Prior Vertebral Fracture Research Articles

The Value of VFA (Vertebral Fracture Assessment) in Routine DXA Scanning

Abstract Background Low-trauma vertebral fractures are strongly predictive of future fracture risk so are generally given osteoporosis treatment regardless of bone density readings, and for every vertebral fracture presenting clinically, it is estimated that there are another two which are ‘silent’ or may have been ascribed to mechanical back pain. VFA (vertebral fracture assessment) during DXA scanning is a means of assessing the lateral spine for evidence of fractures which may have been undiagnosed prior. The International Society of Clinical Densitometry (ISCD) recommends a VFA in those with a T score <-1.0 plus one of: women ≥70 years, men ≥80 years, historical height loss >4cm, self-reported but undocumented prior vertebral fracture, regular use of steroids. Methods We developed a nurse-led DXA service in late 2021, conducting all scans in according with ISCD and HIQA guidelines however we do VFA on all patients aged over 50 years as it adds minimal time and negligible radiation exposure. In 2023 we commenced recording whether VFA fractures were previously diagnosed, in order to evaluate the benefits of VFA and so determine ongoing practice. To this end, we reviewed all DXA results since service launch for VFA evidence of fractures, and for patients from the calendar year 2023, we noted questionnaire responses and referral information as to whether any vertebral fracture was known of prior. Results There were 3,759 DXA scans conducted over the 24-month period 2022-2023 of whom n=3,299 had VFA performed. N=470/3,299 (14%) had a fracture identified on VFA. In the year 2023 only, of the n=289/1,795 (16%) who had a fracture on VFA, n=96 of these had not been diagnosed previously, representing a screening pick up rate of 5%. Conclusion VFA is a high-yield investigation for detecting undiagnosed vertebral fractures. As these fractures have definite treatment implications, wider use of VFA should be considered with routine DXA.

Risk Factors of New Symptomatic Fractures After Vertebroplasty: A Retrospective Cohort Study of 268 Patients with Painful Osteoporotic Vertebral Compression Fracture

ObjectivTo evaluate the risk factors of new osteoporotic vertebral compression fractures (OVCFs) after percutaneous vertebroplasty (PVP). MethodsFrom January 2016 to November 2019, patients suffering from OVCFs were retrospectively reviewed. The independent influence factors for new OVCFs after PVP were assessed, from following variables: age, sex, BMI, BMD, history of alcoholism, smoking, hypertension, diabetes, glucocorticoid use, and prior vertebral fractures, the number of initial fractures, mean cement volume, method of puncture, D-type of cement leakage and regular anti-osteoporosis treatment. ResultsA total of 268 patients with 347 levels met the inclusion criteria and were finally included in this study. 49 levels of new OVCFs among 33 patients (12.31%) were observed during the follow-up period. It indicated that female (Adjusted OR: 6.812, 95%CI: [1.096, 42.337], P = 0.040), lower BMD (Adjusted OR: 0.477, 95%CI: [0.300, 0.759], P = 0.002), prior vertebral fractures (Adjusted OR: 16.145, 95%CI: [5.319, 49.005], P = 0.000), and regular anti-osteoporosis treatment (Adjusted OR: 0.258, 95%CI: [0.086, 0.774], P = 0.016) were independent influence factors for new OVCF. The cut-off value of BMD to reach new OVCF was -3.350, with a sensitivity of 0.660 and a specificity of 0.848. ConclusionFemale, lower BMD (T- score of lumbar), prior vertebral fractures and regular anti-osteoporosis treatment were independent influencing factors. BMD (T- score of lumbar) lower than -3.350 would increase risk for new OVCF, and none osteoporotic treatment has detrimental effect on new onset fractures following PVP.

Stereotactic Body Radiation Therapy for Large Volume Solid Tumor Spinal Metastases Involving Three or More Contiguous Vertebral Levels

