Risk Of Vertebral Fractures In Patients Research Articles

Skeletal and nonskeletal consequences of hypoparathyroidism.

Hypoparathyroidism, despite the conventional therapy with calcium and active vitamin D, can lead to skeletal and nonskeletal abnormalities. Chronic hypoparathyroidism is associated with a significant reduction in bone remodeling, increases in areal and volumetric bone density, and improvement in trabecular microarchitecture and in trabecular bone score. Regardless of these advantages in bone mass and microarchitecture, recent data suggest an increased vertebral fracture risk in patients with nonsurgical hypoparathyroidism. Moreover, chronic hypoparathyroidism can lead to abnormalities in multiple organ systems, including the neurological, cardiovascular, renal, neuropsychiatric, ocular, and immune systems. Nephrocalcinosis, nephrolithiasis, and renal insufficiency, as well as decreased quality of life and cataracts, are common in patients with hypoparathyroidism. An increased incidence of hospitalization due to infections and a greater risk of cardiovascular diseases are observed in patients with hypoparathyroidism, particularly in those with nonsurgical disease. All these abnormalities may be because of the disease itself or complications of therapy. We herein reviewed the skeletal and nonskeletal consequences of hypoparathyroidism in patients conventionally managed with calcium and active vitamin D.

The efficiency and safety of alendronate versus teriparatide for treatment glucocorticoid-induced osteoporosis: A meta-analysis and systematic review of randomized controlled trials.

Glucocorticoid-induced osteoporosis (GIOP) is the most common secondary osteoporosis, alendronate (ALE) and teriparatide (TPTD) are widely used in the treatment of GIOP. However, which of these two drugs has a better curative effect needs the support of evidence-based medicine. We searched PubMed, Embase, Cochrane Library, Web of Science, and Google Scholar for randomized controlled trials of ALE and TPTD in the treatment of glucocorticoid-induced osteoporosis until February 2022. These patients included in the study took glucocorticoid doses greater than 7.5 mg/d for more than 3 months before treatment with ALE and TPTD. The risk ratio (RR) and its 95% confidence interval (CI) are used as the influence index of discontinuous data, and the standardized mean difference (SMD) and its 95% CI are used as the influence index of continuous data. A total of 4102 patients were enrolled in all 5 studies that met the admission criteria. We found that compared with ALE, TPTD could reduce the rate of new vertebral fracture (RR = 0.13, 95% CI: 0.05-0.34, P<0.00001). TPTD increased LS bone mineral density (BMD) (0.53, 95% CI 0.42-0.64, P<0.00001), TH BMD (0.17, 95% CI 0.05-0.28, P = 0.004) and FN BMD (0.17, 95% CI 0.05-0.29, P = 0.006) compared to ALE. However, there was no significant difference in the incidence of non-vertebral fracture and adverse events between the two groups. Compared with ALE, TPTD is an effective drug to reduce vertebral fracture risk in patients with GIOP. Furthermore, long-term use of TPTD can increase the bone mineral density of LS, FN, and TH.

Incidence and risk factors for vertebral fracture in rheumatoid arthritis: an update meta-analysis.

This study was conducted to investigate the prevalence of vertebral fracture (VF) and its risk in patients with rheumatoid arthritis (RA) as compared to healthy individuals, and to explore the underlying risk factors. The electronic databases of PubMed, EMBASE, and the Cochrane Library were applied to search for the relevant literatures, which reported the prevalence of VF in both RA patients and healthy controls (up to Mar 31, 2021). The non-weighted prevalence of VF, pooled estimates of odds ratio (OR), and its 95% confidence intervals (CI) were calculated with the use of random-effects model; between-study heterogeneity was evaluated by Cochrane Q statistic, then was quantified with I2. Publication bias was evaluated using Egger's linear regression test. A number of 867 literatures were identified after searching for online databases, based on the inclusion and exclusion criteria, 11 eligible studies, which comprising 3805 RA patients and 59,517 healthy participants, were finally incorporated in meta-analysis. The results showed that RA patients had an increased prevalence of VF (20.29 vs 8.63%), and an elevated risk for VF (OR = 3.04, 95% CI 1.97-4.71) as compared to healthy population. Additional subgroup analysis suggested that age, body mass index (BMI), disease activity, and drug therapy might be associated with risk of VF in RA. Overall, our study demonstrated an increased risk of VF in patients with RA, suggesting that age, race, BMI, disease activity, and drug therapy may be represented as risk factors contributing to the occurrence of VF in RA. Key Points • RA patients had the increased prevalence and risk of vertebral fracture (VF) as compared to healthy population. • Age, race, BMI, disease activity, and drug therapy might be associated with VF in RA. • Our findings would be helpful for the early evaluation of RA patients with high VF risk.

