Vertebral Fractures In Postmenopausal Women Research Articles

Prevalent morphometric vertebral fractures as a risk factor for subsequent clinical vertebral fractures after shortfusion surgery in older Japanese women with degenerative spondylolisthesis.

A retrospective cohort study using the Kaplan-Meier method with propensity-score matching. To evaluate whether the presence of prevalent morphometric vertebral fractures (VFs) poses a risk for subsequent clinical VFs after short-fusion surgery in women aged ≥60 years with degenerative spondylolisthesis. VFs are common osteoporotic fractures and are associated with a low quality of life. Subsequent VFs are a complication of instrumented fusion in patients with degenerative lumbar disorders. Thus, risk factors for subsequent VFs after fusion surgery must be analyzed. Population-based studies have suggested that prevalent morphometric VFs led to a higher incidence of subsequent VFs in postmenopausal women; however, no studies have investigated whether prevalent morphometric VFs are a risk factor for subsequent VFs after fusion surgery in patients with degenerative spondylolisthesis. The study enrolled a total of 237 older female patients: 50 and 187 patients had prevalent morphometric VFs (VF [+] group) and nonprevalent morphometric VFs (VF [-] group), respectively. The time to subsequent clinical VFs after fusion surgery was compared between the two groups using the Kaplan-Meier method. Moreover, 40 and 80 patients in the VF (+) and VF (-) groups, respectively, were analyzed and matched by propensity scores for age, follow-up duration, surgical procedure, number of fused segments, body mass index, and number of patients treated for osteoporosis. Kaplan-Meier analysis indicated that the VF (+) group had a higher incidence of subsequent clinical VFs than the VF (-) group, and Cox regression analysis showed that the presence of prevalent morphometric VFs was an independent risk factor for subsequent clinical VFs before matching. Kaplan-Meier analysis demonstrated comparable results after matching. The presence of prevalent morphometric VFs may be a risk factor for subsequent clinical VFs in older women with degenerative spondylolisthesis who underwent short-fusion surgery.

Serum branched-chain amino acid levels are associated with fracture risk in Japanese women.

Branched-chain amino acids (BCAAs) have been shown to exert beneficial effects on muscle and bone metabolism; however, no studies to date have investigated whether BCAAs have beneficial effects on bone fractures. Herein, we aim to prospectively investigate the relationship between serum BCAA concentrations and the occurrence of vertebral fractures (VFs) in Japanese women. During the observation period (7.5 ± 6.1 years), 188 of 983 participants experienced VF. Kaplan-Meier analyses were conducted to examine time-dependent variations in the vertebral compression fracture occurrence rate. Patients were stratified into quartiles based on serum BCAA concentration for this analysis. The analysis results indicated that the group with the lowest BCAA level developed VFs significantly earlier and with a higher frequency than the other groups (P < 0.001). A Cox proportional hazards model showed that BCAA concentration was a significant risk factor for incident fracture, even after adjusting for possible confounding factors. A series of multiple regression analyses were performed to identify factors related to serum BCAA concentration, with the results identifying levels of glycated hemoglobin (P < 0.001), adiponectin (P < 0.001), and NOx (P = 0.011) as significant factors associated with serum BCAA. Overall, the present study revealed that a lower serum BCAA level was an independent risk factor for incident VF in postmenopausal women. Geriatr Gerontol Int 2024; 24: 603-608.

Spinal osteoarthritis is a risk of vertebral fractures in postmenopausal women

Recent studies have revealed that despite high bone mineral density (BMD), osteoarthritis (OA) is a risk factor for osteoporotic fractures. However, the relationship between spinal OA and vertebral fractures has not yet been fully investigated. This longitudinal analysis used a subset of ongoing cohort study consist with Japanese postmenopausal women. The prevalence of spinal OA was determined using Kellgren–Lawrence grading method. The incidence of vertebral fractures were determined by semiquantitative analysis of spinal X-ray films. The relationship between the presence of spinal OA and incidence of vertebral fractures was evaluated using the Cox regression analysis. In total, 1480 women were followed up for 8.1 ± 6.4 years. Among them, 923 were diagnosed with spinal OA, and incident vertebral fractures were observed in 473 participants. After adjusting for confounding variables, the spinal OA (≥ grade 2) was a significant predictor of incident vertebral fractures (hazard ratio, 1.52; 95% confidence interval: 1.19–1.93, p = 0.001). Using ROC analysis, the thresholds of lumbar BMD for incident vertebral fractures were 0.952 g/cm2 for patients with spinal OA and 0.753 g/cm2 for patients without spinal OA. The presence of spinal OA is a risk factor for incident vertebral fractures despite high lumbar BMD.

Effect of adipokine and ghrelin levels on BMD and fracture risk: an updated systematic review and meta-analysis.

