Prevention Of Vertebral Fractures Research Articles

Biomechanical Analysis of Diffuse Idiopathic Skeletal Hyperostosis and Osteoporosis: Vertebral Fracture Risk Evaluation Using Finite Element Modeling with Clinical and Micro-CT Data in an Elderly Donor

Introduction: Biomechanical analysis of spinal structures is crucial in the evaluation of injuries, the risk of fracture, and age-related changes. Osteoporotic vertebrae are very fragile and therefore constitute a serious risk, especially in the elderly. Methods: At present, clinically relevant decision making in fracture risk assessment is predicated upon finite element analysis (FEA), which utilizes high-resolution computed tomography (CT) scans from clinical practice alongside micro-CT scans from laboratory settings. Of particular interest is the utilization of cortical vertebral body thicknesses, as meticulously measured via micro-CT. The data from a body donation over 80 years old with diffuse idiopathic skeletal hyperostosis (DISH) and osteoporosis (OP) were utilized through FEA to evaluate stresses in cortical and trabecular bone and to predict the stiffness and deformability of the examined vertebral bodies. Results: The investigation revealed a higher density of cortical and cancellous bone in vertebrae affected by DISH. Cortical density was highest in the thoracic section (median 188 µm), while cancellous bone density was 222 HU in the cervical vertebrae. The load on cortical bone increased as we progressed towards the lumbar spine; however, it remained quite constant in cancellous bone. Despite a low bone density, we registered no fractures in vertebrae. Conclusions: The data showed that DISH increased the thickness of the cortical bone and the density of the cancellous bone. The combination of increased cortical and cancellous bone density might reduce the risk of fracture in patients with low bone density. These conclusions emphasize the significance of biomechanical properties in the assessment of fracture risk and have important implications for clinical practice, particularly in relation to the prevention of vertebral fractures in osteoporotic patients with DISH.

Bone Remodeling and Modeling: Cellular Targets for Antiresorptive and Anabolic Treatments, Including Approaches Through the Parathyroid Hormone (PTH)/PTH-Related Protein Pathway.

Bone is continuously in a state of building and renewal, though the process of remodeling that takes place at many sites asynchronously throughout the skeleton, with bone formation and resorption equal at these sites (bone multicellular units). Remodeling takes place on bone surfaces, both on trabeculae and in the cortex, and serves the purposes of replacing old bone or that damaged by microfractures throughout the skeleton. The bone loss and consequent osteoporotic fractures that result from excess resorption over formation have mainly been prevented or treated by antiresorptive drugs that inhibit osteoclast formation and/or activity. Virtually all of the evidence leading to acceptance of antiresorptive drugs as treatment has depended upon their prevention of vertebral fractures. In recent decades, new prospects came of anabolic treatments that partly restore bone volume and microstructure restore bone that has been lost. The first of these was parathyroid hormone (PTH), shown by daily injection to increase markers of bone formation and prevent fractures. This field of interest enlarged with the discovery of PTH-related protein (PTHrP), so closely related in structure and action to PTH. The structural relationship between PTH and PTHrP is important in assessing their physiological and pharmacological roles, with the N-terminal domains of the 2 having virtually equal actions on target cells. Abaloparatide, a peptide analogue based on the structures of PTHrP and PTH, has been approved in some countries as a therapy for osteoporosis. Treatment through the PTH receptor activation pathway, and probably with any anabolic therapy, needs to be followed by antiresorptive treatment in order to maintain bone that has been restored. No matter how effective anabolic therapies for the skeleton become, it seems highly likely that there will be a continuing need for antiresorptive drugs.

Denosumab Versus Bisphosphonates for the Prevention of the Vertebral Fractures in Men with Osteoporosis: An Updated Network Meta-Analysis.

The efficacy of the prevention of vertebral fractures in men with osteoporosis by treatment with denosumab is debated. This study aimed to update the comparative effectiveness of denosumab and bisphosphonates for preventing vertebral fractures in men with osteoporosis. We searched PubMed, EMBASE, and Cochrane Central Register of Controlled Trials for randomized controlled trials that enrolled men with osteoporosis. Fixed-effects network meta-analysis was performed to evaluate the risk of vertebral fractures, and the relative risk (RR) and 95% confident interval (CI) values were calculated. Sixteen studies were included, and the identified bisphosphonates were risedronate, alendronate, zoledronic acid, and ibandronate. Compared with placebo or control, a significant reduction in vertebral fractures was observed for denosumab (RR 0.30, 95%CI 0.13 0.68), risedronate (RR 0.39, 95%CI 0.19 0.77), and zoledronic acid (RR 0.45, 95%CI 0.21 0.98). According to the surface under the cumulative ranking curve (SUCRA), denosumab was the most effective one among the included agents for the risk reduction of vertebral fracture. However, compared with each bisphosphonate, the RR values of denosumab were not significant [RR 0.78 (95%CI 0.25 2.43) vs. risedronate, RR 0.55 (95%CI 0.18 1.75) vs. alendronate, RR 0.66 (95%CI 0.19 2.32) vs. zoledronic acid and RR 1.12 (95%CI 0.08 14.83) vs. ibandronate]. Denosumab effectively reduced the risk of vertebral fractures in men with osteoporosis, and this effect was comparable to that of bisphosphonates.