Treatment of Acromegalic Osteopathy in Real-life Clinical Practice: The BAAC (Bone Active Drugs in Acromegaly) Study.

Vertebral fractures (VFs) are a frequent complication of acromegaly, but no studies have been so far published on effectiveness of antiosteoporotic drugs in this clinical setting. To evaluate whether in real-life clinical practice bone active drugs may reduce the risk of VFs in patients with active or controlled acromegaly. Retrospective, longitudinal study including 9 tertiary care endocrine units. Two hundred and forty-eight patients with acromegaly (104 males; mean age 56.00 ± 13.60 years) were evaluated for prevalent and incident VFs by quantitative morphometric approach. Bone active agents were used in 52 patients (20.97%) and the median period of follow-up was 48 months (range 12-132). During the follow-up, 65 patients (26.21%) developed incident VFs in relationship with pre-existing VFs (odds ratio [OR] 3.75; P < .001), duration of active acromegaly (OR 1.01; P = .04), active acromegaly at the study entry (OR 2.48; P = .007), and treated hypoadrenalism (OR 2.50; P = .005). In the entire population, treatment with bone active drugs did not have a significant effect on incident VFs (P = .82). However, in a sensitive analysis restricted to patients with active acromegaly at study entry (111 cases), treatment with bone active drugs was associated with a lower risk of incident VFs (OR 0.11; P = .004), independently of prevalent VFs (OR 7.65; P < .001) and treated hypoadrenalism (OR 3.86; P = .007). Bone active drugs may prevent VFs in patients with active acromegaly.

The Risk and Consequences of Vertebral Fracture in Patients with Ankylosing Spondylitis: A Population-based Data Linkage Study.

To compare the long-term prevalence, incidence, and outcomes of vertebral fracture (VF) between ankylosing spondylitis (AS) patients and matched controls, including the role of extraarticular manifestations (EAM) and osteoporosis. This was a statewide observational study using linked health data for 2321 patients with AS and 22,976 controls presenting to hospital from 1980 to 2015. Data were analyzed using incidence rates (per 1000 person-yrs) and ratios (IRR), multivariable Cox proportional hazards regression, and Kaplan-Meier survival curves. Over a median 13.92 (interquartile range 7.58-21.67) years of follow-up, patients with AS had a greater VF prevalence and greater incidence of developing a new VF compared to controls (9.3% vs 2.5%, 6.8% vs 1.9%, respectively, all P < 0.001). Patients with AS had an increased risk of developing a VF after adjustments for age, sex, and osteoporosis (HR 2.55, 95% CI 2.11-3.09) compared to controls; this risk remained throughout the study period. Patients with AS were 5 years younger at time of first VF (P = 0.008) and had a greater likelihood of a recurrent VF (IRR 4.64; 95% CI 4.54-4.75) compared to respective controls. Mortality overall was comparable between patients with AS and controls after adjustment for age, sex, osteoporosis, and VF status (HR 0.90; 95% CI 0.80-1.01). The significantly increased risk of VF in patients with AS has not altered following the introduction of tumor necrosis factor inhibitor treatment. Although patients with AS experience a first VF at a younger age than controls, this does not lead to an increased risk of death.

Digital Tomosynthesis and Fractal Analysis Predict Prevalent Vertebral Fractures in Patients With Multiple Myeloma: A Preliminary In Vivo Study.