Circulating adipokines and ghrelin affect bone remodeling by regulating the activation and differentiation of osteoblasts and osteoclasts. Although the correlation between adipokines, ghrelin, and bone mineral density (BMD) has been studied over the decades, its correlations are stillcontroversial. Accordingly, an updated meta-analysis with new findings is needed. This study aimed to explore the impact of serum adipokine and ghrelin levels on BMD and osteoporotic fractures through a meta-analysis. Studies published till October 2020 in Medline, Embase, and the Cochrane Library were reviewed. We included studies that measured at least one serum adipokine level and BMD or fracture risk in healthy individuals. We excluded studies with one or more of the following: patients less than 18 years old, patients with comorbidities, who had undergone metabolic treatment, obese patients, patients with high physical activities, and a study that did not distinguish sex or menopausal status. We extracted the data that include the correlation coefficient between adipokines (leptin, adiponectin, and resistin) and ghrelin and BMD, fracture risk by osteoporotic status from eligible studies. A meta-analysis of the pooled correlations between adipokines and BMD was performed, demonstrating that the correlation between leptin and BMD was prominent in postmenopausal women. In most cases, adiponectin levels were inversely correlated with BMD. A meta-analysis was conducted by pooling the mean differences in adipokine levels according to the osteoporotic status. In postmenopausal women, significantly lower leptin (SMD = -0.88) and higher adiponectin (SMD = 0.94) levels were seen in the osteoporosis group than in the control group. By predicting fracture risk, higher leptin levels were associated with lower fracture risk (HR = 0.68), whereas higher adiponectin levels were associated with an increased fracture risk in men (HR = 1.94) and incident vertebral fracture in postmenopausal women (HR = 1.18). Serum adipokines levels can utilize to predict osteoporotic status and fracture risk of patients. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42021224855, identifier CRD42021224855.

Efficacy and safety of pharmacologic therapies for prevention of osteoporotic vertebral fractures in postmenopausal women

BackgroundThere are many pharmaceutical interventions available to prevent osteoporotic vertebral fractures in postmenopausal women, but the efficacy and safety of these drugs are unknown. This study aimed to investigate the efficacy and safety of drugs in the prevention of osteoporotic vertebral fractures. MethodsPubMed, Embase, and the Cochrane Library were comprehensively searched for randomized controlled trials (RCTs) published up to February 15, 2020, including postmenopausal women with osteoporosis. Network meta-analysis was conducted based on the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The relative risk (RR) and 95% confidence interval (CI) were used to report the results. This study was registered with PROSPERO, number CRD42020201167. Main Outcomes were incidences of new vertebral fracture and serious adverse events. ResultsFifty-five RCTs (n = 104 580) evaluating vertebral fractures of sixteen kinds of pharmacologic therapies were included in the network meta-analysis. Abaloparatide (RR, 0.21; [95% CI, 0.09 to 0.51]), alendronate (RR, 0.55; [95% CI, 0.38 to 0.81]), calcitonin (RR, 0.44; [95% CI, 0.25 to 0.78]), denosumab (RR, 0.33; [95% CI, 0.14 to 0.61]), parathyroid hormone (PTH) (RR, 0.32; [95% CI, 0.10 to 0.97]), risedronate (RR, 0.65; [95% CI, 0.42 to 1.00]), romosozumab (RR, 0.31; [95% CI, 0.16 to 0.61]), strontium ranelate (RR, 0.62; [95% CI, 0.42 to 0.93]), teriparatide (RR, 0.27; [95% CI, 0.17 to 0.43]), and zoledronate (RR, 0.41; [95% CI, 0.93]) were associated with lower vertebral fracture risk compared to placebo. PTH was associated with more adverse event rates. For any two drug treatments, the RR of serious adverse events was not statistically significant. Hormone replacement therapy (HRT) and calcitonin may be slower to work because they have only been shown to reduce the risk of vertebral fractures in long-term (>18 months) follow-up. ConclusionsA variety of drugs are safe and effective in preventing osteoporotic vertebral fractures. HRT and calcitonin only reduced the risk of vertebral fractures during a follow-up of 21–72 months.

Associations of Neutrophil-to-Lymphocyte Ratio, Platelet-to-Lymphocyte Ratio and Monocyte-to-Lymphocyte Ratio with Osteoporosis and Incident Vertebral Fracture in Postmenopausal Women with Rheumatoid Arthritis: A Single-Center Retrospective Cohort Study.

