Postmenopausal Osteoporotic Patients Research Articles

Targeting the osteoclastogenic cytokine IL-9 as a novel immunotherapeutic strategy in mitigating inflammatory bone loss in post-menopausal osteoporosis.

Recent discoveries have established the pivotal role of IL-9-secreting immune cells in a wide spectrum of inflammatory and autoimmune diseases. However, little is known about how IL-9 contributes to the etiology of inflammatory bone loss in PMO. We observed that IL-9 has a pathological impact on inflammatory bone loss in ovariectomized (Ovx) mice. Our in vivo temporal kinetics analysis revealed that estrogen deprivation enhanced the production of IL-9 from Th cells (majorly Th9 and Th17). Both our ex vivo and in vivo studies corroborated these findings in Ovx mice, as estrogen diminishes the potential of Th9 cells to produce IL-9. Mechanistically, Th9 cells in an IL-9-dependent manner enhance osteoclastogenesis and thus could establish themselves as a novel osteoclastogenic Th cell subset. Therapeutically neutralizing/blocking IL-9 improves bone health by inhibiting the differentiation and function of osteoclasts, Th9, and Th17 cells along with maintaining gut integrity in Ovx mice. Post-menopausal osteoporotic patients have increased IL-9-secreting Th9 cells, which may suggest a potential role for IL-9 in the development of osteoporosis. Collectively, our study identifies IL-9-secreting Th9 cells as a driver of bone loss with attendant modulation of gut-immune-bone axis, which implies IL-9-targeted immunotherapies as a potential strategy for the management and treatment of inflammatory bone loss observed in PMO.

Comparison of Vitamin D Levels of Postmenopausal Osteoporotic Female Patients with and Without Fibromyalgia

Comparison of Vitamin D Levels of Postmenopausal Osteoporotic Female Patients with and Without Fibromyalgia

Effects of denosumab on bone mineral density around proximal femoral prosthesis after total hip replacement in postmenopausal osteoporotic patients

To evaluate the effect of denosumab on bone mineral density around proximal femoral prosthesis after total hip arthroplasty(THA) in the postmenopausal osteoporotic patients. Fifty-four consecutive patients underwent unilateral primary THA were included in this retrospective study. Twenty-five patients received denosumab for osteoporosis as the treatment group, and the twenty-nine without denosumab were the control group. At 1 week, 3month, 6 months, and 12 months after THA, bone turnover markers and proximal femoral periprosthetic bone mineral density (BMD) were measured. At 3, 6 and 12 months after operation, the level of TRACP-5b in the control group was significantly higher than that in the treatment group (P<0.05);the level of bone-specific alkaline phosphatase (BALP) between two groups showed significant difference in 12 months after operation (control group was higher than treatment group, P<0.05). The BMD of Gruen 1 and Gruen 7 decreased at 3, 6 and 12 months after operation compared with 1 week after operation. Comparing the treatment group and the control group, the differences of the the decrease of BMD in Gruen 1 and Gruen 7 were no significant at 3 months after surgery. In Gruen 1, Gruen 7 at 6 months after operation and Gruen 1, Gruen 7 at 12 months after operation, the decrease of BMD in the control group was significantly higher than that in the treatment group(P<0.05). It is suggested that desudumab could inhibit the loss of BMD after 6 months, and continuously show a protective effect on bone mass at 12 months after operation. After THA in postmenopausal patients with osteoporotic femoral neck fracture, Desuzumab can reduce the loss of BMD around the proximal femoral prosthesis and effectively inhibit bone resorption.

Disturbed bone marrow adiposity in patients with Cushing's syndrome and glucocorticoid- and postmenopausal- induced osteoporosis.