OBJECTIVE. The objective of this study was to investigate the association of fractal-derived bone microstructural parameters with vertebral fracture status using in vivo digital tomosynthesis images of the spine. MATERIALS AND METHODS. Digital tomosynthesis images of the thoracic and lumbar spine from T1 to L5 were acquired from 36 patients with newly diagnosed multiple myeloma or monoclonal gammopathy of uncertain significance (age range, 39-85 years old). Scans were performed with patients in the supine position with reconstructed planes formed in the coronal direction. Bone mineral density (BMD) was recorded for 10 patients who had recently undergone dual x-ray absorptiometry. Vertebral fracture and lytic lesion status was determined by a radiologist from digital radiographs. Radiologist interpretation was reviewed to identify levels with a minimum number of fractures or lesions. For fractal analysis, the largest possible cuboid volume of interest within the cancellous bone was cropped from T7 and T11 images. Mean and SD of fractal variables between slices of fractal dimension (FD, a measure of self-similarity in the texture), mean lacunarity (λ, a measure of heterogeneity) and the slope of lacunarity versus box size relationship (Sλ, a measure of sensitivity of heterogeneity to size scale) were calculated using a box-counting method. A generalized estimating equation (GEE) platform was used to examine fractal variables as predictors of fracture status. RESULTS. Fracture status was not significantly associated with sex, race, age, stage of myeloma, presence of lesion in the spine, or BMD. In light of these results, no correction was made for these variables in further analyses of fractal variables. No interaction was found between vertebral level and any of the fractal variables (p = 0.12-0.77). Therefore, vertebral level was not considered further as an independent variable. Logistic regression analysis within GEE indicated that probability of fracture decreased with increasing mean FD (p = 0.02). In contrast, probability of fracture increased with increasing mean λ (p = 0.03). Although not to a statistically significant degree, probability of fracture increased with increasing mean Sλ (p = 0.08), SD of FD (p = 0.07), SD of λ (p = 0.07), and SD of Sλ (p = 0.06). CONCLUSION. We found FD and lacunarity calculated within the cancellous centrum of T7 and T11 vertebrae to be significantly associated with the presence of a vertebral fracture in this cohort. The decreased probability of fracture with increasing fractal dimension and increased probability of fracture with increasing lacunarity are consistent with the idea that cancellous bone with a better organized trabecular architecture is mechanically more competent. To our knowledge, this is the first in vivo evidence that fractal analysis of vertebral bone from tomosynthesis images may be useful in assessing vertebral fracture risk in patients with multiple myeloma.

A scoring assessment tool for the risk of vertebral fractures in patients with type 2 diabetes mellitus.

Development of assessment tool for fracture risk is an urgent task, because bone mineral density (BMD) is less useful for evaluating fracture risk in type 2 diabetes mellitus (T2DM). In total, 808 T2DM patients were enrolled in this cross-sectional study. To develop a scoring assessment tool using clinical risks for vertebral fracture (VF), we evaluated which variables were associated with VF by logistic regression analysis, and categorized these variables based on cut-off values obtained by using receiver operating characteristic (ROC) curves. For calculation of the score, the relative weight of the factors was determined, and a tentative score was assigned. Then, cut-off point of the score was examined to predict VF. Logistic regression analyses showed that age, diabetes duration, body mass index (BMI), serum albumin, and T score at femoral neck (FN-T score) were associated with VF risk. Parameter estimates for each risk factor obtained by logistic analyses were converted to risk scores (maximum score 23). ROC analysis showed that 8.5 was the cut-off value for detecting VF. Multiple logistic regression analysis adjusted for confounding factors showed that score ≥9 was significantly associated with an increased risk of prevalent VF (odds ratio 1.99, 95% confidence interval 1.22-3.24, p = 0.006). This is the first study to show that a scoring assessment tool using age, duration of diabetes, BMI, serum albumin, and FN-T score is useful to estimate VF risk in patients with T2DM, being more sensitive than BMD alone in detecting bone fragility.

Mortality and vertebral fracture risk associated with long-term oral steroid use in patients with chronic obstructive pulmonary disease: A systemic review and meta-analysis.