Comparative efficacy and safety of alendronate and teriparatide in bone loss reduction and prevention of vertebral fracture in osteoporotic Chinese patients

Purpose: To compare the effect of teriparatide and alendronate (bisphosphonate, BPP) among Chinese patients with osteoporosis (OoP).Method: Chinese subjects aged > 40 years with a history of vertebral/non-vertebral osteoporotic fragility/fractures were enrolled, and administered either teriparatide (TPT 20 μg/day) subcutaneously or alendronate (BPP)10 mg orally once daily for 12 months. Bone mineral density (BMD), measured using x-ray techniques, and bone formation biomarkers such as osteocalcin [OTC] and bone alkaline phosphatase, were assessed at baseline, and after 6 and 12 months of treatment. The proportion of patients with fractures as well as fracture rate were also recorded. The safety of the drugs was evaluated based treatment emergent adverse events.Result: In Chinese men with OoP, substantially greater improvement in BMD was observed in TPT group, compared to BPP group. TPT demonstrated substantially greater improvement in OTC and, bone alkaline phosphatase than in BPP. Also, patients treated with TPT had significantly lower incidence of new fracture than BPP group during the study period, irrespective of gender distribution (relative risk reduction at 6 and 12 months was 45 and 47 % respectively). The results showed that TPT was superior to BPP in increasing BMD and bone formation biomarkers and reducing new fractures in both male and female patients with osteoporosis.Conclusion: Teriparatide is effective and safe in reducing bone loss and preventing vertebral fractures in Chinese patients with osteoporosis. Furthermore, the results show that there is no gender difference in the efficacy and safety of teriparatide in osteoporosis.

Prevalence of Osteoporosis and Fracture in China

The aging of the population is associated with an increasing burden of fractures worldwide. However, the epidemiological features of fractures in mainland China are not well known. To assess the prevalence of and factors associated with osteoporosis, clinical fractures, and vertebral fractures in an adult population 40 years or older in mainland China. This cross-sectional study, the China Osteoporosis Prevalence Study, was conducted from December 2017 to August 2018. A random sample of individuals aged 20 years or older who represented urban and rural areas of China were enrolled, with a 99% participation rate. Weighted prevalence of osteoporosis, clinical fracture, and vertebral fracture by age, sex, and urban vs rural residence as determined by x-ray absorptiometry, questionnaire, and radiography. A total of 20 416 participants were included in this study; 20 164 (98.8%; 11 443 women [56.7%]; mean [SD] age, 53 [13] years) had a qualified x-ray absorptiometry image and completed the questionnaire, and 8423 of 8800 (95.7%) had a qualified spine radiograph. The prevalence of osteoporosis among those aged 40 years or older was 5.0% (95% CI, 4.2%-5.8%) among men and 20.6% (95% CI, 19.3%-22.0%) among women. The prevalence of vertebral fracture was 10.5% (95% CI, 9.0%-12.0%) among men and 9.7% (95% CI, 8.2%-11.1%) among women. The prevalence of clinical fracture in the past 5 years was 4.1% (95% CI, 3.3%-4.9%) among men and 4.2% (95% CI, 3.6%-4.7%) among women. Among men and women, 0.3% (95% CI, 0.0%-0.7%) and 1.4% (95% CI, 0.8%-2.0%), respectively, with osteoporosis diagnosed on the basis of bone mineral density or with fracture were receiving antiosteoporosis treatment to prevent fracture. In this cross-sectional study of an adult population in mainland China, the prevalence of osteoporosis and vertebral fracture were high and the prevalence of vertebral fracture and clinical fracture was similarly high in men and women. These findings suggest that current guidelines for screening and treatment of fractures among patients in China should focus equally on men and women and should emphasize the prevention of vertebral fractures.