Skeletal stem/progenitor cells (SSPCs) in the bone marrow can differentiate into osteoblasts or adipocytes in response to microenvironmental signalling input, including hormonal signalling. Glucocorticoids (GC) are corticosteroid hormones that promote adipogenic differentiation and are endogenously increased in patients with Cushing´s syndrome (CS). Here, we investigate bone marrow adiposity changes in response to endogenous or exogenous GC increases. For that, we characterize bone biopsies from patients with CS and post-menopausal women with glucocorticoid-induced osteoporosis (GC-O), compared to age-matched controls, including postmenopausal osteoporotic patients (PM-O). Transiliac crest bone biopsies from CS patients and healthy controls, and from postmenopausal women with GC-O and matched controls were analysed; an additional cohort included biopsies from women with PM-O. Plastic-embedded biopsies were sectioned for histomorphometric characterization and quantification of adipocytes. The fraction of adipocyte area per tissue (Ad.Ar/T.Ar) and marrow area (Ad.Ar/Ma.Ar), mean adipocyte profile area (Ad.Pf.Ar) and adipocyte profile density (N.Ad.Pf/Ma.Ar) were determined and correlated to steroid levels. Furthermore, the spatial distribution of adipocytes in relation to trabecular bone was characterized and correlations between bone marrow adiposity and bone remodeling parameters investigated. Biopsies from patients with CS and GC-O presented increased Ad.Ar/Ma.Ar, along with adipocyte hypertrophy and hyperplasia. In patients with CS, both Ad.Ar/Ma.Ar and Ad.Pf.Ar significantly correlated with serum cortisol levels. Spatial distribution analyses revealed that, in CS, the increase in Ad.Ar/Ma.Ar near to trabecular bone (<100 µm) was mediated by both adipocyte hypertrophy and hyperplasia, while N.Ad.Pf/Ma.Ar further into the marrow (>100 µm) remained unchanged. In contrast, patients with GC-O only presented increased Ad.Ar/Ma.Ar and mean Ad.Pf.Ar>100 µm from trabecular bone surface, highlighting the differential effect of increased endogenous steroid accumulation. Finally, the Ad.Ar/Ma.Ar and Ad.Ar/T.Ar correlated with the canopy coverage above remodeling events. Increased cortisol production in patients with CS induces increased bone marrow adiposity, primarily mediated by adipocyte hypertrophy. This adiposity is particularly evident near trabecular bone surfaces, where hyperplasia also occurs. The differential pattern of adiposity in patients with CS and GC-O highlights that bone marrow adipocytes and their progenitors may respond differently in these two GC-mediated bone diseases.

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.

Relationship between sacral‐abdominal wall distance and grip strength in postmenopausal osteoporotic patients

AbstractBackgroundAn increase in waist circumference (WC) is a factor in lifestyle‐related diseases. The rectus abdominis muscle is a skeletal muscle that attaches to the pelvis from the xiphoid process and is thought to be affected by kyphosis deformity and posterior pelvic tilt. The purpose of this study is to examine differences between sacral‐abdominal wall distance (SAD) and WC and to determine whether they are associated with fall risk, frailty, markers of sarcopenia (grip strength and lean body mass), and spinal alignment. A secondary objective is to examine these differences by stratification by grip strength.MethodsThis retrospective study included 239 women aged 65 years or older (mean age 76.5 ± 6.7 years) attending an outpatient osteoporosis clinic. Bone mineral density and skeletal body composition (muscle mass index and trunk lean mass) were measured using dual‐energy X‐ray absorptiometry. SAD, pelvic tilt, and sagittal longitudinal axis were measured from simple X‐ray images of the spine sides. WC, grip strength, frailty, and fall risk score were investigated. Statistics were performed using Stat Flex, with two‐sided P &lt; 0.05 being significantly different.ResultsWC was correlated with SAD (R = 0.68, P &lt; 0.001). The SAD cut‐off value for a WC of 90 cm was 167 mm. The relationship between grip strength, SAD, and WC, weaker grip strength was associated with greater SAD; however, no significant difference was noted in WC. WC was not correlated with pelvic alignment but was correlated with body mass index (P &lt; 0.01). Meanwhile, SAD was correlated with body mass index, pelvic tilt, sagittal longitudinal axis (P &lt; 0.01), spinal alignment, and WC. Logistic regression analysis was performed with a grip strength of less than 18 kg as the objective variable. We found that the conditions for a grip strength of less than 18 kg were older age (P &lt; 0.001), increased SAD (P = 0.02), and decreased trunk lean body mass. There was a decrease in grip strength (P &lt; 0.05) and an increase in frailty (P &lt; 0.05) and falls (P &lt; 0.01) score in patients with SAD of 167 mm or greater.ConclusionsSAD and WC were found to be correlated; SAD was associated with body weight, posterior pelvic tilt, and anterior spinal tilt deformity, while WC was related to body weight. Increased SAD was found to be linked with decreased grip strength and increased risk of falls. This study was the first to examine a new measurement, SAD, for its utility in assessing grip strength, spinal alignment, frailty, and fall risk.