Short-term oral steroid use may improve lung function and respiratory symptoms in patients with stable chronic obstructive pulmonary disease (COPD). However, long-term oral steroid (LTOS) use is not recommended owing to its potential adverse effects. Our study aimed to investigate whether chronic use of oral steroids for more than 4 months would increase mortality and vertebral fracture risk in patients with stable COPD. A systemic search of the PubMed database was conducted, and meta-analysis was performed using Review Manager 5.3. Five studies with a total of 1795 patients showed there was an increased risk of mortality in patients using LTOS (relative risk, 1.63; 95% confidence interval (CI), 1.19–2.23; p < 0.0001; I 2 = 86%). In addition, four studies with a total of 17,764 patients showed there was an increased risk of vertebral fracture in patients using LTOS (odds ratio, 2.31; 95% CI, 1.52–3.50; p = 0.03; I 2 = 65%). Our meta-analysis showed LTOS was associated with increased mortality and vertebral fracture risk in patients with COPD, and this risk may be due to the adverse effects of LTOS and progression COPD.

Overweight and underweight are risk factors for vertebral fractures in patients with type 2 diabetes mellitus.

The aim of this cross-sectional study was to examine the association between body mass index (BMI) and the prevalence of vertebral fracture (VF) in Japanese patients with type 2 diabetes (T2DM). A total of 798 patients with T2DM were enrolled. VF was determined semi-quantitatively using lateral X-ray films. The association between BMI quartiles (Q1: ≤ 21.2kg/m2, Q2: 21.3-23.4kg/m2, Q3: 23.5-25.8kg/m2, Q4: 25.9≤ kg/m2) and the presence of VF was examined. Multiple logistic regression analyses adjusted for age, sex, diabetes duration, hemoglobin A1c (HbA1c), estimated glomerular filtration rate, and albumin showed that Q1, Q3, and Q4 were significantly associated with an increased VF risk compared to Q2, which served as a reference [Q1; odds ratio (OR) = 1.91, 95% confidence interval (CI) 1.24-2.95, p = 0.004, Q3; OR = 1.65, 95% CI 1.07-2.55, p = 0.023, and Q4; OR = 2.18, 95% CI 1.39-3.41, p < 0.001]. Moreover, these associations remained significant after additional adjustment for femoral neck T-score, a bone resorption marker, urinary N-terminal cross-linked telopeptide of type-I collagen, and use of insulin and thiazolidinedione. Our study shows for the first time that both overweight and underweight were associated with the bone mineral density (BMD)-independent risk of VF in patients with T2DM. Therefore, body weight control should be considered as a protective measure against diabetes-related bone fragility.

Inducible Wnt16 inactivation: WNT16 regulates cortical bone thickness in adult mice.

Substantial progress has been made in the therapeutic reduction of vertebral fracture risk in patients with osteoporosis, but non-vertebral fracture risk has been improved only marginally. Human genetic studies demonstrate that the WNT16 locus is a major determinant of cortical bone thickness and non-vertebral fracture risk and mouse models with life-long Wnt16 inactivation revealed that WNT16 is a key regulator of cortical thickness. These studies, however, could not exclude that the effect of Wnt16 inactivation on cortical thickness might be caused by early developmental and/or growth effects. To determine the effect of WNT16 specifically on adult cortical bone homeostasis, Wnt16 was conditionally ablated in young adult and old mice through tamoxifen-inducible Cre-mediated recombination using CAG-Cre-ER; Wnt16flox/flox (Cre-Wnt16flox/flox) mice. First, 10-week-old Cre-Wnt16flox/flox and Wnt16flox/flox littermate control mice were treated with tamoxifen. Four weeks later, Wnt16 mRNA levels in cortical bone were reduced and cortical thickness in femur was decreased in Cre-Wnt16flox/flox mice compared to Wnt16flox/flox mice. Then, inactivation of Wnt16 in 47-week-old mice (evaluated four weeks later) resulted in a reduction of Wnt16 mRNA levels, cortical thickness and cortical bone strength with no effect on trabecular bone volume fraction. Mechanistic studies demonstrated that the reduced cortical bone thickness was caused by a combination of increased bone resorption and reduced periosteal bone formation. In conclusion, WNT16 is a crucial regulator of cortical bone thickness in young adult and old mice. We propose that new treatment strategies targeting the adult regulation of WNT16 might be useful to reduce fracture risk at cortical bone sites.