Prevention of vertebral fractures in primary osteoporosis with once-weekly teriparatide

Aims: The present meta-analysis was undertaken to summarize the data from hitherto available randomized controlled trials (RCTs) on the prevention of incident fractures in patients with primary osteoporosis following the use of once-weekly teriparatide. Methods: PubMed/MEDLINE, Web of Science, and Google Scholar databases were systematically searched till May 21, 2021, to identify RCTs with duration ≥72 weeks, evaluating the efficacy of once-weekly teriparatide (at a dose of 56.5 μg/week or 28.2 μg/week) in the prevention of incident fractures as compared to placebo or active comparator. Results: We identified 3 eligible RCTs, pooling data retrieved from 1643 participants with primary osteoporosis. Pooled data showed that the risk of incident morphometric vertebral fractures was significantly lower with once-weekly teriparatide compared to placebo/active comparator (RR 0.33, 95% confidence intervals [CI]: 0.12,0.90,P= 0.03; I 2 =86%). Sensitivity analysis after exclusion of the study where an active comparator had been used instead of placebo also showed a similar result (RR 0.20, 95% CI: 0.11,0.37,P< 0.00001; I 2 =0%). Data on clinical vertebral fractures or nonvertebral fractures were inadequately reported across the RCTs and hence could not be pooled together. Nevertheless, all the RCTs did not find any significant difference in the risk of incident nonvertebral fractures. Conclusions: The present systematic review and meta-analysis show that once-weekly teriparatide leads to a 67% reduction in the risk of incident morphometric vertebral fractures. Considering the reasonable efficacy, once-weekly dose, and reduced cost, the formulation can be an important antiosteoporotic drug, especially in resource-constraint settings, like India.

The effects of teriparatide and bisphosphonates on new fractures in postmenopausal women with osteoporosis: A protocol for systematic review and meta-analysis.

Background:To systematically evaluate the efficacy of teriparatide and bisphosphonates in preventing fractures in postmenopausal women with osteoporosis.Materials and methods:We performed a systematic search of PubMed, Embase, and the Cochrane Library for randomized controlled trials (RCTs) that compared teriparatide and bisphosphonates for osteoporosis treatment. Searches were performed without language restrictions and included studies from beginning of time to March 2019. Two authors independently screened and extracted the selected article. The quality of the included studies was evaluated using the Cochrane system evaluation method. Data were extracted and analysed using RevMan 5.2 software.Results:Nine RCTs were included for a total of 2990 postmenopausal women with osteoporosis. Of these, 1515 patients were treated with teriparatide and 1475 were treated with bisphosphonates. After pooling the data of 9 studies, there were significant differences between teriparatide and bisphosphonates [relative risk (RR): 0.61, 95% confidence interval (CI) (0.51, 0.74)] in the prevention of fractures according to different follow-up durations (P < .05), whatever alendronate [RR: 0.51, 95% CI (0.27, 0.95)] and other bisphosphonates [RR: 0.63, 95% CI (0.51, 0.77)]. In addition, we found significant differences between teriparatide and bisphosphonates in the prevention of vertebral fractures [RR: 0.47, 95% CI (0.35, 0.64)] and non-vertebral fractures [RR: 0.76, 95% CI (0.58,0.99)]. There were no significant differences in adverse effects between teriparatide and bisphosphonates [RR: 0.89, 95% CI (0.76, 1.03)].Conclusions:Based on the results of our meta-analysis, teriparatide was better than bisphosphonates in preventing fractures in postmenopausal women with osteoporosis both in the short-term and long-term follow-up periods. Teriparatide was superior to bisphosphonates in preventing vertebral and non-vertebral fractures. These drugs did not differ in terms of their adverse effects. More high-quality studies are needed to compare other factors such as costs and adverse reactions.

Prevention of vertebral fractures and complications : Important points in physical therapy

Prevention of vertebral fractures and complications : Important points in physical therapy

Romosozumab Enhances Vertebral Bone Structure in Women With Low Bone Density.