CX3CL1 deficiency ameliorates inflammation, apoptosis and accelerates osteogenic differentiation, mineralization in LPS-treated MC3T3-E1 cells via its receptor CX3CR1

BackgroundOsteoporosis is a devastating skeletal disease responsible for bone fragility and fracture. CX3C chemokine ligand 1 (CX3CL1) is an inflammatory chemokine which has been identified to possess increased expression in the serum of postmenopausal osteoporotic patients. This paper was to illuminate the impacts of CX3CL1 on inflammation, apoptosis and osteogenic differentiation, mineralization in LPS-treated osteoblasts and investigate the regulatory mechanism. MethodsThe viability of MC3T3-E1 cells exposed to elevating doses of LPS was detected by CCK-8 assay. CX3CL1 and C-X3-C motif chemokine receptor 1 (CX3CR1) expression were detected by RT-qPCR and western blot. CX3CR1 expression was examined again following CX3CL1 depletion. The binding of CX3CL1 with CX3CR1 was testified through Co-IP assay. In MC3T3-E1 cells co-transduced with CX3CL1 interference and CX3CR1 overexpression plasmids following LPS exposure, cell activity and inflammation were separately estimated via CCK-8 assay and RT-qPCR. Apoptosis was measured by TUNEL assay and western blot. Osteoblast differentiation was evaluated by ALP activity assay, RT-qPCR and western blot. Osteoblast mineralization was assessed by ARS staining, RT-qPCR and western blot. ResultsThe experimental data presented that LPS attenuated the viability and enhanced CX3CL1 and CX3CR1 expression in MC3T3-E1 cells in a dose-dependent manner. CX3CR1 interacted with CX3CL1 and was positively modulated by CX3CL1. The suppressive role of CX3CL1 absence in LPS-evoked viability decrease, inflammation and apoptosis in MC3T3-E1 cells was reversed by CX3CR1 elevation. Besides, CX3CR1 reversed the promoted osteoblast differentiation and mineralization imposed by CX3CL1 interference. ConclusionsCX3CL1 knockdown eased inflammation, apoptosis and promoted osteogenic differentiation, mineralization in MC3T3-E1 cells upon LPS exposure through down-regulating CX3CR1.

Risk factors of primary and recurrent fractures in postmenopausal osteoporotic Chinese patients: A retrospective analysis study