Indications of Increased Vertebral Fracture Risk in Patients With Type 2 Diabetes

To the Editor: We welcome the timely study by Napoli and colleagues.1 Patients with type 2 diabetes suffer from an increased risk of hip fractures in spite of normal to higher than normal bone mineral density. In contrast to hip fractures, vertebral fractures may be underdiagnosed in observational studies that rely on registry data. Registries are often based on clinical findings, and examination of the spine with X-ray is only performed in cases of clinical indication or as a chance finding. The prevalence of vertebral fractures in males with type 2 diabetes have been reported as high as 42%,2 and a recent meta-analysis of observational studies report increased rates of fragility fractures in both men and women with type 2 diabetes.3 In the meta-analysis, the incident rate ratio for vertebral fractures in type 2 diabetes (both men and women) was 1.22 (95% confidence interval (CI), 0.98 to 1.48) and thus borderline significantly increased. The odds ratio reported by Napoli and colleagues1 when adjusted by areal bone mineral density, 1.28 (95% CI, 0.81 to 2.00), is very similar to the findings of the mentioned meta-analysis and also the registry-based odds ratio of 1.34 (95% CI, 0.97 to 1.86) previously reported by Vestergaard and colleagues.4 Although the authors conclude that the risk of prevalent or incident vertebral fracture in elderly men with type 2 diabetes is not substantially increased compared with men without diabetes, we propose that this finding may be caused by a type II error. The number of incident fractures in the study was low and the power to detect modest associations (as mentioned by the authors themselves) is modest. A trend is present toward a 20% to 30% increased risk of vertebral fracture in patients with type 2 diabetes, although the estimates are only borderline significant.1, 3, 4 Type 2 diabetes is associated with a 30% increased post–vertebral fracture mortality.5 Therefore, we wish to highlight the importance of further evaluation of the risk of vertebral fracture in both men and women with type 2 diabetes, because these patients may be at an increased risk of vertebral fracture in addition to the high risk of hip fracture. Dr. Langdahl reports personal fees from Amgen, personal fees from Eli Lilly, personal fees from UCB, personal fees from Teva, grants from Novo Nordisk, grants from Amgen, outside the submitted work. Dr. Harsløf, Dr. Hygum, and Dr. Starup-Linde report no conflict of interest.

Reply to: Indications of Increased Vertebral Fracture Risk in Patients With Type 2 Diabetes

Reply to: Indications of Increased Vertebral Fracture Risk in Patients With Type 2 Diabetes

Incidence of Symptomatic Vertebral Fractures Among Newly Diagnosed Autoimmune Diseases Initiating Glucocorticoid Therapy.

Few data are available regarding vertebral fracture risk in patients treated with corticosteroids including patients with interstitial lung disease (ILD). The aim of the present study was to identify risk factors for symptomatic vertebral fracture analyzed in patients with newly diagnosed autoimmune diseases.This was an observational cohort study conducted in the National Hospital Organization-EBM study group from 2006 to 2008. The study subjects were autoimmune disease patients who were newly treated with glucocorticoids (GCs). The primary endpoint was the first occurrence of vertebral fracture diagnosed by x-rays. Cox proportional-hazards regression was used to determine independent risk factors for vertebral fracture with covariates including sex, age, comorbidity, laboratory data, use of immunosuppressants, and dose of GCs. Survival was analyzed according to the Kaplan–Meier method and assessed by the log-rank test.Among 604 patients of mean age 59.5 years and mean GC dose 50.4 mg/d (first 1 months), 19 patient (3.1%) had at least 1 symptomatic vertebral fracture during 1.9 years of follow-up period. Cox regression model demonstrated that the relative risk for symptomatic vertebral fracture was independently higher in patient with ILD (hazard ratio [HR] = 2.86, 95% confidence interval [CI] = 1.10–7.42, P = 0.031) and in every 10-year increment of the age of disease onset (HR = 1.57, 95% CI = 1.09–2.26, P = 0.015). Kaplan–Meier analyses demonstrated that the incidence of vertebral fractures in patients with ILD was significantly higher in comparison with those without ILD.Our results indicate a higher risk of vertebral facture in patients with ILD and elderly patients during the initial GC treatment against autoimmune diseases. There is a need for further, even longer-term, prospective studies subjected patients with autoimmune disease, including ILD, under GC treatment.

Factors associated with vertebral fracture risk in patients with primary hyperparathyroidism.

