Determination of the Combined Effects of Asian Herbal Medicine with Calcium and/or Vitamin D Supplements on Bone Mineral Density in Primary Osteoporosis: A Systematic Review and Meta-Analysis.

Our review of 52 RCTs from 5 databases suggests a tendency for notable improvement in BMD when combining herbal medicine with supplements (calcium and vitamin D variants) compared to supplement monotherapy in primary osteoporosis. However, caution is needed in interpreting results due to substantial heterogeneity among included studies. PURPOSE: To conduct a systematic review and meta-analysis to determine whether herbal medicine (HM) plus supplements such as calcium (Ca) or vitamin D (Vit.D) improves bone mineral density (BMD) compared to supplements alone in primary osteoporosis (OP) patients. METHODS: We searched 5 databases for randomized controlled trials (RCTs) using HMs with supplements (Ca or Vit.D variants) as interventions for primary OP patients published until August 31, 2022. Meta-analysis using BMD score as the primary outcome was performed using RevMan 5.4 version. Risk of bias in the included studies was assessed useing RoB 2.0 tool. RESULTS: In total, 52 RCTs involving 4,889 participants (1,408 men, 3,481 women) were included, with average BMD scores of 0.690 ± 0.095 g/cm2 (lumbar) and 0.625 ± 0.090 g/cm2 (femoral neck). As a result of performing meta-analysis using BMD scores for all 52 RCTs included in this review, combination of HMs with Ca and Vit.D variants improved the BMD score by 0.08 g/cm2 (lumbar, 38 RCTs, 95% CI: 0.06-0.10, p < 0.001, I2 = 97%) and 0.06 g/cm2 (femoral neck, 19 RCTs, 95% CI: 0.04-0.08, p < 0.001, I2 = 92%)compared to controls. However, statistical significance of the lumbar BMD improvement disappeared after adjusting for potential publication bias. CONCLUSION: Our data suggest that combining of HM and supplements tends to be more effective in improving BMD in primary OP than supplements alone. However, caution is needed in interpretation due to the reporting bias and high heterogeneity among studies, and well-designed RCTs are required in the future.

Endoplasmic reticulum protein of 57 kDa sulfhydration promotes intestinal calcium absorption to attenuate primary osteoporosis.

Endogenous hydrogen sulfide (H2S) plays an important role in bone metabolism. However, the exact role of H2S in intestinal calcium and phosphorus absorption and its potential in preventing and treating primary osteoporosis remains unknown. Therefore, this study aimed to investigate the potential of H2S in promoting intestinal calcium and phosphorus absorption and alleviating primary osteoporosis. We measured the apparent absorptivity of calcium, femoral bone density, expression and sulfhydration of the duodenal endoplasmic reticulum protein of 57 kDa (ERp57), duodenal cystathionine γ-lyase (CSE) expression, and serum H2S content in adult and old CSE-knockout and wild-type mice. We also assessed intracellular reactive oxygen species (ROS) and Ca2+ content in CSE-overexpressing or knockout intestinal epithelial cell (IEC)-6 cells. In senile mice, CSE knockout decreased endogenous H2S, ERp57 sulfhydration, and intestinal calcium absorption and worsened osteoporosis, which were partially reversed by GYY4137, an H2S donor. CSE overexpression in IEC-6 cells increased ERp57 sulfhydration, protein kinase A and C activity, and intracellular Ca2+, whereas CSE knockout exerted the opposite effects. Furthermore, hydrogen peroxide (H2O2) stimulation had similar effects as in CSE knockout, which were reversed by pretreatment with sodium hydrosulfide before H2O2 stimulation and restored by DL-dithiothreitol. These findings suggest that H2S attenuates primary osteoporosis by preventing ROS-induced ERp57 damage in intestinal epithelial cells by enhancing ERp57 activity and promoting intestinal calcium absorption, thereby aiding in developing therapeutic interventions to prevent osteoporosis.

Prevalence rate of primary osteoporosis in China: a meta-analysis.