Data for treating 3 or more contiguous vertebral bodies with SBRT is limited. The purpose of this study was to explore oncologic outcomes and toxicity of spine SBRT delivered to large volume solid tumor metastases involving 3 or more contiguous vertebral levels. Patients treated with spine SBRT for vertebral metastases involving 3 or more contiguous levels between 2009 and 2021 were retrospectively reviewed. Data on demographics, dosimetry, toxicity, and outcomes were collected. Radiographic local failure was defined as progressive disease on CT and/or MRI in the treatment volume compared to the pre-SBRT baseline. Local control (LC) and overall survival (OS) were calculated from end of SBRT using the Kaplan-Meier and log-rank test. A total of 141 patients were included with a median follow-up of 9.7 months. The majority of patients had either 3 (74%) or 4 (16%) involved contiguous vertebral levels. Twenty-two percent, 57%, 14%, and 7% of treated lesion began in the cervical, thoracic, lumbar, and sacral vertebral levels, respectively. The most common primary sites were NSCLC (15.6%), kidney (14.9%), and breast (13.5%). Thirty-two percent of patients had prior external beam radiation to the same vertebral level, 63% had prior surgery, and 43% had prior vertebral fracture. Paraspinal extension was identified in 26% at time of SBRT. Median pre-SBRT Bilsky grade was 2 (range 0-3). The median total prescription dose was 27 Gy (range: 12-43 Gy) with the most common dose (Gy)/fractionation schedules of 27/5 (32%), 30/5 (25%), and 25/5 (18%). The median Dmax was 4727 cGy (range 2070-7857) with a median prescription isodose of 58% (range 48-97). The median OS was 12.4 months (95% CI 9.6-15.3). 1- and 2- year OS were 51% and 35%, respectively. Local progression occurred across all histologies, most commonly in colon and NSCLC (16.7%). 1- and 2-year LC were 70% and 57%, respectively. In the radiation-naïve cohort, 1- and 2-year LC were 75% and 63%, respectively and 52% and 34% in the prior radiation group with no statistically significant difference in time to local progression (p = 0.075). There was no statistically significant difference in LC when comparing 3 versus 4 or more contiguous lesions (p = 0.66). Forty percent of patients that progressed underwent salvage treatment (58% surgery, 33% SBRT, 8% systemic therapy). Post-SBRT vertebral compression fracture rate was 11.6%. We present the largest series to date of patients treated with SBRT for large volume spinal metastases involving 3 or more contiguous levels. These data suggest reasonable local control and low toxicity with SBRT; therefore, SBRT should be considered a practical modality to offer this cohort.

Development and validation of a predictive model for spinal fracture risk in osteoporosis patients.

Spinal osteoporosis is a prevalent health condition characterized by the thinning of bone tissues in the spine, increasing the risk of fractures. Given its high incidence, especially among older populations, it is critical to have accurate and effective predictive models for fracture risk. Traditionally, clinicians have relied on a combination of factors such as demographics, clinical attributes, and radiological characteristics to predict fracture risk in these patients. However, these models often lack precision and fail to include all potential risk factors. There is a need for a more comprehensive, statistically robust prediction model that can better identify high-risk individuals for early intervention. To construct and validate a model for forecasting fracture risk in patients with spinal osteoporosis. The medical records of 80 patients with spinal osteoporosis who were diagnosed and treated between 2019 and 2022 were retrospectively examined. The patients were selected according to strict criteria and categorized into two groups: Those with fractures (n = 40) and those without fractures (n = 40). Demographics, clinical attributes, biochemical indicators, bone mineral density (BMD), and radiological characteristics were collected and compared. A logistic regression analysis was employed to create an osteoporotic fracture risk-prediction model. The area under the receiver operating characteristic curve (AUROC) was used to evaluate the model's performance. Factors significantly associated with fracture risk included age, sex, body mass index (BMI), smoking history, BMD, vertebral trabecular alterations, and prior vertebral fractures. The final risk-prediction model was developed using the formula: (logit [P] = -3.75 + 0.04 × age - 1.15 × sex + 0.02 × BMI + 0.83 × smoking history + 2.25 × BMD - 1.12 × vertebral trabecular alterations + 1.83 × previous vertebral fractures). The AUROC of the model was 0.93 (95%CI: 0.88-0.96, P < 0.001), indicating strong discriminatory capabilities. The fracture risk-prediction model, utilizing accessible clinical, biochemical, and radiological information, offered a precise tool for the evaluation of fracture risk in patients with spinal osteoporosis. The model has potential in the identification of high-risk individuals for early intervention and the guidance of appropriate preventive actions to reduce the impact of osteoporosis-related fractures.

Prevalent vertebral fractures among urban-dwelling Chinese postmenopausal women: a population-based, randomized-sampling, cross-sectional study