Background and Objectives: We investigated whether nutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphoycte ratio (PLR), and monocyte-to-lymphocyte ratio (MLR) are associated with the presence of osteoporosis (OP) and vertebral fractures in patients with rheumatoid arthritis (RA). Materials and Methods: This retrospective cohort study included 413 postmenopausal patients with RA and 200 healthy controls who underwent dual-energy X-ray absorptiometry (DEXA) between January 2005 and December 2017. DEXA examination data were defined as the index date, and all laboratory values were measured within one month from the index date. OP was defined as a T-score < −2.5, and incident vertebral fractures were defined as the first occurrence of non-traumatic fractures after the index date. NLR, PLR, and MLR measures were dichotomized by a median split (low vs. high). Results: The median NLR, PLR, and MLR in RA patients were significantly higher than those in controls. The frequencies of OP of the lumbar spine, hip, and either site in postmenopausal patients with RA were 24.7%, 15.5%, and 32%, respectively, and were significantly higher than those in controls. After adjusting for confounding factors, a high baseline NLR was significantly associated with OP at either site (OR = 1.61, p = 0.041). In addition, high baseline NLR (OR = 2.11, p = 0.025) and PLR (OR = 2.3, p = 0.011) were related with the presence OP at hip. During the follow-up period, 53 (12.8%) patients with RA developed vertebral fractures incidentally. In multivariable Cox regression models, a high baseline NLR (HR = 4.72, p < 0.001), PLR (HR = 1.96, p = 0.024), and MLR (HR = 2.64, p = 0.002) were independently associated with a higher risk of incidental vertebral fractures. Conclusions: Our data suggest that NLR, PLR, and MLR can be used as potential markers of systemic bone loss among individuals with RA.

Reduced Circulating Levels of miR-491-5p and miR-485-3p Are Associated with the Occurrence of Vertebral Fractures in Postmenopausal Women with Osteoporosis.

Objective Postmenopausal women experiences osteoporotic structural damage and bone fragility resulting from reduced bone formation and increased bone resorption. Osteoporosis frequently affects the vertebral column and causes compression fractures. This study aims to characterize roles of miRNAs in osteoporosis and subsequent incidence risk of vertebral fractures for postmenopausal women. Methods. Differentially expressed miRNAs between osteoporotic patients with vertebral fractures and osteoporotic patients without fracture were identified. This retrospective study included 78 osteoporotic patients with vertebral fractures and 82 osteoporotic patients without vertebral fractures. The plasma levels of bone metabolic markers, 25-hydroxyvitamin D (25-(OH)VitD), propeptide of type I procollagen (PINP), and β-Carboxyl terminal peptide (β-CTx), were detected using the patented electro-chemiluminescence (ECLIA) method. The expression levels of miR-491-5p and miR-485-3p were determined by qRT-PCR. Pearson correlation analysis was carried out to assess the relationship between miR-491-5p, miR-485-3p, and bone metabolic markers. Receiver operating characteristic (ROC) curves and the area under the ROC curve (AUC) were used to evaluate the performance of miR-491-5p and miR-485-3p in diagnosing the occurrence of vertebral fractures in osteoporotic patients.Results: The plasma levels of PINP and β-CTx were elevated but the plasma level of 25-(OH)VitD was declined in osteoporotic patients with vertebral fractures when comparable to those without (< 0.05). The plasma expression levels of miR-491-5p and miR-485-3p were declined osteoporotic patients with vertebral fractures when comparable to those without (< 0.001). Pearson correlation analysis revealed that the relative expression level of miR-491-5p was negatively correlated with the level of 25-(OH)VitD (r = -0.518, < 0.001) but positively correlated with the levels of PINP (r = 0.547, < 0.001) and β-CTx (r = 0.380, < 0.001). We also observed a negative correlation between the relative expression level of miR-485-3p and 25-(OH)VitD (r = -0.388, < 0.001), a positive correlation between miR-485-3p and PINP (r = 0.422,< 0.001). ROC curves for prediction of vertebral fracture following osteoporosis in postmenopausal women by miR-491-5p expression yielded 0.866 AUC and by miR-485-3p expression produced 0.848 AUC. Conclusion The data suggest that downregulated expressions of miR-491-5p and miR-485-3p may be involved in the occurrence of vertebral fractures in postmenopausal women with osteoporosis.

Vertebral fractures are increased in rheumatoid arthritis despite recent therapeutic advances: a case-control study.