BACKGROUND: Primary osteoporosis (POP) is recognized as a "silent disease" and often ignored. This meta-analysis aimed to determine the prevalence of POP in the Chinese population over the past 20 years to raise awareness of the disease's epidemiology, which is hoped to help prevent and treat the condition better. METHODS: Eight English and three Chinese language databases were searched systematically from January 2002 to December 2023. Relevant data were analysed using Stata 16.0. Meta-regression and subgroup analyses were performed to explore causes of heterogeneity. A funnel plot was further drawn in combination with Egger and Begg tests to determine publication bias. RESULTS: A total of 45 studies (241,813 participants) were included. The meta-analysis revealed that the overall prevalence of POP in the Chinese population was 18.2% (95% CI: 14.7-21.7%), showing a positive correlation with age. Specifically, prevalence rates were 23.4% (18.3-28.5%) in women and 11.5% (9.1-13.9%) in men. A notable increase was observed within the span of 20 years (16.9% before 2010 and 20.3% in 2011-2020). Notably, regional variations were observed, with southern China reporting a lower prevalence of 16.4% compared to 20.2% in northern China. Meta-regression suggested that sample size significantly influenced the estimation of point prevalence (P = 0.037). CONCLUSIONS: Over the past two decades, there has been an increase in the prevalence of POP within the Chinese population. The growing prevalence of older individuals and women further highlights the urgency for tailored disease prevention and control measures.

ER-ß accelerates the process of primary osteoporosis by promoting VEGFA-mediated apoptosis of osteoblasts.

Primary osteoporosis (POP) is a widespread and severe disorder of bone metabolism characterized by reduced bone mass and destruction of bone structure, frequently inducing fracture risk and imposing a heavy economic burden on public life. The development of POP partially revolves around the estrogen receptor ß (ER-ß), one of the major mediator receptors of estrogen that influences apoptosis in a range of cells. We performed KEGG and GO analysis by mining the transcriptomic dataset of POP samples showing significant enrichment of differentially expressed genes (DEGs) in multiple apoptosis-related pathways. The results of the Spearman correlation analysis and Protein-Protein Interaction (PPI) Networks screening of hub genes indicated that vascular endothelial growth factor A (VEGFA) may be a key target of ER-ß in controlling osteoblast apoptosis. Further, we carried out high-throughput sequencing of ESR2-silenced MC3T3-E1 cells and noticed a substantial suppression in VEGFA expression and all apoptosis-related pathways. In addition, we determined the cell cycle and apoptosis by constructing a VEGFA-silenced cell model utilizing flow cytometry (FCM), and the results showed that ER-ß could regulate the osteoblast cycle and thus promote osteoblast apoptosis by promoting VEGFA expression. And Western blot results showed that apoptosis was most likely realized through the regulation of downstream apoptosis markers c-JUN (c-Jun N-terminal kinase, JNK) and GADD45G (Growth Arrest and DNA Damage-Inducible Protein 45 gamma). The effects of ESR2 and VEGFA on the proliferation of osteoblasts were lastly assessed using the cell counting kit- 8 (CCK-8) assay. In conclusion, this study identifies that the roles of ER-ß in the regulation of osteoblast apoptosis are closely related to VEGFA and provides a new target for POP treatment.

Prevalence and influencing factors of kinesiophobia in older patients with primary osteoporosis: A cross-sectional survey.

AIM: To explore the prevalence of kinesiophobia in older patients with primary osteoporosis and analyze its influencing factors. METHODS: A cross-sectional survey was conducted among 221 older patients with primary osteoporosis in a general hospital in Kunming, China. Data were collected through a sociodemographic-clinical questionnaire, Tampa Scale for Kinesiophobia-11 (TSK-11), Global Pain Scale (GPS), Five Facets Mindfulness Questionnaire-Short Form (FFMQ-SF), and Hospital Anxiety and Depression Scale (HADS). SPSS 27.0 software was utilized for univariate and binary logistic regression analyses. RESULTS: The findings revealed that the prevalence of kinesiophobia in this study was 57.01 %. Age, history of fractures, chronic obstructive pulmonary disease (COPD), lumbar disc herniation, chronic pain, mindfulness, anxiety, and depression were identified as significant influencing factors of kinesiophobia in the binary logistic regression analyses. CONCLUSION: Healthcare professionals should be attentive to occurrence of kinesiophobia. Timely measures should be implemented to improve pain, anxiety and depression, and employ mindfulness interventions to mitigate kinesiophobia.

Regular sling core stabilization training improves bone density based on calcium and vitamin D supplementation.