BackgroundAs postmenopausal osteoporotic fractures can cause higher rates of disability and mortality in women; it is essential to analyze the factors associated with primary and recurrent fractures in postmenopausal osteoporosis (PMOP) patients.MethodsRetrospective analysis of 2478 PMOP patients aged ≥ 50 years who attended the Shanghai General Hospital from January 2007 to December 2016, including 1239 patients with no fractures and 1239 patients with histories of fractures (1008 in the primary fracture group and 231 in the re-fracture group). All patients' basic clinical data, serum biochemical and bone metabolic markers, bone mineral density (BMD), and other indicators were recorded uniformly. Comparing the differences between the clinical characteristics of patients with primary and recurrent fractures, as well as the differences in the clinical characteristics of patients with primary and recurrent fractures in combination with different diseases, further analyses the risk factors for primary and recurrent fractures in PMOP patients. SPSS.26 was used for statistical analysis.ResultsCompared to the unfractured group, the fractured group was older and had lower height and bone mineral density (all P < 0.01), with the re-fractured group having lower BMD at each key site than the primary fracture group (all P < 0.01). Analysis of the combined disease subgroups showed that serum BGP levels were lower in the primary and re-fracture patients with diabetes than in the non-diabetic subgroup (P < 0.05), and serum CTX levels were lower in the re-fracture group with diabetes than in the primary fracture group with diabetes (P < 0.05). Patients with recurrent fractures with cardio-vascular diseases had lower BMD than the subgroup without cardio-vascular diseases (P < 0.05) and also had lower BMD than the group with primary fractures with cardio-vascular diseases (P < 0.05). Multiple logistic regression analysis showed that advanced age, overweight, low lumbar spine and total hip BMD were risk factors for primary and recurrent fractures; and comorbid chronic liver and kidney diseases were risk factors for primary fractures.ConclusionPMOP patients with advanced age, overweight, low bone mineral density, and comorbid chronic liver and kidney diseases are at greater risk of fractures and require early intervention to reduce fractures occurrence. Moreover, those who are elderly, overweight, and have low bone density should also be aware of the risk of re-fractures.

Association of the Bioimpedance Phase Angle and Quality of Life in Postmenopausal Osteoporosis

Objectives: Osteoporosis patients with fragility fractures and vertebral deformities have impaired quality of life (QOL). The phase angle, an index calculated from bioelectrical impedance analysis (BIA) measurements, has been reported to be related to clinical outcomes, mortality, and QOL in various diseases. We aimed to investigate the relationship between the phase angle and QOL in patients with postmenopausal osteoporosis. Methods: 81 female patients treated for postmenopausal osteoporosis from September 2019 to March 2020 underwent measurement of bone mineral density (BMD) by dual-energy X-ray absorptiometry, body composition by BIA, and QOL by the 36-item Short-Form Health Survey (SF-36). Results: The phase angle showed significant positive correlations with physical functioning (r = 0.270, p = 0.015) and physical component summary (PCS) (r = 0.251, p = 0.024) of the SF-36. The phase angle showed significant positive correlations with appendicular skeletal muscle mass index (ASMI) (r = 0.456, p < 0.001), lumbar spine BMD (r = 0.241, p = 0.030), and femoral neck BMD (r = 0.26, p = 0.021) and a significant negative correlation with age (r = −0.526, p < 0.001). Multiple regression analysis of the factors potentially associated with SF-36 PCS showed that the phase angle (r = 7.506, p = 0.012) was a significant contributor to PCS (R² = 0.184). Conclusion: The phase angle in postmenopausal osteoporotic patients was significantly related to QOL after adjusting for age, BMI, ASMI, and BMD. As the phase angle is a parameter that can be measured easily and noninvasively, it might be a useful aid for QOL assessment in osteoporotic patients.

Efficacy and safety of the biosimilar denosumab candidate (Arylia) compared to the reference product (Prolia®) in postmenopausal osteoporosis: a phase III, randomized, two-armed, double-blind, parallel, active-controlled, and noninferiority clinical trial