There is little quality data on the updated prevalence of fractures in rheumatoid arthritis (RA) that may have changed due to advances in the therapeutic strategy in recent years. This study was aimed at analysing the prevalence and risk factors of vertebral fractures in postmenopausal women with RA and comparing it with that of the general population. We included 323 postmenopausal women diagnosed with RA from 19 Spanish Rheumatology Departments, randomly selected and recruited in 2018. Lateral radiographs of the thoracic and lumbar spine were obtained to evaluate morphometric vertebral fractures and the spinal deformity index. We analysed subject characteristics, factors related to RA, and fracture risk factors. The control group consisted of 660 age-matched Spanish postmenopausal women from the population-based Camargo cohort. Seventy-eight (24.15%) RA patients had at least one vertebral fracture. RA patients had increased fracture risk compared with controls (106 of 660, 16.06%) (p = 0.02). Logistic regression analysis showed that age (OR 2.17; 95% CI 1.27-4.00), glucocorticoids (OR 3.83; 95% CI 1.32-14.09) and falls (OR 3.57; 95% CI 1.91-6.86) were the independent predictors of vertebral fractures in RA patients. The subgroup with vertebral fractures had higher disease activity (DAS28: 3.15 vs. 2.78, p = 0.038) and disability (HAQ: 0.96 vs. 0.63, p = 0.049), as compared with those without vertebral fractures. The risk of vertebral fracture in RA is still high in recent years, when compared with the general population. The key determinants of fracture risk are age, glucocorticoids and falls. Patients with vertebral fractures have a more severe RA.

The Interaction of Lean Body Mass With Fat Body Mass Is Associated With Vertebral Fracture Prevalence in Women With Early Breast Cancer Undergoing Aromatase Inhibitor Therapy.

ABSTRACTAromatase inhibitors (AIs) induce depletion of estrogen levels, causing bone loss and increased fracture risk in women with breast cancer. High‐fat body mass (FBM) emerged as an independent factor associated with the prevalence of morphometric vertebral fractures (VFs) in patients undergoing AIs. We explored the role of lean body mass (LBM) and the interaction of LBM with FBM in predicting the occurrence of VFs in postmenopausal women who were either AI‐naïve or AI‐treated. A total of 684 consecutive breast cancer patients were enrolled in this cross‐sectional study. Each woman underwent a dual‐energy X‐ray absorptiometry (DXA) scan, measuring bone mineral density (BMD), LBM, and FBM; VFs were assessed using a quantitative morphometric analysis of DXA images. After propensity score matching, the study population was restricted to 480 women, 240 AI‐naïve and 240 AI‐treated. We used multivariable logistic regression models to explore the associations between baseline characteristics, VF prevalence and the interaction between LBM, FBM and AI therapy. No interaction between LBM and AI therapy on VF prevalence was shown. Conversely, we reported a significant interaction between LBM, FBM and AI therapy (p = .0311). Among AI‐treated women having LBM below and FBM above or equal the median value, VF prevalence was numerically higher (15/31; 48.4%) than in other subgroups (VF prevalence: 35.7% in high‐LBM and low‐FBM group, 23.2% in high‐LBM and high‐FBM group, and 19.8% in low‐LBM and low‐FBM group). Among AI‐naïve women, the greatest VF proportion was observed in the subgroup with LBM and FBM below median value (25/92; 27.2%). This study suggests a synergism between LBM and FBM in predicting the morphometric VF in women with early breast cancer undergoing AIs. This observation is new and deserves further investigation. The assessment of body composition by DXA might be useful when estimating fracture risk in this population. © 2020 American Society for Bone and Mineral Research © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

The Value of Historical Height Loss for Detecting Vertebral Fractures in Postmenopausal Women in China

ABSTRACT Objectives The diagnosis and management of osteoporosis and osteoporotic fractures are challenging in rural and underdeveloped areas of China because medical resources are inaccessible; thus, a simple and accurate method is essential for the detection of vertebral fractures. We aimed to examine the relationship between historical height loss (HHL) and vertebral fractures in postmenopausal Chinese women. Material and Methods A cross-sectional study of 255 postmenopausal women aged 50 years or older was conducted in September 2017. Demographic data, including self-reported tallest historical height and current height were analyzed. Vertebral fractures were assessed using X-ray radiography and HHL thresholds were examined using specificity and sensitivity testing. Results The average age of the 255 participants was 66.3 ± 9.0 years and their mean HHL was 3.5 ± 2.8 cm. The 24 women who were found to have vertebral fractures were older, had more years since menopause (YSM), and a larger HHL compared to those without vertebral fractures. Logistic regression analysis showed that age was a better predictor of vertebral fractures than HHL was, and the cutoff age for detecting vertebral fractures was 71 years, with an area under the receiver operating characteristic curve of 0.750. Conclusions Although the women in this study with vertebral fractures had a greater height loss than those without fractures, it was apparent that age, rather than HHL, is the best way to determine who is most likely to develop vertebral fractures.

Spinal Osteoarthritis Is Associated With Stature Loss Independently of Incident Vertebral Fracture in Postmenopausal Women.