BACKGROUND: Primary osteoporosis refers to a disease of aging characterized by reduced bone mass, damage to bone tissue microarchitecture, and predisposition to fracture.Sling core stabilization training emphasizes activating the deep local muscles of the spine under unstable conditions, and enhancing the body's balance and control during exercise. CASE PRESENTATION: A 70-year-old female went to the Acupuncture and Rehabilitation Department due to low back pain caused by osteoporosis.The patient received sling core stabilization training three times a week based on Calcium and Vitamin D Supplementation. After training, the patient's back pain was significantly relieved and insisted one year. In the physical examination of bone mineral density, the results showed that the value of bone mineral density was better than last year.The patients adhered to sling core stabilization training and observed the changes of bone mineral density every year basis on calcium and vitamin D supplementation. DISCUSSION: However, cases of calcium and vitamin D supplementation-based regular sling core stabilization training that improves bone density in osteoporosis patients have been rarely reported. Our group shared cases and analyzed possible mechanisms, hoping to provide reference for the prevention and treatment of primary osteoporosis.

[Systematic review and Meta-analysis of Gusongbao preparation in treatment of primary osteoporosis].

This study aims to provide evidence for clinical practice by systematically reviewing the efficacy and safety of Gusongbao preparation in the treatment of primary osteoporosis(POP). The relevant papers were retrieved from four Chinese academic journal databases and four English academic journal databases(from inception to May 31, 2022). The randomized controlled trial(RCT) of Gusongbao preparation in the treatment of POP was included after screening according to the inclusion and exclusion criteria. The quality of articles was evaluated using risk assessment tools, and the extracted data were subjected to Meta-analysis in RevMan 5.3. A total of 657 articles were retrieved, in which 15 articles were included in this study, which involved 16 RCTs. A total of 3 292 patients(1 071 in the observation group and 2 221 in the control group) were included in this study. In the treatment of POP, Gusongbao preparation+conventional treatment was superior to conventional treatment alone in terms of increasing lumbar spine(L2-L4) bone mineral density(MD=0.03, 95%CI[0.02, 0.04], P<0.000 01) and femoral neck bone mineral density, reducing low back pain(MD=-1.69, 95%CI[-2.46,-0.92], P<0.000 1) and improving clinical efficacy(RR=1.36, 95%CI[1.21, 1.53], P<0.000 01). Gusongbao preparation was comparable to similar Chinese patent medicines in terms of improving clinical efficacy(RR=0.95, 95%CI[0.86, 1.04], P=0.23). Gusongbao preparation was inferior to similar Chinese patent medicines in reducing traditional Chinese medicine syndrome scores(MD=1.08, 95%CI[0.44, 1.71], P=0.000 9) and improving Chinese medicine syndrome efficacy(RR=0.89, 95%CI[0.83, 0.95], P=0.000 4). The incidence of adverse reactions of Gusongbao preparation alone or combined with conventio-nal treatment was comparable to that of similar Chinese patent medicines(RR=0.98, 95%CI[0.57, 1.69], P=0.94) or conventio-nal treatment(RR=0.73, 95%CI[0.38, 1.42], P=0.35), and the adverse reactions were mainly gastrointestinal discomforts. According to the available data, Gusongbao preparation combined with conventional treatment is more effective than conventional treatment alone in increasing lumbar spine(L2-L4) bone mineral density and femoral neck bone mineral density, reducing low back pain, and improving clinical efficacy. The adverse reactions of Gusongbao preparation were mainly gastrointestinal discomforts, which were mild.

Osteoporosis in children and adolescents: when to suspect and how to diagnose it.