Background/objectiveOsteoporosis is a global health concern with an increasing prevalence worldwide. Denosumab is an antiresoptive agent that has been demonstrated to be effective and safe in osteoporotic patients. This study aimed to compare the efficacy and safety of the biosimilar denosumab candidate (Arylia) to the originator product (Prolia®) in postmenopausal osteoporotic patients.MethodsIn this randomized, double-blind, active-controlled, noninferiority trial, postmenopausal osteoporotic patients received 60 mg of subcutaneous Arylia or Prolia® at months 0, 6, and 12 and were followed up for 18 months. The primary endpoint was the noninferiority of the biosimilar product to the reference product in the percentage change of bone mineral density (BMD) in 18 months at the lumbar spine (L1-L4), total hip, and femoral neck. The secondary endpoints were safety assessment, the incidence of new vertebral fractures, and the trend of bone turnover markers (BTMs).ResultsA total of 190 patients were randomized to receive either biosimilar (n = 95) or reference (n = 95) denosumab. In the per-protocol (PP) analysis, the lower limits of the 95% two-sided confidence intervals of the difference between Arylia and Prolia® in increasing BMD were greater than the predetermined noninferiority margin of − 1.78 at the lumbar spine, total hip, and femoral neck sites (mean differences [95% CIs] of 0.39 [− 1.34 to 2.11], 0.04 [− 1.61 to 1.69], and 0.41 [− 1.58 to 2.40], respectively). The two products were also comparable in terms of safety, new vertebral fractures, and trend of BTMs.ConclusionThe efficacy of the biosimilar denosumab was shown to be noninferior to that of the reference denosumab, with a comparable safety profile at 18 months.Trial registrationClinicalTrials.gov, NCT03293108; Registration date: 2017–09-19.

Medication possession ratio in postmenopausal osteoporotic patients: a cross sectional study

Medication possession ratio in postmenopausal osteoporotic patients: a cross sectional study

Efficacy and Safety of Oral Ibandronate versus Intravenous Zoledronic Acid on Bone Metabolism and Bone Mineral Density in Postmenopausal Japanese Women with Osteoporosis.

There are no published clinical reports comparing ibandronate (IBN) treatment and zoledronic acid (ZOL) treatment in Japanese postmenopausal osteoporotic patients. This investigation therefore compared the efficacy and safety of the drugs on improving bone metabolism and bone mineral density (BMD) in Japanese postmenopausal women with primary osteoporosis. Eighty-two treatment-naïve primary osteoporotic female patients were randomly divided into IBN-treated or ZOL-treated groups. Bone turnover markers and BMD were examined immediately prior to treatment (baseline) and at 6, 12, 18, 24, and 30 months of therapy. Compared with baseline levels, the values of type 1 procollagen N-terminal propeptide, bone-specific alkaline phosphatase (BAP), urinary type-I collagen amino-terminal telopeptide (NTX), and tartrate-resistant acid phosphatase 5b were all significantly decreased at every time point in both groups apart from BAP at 30 months in the ZOL group, urinary NTX at 12 months in the ZOL group and at 24 and 30 months in both groups. Lumbar BMD values were significantly increased at 6, 12, 18, and 24 months in the IBN group and at 6 and 12 months in the ZOL group compared with pre-treatment levels. Hip BMD values were also significantly increased at 6, 12, 18, and 24 months in the IBN group and at 6, 12, and 18 months in the ZOL group compared with baseline values. The percentage changes of hip BMD at 18 and 24 months in the ZOL group were significantly higher than those in the IBN group (both p < 0.05). No remarkable adverse events were noted in either group. In conclusion, both IBN and ZOL significantly and safely improved bone turnover markers and BMD during 30 months of treatment in Japanese osteoporosis patients. The ZOL group tended to exhibit greater gains in BMD as compared with the IBN group, which merits further investigation.

Treatment of osteoporosis with teriparatide: The Slovenian experience.