SummaryIn this population-based, cross-sectional study, we investigated vertebral fracture (VF) prevalence among Chinese postmenopausal women. We found 14.7% of population had VFs, which increased with age. Age ≥ 65 years, hip fracture, and densitometric osteoporosis were significantly associated with VFs. The prevalence of osteoporosis was remarkably high.PurposeTo investigate VF prevalence among Chinese postmenopausal women in this population-based, randomized-sampling, cross-sectional study.MethodsThe investigator obtained lists of women from communities. Randomization was performed using SAS programming based on age group in each region. Postmenopausal women aged ≥ 50 years in the urban community were included. The investigator interviewed subjects to collect self-reported data and measured BMD. Spine radiographs were adjudicated by Genant’s semi-quantitative method. VFs were defined as fractures of at least one vertebra classified by Genant’s score 1–3 and were analyzed using descriptive statistics.ResultsA total of 31,205 women listed for randomized sampling from 10 Tier-3 hospitals at 5 regions. Of 2634 women in the full analysis set, 14.7% (388/2634, 95% CI: 13.4, 17.1) had prevalent VFs. VF prevalence increased with age (Cochran–Armitage test p < 0.0001) and was significantly higher in women aged ≥ 65. VF prevalence did not differ between North (14.4%, 95% CI: 12.5, 16.4) and South China (15.1%, 95% CI: 13.3, 17.1). In women with no prior VFs, prevalent VFs were 12.4% (95% CI: 11.2, 13.7). Age ≥ 65 years (OR: 2.57, 95% CI: 1.91, 3.48), hip fracture (OR: 2.28, 95% CI: 1.09, 4.76), and densitometric osteoporosis (OR: 2.52, 95% CI: 1.96, 3.22) were significantly associated with prevalent VFs. Prevalence of osteoporosis was 32.9% measured by BMD and 40.8% using NOF/IOF clinical diagnosis criteria.ConclusionVFs are prevalent among Chinese postmenopausal women who were ≥ 50 years and community-dwelled. Osteoporosis prevalence is remarkable when fragile fractures were part of clinical diagnosis.

Clinical risk factor status in patients with vertebral fracture but normal bone mineral density

BACKGROUND CONTEXTNormal bone mineral density (BMD) as measured by dual-energy x-ray absorptiometry (DXA) is present in approximately 10% of older adults with fracture. BMD alone does not evaluate bone quality or clinical risk factors, and therefore, may not adequately capture a patient's fracture risk. Thus, despite a normal DXA-measured BMD, the underlying bone may be abnormal, suggesting that further bone health evaluation, and potentially, pharmacologic treatment may be warranted. PURPOSETo determine the prevalence of normal BMD, clinical fracture risk factors, and quantitative risk of fracture using the Fracture Risk Assessment Tool (FRAX) in vertebral fracture patients with normal BMD enrolled in the Own the Bone registry, thus facilitating identification of those who meet criteria for anti-osteoporosis therapy. STUDY DESIGN/SETTINGRetrospective, national registry-based cohort. PATIENT SAMPLEFrom July 2016 to July 2021, 1,807 patients age ≥50 who sustained a vertebral fracture and had DXA data available from within 2 years prior to enrollment in the American Orthopaedic Association's Own the Bone (AOA OTB) registry were included. OUTCOME MEASURESWorld Health Organization (WHO) DXA T-score based bone classification criteria; FRAX risk scores of major osteoporotic fracture or hip fracture. METHODSDemographic data, prior fracture site, and clinical fracture risk factors were collected. BMD status was classified by the WHO T-score criteria: ≥ -1.0 normal, -1.1 to -2.4 osteopenia, and ≤ -2.5 osteoporosis, with low bone mass including either osteopenia or osteoporosis. In normal BMD patients, FRAX scores were calculated with and without BMD, with the treatment threshold defined as a major osteoporotic fracture risk ≥20% or hip fracture risk ≥3%. RESULTSMean±SD age was 72.0±9.7, 78.1% were female, and 92.4% were Caucasian. Normal BMD was present in 7.9%. Clinical fracture risk factors including alcohol use ≥3 units/day and history of ≥2 falls in the year prior to enrollment were more common in normal BMD (11.2% and 28%, respectively) compared to low bone mass patients (3.4% and 25.2%, respectively). A prior vertebral fracture had occurred in 49.5% with normal BMD compared to 45.8% with low bone mass, while a prior non-major osteoporotic fracture occurred in 28.9% and 29.3% of normal BMD and low bone mass patients, respectively. In normal BMD patients, either a prior fracture or FRAX risk with BMD meeting treatment thresholds was present in 85%. CONCLUSIONSClear indications for receipt of pharmacologic therapy, ie, prior fracture or elevated fracture risk, were present in most patients with vertebral fracture and normal BMD enrolled in the AOA OTB. Prior non-major osteoporotic fractures were common and may be useful indicators of underlying bone disease. Surgeons must recognize that other important risk factors apart from BMD may indicate poor bone health, and thus, help guide further bone health evaluation.