ABSTRACTRomosozumab monoclonal antibody treatment works by binding sclerostin and causing rapid stimulation of bone formation while decreasing bone resorption. The location and local magnitude of vertebral bone accrual by romosozumab and how it compares to teriparatide remains to be investigated. Here we analyzed the data from a study collecting lumbar computed tomography (CT) spine scans at enrollment and 12 months post‐treatment with romosozumab (210 mg sc monthly, n = 17), open‐label daily teriparatide (20 μg sc, n = 19), or placebo (sc monthly, n = 20). For each of the 56 women, cortical thickness (Ct.Th), endocortical thickness (Ec.Th), cortical bone mineral density (Ct.bone mineral density (BMD)), cancellous BMD (Cn.BMD), and cortical mass surface density (CMSD) were measured across the first lumbar vertebral surface. In addition, color maps of the changes in the lumbar vertebrae structure were statistically analyzed and then visualized on the bone surface. At 12 months, romosozumab improved all parameters significantly over placebo and resulted in a mean vertebral Ct.Th increase of 10.3% versus 4.3% for teriparatide, an Ec.Th increase of 137.6% versus 47.5% for teriparatide, a Ct.BMD increase of 2.1% versus a −0.1% decrease for teriparatide, and a CMSD increase of 12.4% versus 3.8% for teriparatide. For all these measurements, the differences between romosozumab and teriparatide were statistically significant (p < 0.05). There was no significant difference between the romosozumab‐associated Cn.BMD gains of 22.2% versus 18.1% for teriparatide, but both were significantly greater compared with the change in the placebo group (−4.6%, p < 0.05). Cortical maps showed the topographical locations of the increase in bone in fracture‐prone areas of the vertebral shell, walls, and endplates. This study confirms widespread vertebral bone accrual with romosozumab or teriparatide treatment and provides new insights into how the rapid prevention of vertebral fractures is achieved in women with osteoporosis using these anabolic agents. © 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 BALB/c mouse as a preclinical model of the age-related deterioration in the lumbar vertebra.

The likelihood of experiencing an osteoporotic fracture of one or more vertebral bodies increases with age, and this increase is not solely due to sex steroid deficiency. For the purpose of assessing the effectiveness of novel therapeutic strategies in the prevention of vertebral fractures among the elderly, we hypothesized that the BALB/c mouse model of aging phenocopies the age-related decrease in human VB strength. To test this hypothesis, we assessed the age-related changes in trabecular architecture of the L6 VB, with respect to those in the distal femur metaphysis, between 6-mo. (young adulthood, n=20/sex) and 20-mo. of age (old age, n=18/sex) and then determined how well the architectural characteristics, volumetric bone mineral density (vBMD), and predicted failure force from μCT-derived finite element analysis (μFEA) with linear elastic failure criteria explained the age-related variance in VB strength, which was the ultimate force during quasi-static loading of the VB in compression. While there was a pronounced age-related deterioration in trabecular architecture in the distal femur metaphysis of female and male BALB/c mice, the decrease in trabecular bone volume fraction and trabecular number between 6-mo. and 20-mo. of age occurred in male mice, but not in female mice. As such, the VB strength was lower with age in males only. Nonetheless, BV/TV and volumetric bone mineral density (vBMD) positively correlated with the ultimate compressive force of the L6 VB for both females and males. Whether using a fixed homogeneous distribution of tissue modulus (Et=18GPa) or a heterogeneous distribution of Et based on a positive relationship with TMD, the predicted failure force of the VB was not independent of age, thereby suggesting linear μFEA may not be a suitable replacement for mechanical-based measurements of strength with respect to age-related changes. Overall, the BALB/c mouse model of aging mimics the age-related in decline in human VB strength when comparing 6-mo. and 20-mo. old male mice. The decrease in VB strength in female mice may occur over a different age range.

Bisphosphonates for Secondary Prevention of Osteoporotic Fractures: A Bayesian Network Meta-Analysis of Randomized Controlled Trials.

Purpose To investigate the comparative efficacies of the five most commonly used bisphosphonates for the secondary prevention of osteoporotic fractures in a Bayesian network meta-analysis. Methods Five databases and the reference lists of all acquired articles from inception to July 2017 were searched. A Bayesian random-effects model was employed, and vertebral, hip and nonvertebral nonhip fractures were assessed by odds ratios (ORs) and 95%credible intervals. Furthermore, with respect to each endpoint, rank probabilities for each bisphosphonate were evaluated using the surface under the cumulative ranking curve (SUCRA) value. Results Thirteen eligible studies were identified involving 11,822 patients with osteoporotic fractures. Overall in the pairwise meta-analyses, bisphosphonate use significantly reduced the risk of new vertebral, hip, and nonvertebral nonhip fractures, with ORs and 95% confidence intervals of 0.56 (0.49–0.64), 0.69 (0.48–0.98), and 0.82 (0.70–0.97), respectively. In network meta-analyses, significant differences were found between placebo and any one of the five bisphosphonates for new vertebral fractures. The rank probability plot and the SUCRA calculation results suggested that alendronate was the best intervention (14.6%) for secondary prevention of vertebral fractures, followed by zoledronate (15.3%) and etidronate (22.1%). In terms of the incidence of new hip fractures, alendronate was associated with the lowest incidence (18.5%), followed by zoledronate (43.1%) and risedronate (52.5%). However, zoledronate ranked lowest (16.6%) regarding the incidence of new nonvertebral nonhip fractures, followed by risedronate (23.8%) and alendronate (44.1%). Conclusions Bisphosphonates show significant efficacy for secondary prevention of new vertebral fractures, and alendronate is most likely to be successful at secondary prevention of vertebral and hip fractures compared with the other four bisphosphonates.