Retrospective observational study from the Nagano Cohort Study. Clarify the association between spinal osteoarthritis and loss of stature in postmenopausal women. Loss of stature with aging is known to deteriorate health-related quality of life and has been implicated with increased mortality. Although the association of vertebral fracture with height loss has been well documented, the relationship between stature loss and spinal osteoarthritis remains unclear. We retrospectively investigated Japanese postmenopausal women recruited from the Nagano Cohort Study. The participants were outpatients at a primary care institute in Nagano prefecture, Japan. A total of 977 postmenopausal patients (mean age: 65.8 yr) completed a minimum of 1 year of follow-up, with an average observation period of 7.6 years. Quartile analysis on the prevalence of spinal osteoarthritis and occurrence of incident fracture was performed based on the rate of stature change per year (Δ cm/yr). Multiple regression analysis was also conducted to identify the determinants of stature change. The lower quartiles of stature change rate (i.e., more rapid stature loss) displayed a significantly higher prevalence of spinal osteoarthritis (P < 0.001) and incident vertebral fracture (P < 0.001). A statistically significant independent negative association for spinal osteoarthritis prevalence with change in stature was revealed by multiple regression analysis after adjusting for confounders including incident vertebral fracture. The partial regression coefficient for spinal osteoarthritis was -0.18 (95% confidence interval -0.33 to -0.03; P = 0.016). This study demonstrated an independent association of spinal osteoarthritis with stature loss in postmenopausal women. Adequate understanding of this relationship and appropriate treatment approaches will help improve health-related quality of life in elderly patients. 3.

Serum microRNAs as novel biomarkers for osteoporotic vertebral fractures.

Vertebral fractures are the hallmark of osteoporosis. MicroRNAs (miRNAs) are a prominent class of gene regulators likely to affect bone homeostasis, including bone remodelling and fracture healing by altering gene expression in bone cells. This study sought to compare the levels of circulating miRNAs in older women with osteoporotic vertebral fractures, and/or low BMD and healthy controls, and to correlate miRNAs expression levels with BTMs. A single-site, case-control, observational, cross-sectional study at a university hospital. Altogether, 126 postmenopausal women belonging to four different groups were included: healthy (n=42), low BMD and no vertebral fractures (n=39), vertebral fractures and low BMD without a treatment (n=26), or receiving a treatment for osteoporosis (n=19). Serum samples from all participants were analyzed for 21 microRNA bone biomarkers. We identified 7 significantly (p<0.05) up-regulated miRNAs (miR-375, miR-532-3p, miR-19b-3p, miR-152-3p, miR-23a-3p, miR-335-5p, miR-21-5p) in patients with vertebral fractures and low BMD compared to low BMD and healthy individuals, regardless of osteoporosis treatment. No significant differences existed between low BMD and healthy controls. We observed 24 significant correlations (P<0.05) between miRNAs and BTMs (CTX, PINP, OC and bone ALP). Specific circulating miRNAs reflect the presence of osteoporotic vertebral fractures in postmenopausal women. They are unlikely to reflect low BMD, and more likely changes in bone quality or fracture healing. The effects of osteoporosis treatment on the selected miRNAs appear to be weaker than effects caused by vertebral fractures. The correlation between miRNAs and BTMs suggest that miRNAs may be involved in bone turnover or fracture healing.

Association of Fat Body Mass With Vertebral Fractures in Postmenopausal Women With Early Breast Cancer Undergoing Adjuvant Aromatase Inhibitor Therapy

Aromatase inhibitors induce a profound depletion in serum estrogen levels. Postmenopausal obese women receiving aromatase inhibitor therapy may be at increased risk of bone fractures owing to the detrimental association of adiposity with bone quality and the loss of the protective effect of estrogens on bone mineral density. To determine whether fat body mass (FBM), as measured by dual-energy x-ray absorptiometry, is associated with vertebral fracture prevalence in postmenopausal women undergoing adjuvant aromatase inhibitor therapy for breast cancer. In this single-center, cross-sectional study, 556 postmenopausal women with early-stage breast cancer were consecutively enrolled from October 15, 2013, to June 30, 2018, and stratified according to whether they were aromatase inhibitor-naive or aromatase inhibitor-treated for at least 2 years. The database was locked on December 31, 2018, and data analysis was completed on February 28, 2019. Eligible patients in both groups had normal renal function, no metabolic diseases, and no previous or current treatment with antiosteoporotic drugs or glucocorticoids. Previous chemotherapy, but not tamoxifen, was permitted. Data were gathered once, at baseline. Vertebral fracture prevalence associated with FBM in aromatase inhibitor-naive and aromatase inhibitor-treated patients. Of the 556 women enrolled, the mean age was 63.0 years (95% CI, 62.2-63.8 years). The 195 aromatase inhibitor-treated patients were older than the 361 aromatase inhibitor-naive patients (mean age, 66.1 vs 61.3 years; P < .001), had a higher body mass index (mean, 26.4 vs 25.3; P = .009), were less likely to engage in physical activity (65.3% vs 73.7%; P = .03), and were less likely to consume alcoholic beverages (68.4% vs 80.9%; P = .001). Among the aromatase inhibitor-naive patients, the vertebral fracture prevalence was higher in the subgroup with FBM below the median value than in those with high FBM, but the difference was not statistically significant (19.2% vs 13.3%; P = .13). Conversely, the proportion of vertebral fractures in the aromatase inhibitor-treated group was 20.0% in patients with low FBM vs 33.3% in patients with high FBM (P = .04). An opposite trend in the association of FBM with vertebral fracture prevalence according to aromatase inhibitor group was shown by multivariable analysis in the propensity score-matched sample: odds ratio, 0.38 (95% CI, 0.12-1.19) and 1.94 (95% CI, 0.67-5.64) in the aromatase inhibitor-naive and aromatase inhibitor-treated groups, respectively (odds ratio for the interaction, 5.77 [95% CI, 1.08-30.81]; P for interaction term = .03). Fat body mass may be associated with fragility-related fractures in patients with breast cancer who undergo aromatase inhibitor therapy. If these data are confirmed, obesity could be included in the algorithm for assessing fracture risk and selecting patients to receive bone resorption inhibitors.