Early recognition of osteoporosis in children and adolescents is important in order to establish an appropriate diagnosis of the underlying condition and to initiate treatment if necessary. In this review, we present the diagnostic work-up, and its pitfalls, of pediatric patients suspected of osteoporosis including a careful collection of the medical and personal history, a complete physical examination, biochemical data, molecular genetics, and imaging techniques. The most recent and relevant literature has been reviewed to offer a broad overview on the topic. Genetic and acquired pediatric bone disorders are relatively common and cause substantial morbidity. In recent years, there has been significant progress in the understanding of the genetic and molecular mechanistic basis of bone fragility and in the identification of acquired causes of osteoporosis in children. Specifically, drugs that can negatively impact bone health (e.g. steroids) and immobilization related to acute and chronic diseases (e.g. Duchenne muscular dystrophy) represent major risk factors for the development of secondary osteoporosis and therefore an indication to screen for bone mineral density and vertebral fractures. Long-term studies in children chronically treated with steroids have resulted in the development of systematic approaches to diagnose and manage pediatric osteoporosis. CONCLUSIONS: Osteoporosis in children requires consultation with and/or referral to a pediatric bone specialist. This is particularly relevant since children possess the unique ability for spontaneous and medication-assisted recovery, including reshaping of vertebral fractures. As such, pediatricians have an opportunity to improve bone mass accrual and musculoskeletal health in osteoporotic children. WHAT IS KNOWN: • Both genetic and acquired pediatric disorders can compromise bone health and predispose to fractures early in life. • The identification of children at risk of osteoporosis is essential to make a timely diagnosis and start the treatment, if necessary. WHAT IS NEW: • Pediatricians have an opportunity to improve bone mass accrual and musculoskeletal health in osteoporotic children and children at risk of osteoporosis. • We offer an extensive but concise overview about the risk factors for osteoporosis and the diagnostic work-up (and its pitfalls) of pediatric patients suspected of osteoporosis.

Risk of primary osteoporosis score (RPOPs): an algorithm model for primary osteoporosis risk assessment in grass-roots hospital.

BACKGROUND: This study aimed to develop and validate a lasso regression algorithm model which was established by correlation factors of bone mineral density (BMD) and could be accurately predicted a high-risk population of primary osteoporosis (POP). It provides a rapid, economical and acceptable early screening method for osteoporosis in grass-roots hospitals. METHODS: We collected 120 subjects from primary osteoporosis screening population in Zhejiang Quhua Hospital between May 2021 and November 2021 who were divided into three groups (normal, osteopenia and osteoporosis) according to the BMD T-score. The levels of three micro-RNAs in the plasma of these people were detected and assessed by qRT-PCR. At the same time, the levels of ß-CTX and t-P1NP in serum of the three groups were determined. Based on the cluster random sampling method, 84 subjects (84/120, 70%) were selected as the training set and the rest were the test set. Lasso regression was used to screen characteristic variables and establish an algorithm model to evaluate the population at high risk of POP which was evaluated and tested in an independent test cohort. The feature variable screening process was used 10-fold cross validation to find the optimal lambda. RESULTS: The osteoporosis risk score was established in the training set: Risk of primary osteoporosis score (RPOPs) = -0.1497785 + 2.52Age - 0.19miR21 + 0.35miR182 + 0.17ß-CTx. The sensitivity, precision and accuracy of RPOPs in an independent test cohort were 79.17%, 82.61% and 75%, respectively. The AUC in the test set was 0.80. Some risk factors have a significant impact on the abnormal bone mass of the subjects. These risk factors were female (p = 0.00013), older than 55 (p < 2.2e-16) and BMI < 24 (p = 0.0091) who should pay more attention to their bone health. CONCLUSION: In this study, we successfully constructed and validated an early screening model of osteoporosis that is able to recognize people at high risk for developing osteoporosis and remind them to take preventive measures. But it is necessary to conduct further external and prospective validation research in large sample size for RPOPs prediction models.

Effect of bisphosphonates or teriparatide on mechanical complications after posterior instrumented fusion for osteoporotic vertebral fracture: a multi-center retrospective study.

BACKGROUND: The optimal treatment of osteoporosis after reconstruction surgery for osteoporotic vertebral fractures (OVF) remains unclear. In this multicentre retrospective study, we investigated the effects of typically used agents for osteoporosis, namely, bisphosphonates (BP) and teriparatide (TP), on surgical results in patients with osteoporotic vertebral fractures. METHODS: Retrospectively registered data were collected from 27 universities and affiliated hospitals in Japan. We compared the effects of BP vs TP on postoperative mechanical complication rates, implant-related reoperation rates, and clinical outcomes in patients who underwent posterior instrumented fusion for OVF. Data were analysed according to whether the osteoporosis was primary or glucocorticoid-induced. RESULTS: A total of 159 patients who underwent posterior instrumented fusion for OVF were included. The overall mechanical complication rate was significantly lower in the TP group than in the BP group (BP vs TP: 73.1% vs 58.2%, p = 0.045). The screw backout rate was significantly lower and the rates of new vertebral fractures and pseudoarthrosis tended to be lower in the TP group than in the BP group. However, there were no significant differences in lumbar functional scores and visual analogue scale pain scores or in implant-related reoperation rates between the two groups. The incidence of pseudoarthrosis was significantly higher in patients with glucocorticoid-induced osteoporosis (GIOP) than in those with primary osteoporosis; however, the pseudoarthrosis rate was reduced by using TP. The use of TP also tended to reduce the overall mechanical complication rate in both primary osteoporosis and GIOP. CONCLUSIONS: The overall mechanical complication rate was lower in patients who received TP than in those who received a BP postoperatively, regardless of type of osteoporosis. The incidence of pseudoarthrosis was significantly higher in patients with GIOP, but the use of TP reduced the rate of pseudoarthrosis in GIOP patients. The use of TP was effective to reduce postoperative complications for OVF patients treated with posterior fusion.