A cross-sectional and 6-year follow-up study of associations between leisure time physical activity and vertebral fracture in adults

IntroductionVertebral fractures are common osteoporotic fractures, affecting 2–46% of the population, causing morbidity and increased risk of mortality. Physical activity has beneficial effects for bone health, including increased bone mineral density and reduced hip fractures. However, evidence concerning prevention of vertebral fractures is scarce. Therefore, the aim of this study was to investigate the association between leisure time physical activity and vertebral fracture risk.MethodsThe data were retrieved from the 2001 and 2007–2008 surveys of the Tromsø Study, a longitudinal population study in Norway. A total of 1904 participants (1030 women and 874 men, age 38–87 yr and 40–87 yr respectively) were included in the cross-sectional analysis (2007–2008). Prospective follow-up data (2001 to 2007) on physical activity were available for 1131 participants (636 women and 495 men, age 32–69 yr and 33–69 yr respectively). Physical activity was assessed by a questionnaire and vertebral fracture by lateral vertebral fracture assessment from dual-energy x-ray absorptiometry scans. Logistic regression was used to examine associations between physical activity and vertebral fracture.ResultsAfter controlling for confounders (age, height, weight, smoking, osteoporosis, osteoporosis medication, left hip total bone mineral density, and use of hormones in women only), no cross-sectional associations between physical activity levels and vertebral fracture were observed, OR 1.13 (95% CI: 0.59–2.13), for moderately active women and 1.44 (0.61–3.42) for highly active women, compared with sedentary women. In men, the respective ORs were 1.74 (95% CI: 0.91–3.35) and 1.64 (0.78–3.41). In the prospective analyses, OR for vertebral fracture in women with reduced physical activity was 0.81 (95% CI: 0.18–3.62), 1.24 (95% CI: 0.29–5.26) for increased physical activity and 1.54 (95% CI: 0.43–5.50) for active unchanged physical activity pattern, compared with sedentary unchanged physical activity. In men, the respective ORs were 2.05 (95% CI: 0.57–7.42), 2.23 (95% CI: 0.63–7.87), and 1.81 (95% CI: 0.54–6.02). Subanalyses of women and men ≥50 yr showed similar results.ConclusionsOur findings suggest that physical activity does not play a major role in preventing vertebral fractures in Norwegian adults. Future studies may benefit from data on incident vertebral fracture, and objectively measured physical activity.

Prevalence of and factors associated with dysfunctional low back pain in patients with rheumatoid arthritis

PurposeTo investigate the prevalence of and factors associated with dysfunctional low back pain (LBP) in patients with rheumatoid arthritis (RA).MethodsThis cross-sectional study included 1276 RA outpatients from two hospitals. The Roland–Morris Disability Questionnaire was used to address the functional–dysfunctional state criterion. Clinical variables, such as medical status, disease activity, bone mineral density, and spinopelvic alignment parameters, were compared between patients with and without dysfunctional LBP.ResultsMean age and disease duration were 64.6 and 13.4 years, respectively; the prevalence of dysfunctional LBP was 32.8%. On univariate analysis, significant differences existed in many variables, except sex, body weight, C-reactive protein (CRP) level, and prevalence of biological agent users, between patients with and without dysfunctional LBP. Multivariate logistic regression analysis revealed body mass index (BMI; odds ratio [OR], 1.116; P < 0.001), onset age of RA (OR, 1.020; P = 0.020), disease duration of RA (OR, 1.043; P < 0.001), methotrexate (MTX) use (OR, 0.609; P = 0.007), vertebral fractures (OR, 2.189; P = 0.001), vertebral endplate and/or facet erosion (OR, 1.411; P = 0.043), disease activity score (DAS) in 28 joints-CRP (DAS-28CRP) (OR, 1.587; P = 0.001), pelvic tilt (PT; OR, 1.023; P = 0.019), and sagittal vertical axis (SVA; OR, 1.007; P = 0.043) as associated factors.ConclusionThe factors associated with dysfunctional LBP in patients with RA were more vertebral fractures, higher DAS-28CRP, vertebral endplate and/or facet erosion, higher BMI, longer disease duration, greater PT, older onset age, greater SVA, and less MTX use. Strictly controlling patients’ body weight and disease activity with MTX and avoiding spinopelvic malalignment through vertebral fracture prevention are important.Graphical abstractThese slides can be retrieved under Electronic Supplementary Material.