The Effect of 1 Year of Romosozumab on the Incidence of Clinical Vertebral Fractures in Postmenopausal Women With Osteoporosis: Results From the FRAME Study.

ABSTRACTRadiographic vertebral fractures (VFxs) are the most common fractures in osteoporosis and are associated with increased morbidity, mortality, and costs. A subset of VFxs manifest clinically, usually with a sudden onset of severe back pain. Romosozumab is a monoclonal antibody that binds and inhibits sclerostin, increasing bone formation and decreasing bone resorption, leading to rapid and large increases in bone density and strength and reduction in fracture risk. The FRAME (Fracture Study in Postmenopausal Women with Osteoporosis) study of postmenopausal women with osteoporosis demonstrated a significant reduction in new VFxs with romosozumab versus placebo. Here, we report the effect of romosozumab versus placebo on clinical VFx incidence over 12 months in women reporting back pain suggestive of VFxs. FRAME enrolled 7180 postmenopausal women with osteoporosis, mean age 70.9 years (hip T‐score −2.5 to −3.5). In the first year of the study, women received monthly romosozumab 210 mg (n = 3589) or placebo (n = 3591). At regular monthly visits, women reporting back pain suggestive of a clinical VFx had a confirmatory spine X‐ray. Clinical VFx risk in the romosozumab group versus the placebo group was calculated by Cox‐proportional hazards model. Of 119 women in FRAME with back pain suggestive of a clinical VFx over 12 months, 20 were confirmed to have experienced a new/worsening VFx. Three women receiving romosozumab had a clinical VFx (<0.1% of 3589 women) versus 17 (0.5% of 3591 women) receiving placebo resulting in a reduction in clinical VFx risk of 83% in the romosozumab group versus placebo through 12 months (HR 0.17; 95% CI, 0.05 to 0.58; p = 0.001). In the three romosozumab‐treated women, clinical VFxs occurred within the first 2 months of the study with no further clinical VFxs throughout the year. Romosozumab treatment for 12 months was associated with rapid and large reductions in clinical VFx risk versus placebo. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

The Impact of Smoking on Bone Metabolism, Bone Mineral Density and Vertebral Fractures in Postmenopausal Women

Background: Smoking is recognized among the risk factors for osteoporosis, but only few studies have comprehensively explored its influence on bone metabolism and strength. We aimed to evaluate smoking effects on calcium-phosphate metabolism, bone mineral density (BMD) and fracture risk in postmenopausal women. Methods: Our sample included 1067 postmenopausal women who arrived to our osteoporosis outpatient clinic. Anamnestic data, smoking habits (categorized as never, former, and current; and by smoking intensity and duration), biochemical parameters, lumbar/femoral BMD, and presence of vertebral fractures were recorded. In a subsample of 357 women, the changes in BMD after a 2-yr follow-up period were also assessed. Results: Current smokers had shorter reproductive age, lower body mass index, and higher prevalence of heavy alcohol consumption than former/never smokers. They also had lower PTH values and weaker linear association between serum vitamin D and parathyroid hormone (current β = −0.11[SE = 0.004]; former β = −0.14[SE = 0.01]; never β = −0.20[SE = 0.003]; p < 0.01 for all). Baseline BMD did not reflect differences based on smoking habits, duration or intensity. However, after 2 years, only current smokers significantly worsened in femural BMD. After adjustment for confounders, the chance of having sustained vertebral fractures at the first evaluation increased by 74% (95% confidence interval:1.07–2.83) in current compared with never smokers, especially among heavy smokers. Conclusions: Smoking may negatively affect bone by inhibiting vitamin D-parathyroid hormone axis, reducing estrogen exposure, promoting risky health behaviors, and accelerating bone loss, especially at the femur. No significant differences were observed in these outcomes among former smokers, suggesting that quitting smoking has beneficial effects on bone health.