The systemic bone protective effects of Gushukang granules in ovariectomized mice by inhibiting osteoclastogenesis and stimulating osteoblastogenesis.

Primary osteoporosis (POP), which is caused by unbalanced bone remodeling, leads to significant economic and societal burdens globally. Gushukang (GSK) granule serves as one commonly used prescription for POP in Traditional Chinese Medicine (TCM). The present study aimed to clarify the exact roles of GSK in bone remodeling with in vivo and in vitro assays. Here we showed that GSK prevented bone loss and the alternations of osteoporotic bone parameters as well as the decreased density of osteoclast in ovariectomized (OVX) mice. GSK inhibited receptor activator for nuclear factor-κ B Ligand (RANKL)-activated osteoclastogenesis in bone marrow macrophages (BMMs). At the molecular levels, GSK inhibited the expression of nuclear factor of activated T cells cytoplasm 1(NFATc1) and c-Fos, two master regulators of osteoclastogenesis. GSK also inhibited bone resorbed genetic expression of matrix metalloproteinase 9 (MMP9), cathepsin K (Ctsk), TRAP and carbonic anhydrase II (Car2). Meanwhile, GSK stimulated osteoblastogenesis from bone primary mesenchymal stem cells (MSCs) and enhanced the expression of Osteirx, and Runx2. GSK also stimulated the expression of Col-1, Osteocalcein and alkaline phosphatase (ALP). Our investigation established the systemic bone protective effects of GSK by suppressing osteoclastogenesis and stimulating osteoblastogenesis and laid bases for new drugs discovery in treating POP.

Influence of DNA methylation on the expression of OPG/RANKL in primary osteoporosis.

Purpose: A key factor in regulating bone absorption is the proportion of RANKL/OPG. Although many reports showing diverse transcription factors or epigenetic modification could be responsible for regulating RANKL&OPG ratio, there is still little exploration on promoter methylation status of both genes in osteoporotic bone tissues. Our aim is to investigate the changes of methylation in CpG island of these genes' promoters in patients with primary osteoporosis. Methods: The diagnosis of osteoporosis was based on the results of dual energy X-ray absorptiometry measurements. All femoral bone tissues were separated in surgeries. After extracting total RNA, we checked the relative expression levels of OPG and RANKL by quantitative real time PCR. The genomic DNA of Non-OPF (Non-osteoporotic fracture bone tissues) & OPF (osteoporotic fracture bone tissues) were treated by bisulfite modification, and methylation status of CpG sites in the CpG island of OPG/RANKL promoters were determined by DNA sequencing. Results: RANKL expression in the OPF group was significantly higher than that in Non-OPF group, and the CpG methylation status in RANKL gene promoter was significantly lower. However, for OPG, lower gene expression level and higher methylation degree were found in the OPF group. Conclusion: Our study demonstrated that DNA methylation influenced the transcriptional expression of OPG and RANKL, which probably take on a "main switch" role in pathogenesis of primary osteoporosis.

The effects of switching daily teriparatide to oral bisphosphonates or denosumab in patients with primary osteoporosis.