The aim of this study was to investigate the characteristics of postmenopausal women prescribed with teriparatide in Slovenia, during the first decade after its approval, and the predictors of bone mineral density (BMD) improvement with treatment. We retrospectively studied postmenopausal osteoporotic patients prescribed with teriparatide at tertiary center from 2006 to 2015. BMD was measured at standard sites by DXA at baseline, after 12 and 24 months. 25-hydroxyvitamin D and procollagen type I N-terminal propeptide (PINP) were measured at the same time-points. The inclusion criteria were met by 188 women (aged 71 years on average), 151 (80.3%) with postmenopausal and 37 (19.7%) with glucocorticoid-induced osteoporosis. Everyone had at least one fracture, 159 (84.6%) had ≥2 fractures, with vertebral fractures in 172 patients (91.5%). All patients had been previously on antiresorptives for 8.6 years on average. The average BMD change at lumbar spine, total hip, and femoral neck was +5.0%, −1.1%, and +0.3% after 24 months of treatment, respectively. Higher baseline PINP was associated with higher BMD increase at all sites after the first 12 months. Teriparatide was prescribed mostly to elderly women with severe osteoporosis who had sustained two or more fractures despite long-term antiresorptive therapy. Baseline PINP might predict initial BMD increase with teriparatide.

Relation between Circulating Vitamin k2 level and Osteoporosis in Post-Menopausal Women

Abstract Objective We aimed to measure the serum level of vitamin k2 in postmenopausal osteoporotic patients to determine its role in the disease. Patients and Methods Our study was designed as a cross sectional study, with 15 postmenopausal osteoporotic patients (with reduced bone mineral density BMD), aged between 54-58 years old compared to 15 healthy controls (with normal BMD at all of lumbar spine, femoral neck and hip) matched in age with the patients. All participants were subjected to full medical history taking, physical examination and functional assessment of the activity of daily livings (ADL). Biochemical assays of thyroid stimulating hormone, parathyroid hormone, total calcium, phosphorus, alkaline phosphatase (ALP), 25-hydroxyvitamin D (25 (OH) D), erythrocyte sedimentation rate, Kidney and liver function tests and serum levels of vitamin k2 were performed. Results The patients showed highly significantly lower vitamin k2 levels (P &amp;lt; 0.05) and non-significant correlations between vitamin k2 and the activity of daily living (ADL) nor the other laboratory assessment parameters (P &amp;gt; 0.05) among the patient’s group. Conclusion Vitamin K deficiency is highly prevalent in the majority of our patients and should be considered an associating factor in the etiology of postmenopausal osteoporosis. Vitamin k2 deficiency could result in a decrease in the bone mineral density in postmenopausal women, so vitamin k2 levels should be checked in post-menopausal osteoporosis and any deficiency must be treated and corrected to improve the bone mineral density.

Effects of removable dental prostheses on mandibular bone density in postmenopausal osteoporotic patients

Aim: To investigate the effects of removable dental prostheses on mandibular bone density in postmenopausal osteoporotic patients.&#x0D; Methodology: The prospective study included 30 female patients aged 45–70 years who had been previously diagnosed with postmenopausal osteoporosis. The patients had no diseases affecting bone metabolism. The patients were divided into two groups: (i) patients who were using removable dental prostheses (n=15) and (ii) patients who were not using removable dental prostheses (n=15) (the control group). A whole-body dual energy x-ray absorptiometry (DXA) scan was performed to calculate the mandibular bone densities of the patients.&#x0D; Results: The use of removable mandibular prostheses did not cause a significant change in mandibular bone density.&#x0D; Conclusion: The fact that removable mandibular prostheses did not cause a significant change in mandibular bone density could be because the patients started using the removable prostheses long after they lost their teeth.&#x0D; &#x0D; How to cite this article: Akın Tartuk G, Kaya S. The effect of different final irrigation solutions on apical impermeability. Int Dent Res 2021;11(Suppl.1):201-5. https://doi.org/10.5577/intdentres.2021.vol11.suppl1.28&#x0D; &#x0D; Linguistic Revision: The English in this manuscript has been checked by at least two professional editors, both native speakers of English.

The Effect of Yoga Asana "Vrksasana (Tree Pose)" on Balance in Patients With Postmenopausal Osteoporosis: A Randomized Controlled Trial.