Abaloparatide for risk reduction of nonvertebral and vertebral fractures in postmenopausal women with osteoporosis: a network meta-analysis

SummaryThis network meta-analysis assessed the efficacy of abaloparatide versus other treatment options to reduce the risk of fractures in women with postmenopausal osteoporosis. The analysis indicates that abaloparatide reduces the risk of fractures in women with postmenopausal osteoporosis versus placebo and compared with other treatment options.IntroductionThis network meta-analysis (NMA) assessed the relative efficacy of abaloparatide versus other treatments to reduce the risk of fractures in women with postmenopausal osteoporosis (PMO).MethodsPubMed®, Embase®, and the Cochrane Central Register of Controlled Trials were searched for randomized controlled trials published before December 20, 2017, that included women with PMO who were eligible to receive interventions for primary or secondary fracture prevention. The NMA was conducted by fracture site (vertebral [VF], nonvertebral [NVF], and wrist), with the relative risk (RR) of fracture versus placebo the main clinical endpoint. The NMA used fixed-effects and random-effects approaches.ResultsA total of 4978 articles were screened, of which 22 were included in the analysis. Compared with other treatments, abaloparatide demonstrated the greatest treatment effect relative to placebo in the VF network (RR = 0.13; 95% credible interval [CrI] 0.04–0.34), the NVF network (RR = 0.50; 95% CrI 0.28–0.85), and the wrist fracture network (RR = 0.39; CrI 0.15–0.90). Treatment ranking showed that abaloparatide had the highest estimated probability of preventing fractures in each of the networks (79% for VF, 70% for NVF, and 53% for wrist fracture) compared with other treatments. Individual networks demonstrated a good level of agreement with direct trial evidence and direct pair-wise comparisons.ConclusionsThis NMA indicates that abaloparatide reduces the RR of VF, NVF, and wrist fracture in women with PMO with or without prior fracture versus placebo, compared with other treatment options. Limitations include that adverse events and drug costs were not considered, and that generalizability is limited to the trial populations and endpoints included in the NMA.

Status of bone strength and factors associated with vertebral fracture in postmenopausal women with type 2 diabetes.

The aim of this study was to assess the status of bone mass, microarchitecture, and factors associated with vertebral fracture in postmenopausal women with type 2 diabetes mellitus (T2DM). We consecutively enrolled 285 women (aged 60.7 ± 6.9 y) with T2DM who underwent bone mineral density (BMD) and trabecular bone score (TBS) assessment using dual-energy x-ray absorptiometry; T8-S1 lateral spine radiographs; laboratory evaluation; and interviews regarding clinical risk factors based on the fracture risk assessment tool (FRAX). Low bone mass and deteriorated bone microarchitecture were observed in 63.2% and 72.6% of women with T2DM, respectively. TBS was correlated with lumbar spine, femoral neck, and total hip BMD. Significant differences in TBS were observed between the normal BMD, osteopenia, and osteoporosis groups. Age, vertebral fracture, and bone-specific alkaline phosphatase significantly differed among groups with different T scores or those classified by TBS categories. Bone-specific alkaline phosphatase was inversely correlated with BMD and TBS but positively with glycated hemoglobin. BMD showed a weaker correlation with vertebral fracture than TBS, TBS and BMD, FRAX, and TBS-adjusted FRAX. Low bone mass and deteriorated TBS were noted in approximately two-thirds of T2DM women and was also associated with vertebral fracture. In addition to aging, poor glycemic control may play an important role in bone remodeling, which may be associated with changes in bone strength in T2DM women. Bone strength together with clinical risk factors has the strongest association with fracture, and may potentially be useful to identify women with T2DM at risk.

High-intensity exercise did not cause vertebral fractures and improves thoracic kyphosis in postmenopausal women with low to very low bone mass: the LIFTMOR trial.