The aim of this 12-month, observational study was to compare the effects of switching daily teriparatide (TPTD) to oral bisphosphonates (BP) therapy or denosumab (DMAb) therapy in patients with primary osteoporosis. Patients [n = 78; 71 postmenopausal women and seven men; mean age 76.3 (64-94) years; mean duration of prior daily TPTD therapy 20.1 (6-24) months] were allocated to either the (1) "switch-to-BP" group [n = 36; weekly alendronate 35 mg (n = 19), weekly risedronate 17.5 mg (n = 12), monthly minodronate 50 mg (n = 5)]; or (2) "switch-to-DMAb" group (n = 42; 60 mg sc every 6 months) based on each physicians' decision. Changes in bone mineral density (BMD) and serum bone turnover markers were monitored every 6 months. No significant difference was observed in baseline clinical characteristics between the groups. After 12 months, the increase in BMD was significantly greater in the switch-to-DMAb group compared to the switch-to-BP group: lumbar spine (6.2 vs. 2.6 %; P < 0.01), total hip (4.2 vs. 1.1 %; P < 0.05), and femoral neck (3.5 vs. 1.4 %; P < 0.05). In addition, the patients in the switch-to-DMAb group showed a significant decrease compared to those in the switch-to-BP group in TRACP-5b (-55.8 vs. -32.8 %; P < 0.01) and ucOC (-85.5 vs. -65.0 %; P < 0.001), while no significant difference was observed in PINP (-67.5 vs. -62.1 %). Switching daily TPTD to DMAb significantly increased BMD and decreased bone resorption marker compared to switching to oral BP at 12 months, and thus may provide an effective sequential treatment option after daily TPTD treatment.

Recent Discoveries in Monogenic Disorders of Childhood Bone Fragility.

PURPOSE OF REVIEW: This review summarizes our current knowledge on primary osteoporosis in children with focus on recent genetic findings. RECENT FINDINGS: Advances in genetic research, particularly next-generation sequencing, have found several genetic loci that associate with monogenic forms of inherited osteoporosis, widening the scope of primary osteoporosis beyond classical osteogenesis imperfecta. New forms of primary osteoporosis, such as those related to WNT1, PLS3, and XYLT2, have identified defects outside the extracellular matrix components and collagen-related pathways, in intracellular cascades directly affecting bone cell function. Primary osteoporosis can lead to severe skeletal morbidity, including abnormal longitudinal growth, compromised bone mass gain, and noticeable fracture tendency beginning at childhood. Early diagnosis and timely care are warranted to ensure the best achievable bone health. Future research will most likely broaden the spectrum of primary osteoporosis, hopefully provide more insight into the genetics governing bone health, and offer new targets for treatment.

Qianggu capsule for the treatment of primary osteoporosis: evidence from a Chinese patent medicine.

BACKGROUND: Qianggu Capsule, a Chinese patent medicine, has been widely applied in the clinical practice of primary osteoporosis (POP) in recent years. This study aims to summarize the effectiveness and safety of Qianggu Capsule in treating POP. METHODS: We searched seven electronic databases, all searches ended in 30 September, 2015. All randomised controlled trials comparing the efficacy of Qianggu Capsule treatment with no treatment, placebo or conventional therapy for POP were included. Combined therapies of Qianggu Capsule were also included. Cochrane risk of bias tool was used to assess methodological quality of primary studies. Revman 5.2.0 software was used for data analysis. RESULTS: Ten trials were enrolled. The combined effect showed that Qianggu Capsule plus Caltrate D was better than Caltrate D on lumbar spine bone mineral density (BMD) (MD = 0.05 g/cm2; 95% CI: 0.02-0.07; P = 0.0004), femoral neck BMD (MD = 0.03 g/cm2; 95% CI: 0.01-0.05; P = 0.001), femoral great trochanter BMD (MD = 0.04 g/cm2; 95% CI: 0.03-0.06; P < 0.001). Meta-analysis exhibited a significant antiosteoporosis effect of Qianggu Capsule on femoral neck BMD (MD = 0.03 g/cm2; 95% CI: 0.01-0.05; P = 0.003) and femoral trochanteric BMD (MD = 0.07 g/cm2; 95% CI: 0.02-0.12; P = 0.006) compared with α-D3 capsule. However, the methodological quality of included studies was low. Constipation and dry mouth were the most common adverse drug reactions of Qianggu Capsule. Finally the evidence level was evaluated to be low or very low. CONCLUSIONS: The effect of Qianggu Capsule for POP was supported in improving BMD. Due to the methodological drawbacks of the included studies, the conclusions should be treated with caution for future research.

Comparative efficacy of bisphosphonates in short-term fracture prevention for primary osteoporosis: a systematic review with network meta-analyses.