To examine factors, in addition to bone mineral density (BMD), such as the common calcium-sensing receptor (CASR) gene polymorphisms, associated with vertebral fracture (VFx) risk in primary hyperparathyroidism (PHPT). A cross-sectional analysis of 266 Caucasian PHPT seen as outpatients. Serum calcium (sCa) phosphate metabolism parameters were measured. BMD was assessed by dual-energy X-ray absorptiometry (expressed as Z-score) at lumbar spine (Z-LS) and femoral neck, morphometric VFx by radiograph, and CASR A986S/R990G genotypes by PCR amplification and genomic DNA sequencing. Fractured patients (n=100, 37.6%) had lower sCa (10.8±0.7 mg/dl) and Z-LS BMD (-1.0±1.44), higher age (61±10 years), and prevalence (51%) of ≥1 S alleles of the CASR A986S single-nucleotide polymorphism (SNP; AS/SS), than those not fractured (n=166, 11.2±1.0 mg/dl, -0.57±0.97, 58±13 years, and 38% AS/SS, respectively, P<0.05 for all comparisons). Logistic regression, with VFx as dependent variable, showed independent risks associated with increased age (OR 1.03, 95% CI 1.01-1.06, P=0.006), decreased sCa (OR 1.86, 95% CI 1.28-2.7, P=0.001), and Z-LS BMD (OR 1.4, 95% CI 1.12-1.7, P=0.002) and presence of AS/SS (OR 1.8, 95% CI 1.1-2.9, P=0.05). The presence of two out of three factors (age ≥58 years, sCa <10.8 and Z-LS BMD≤-1.0, and AS/SS genotype) gave an overall OR of 4.2 (95% CI 2.25-7.85, P<0.0001). In PHPT, VFx is associated positively with age, negatively with sCa and spinal BMD, and presence of at least one copy of the CASR A986S SNP.

Once-weekly teriparatide reduces the risk of vertebral fracture in patients with various fracture risks: subgroup analysis of the Teriparatide Once-Weekly Efficacy Research (TOWER) trial

Once-weekly teriparatide (human parathyroid hormone [1-34]) (56.5 μg for 72 weeks) injections provided a vertebral fracture risk reduction in Japanese osteoporotic patients evaluated in the Teriparatide Once-Weekly Efficacy Research (TOWER) trial. Using data from the TOWER trial, a subgroup analysis was performed to study the efficacy of once-weekly teriparatide for a variety of baseline clinical risk factors in placebo (n = 281) and teriparatide (n = 261) groups. Significant fracture risk reductions were observed in the subgroups of individuals aged <75 years [relative risk (RR) 0.06, p = 0.007] and ≥75 years (RR 0.32, p = 0.015). A significant risk reduction was observed among patients with prevalent vertebral fracture in the subgroup with 1 (RR 0.08, p = 0.015) or ≥2 (RR 0.29, p = 0.009) prevalent vertebral fractures, and in those with grade 3 deformity (RR 0.26, p = 0.003). Significant risk reduction was observed in the subgroup with lumbar bone mineral density (BMD) < -2.5 SD (RR 0.25, p = 0.035). In the teriparatide group, no incident fracture was observed in the subgroups with a prevalent vertebral fracture number of 0, with grade 0-2 vertebral deformity, or with lumbar BMD ≥2.5 SD. Significant risk reduction was observed in all of the bone turnover marker and estimated glomerular filtration rate subgroups. In conclusion, once-weekly 56.5 μg teriparatide injection reduced the vertebral fracture risk in patients with varying degrees of fracture risk, age, vertebral fracture number and grade, bone turnover level, and renal function.

