVX osteoporosis model was established in female C57BL/6 mice by full bilateral ovariectomy. According to our findings, PSMC6 gene knockout would elevate bone mineral density (BMD) and the phosphorylation level of PI3K protein and increased the protein level of cleaved caspase-3/-9 in OVX osteoporosis mice. Further, MTT, bromodeoxyuridine, and flow cytometry assays revealed that PSMC6 inhibition promoted the progression of cell cycle and cell proliferation, whereas, PSMC6 overexpression promoted the apoptosis and inhibited cell cycle progression and cell proliferation in vitro. Besides, we found that PI3K activation significantly decreased PSMC6-induced osteoblast apoptosis and promoted cell proliferation through regulating the protein levels of p53, cyclinD1, and cleaved caspase-3/9. In conclusion, PSMC6 aggravated the degree of OVX-induced osteoporosis by inhibiting the PI3K/AKT signal transduction pathway, thereby promoting the apoptosis of osteoblasts.

The efficacy and safety of ipriflavone in postmenopausal women with osteopenia or osteoporosis: A systematic review and meta-analysis.

OBJECTIVES: Ipriflavone (IP) is one of the over-the-counter drugs and found in foods, which is available for prevention of osteoporosis (OP) since 1989 in over 22 countries. Although some clinical trials have suggested that IP is appropriate for treatment of OP, there continues to be controversy regarding the efficacy and safety due to some contradictory reports. With the wide usage of IP for osteoporotic women, there is a critical need for evaluation of the evidence for IP in clinical practice. METHODS AND MATERIALS: We searched randomized control trials (RCTs) in PubMed, CENTRAL and CNKI which used the regimen of IP in postmenopausal women with osteopenia or OP. The efficacy referred to the absolute change and relative change in bone mineral density (BMD) and bone turnover markers. The safety profiles were associated with adverse events and the number of subject withdrawals due to adverse reactions. RESULTS: Eleven RCTs (n = 1605) met the eligibility criteria were included. The increase of the BMD in lumbar spine of the IP group is greater than that of the placebo group (random effect model: SMD = 0.36; 95%CI= (0.09, 0.62)). For safety profile, most frequent reactions are gastrointestinal symptoms, but withdrawals due to adverse reactions are similar in both the IP group and placebo control at the same time intervals. CONCLUSIONS: IP significantly increases BMD and has inhibitory effect on bone resorption markers in postmenopausal women with osteopenia or OP. Gastrointestinal symptoms may occur, but adverse drug withdrawal events were not statistically increased when compared with placebo group.

Assessment of eldecalcitol and alendronate effect on postural balance control in aged women with osteoporosis.

INTRODUCTION: Older people aged over 75 are more prone to falls because physical functions become deteriorated along with aging, and also fracture risk is strongly correlated with age. We evaluated the effects of anti-osteoporosis agents, eldecalcitol (ELD) and alendronate (ALN) on physical functions by assessing dynamic and static postural balance in aged patients with osteoporosis. MATERIALS AND METHODS: A randomized, open-label, controlled clinical trial has been conducted with 124 female patients aged 65 or over with osteoporosis. Patients were randomly assigned to receive either 0.75 µg of ELD once-a-day or 35 mg of ALN once-a-week for 24 weeks. The primary endpoint was the change in a postural balance index, adjusted composite equilibrium score (CES) of sensory organization test (SOT). The SOT equilibrium scores, leg muscle strength, and other physical functions were also evaluated. RESULTS: The Adjusted CES increased from baseline by 6.10% in the ELD group and 6.28% in the ALN group. There was no statistically significant difference between the two groups. The static postural balance at fixed platform were maintained in the ELD group, but declined in the ALN group. The dynamic postural balance at swaying platform and knee extension power increased from baseline in both groups. CONCLUSIONS: These results suggest that ELD and ALN treatments may each be beneficial to improve postural balance control in older patients with osteoporosis via different mechanisms of action.

Bazedoxifene improves renal function and increases renal phosphate excretion in patients with postmenopausal osteoporosis.

INTRODUCTION: Because aging is a predictor of renal insufficiency in the general population, renal function is a concern in postmenopausal patients undergoing treatment for osteoporosis. Although high serum phosphate concentration is a predictor of renal insufficiency, the effect of selective estrogen receptor modulator (SERM) on renal function and phosphate homeostasis remains to be established. MATERIALS AND METHODS: We administered 20 mg/day bazedoxifene to 48 postmenopausal osteoporotic women who had been taking alfacalcidol for ≥ 6 months, and assessed lumbar spine bone mineral density (LS-BMD), renal function (by calculating estimated glomerular filtration rate using serum cystatin-C levels [eGFRcys] [range 38.0-98.2 mL/min/1.73 m2]), and phosphate homeostasis. RESULTS: LS-BMD was significantly higher 6 months after the initiation of bazedoxifene administration. eGFRcys had increased by 3 months after initiation and was stable until 12 months. Serum phosphate gradually decreased after initiation, reaching statistical significance at 6 months. The changes in serum phosphate were also significant when the maximum tubular reabsorption rate of phosphate was normalized to glomerular filtration rate (TmP/GFR), indicating that bazedoxifene treatment reduces serum phosphate by increasing the urinary excretion of phosphate. The change in eGFRcys after the initiation of bazedoxifene was significantly negatively correlated with the change in serum phosphate, suggesting that a reduction in serum phosphate improves renal function. CONCLUSION: Bazedoxifene improves renal function, possibly by increasing renal phosphate excretion, in postmenopausal osteoporotic women without severe renal insufficiency.

Sensitivity and specificity assessment of DWI and ADC for the diagnosis of osteoporosis in postmenopausal patients.

OBJECTIVE: In this study, we prospectively investigated the diagnostic capability of diffusion-weighted magnetic resonance imaging (DWI) in assessing vertebral marrow changes in postmenopausal women with osteoporosis. MATERIALS AND METHODS: Sixty postmenopausal women (mean age 60.2 ± 6.11 years) underwent both dual-energy X-ray absorptiometry (DEXA) of the spine and MRI. Results were acquired from each patient's L2 to L4, for a total of 180 lumbar vertebrae. Based on bone mineral density (BMD) measurements obtained from DEXA, the vertebrae were divided into three groups as follows: normal (n = 52), osteopenic (n = 92), and osteoporotic (n = 36). DWI of the vertebral body was performed to assess the apparent diffusion coefficient (ADC). The ADC outcomes were compared among the three groups and correlated with BMD. RESULTS: ADC values (× 10-6 mm2/s) were significantly lower in the osteoporotic group (135.67 ± 44.10) in comparison to the normal group (561.85 ± 190.37) (P = 0.0001). The results showed a positive correlation between ADC and BMD values (r = 0.748, P = 0.0001). In receiver operating characteristic (ROC) analysis, the area under the curve for DWI was 0.912 (P = 0.001). A cut-off value of 400 mm2/s for the diagnosis of osteoporosis; had sensitivity, specificity, accuracy, positive predictive value, and negative predictive value of 90.90%, 83.34%, 88.89%, 93.75%, and 76.93%, respectively. CONCLUSION: ADC values correlated positively with BMD in women. DWI can allow quantitative evaluation of bone marrow changes and osteoporosis in postmenopausal women.