Our network meta-analyses compared the efficacy of different bisphosphonates preventing fractures for primary osteoporosis. By including 36 studies, we found that zoledronic acid seemed the most effective in preventing vertebral fracture, nonvertebral fracture, and any fracture, and alendronate or zoledronic acid seemed the most effective in preventing hip fracture. INTRODUCTION: This study was conducted in order to analyze the available evidence on the efficacy of bisphosphonates for preventing fractures. METHODS: We considered randomized trials comparing any bisphosphonate with other bisphosphonate or placebo. We searched Cochrane Library, Embase, and PubMed and manually searched reference list of relevant articles. Pairwise and network meta-analyses were performed. The primary outcome is vertebral fracture. Secondary outcomes include nonvertebral fracture, hip fracture, wrist fracture, and any fracture. RESULTS: Thirty-six studies were included. Significant difference was found between bisphosphonates for vertebral fracture and nonvertebral fracture (P < 0.0001 and P = 0.04, respectively). Compared with placebo, alendronate, clodronate, ibandronate, minodronate, pamidronate, risedronate, and zoledronic acid significantly prevented vertebral fracture. Zoledronic acid significantly reduced the risk of vertebral fracture, compared with alendronate, clodronate, etidronate, ibandronate, risedronate, and tiludronate (0.65 (0.46, 0.91), 0.53 (0.33, 0.86), 0.45 (0.27, 0.74), 0.52 (0.36, 0.75), 0.59 (0.42, 0.83), and 0.31 (0.21, 0.48), respectively). Compared with etidronate, clodronate and zoledronic acid significantly prevented nonvertebral fracture. Compared with alendronate, zoledronic acid significantly prevented any fracture. The possibility rankings showed that zoledronic ranked first in preventing vertebral fracture, hip fracture, and any fracture, and pamidronate ranked first in preventing nonvertebral fracture and wrist fracture. In the sensitivity analyses, zoledronic acid ranked first in preventing nonvertebral fracture, and alendronate ranked first in preventing hip fracture and wrist fracture. CONCLUSION: Zoledronic acid seemed the most effective in preventing vertebral fracture, nonvertebral fracture, and any fracture, and alendronate or zoledronic acid seemed the most effective in preventing hip fracture. Uncertainty still remains and future studies are needed to accurately evaluate the comparative efficacy of bisphosphonates.

Patient preference for monthly bisphosphonate versus weekly bisphosphonate in a cluster-randomized, open-label, crossover trial: Minodroate Alendronate/Risedronate Trial in Osteoporosis (MARTO).

Minodronate is a potent nitrogen-containing bisphosphonate that can be administered according to a monthly (every 4 weeks) dosing regimen. A 6-month, cluster-randomized, open-label, multicenter, crossover trial was conducted to test the preference of Japanese patients with osteoporosis for monthly bisphosphonate versus weekly bisphosphonate. One hundred and forty-seven patients (postmenopausal women and men) with primary osteoporosis were recruited at eight outpatient clinics. The clinics were randomized into two groups according to the dosing protocol-monthly minodronate followed by weekly alendronate or risedronate for a total of 24 weeks, or weekly alendronate or risedronate followed by monthly minodronate for 24 weeks. Patient preference for either the monthly or weekly bisphosphonate regimen was evaluated using a preference questionnaire. One hundred and fifteen patients (78.2 %) who completed the trial were processed for the analyses. Significantly more patients preferred the monthly bisphosphonate regimen (65.2 %) than the weekly bisphosphonate regimen (15.7 %) (P = 0.007). 'Dosing schedule fits lifestyle better' was the most common reason given for the patient preference for both the monthly (32.0 %) and weekly bisphosphonate (33.3 %) regimens. Significantly more patients found the monthly bisphosphonate regimen to be more convenient (73.0 %) than the weekly bisphosphonate regimen (13.9 %) (P < 0.0001). The safety profiles of the two regimens were similar. The present trial demonstrated a strong patient preference for and the convenience of the monthly bisphosphonate regimen over the weekly bisphosphonate regimen in Japanese patients with osteoporosis.

Comparison of the effects of 12 months of monthly minodronate monotherapy and monthly minodronate combination therapy with vitamin K2 or eldecalcitol in patients with primary osteoporosis.