Comparison of the Therapeutic Effect of Teriparatide With That of Combined Vertebroplasty With Antiresorptive Agents for the Treatment of New-onset Adjacent Vertebral Compression Fracture After Percutaneous Vertebroplasty

Comparing a prospective group of 32 patients, who underwent percutaneous vertebroplasty (PVP) and who were treated with teriparatide for at least 18 months after a new-onset adjacent vertebral compression fracture (VCF), and compared it with a retrospective group of 33 patients, who received antiresorptive agents combined with repeated PVPs for post-PVP new-onset adjacent VCFs. This comparative study aimed to assess the immediate and mid-term efficacy and safety of teriparatide for treating new adjacent VCFs after vertebroplasty. Vertebroplasty may provoke fractures in adjacent, nonaugmented vertebrae. Subsequent VCFs can occur much sooner and more frequently after PVPs. Antiresorptive agents do not effectively prevent new-onset VCFs or prompt pain relief. Treatment with teriparatide is effective and rapid in increasing spinal bone mineral density (BMD) and in decreasing vertebral fracture risk in patients with osteoporosis. Relevant clinical data were compared between a prospective group of patients who received teriparatide and a retrospective group of patients who received antiresorptive agents and repeated PVPs for new-onset adjacent VCFs after PVP. Data in prospective group, including visual analogue scale scores and BMD were compared with those in a retrospective group. In group A, only 1 new-onset VCF occurred during the mean follow-up period of 22.56 months. In group B, 5 patients (6 vertebrae) developed new-onset VCFs after the second PVP, and 2 of these 5 patients had additional new VCFs after the third PVP. Teriparatide significantly reduced the risk of new VCFs after vertebroplasty (odds ratio=0.18; 95% confidence interval, 0.02-1.64). The increase of lumbar spine BMD was 26.32% after 18 months of treatment with teriparatide and 4.62% after 18 months of treatment with antiresorptive agents. In addition, at the 18-month follow-up, mean visual analogue scale scores had decreased from 8.03±1.97-1.37±0.52 in the teriparatide group and from 7.91±1.95-4.23±1.21 in the antiresorptive group. For the treatment of new-onset adjacent VCF after PVPs, the therapeutic effects of teriparatide is better than that of the combined vertebroplasty and an antiresorptive agent in fracture prevention, BMD change, and sustained pain relief.

Vertebral fractures in patients with chronic obstructive pulmonary disease: the EOLO Study

This study aimed to evaluate the prevalence of vertebral fractures to investigate the determinants of vertebral fracture risk in patients with COPD. The risk of vertebral fractures is strictly related to the severity of the disease. The use of glucocorticoids and the presence of low values of quantitative ultrasound (QUS) may represent additional risk factors. Chronic obstructive pulmonary disease (COPD) appears to be associated with osteoporosis. Our study aimed to evaluate the prevalence of vertebral fractures and to investigate the main determinants of vertebral fracture risk in patients with COPD. In 3,030 ambulatory COPD patients (1,778 men and 1,262 women) aged 50 years or over, we evaluated: COPD severity, presence of vertebral fractures on lateral chest X-ray and bone status by using a quantitative ultrasound device. In men there was a strong association between COPD severity and fractures (p < 0.001), conversely in women the association between COPD severity and fractures was at limit (p = 0.049). In men, but not in women, glucocorticoid treatment was significantly associated with vertebral fractures. The patients with high or moderate risk of osteoporosis presented an increased risk of vertebral fracture (OR 2.71; 95% CI 2.04-3.60 and OR 1.54; 95% CI 1.26-1.88, respectively). Logistic regression analysis showed that COPD severity and glucocorticoid treatment, both inhaled and oral, were associated with increased risk of vertebral fractures. In COPD patients the risk of vertebral fractures is strictly related to the severity of the disease. The use of glucocorticoids and reduced QUS at calcaneous may represent additional risk factors.

Strontium ranelate: An increased bone quality leading to vertebral antifracture efficacy at all stages