Long Acting Zoledronic Acid Treatment for Vertebral Fracture Prevention in Multipl Myeloma Patients with Osteoporosis

BACKGROUND: Zoledronic acid (zoledronate) is the most commonly used bisphosphonate derivative for the prevention of bone related complications in patients with multiple myeloma. Monthly given and yearly given long acting zoledronate are two different forms of zoledronate. Monthly given zoledronate is the novel agent accepted as the standard treatment for the prevention of multiple myeloma bone related complications. Yearly given long acting zoledronate has no data on the use of multiple myeloma bone disease prevention. AIM:Our primary goal is investigating the vertebral fracture protective effects of a long acting zoledronat agent(Aclasta®) in multiple myeloma patients with associated osteoporosis .We choose vertebrae as the target because bones with the most frequent fractures in multiple myeloma are the vertebrae. As a secondary goal ;we planned to evaluate in preventing fracture development in other bones. METHODS:Patients diagnosed with active multiple myeloma in the Sanlıurfa Mehmet Akif Inan Education and Research Hospital Hematology Clinic at year 2017 were evaluated. Patients fulfilled the inclusion criteria(men and women over the age of 18 and newly diagnosed patients with multiple myeloma,who have lomber vertebra( L1-L4 total or L2-L4) or total femur or femur neck measurements of “(-)1 or lower of any of the T-values” by bone mineral densitometry). Five pa tients were identified who fulfilled these criteria. Four of the patients were female and one patient was male,the age range was between 42 and 76 years.All patients received weekly VCD (bortezomib 1.3 mg /m2 cyclophosphamide 500 mg ,dexamethasone 20 mg) intravenously.During the first administration of chemotherapy , long acting zoledronat (Aclasta®),5 mg was administered with a half-hour intravenous infusion . Simultaneously with the first administration of long acting zolendronat(Aclasta®),600 mg elemental calcium and 400 U vitamin D3 were administered daily to the patients. At the first evaluation time point ,sixth month of treatment beginning ,MRI evaluation of the vertebral column was planned to undergo for all five patients.At the same time patients were questioned for complaints consistent with bone fractures before each chemotherapy session and patients with suspected fracture are planned to be evaluated with MRI.RESULTS: All patients were in complete remission at the end of the induction treatment.Two of the patients had autologous stem cell transplants.One patient had a tooth extraction before autologous bone marrow transplantation.Any jaw complications did not develop in this patient.None of the five patients developed myeloma-related bone complications ,neither vertebral nor other bones, at the sixth month of therapy.No adverse effects(electrolyte disorders ,albuminuria,etc.) were observed in patients during the administration and follow up period of the drug.CONCLUSION: It is universaly recommended to apply zoledronate once a month for intravenously at least two years in patients with myeloma. Before every application serum creatinine, serum electrolytes, serum calcium levels and every 3 months albuminuria should be evaluated . Zoledronates have side effects such as fatigue (30%), low blood pressure (11%) and nausea (29%) .Every month we need blood testing to detect electrolyte abnormalities before the therapy and follow up albuminüria as possible side effects of the drug.There is a risk of exposure to side effects every month too.But most important point is ease of application and the cost. Monthly treatment's cost is 1080 USD with it's cheapest generic (U.S market price).When we compare monthly zoledronate with the application of yearly long-acting zoledronate , patients will not have to live all the above-mentioned side effects ,necessity of laboratory evaluation every month, and the cost is only 350 USD with cheapest generic(U.S market price).Long-acting zoledronate is more advantageous considering factors such as cost, ease of administration and frequency of side effects. What is missing here is the large clinical efficacy studies. Our study is first study in the literature and the result are not inconclusive because patient group is very small.But at the same time, we are thinking that long acting zoledronate is a promising agent for preventing bone complications in multiple myeloma patients.So we are planning a phase 3 study to reevaluate our proposal in a larger patient group. DisclosuresNo relevant conflicts of interest to declare.

Gravidity, Parity, and Vertebral Dimensions in the Northern Finland Birth Cohort 1966.