The aim of this observational, nonrandomized study was to compare the effects of 12 months of monthly minodronate (MIN; 50 mg/month) monotherapy and MIN combination therapy with vitamin K2 (VK; 45 mg/day) or eldecalcitol (ELD; 0.75 µg/day) in treatment-naïve patients with primary osteoporosis. Patients (n = 193; 178 postmenopausal women and 15 men; mean age 71.6 years) were treated with (1) MIN monotherapy (n = 63), (2) MIN plus VK combination therapy (n = 50), or (3) MIN plus ELD combination therapy (n = 80) for 12 months. Changes in bone mineral density (BMD) and the levels of serum bone turnover markers were monitored. No significant difference was observed in baseline BMD among the three groups. After 12 months, BMD increased by 2.93, 4.65, and 6.55 % in the lumbar spine, 0.66, 2.57, and 3.42 % in the total hip, and 0.05, 2.06, and 3.58 % in the femoral neck in groups 1, 2, and 3, respectively. The BMD increase induced by MIN plus ELD combination therapy was significantly greater than that induced by MIN monotherapy in the lumbar spine (P = 0.0002), total hip (P = 0.003), and femoral neck (P = 0.004), and also that induced by MIN plus VK combination therapy in the lumbar spine (P = 0.03). MIN plus ELD combination therapy compared with MIN monotherapy resulted in a greater decrease in serum procollagen type I N-terminal propeptide levels (-37.4 % vs -54.6 %; P = 0.001) and tartrate-resistant acid phosphatase isoform 5b levels (-41.1 % vs -52.9 %; P = 0.009) at 3 months, and a greater decrease in procollagen type I N-terminal propeptide levels (-64.3 % vs -50.3 %; P = 0.03) and a decrease in intact parathyroid hormone levels (-12.3 % vs 14.0 %; P = 0.01) at 12 months. Combination therapy with MIN and VK or ELD for 12 months showed additive effects in decreasing the levels of bone turnover markers compared with MIN monotherapy, whereas MIN plus ELD combination therapy resulted in the highest BMD increase compared with MIN monotherapy and MIN plus VK combination therapy.

Perceptions Toward Exercise or Mindful Exercise Participation Among Patients With Primary Osteoporosis: A Qualitative Study.

Exercise is significantly beneficial for patients with osteoporosis. However, physiological and psychological factors such as pain and kinesiophobia prevent patients from participating in exercise. Therefore, it is important to understand how these patients perceive participation in exercise. This qualitative study was conducted in China using conventional content analysis. Using a purposeful sampling method, 17 patients with primary osteoporosis were recruited. Data were collected through a semi-structured interview and managed using ATLAS.ti 21. Nine generic categories were developed from 26 subcategories and two main categories were identified: Barriers and facilitators, support systems, network resources, positive emotions, and reactions were the facilitators for exercise in this study. In addition, mindful exercise was positively viewed by the patients. Inefficient awareness, weak support systems, and burdens were identified as barriers. To improve compliance in clinical practice, targeted exercise protocols should be developed for patients based on these perceptions.

The effects of resveratrol in animal models of primary osteoporosis: a systematic review and meta-analysis.

BACKGROUND: There is still a lack of sufficient evidence-based medical data on the effect of resveratrol (Res) on primary osteoporosis (OP). This meta-analysis aimed to comprehensively evaluate the role of Res in animal models of primary OP. METHODS: The PubMed, Cochrane Library, Web of Science and Embase databases were searched up to August 2023. The risk of bias was assessed by the SYRCLE RoB tool. Random- or fixed-effects models were used to determine the 90% confidence interval (CI) or standardized mean difference (SMD). Statistical analysis was performed with RevMan 5.4 and Stata 14.0. RESULTS: A total of 24 studies containing 714 individuals were included. Compared with those in the control group, the bone mineral density (BMD) (P < 0.00001), bone volume/total volume (BV/TV) (P < 0.001), trabecular thickness (Tb.Th) (P < 0.00001), and trabecular number (Tb.N) (P < 0.00001) were markedly greater, and the trabecular separation (Tb.Sp) (P < 0.00001) was significantly greater. Compared with the control group, the Res group also exhibited marked decreases in alkaline phosphatase (ALP) (P < 0.05), tartrate-resistant acid phosphatase 5b (TRAP5b) (P < 0.01), and type I collagen strong carboxyl peptide (CTX-1) (P < 0.00001) and a marked increase in osteoprotegerin (OPG) (P < 0.00001). CONCLUSION: In summary, we concluded that Res can markedly increase BMD, improve morphometric indices of trabecular microstructure and serum bone turnover markers (BTMs), and exert a protective effect in animal models of primary osteoporosis. This study can supply experimental reference for Res in primary osteoporosis treatment.