The LIFTMOR trial demonstrated a novel, HiRIT program notably improved bone mass in postmenopausal women with osteopenia and osteoporosis. While no clinical signs or symptoms of vertebral crush fracture were evident during the trial, anecdotal feedback suggests that concerns about safety of HiRIT in the osteoporosis demographic remain.The aim of the current work was to assess vertebral body morphology, Cobb angle, and clinical measures of thoracic kyphosis in participants in the LIFTMOR trial for evidence of vertebral fracture following 8 months of supervised HiRIT. Participants were randomized to either 8months of 30-min, twice-weekly, supervised HiRIT or unsupervised, low-intensity, home-based exercise (CON). Lateral thoracolumbar DXA scans (Medix DR, Medilink, France) were performed at baseline and follow-up. Cobb angle was determined, and vertebral fracture identification was performed using the semiquantitative Genant method. Clinical kyphosis measurements were performed in relaxed standing (neutral posture) and standing tall using an inclinometer and a flexicurve. The HiRIT group exhibited a reduction in inclinometer-determined standing tall thoracic kyphosis compared to CON (- 6.7 ± 8.2° vs - 1.6 ± 8.1°, p = 0.031). Both the HiRIT and CON groups exhibited within-group improvement in kyphosis in relaxed standing as measured by both inclinometer and flexicurve (p < 0.05). There were no changes in vertebral fracture classification in the HiRIT group post-intervention. A single, new, wedge deformity was observed for CON. Supervised HiRIT was not associated with an increased risk of vertebral fracture in postmenopausal women with low bone mass. Indeed, a clinically relevant improvement in thoracic kyphosis was observed following 8months of supervised HiRIT, further supporting its efficacy as an osteoporosis intervention for postmenopausal women with low to very low bone mass.

Оцінка факторів ризику, пов’язаних з рівнем фізичної активності в дитинстві та на момент обстеження, у постменопаузальних жінок з остеопорозом та переломами тіл хребців

Today, discussions are continuing on the effect of regular exercise in childhood in preventing bone loss in postmenopausal women, as well as the positive effect of physical exercise (PE) in the prevention of osteoporotic fractures in older age groups. Purpose : to assess risk factors associated with the level of physical activity (PA) in childhood and at the time of the examination in postmenopausal women with osteoporotic and vertebral body fractures. Material & Methods: in a one-time study examined 115 postmenopausal women aged 50–89 years. For analysis, the patients were divided into two groups: I (control) group – persons without any osteoporotic fractures in history (n=84), II (main) group – patients with vertebral body fractures at the level of the thoracic and lumbar spine (n=31). With the help of a specially developed questionnaire, the authors evaluated the characteristics of the PA of patients at different age periods of life and at the time of the survey. Results : no significant differences were found in the frequency and types of sports in childhood between groups, depending on the presence of vertebral body fractures. The majority of patients with vertebral fractures (85,7%) began regular exercises of PA in childhood with the age of 10 years (41,7% in the control group, p=0,04), and in 57,1% of individuals the duration of these exercises was 1–4 years and did not differ from the control group. The frequency, type and duration of physical activity classes and the duration of physical therapy procedures, as well as the level of daily physical activity, did not significantly differ in women depending on the presence of vertebral body fractures, although the proportion of people who worked on a regular basis in sections was significantly higher among patients with vertebral fractures (41,9%) compared with individuals without fractures (10,7%, p=0,0002). In addition, the proportion of women in the control group who were physically active 6 or more hours per day was significantly higher (14,3%) compared with the corresponding indicator of the main group (3,2%, р=0,04). Conclusion : women with vertebral fractures were more often practiced regularly in sections and less physically active than those without fractures. The duration, regularity and age of starting sports in childhood can affect the risk of vertebral fractures in postmenopausal women, requires further study.

Identification of asymptomatic frailty vertebral fractures in post-menopausal women.

Vertebral fractures are associated with persistent pain, disability and mortality. However, around two thirds of women with vertebral fractures are unaware of them. We aimed to analyze which factors could mostly be associated to the presence of vertebral fractures in post-menopausal women, and evaluate the effectiveness of current screening criteria for the detection of vertebral fractures in an outpatient setting. We evaluated 1132 post-menopausal women referred to the osteoporosis outpatient clinic of the Geriatrics Department of Padova. For each participant we assessed: anthropometric data, femoral and lumbar bone mineral density (BMD), dorso-lumbar X-rays, bone metabolism markers. Current recommendations for X-ray examinations by SIOMMMS (Società Italiana di Osteoporosi, Metabolismo Minerale e Malattie dello Scheletro) and ISCD (International Society of Clinical Densitometry) versus routine X-ray examinations were considered, and fracture risk was assessed through the derived FRAX (DeFRA) tool. Of the women included in our study, 28% presented vertebral fractures, most of these previously unknown (82.8%). Lumbar BMD did not differ between patients with and without vertebral fractures. According to SIOMMMS guidelines, 50% of patients <60 years with unknown vertebral fractures would have been excluded from spinal X-ray examination. According to ISCD recommendations, the number of patients excluded reached 94.6% in the <60 age-group and 84.9% in the 60-70 age-group. The under-identification of vertebral fractures led to the 10-year risk of fractures computed by DeFRA being underestimated by around 15%. BMD, particularly in the lumbar site, may not properly predict the presence of vertebral fractures in post-menopausal women. Improvement of the current recommendations for spinal X-ray examination may lead to early identification and better management of patients with vertebral fractures.