Strontium ranelate is a new antiosteoporotic treatment with a dual mode of action, both increasing bone formation and decreasing bone resorption, which rebalances bone turnover in favor of bone formation and increases bone strength. The antifracture efficacy of strontium ranelate, 2 g per day orally, in the treatment of postmenopausal osteoporosis has been investigated in a large-scale, international, multicenter, phase 3 program in which more than 7000 patients were recruited. This article deals with the vertebral antifracture efficacy of strontium ranelate in postmenopausal women with osteoporosis. A significant early (after 1 year) and sustained (over 3 years) antifracture efficacy of strontium ranelate, compared with placebo, was demonstrated in patients with prevalent vertebral fracture with reductions in risk of new vertebral fracture of 49% after 1 year ( P < 0.001) and 41% over 3 years ( P < 0.001). In addition, the relative risk of clinical vertebral fracture was significantly reduced by 52% ( P = 0.003) after 1 year and by 38% ( P < 0.001) over 3 years in the strontium ranelate group compared with placebo. Strontium ranelate was also demonstrated to significantly decrease the relative risk of vertebral fractures by 45% ( P < 0.001) in patients without prevalent vertebral fracture over 3 years, vs. placebo. Bone mineral density was linearly increased during 3 years of treatment with strontium ranelate in comparison with placebo. Strontium ranelate was well tolerated throughout the entire duration of the clinical trials. Thus, strontium ranelate, 2 g per day orally, is a new, effective, and safe treatment for postmenopausal patients with osteoporosis, to reduce the vertebral fracture risk in patients with or without a history of vertebral fracture.

The Skeletal Response to Teriparatide Is Largely Independent of Age, Initial Bone Mineral Density, and Prevalent Vertebral Fractures in Postmenopausal Women With Osteoporosis

In a recent study of women with postmenopausal osteoporosis, treatment with teriparatide for a median of 19 months increased bone mineral density and decreased the risk of vertebral and nonvertebral fractures. Using the same cohort, the current study evaluated the relationship between these therapeutic effects and the patient's baseline age, vertebral bone mineral density, and prevalent vertebral fractures. In women over 65 years of age, treatment resulted in a greater increase in vertebral bone mineral density than in younger women (treatment-by-age interaction, p = 0.037), but baseline age had no effect on the relative risk reduction for vertebral fractures (treatment-by-age interaction, p = 0.558). In women receiving placebo (with calcium and vitamin D), there was an inverse relationship between baseline vertebral bone mineral density and vertebral fracture risk. When compared across bone mineral density tertiles, the effects of teriparatide on the relative risk for developing new vertebral fractures and increase in vertebral bone mineral density did not differ significantly (p = 0.817 and p = 0.615, respectively). Teriparatide treatment significantly decreased vertebral fracture risk in patients with a vertebral bone mineral density T score of less than -33 or a score between -2.1 and -3.3 (p < 0.001 and p = 0.027, respectively) and showed a trend toward reduced fracture risk in the group with a T score greater than -2.1 (p = 0.115). Placebo-treated women with two or more prevalent vertebral fractures had a significantly greater risk of developing new vertebral fractures than women with zero or one prevalent vertebral fracture (p < 0.001). When compared within prevalent vertebral fracture subgroups, the effects of teriparatide on the relative risk for developing new vertebral fractures were similar. The results of this study indicate that teriparatide offers clinical benefit to patients across a broad range of age and disease severity.

Risedronate is effective in reducing vertebral fracture risk in patients on glucocorticoid therapy

Oral bisphosphonates are the drugs most frequently used for the treatment of osteoporosis. Clinicians usually switch between these drugs in clinical practice based on differences in efficacy. We aim to investigate the reasons associated with switching between oral bisphosphonates and to evaluate bone mass response and the incidence of fractures 12 mo after the exchange in a cohort of patients with osteoporosis seen at a tertiary hospital. Patients with osteoporosis who switched between oral bisphosphonates between January 2007 and December 2014 were included. Bone mass measured by dual-energy X-ray absorptiometry and the incidence of fracture were evaluated. A total of 112 patients (73.1 yr old on average, 95.5% women, 98% postmenopausal) were included. All patients were taking alendronate at the time of the switch to risedronate. In 91 patients (81.3%), the following reasons for the exchange of medication were identified: bone loss (59.8%), adverse events (11.6%), and recent fragility fracture (10.7%). One year after the switch, bone densitometry revealed bone loss in 51 patients (45.5%), bone mass maintenance in 34 (30.4%), and bone mass gain in 27 (24.1%). No new vertebral fracture was detected and no nonvertebral fracture was reported in 12 mo of follow-up. Bone mass outcomes (gain, loss, or maintenance) were not associated with the reason for switching between oral bisphosphonates. Similarly, none of the parameters evaluated could predict good densitometric response (gain or maintenance) in this scenario. Our findings suggest that the use of risedronate should not be recommended in the scenario of treatment failure or adverse events following the use of alendronate.