In this study, the effect of the add-on effect of the Tree Pose (Vrksasana) on the balance of patients with postmenopausal osteoporosis was investigated. Thirty-two patients with postmenopausal osteoporosis were randomly assigned to conservative exercise group (30 mins/d for 12 wks) or Tree Pose-added exercise group (30-min conventional exercise + 2-min Tree Pose/d for 12 wks) by Microsoft Excel randomization option. The balance of the patients was evaluated with Berg Balance Scale, Timed Up and Go Test, single-leg standing test, tandem walk test, tandem stance test, and Korebalance static&dynamic balance tests at baseline, sixth week, and third month of the exercise program. There was no statistically significant difference on baseline data between groups. There was a statistically significant difference between the two groups in the sixth-week measurement of single-leg stance (P < 0.05). In the Berg Balance Scale, static balance test, dynamic balance test, and tandem walk test, a statistically significant difference was found among baseline, sixth-week, and 12th week measurements in both the exercise group and the Tree Pose-added exercise group. Gains in the static and dynamic balance of postmenopausal osteoporotic patients can be obtained by adding "Vrksasana" to conventional exercises.

Bisphosphonates impair the onset of bone formation at remodeling sites.

Bisphosphonates are widely used anti-osteoporotic drugs targeting osteoclasts. They strongly inhibit bone resorption, but also strongly reduce bone formation. This reduced formation is commonly ascribed to the mechanism maintaining the resorption/formation balance during remodeling. The present study provides evidence for an additional mechanism where bisphosphonates actually impair the onset of bone formation after resorption. The evidence is based on morphometric parameters recently developed to assess the activities reversing resorption to formation. Herein, we compare these parameters in cancellous bone of alendronate- and placebo-treated postmenopausal osteoporotic patients. Alendronate increases the prevalence of eroded surfaces characterized by reversal cells/osteoprogenitors at low cell density and remote from active bone surfaces. This indicates deficient cell expansion on eroded surfaces - an event that is indispensable to start formation. Furthermore, alendronate decreases the coverage of these eroded surfaces by remodeling compartment canopies, a putative source of reversal cells/osteoprogenitors. Finally, alendronate strongly decreases the activation frequency of bone formation, and decreases more the formative compared to the eroded surfaces. All these parameters correlate with each other. These observations lead to a model where bisphosphonates hamper the osteoprogenitor recruitment required to initiate bone formation. This effect results in a larger eroded surface, thereby explaining the well-known paradox that bisphosphonates strongly inhibit bone resorption without strongly decreasing eroded surfaces. The possible mechanism for hampered osteoprogenitor recruitment is discussed: bisphosphonates may decrease the release of osteogenic factors by the osteoclasts, and/or bisphosphonates released by osteoclasts may act directly on neighboring osteoprogenitor cells as reported in preclinical studies.

PiRNA-63049 inhibits bone formation through Wnt/β-catenin signaling pathway

Bone remodeling is a dynamic process between bone formation mediated by osteoblasts and bone resorption mediated by osteoclasts. Disrupted bone remodeling is a key factor in postmenopausal osteoporosis, a metabolic disorder characterized by deteriorated bone microarchitecture and increased risk of fracture. Recent studies have shown that piwi-binding RNA (piRNA) is involved in the pathogenesis of certain diseases at the post-transcriptional level. Here, we analyzed piRNA-63049 (piR-63049), which may play an essential role in bone remodeling. The expression of piR-63049 significantly increased in both bone tissues and plasma of osteoporotic rats and postmenopausal osteoporotic patients. Overexpressing piR-63049 could inhibit the osteoblastogenesis of bone marrow stromal cells (BMSCs) while knocking down piR-63049 could promote the osteoblastogenesis of BMSCs through the Wnt2b/β-catenin signaling pathway. Moreover, knocking-down piR-63049 (piR-63049-antagonist) in vivo could attenuate the bone loss in ovariectomized rats by promoting bone formation. Taken together, the current study shows that piR-63049 inhibits bone formation through the Wnt2b/β-catenin signaling pathway. This novel piRNA may be a potential target to increase bone formation in bone loss disorders such as postmenopausal osteoporosis.