A population-based birth cohort study. To investigate the association between gravidity, parity, and vertebral geometry among middle-aged women. Vertebral size is a recognized determinant of vertebral fracture risk. Yet, only a few lifestyle factors that influence vertebral size are known. Pregnancy is a labile period that may affect the maternal vertebral size or shape. The lumbar lordosis angle is permanently deepened by pregnancy, but it remains unclear whether vertebral shape or size contribute to this deepened angle. We aimed to investigate whether gravidity and parity were associated with vertebral cross-sectional area (CSA) and height ratio (anterior height to posterior height) among 705 middle-aged women from the Northern Finland Birth Cohort 1966. We measured the corpus of their fourth lumbar vertebra using magnetic resonance imaging of the lumbar spine at the age of 46. Gravidity and parity were elicited using a questionnaire also at the age of 46. Linear regression analysis was used with adjustments for body mass index, vertebral CSA (height ratio models), and vertebral height (CSA models). We also ran a subgroup analysis that did not include nulliparous women, and we compared nulliparous women with grand multiparous women. The models found no statistically significant associations between the predictors and outcomes. Crude and adjusted results were highly similar, and the subgroup analyses provided analogous results. Pregnancy, or even multiple pregnancies, do not seem to have long-term effects on vertebral geometry. In order to enhance the prevention of vertebral fractures, future studies should aim to reveal more lifestyle determinants of vertebral size. 3.

Minodronate for the treatment of osteoporosis.

Minodronate is a third-generation bisphosphonate that was developed and approved for clinical use in osteoporosis therapy in Japan. The mechanism of action for suppressing bone resorption is the inhibition of farnesyl pyrophosphate synthase, a key enzyme in the mevalonic acid metabolic pathway of osteoclasts, to induce apoptosis of the cells. Minodronate is the strongest inhibitor of bone resorption among the currently available oral bisphosphonates. Large randomized, placebo-controlled, double-blind clinical trials have revealed an increase in bone mineral density of both the lumbar spine and femoral neck over 3 years of daily minodronate therapy and risk reduction in vertebral fractures over 2 years of therapy. The increase in bone mass and the prevention of vertebral fractures are similar to those with alendronate or risedronate. The incidence of adverse events, especially gastrointestinal disturbance, is the same as or less than that with weekly or daily alendronate or risedronate. The unique mechanism of action of minodronate via the inhibition of the P2X(2/3) receptor compared with other bisphosphonates may be an advantage in reducing low back pain in patients with osteoporosis. The monthly regimen of minodronate, introduced in 2011, is expected to have better patient adherence and longer persistence. In experimental animal models, minodronate preserved, or even ameliorated, bone microarchitectures, including microcracks and perforation of the trabeculae in the short term. The lowest incidence of bisphosphonate-related osteonecrosis of the jaw among all bisphosphonates and the lack of atypical femoral fractures attributed to its use to date, however, are partly because only a smaller population used minodronate than those using other bisphosphonates. To date, minodronate is available only in Japan. Hip fracture risk reduction has not been verified yet. More clinical studies on minodronate and its use in osteoporosis treatment, with a large number of subjects, should be conducted to verify hip fracture risk reduction and long-term results.

The efficacy and safety of vertebral fracture prevention therapies in post-menopausal osteoporosis treatment: Which therapies work best? a network meta-analysis.

ObjectivesOsteoporosis has become an increasing concern for older people as it may potentially lead to osteoporotic fractures. This study is designed to assess the efficacy and safety of ten therapies for post-menopausal women using network meta-analysis.MethodsWe conducted a systematic search in several databases, including PubMed and Embase. A random-effects model was employed and results were assessed by the odds ratio (OR) and corresponding 95% confidence intervals (CI). Furthermore, with respect to each outcome, each intervention was ranked according to the surface under the cumulative ranking curve (SUCRA) value.ResultsWith respect to preventing new vertebral fractures (NVF), all ten drugs outperformed placebo, and etidronate proved to be the most effective treatment (OR 0.24, 95% CI 0.14 to 0.39). In addition, zoledronic acid and parathyroid hormone ranked higher compared with the other drugs. With respect to preventing clinical vertebral fractures (CVF), zoledronic acid proved to be the most effective drug (OR = 0.25, 95% CI 0.08 to 0.92), with denosumab as a desirable second option (OR = 0.48, 95% CI 0.22 to 0.96), when both were compared with placebo. As for adverse events (AE) and severe adverse events (SAE), no significant difference was observed. According to SUCRA, etidronate ranked first in preventing CVF; parathyroid hormone and zoledronic acid ranked highly in preventing NVF and CVF. Raloxifene was safe with a high rank in preventing AEs and SAEs though performed unsatisfactorily in efficacy.ConclusionsThis study suggests that, taking efficacy and safety into account, parathyroid hormone and zoledronic acid had the highest probability of satisfactory performance in preventing osteoporotic fractures.Cite this article: G. Wang, L. Sui, P. Gai, G. Li, X. Qi, X. Jiang. The efficacy and safety of vertebral fracture prevention therapies in post-menopausal osteoporosis treatment: Which therapies work best? a network meta-analysis. Bone Joint Res 2017;6:452–463. DOI: 10.1302/2046-3758.67.BJR-2016-0292.R1.