Mast Cells Trigger Disturbed Bone Healing in Osteoporotic Mice.

Mast cells are important tissue-resident sensor and effector immune cells but also play a major role in osteoporosis development. Mast cells are increased in numbers in the bone marrow of postmenopausal osteoporotic patients, and mast cell-deficient mice are protected from ovariectomy (OVX)-induced bone loss. In this study, we showed that mast cell-deficient Mcpt5-Cre R-DTA mice were protected from OVX-induced disturbed fracture healing, indicating a critical role for mast cells in the pathomechanisms of impaired bone repair under estrogen-deficient conditions. We revealed that mast cells trigger the fracture-induced inflammatory response by releasing inflammatory mediators, including interleukin-6, midkine (Mdk), and C-X-C motif chemokine ligand 10 (CXCL10), and promote neutrophil infiltration into the fracture site in OVX mice. Furthermore, mast cells were responsible for reduced osteoblast and increased osteoclast activities in OVX mice callus, as well as increased receptor activator of NF-κB ligand serum levels in OVX mice. Additional in vitro studies with human cells showed that mast cells stimulate osteoclastogenesis by releasing the osteoclastogenic mediators Mdk and CXCL10 in an estrogen-dependent manner, which was mediated via the estrogen receptor alpha on mast cells. In conclusion, mast cells negatively affect the healing of bone fractures under estrogen-deficient conditions. Hence, targeting mast cells might provide a therapeutic strategy to improve disturbed bone repair in postmenopausal osteoporosis. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

The efficacy of teriparatide on lumbar spine bone mineral density, vertebral fracture incidence and pain in post-menopausal osteoporotic patients: A systematic review and meta-analysis

ObjectiveTeriparatide has been increasingly utilized in the management of osteoporosis. The efficacy of low and high dose teriparatide on lumbar spine bone mineral density, vertebral fracture incidence and pain is unknown. We sought to determine the efficacy of teriparatide on these patient-important outcomes using a systematic review and meta-analysis. MethodsA systematic search of electronic databases (MEDLINE, EMBASE, CENTRAL, CINAHL) was performed to identify randomized controlled trials (RCTs) that evaluate teriparatide to any comparator for the treatment of osteoporosis in postmenopausal women. The Grades of Recommendation Assessment, Development and Evaluation (GRADE) criteria were used by two independent reviewers to assess the strength and quality of evidence. ResultsA total of 20 studies (n = 6024) were included in this review, with 2855 patients receiving teriparatide and 3169 patients receiving placebo or control treatment. A teriparatide dose of 20 μg/day increased lumbar spine bone mineral density (BMD) (standardized mean difference (SMD) 0.34 standard deviation (SD) units higher (95% CI 0.19–0.48 SDs higher) in comparison to placebo. Relative to anti-resorptive agents, 20 μg/day of teriparatide had a range from 0.14 SD units to 0.96 SD units higher (95% CI, 0.08 SDs lower to 0.36 SDs higher, CI, 0.33–1.59 SDs higher, respectively). 20 μg/day teriparatide had a significant effect on pain severity to placebo or control (SMD 0.80, 95% CI, 1.16–0.43 SDs lower) and also decreased the incidence of vertebral fractures compared to placebo (relative risk 0.31, 95% CI 0.21 to 0.46). Arthralgia and extremity pain incidence were also calculated; there were 15 and 8 fewer events per 1000 patients with the use of 20 μg/day of teriparatide compared to placebo or control, respectively. ConclusionHigh quality evidence supports the utilization of teriparatide 20 μg/day dose to significantly improve lumbar spine BMD and decrease incidence of vertebral fractures and pain severity relative to all comparators. 40 μg/day dose of teriparatide demonstrated significantly better results with prolonged treatment. This data is valuable for clinicians involved in the care of this growing demographic of patients. Further investigation on the safety and efficacy of teriparatide in higher doses for the long-term treatment of osteoporosis in postmenopausal women should be conducted through high-quality clinical trials.