Retraction Note to: Efficacy of Antiresorptive Agents for Preventing Fractures in Japanese Patients with an Increased Fracture Risk: Review of the Literature.

The aim of the present review was to clarify the efficacy of currently available potent antiresorptive agents for preventing fractures in Japanese patients with an increased fracture risk. PubMed was used to search the literature for randomized controlled trials (RCTs), with the following search terms: fracture, etidronate, alendronate, risedronate, minodronate, raloxifene, bazedoxifene and Japan. The inclusion criteria were papers written in English, ≥50 subjects per group and a study period of ≥1 year. Fourteen RCTs met these criteria. The efficacy of antiresorptive agents for preventing vertebral, nonvertebral and hip fractures was investigated. There was evidence that raloxifene reduced the incidence of clinical vertebral fractures, while etidronate, alendronate and minodronate (but not bazedoxifene) reduced the incidence of morphometric vertebral fractures in patients with postmenopausal or involutional osteoporosis. Head-to-head trials showed that alendronate and raloxifene had similar efficacy for preventing vertebral fractures in patients with postmenopausal osteoporosis, while risedronate was not inferior to etidronate for reducing the incidence of morphometric vertebral fractures in patients with involutional osteoporosis. Alendronate reduced the incidence of hip fractures in patients with Parkinson's disease, and risedronate reduced the incidence of nonvertebral fractures and hip fractures in patients with Alzheimer's disease or stroke. In conclusion, the present review confirmed the efficacy of etidronate, minodronate and raloxifene for the prevention of vertebral fractures, the efficacy of alendronate for vertebral and hip fractures, and the efficacy of risedronate for vertebral, nonvertebral and hip fractures in Japanese patients with an increased fracture risk.

Efficacy on the risk of vertebral fracture with administration of once-weekly 17.5mg risedronate in Japanese patients of established osteoporosis with prevalent vertebral fractures: a 156-week longitudinal observational study in daily practice.

Currently, the only available evidence for the efficacy of once-weekly 17.5mg risedronate in preventing vertebral fractures was obtained in a 48-week study in Japan. We performed a 156-week prospective, longitudinal, observational study to determine the efficacy of the 17.5mg risedronate in preventing vertebral fractures. We included Japanese patients with established osteoporosis who were older than 50years and had radiographically confirmed vertebral fractures. The primary endpoint was the incidence of vertebral fractures every 24weeks, with the final interval spanning 36weeks. We also calculated the change in bone mineral density of the lumbar spine (L2-4 BMD) and urinary N-telopeptide of type I collagen (u-NTX), and assessed the incidence of adverse drug reactions and the drug adherence rate. Data from 241 patients were available for analysis of vertebral fracture prevention. The incidence rate of vertebral fractures decreased in a time-dependent manner (P=0.0006; Poisson regression analysis). The risk ratio (fracture incidence per 100person-years in the final 36weeks versus that in the first 24weeks) was 0.21 (95% confidence interval 0.08-0.55). Compared to baseline values, L2-4 BMD increased by 6.41% at 156weeks, while u-NTX decreased by 36% at 24weeks and was maintained thereafter (P<0.0001). The incidence rate of adverse drug reactions was 9.18%. Drug adherence rates assessed every 4weeks were over 90%. Our results indicate that 156weeks of treatment with once-weekly 17.5mg risedronate effectively reduced the risk of vertebral fracture in Japanese patients with established osteoporosis older than 50years.

Efficacy of Osteoporosis Therapies in Diabetic Patients.

Diabetes is characterized by increased fracture risk and by reduced bone strength for a given density. Contributing factors may include lower bone turnover and accumulation of advanced glycation endproducts. There are concerns that the pharmacological therapies for osteoporosis, particularly anti-resorptive therapies that suppress bone turnover, may not be as effective in the setting of diabetes. This review considers clinical trials and observational studies that have assessed the efficacy of anti-resorptive and anabolic therapies in diabetic patients. Post hoc analyses of randomized trials indicate that raloxifene has similar efficacy for prevention of vertebral fractures in diabetic compared with non-diabetic patients. Evidence from randomized clinical trials is lacking for anti-fracture efficacy of other osteoporosis therapies in diabetes. However, observational studies suggest that bisphosphonates are effective in preventing fractures in diabetic patients. The great majority of diabetic patients in studies to date have been type 2, and efficacy of osteoporosis therapies in type 1 diabetic patients remains to be addressed. Further evaluation of the efficacy of osteoporosis therapies in the setting of diabetes is needed to provide optimal fracture prevention for this population.