Normative Data and Reproducibility for Vertebral Bone Quality Score in Serial Lumbar Spine Magnetic Resonance Imaging

The vertebral bone quality (VBQ) score can independently predict fragility fractures and is useful for osteoporosis screening. It is derived by taking the ratio of the median L1-L4 signal intensity (SI) and L3 cerebral spinal fluid SI on opportunistic T1 weighted (fat sensitive) magnetic resonance imaging (MRI) scans. Higher VBQ score indicates more fat and less bone suggesting osteoporosis. Normative data has not been described. The purpose of this study was to determine whether VBQ score increased with age and remained consistent across serial MRI studies. This retrospective study evaluated 107 lumbar spine patients, age 20-69, who received two T1-weighted MRI within three months of each other between January 2011 and December 2021. Patients were divided into cohorts by decade of life. Patients with prior vertebral fracture, spinal metastasis, instrumentation at two or more levels, and MRI scans with spin sequences outside the optimal range for bone marrow analysis (TR=400-850, TE=8-20) were excluded. Regression analysis was performed to determine correlation of VBQ score with age. Interclass correlation (ICC) was calculated to determine reproducibility between VBQ scores derived from separate MRI scans. 53 males and 54 females were included in the study. 90% were Caucasian. The mean VBQ scores for the first and second set of MRI scans were 2.39±0.74 and 2.30±0.88, 2.68±0.57 and 2.54±0.74, 2.56±0.63 and 2.70±0.69, 2.99±0.72 and 2.77±0.89, 3.27±0.57 and 3.21±0.60 for the age ranges of 20-29, 30-39, 40-49, 50-59, 60-69, respectively. Among males, age positively correlated with VBQ scores measured from the first (r=0.361, p=0.008) and second (r=0.286, p=0.038) MRI scans. Among females, age likewise positively correlated with VBQ scores measured from the first (r=0.395, p=0.003) and second (r=0.398, p=0.003) MRI scans. For the entire cohort, the ICC=0.749. VBQ score is positively correlated with age. The majority of patients age > 50 had VBQ > 3.00, further supporting this threshold as a diagnostic cutoff for potential osteoporosis and additional bone health evaluation. Reproducibility of the VBQ score across serial MRI is good, which supports the possible usefulness of the VBQ score in the pre-operative evaluation of spine surgical patients.

Incidence and predictors of fragility fracture in postmenopausal rheumatoid arthritis patients receiving oral bisphosphonates: a longitudinal observational study

BackgroundAlthough many studies have reported the predictors of fractures in patients with rheumatoid arthritis (RA) who are not receiving anti-osteoporotic treatments or who are receiving unspecified treatments, studies focusing on the predictors of fracture in patients with RA who are currently being treated with oral bisphosphonates (BP) are quite scarce. This study aims to investigate the incidence and predictors of fragility fracture in postmenopausal patients with RA receiving oral BP.MethodsThis retrospective longitudinal observational study comprised 98 postmenopausal RA patients receiving oral BP for a minimum of 6 months between April 2015 and December 2020. The cumulative incidence of fragility fractures including vertebral and nonvertebral fractures was investigated using the Kaplan–Meier method. Cox proportional hazards analysis was used to analyze baseline predictors of future fragility fractures. To determine a cutoff value of continuous predictors, the receiver-operating characteristic curve was applied.ResultsTwenty patients developed fractures during the study period, with a cumulative incidence of 6.1% at 12 months, 10.5% at a median follow-up of 28 months, and 14.4% at 36 months. Multivariable Cox hazards analysis showed a history of prior vertebral fracture (hazard ratio [HR] 6.26, 95% confidence interval [CI] 1.99‒19.68, P = 0.001) and dose of methotrexate (HR 0.87, 95% CI 0.76‒0.99, P = 0.041) to be independent predictors. The cutoff value for methotrexate dose was 4 mg/week.ConclusionsWe found a cumulative incidence of any fractures of 10.5% at 28 months in patients with RA currently being treated with oral BP. A history of prior vertebral fractures and methotrexate dose were positive and negative predictors for fractures, respectively. Practitioners should consider selecting another anti-osteoporotic drug in patients with RA who remain at risk despite receiving oral BP.

Cost-effectiveness of sequential daily teriparatide/weekly alendronate compared with alendronate monotherapy for older osteoporotic women with prior vertebral fracture in Japan

SummaryUsing a Markov microsimulation model among hypothetical cohorts of community-dwelling older osteoporotic Japanese women with prior vertebral fracture over a lifetime horizon, we found that daily subcutaneous teriparatide for 2 years followed by weekly oral alendronate for 8 years was not cost-effective compared with alendronate monotherapy for 10 years.PurposeTeriparatide has proven efficacy in reducing osteoporotic fractures, but with substantial cost. We examined the cost-effectiveness of sequential teriparatide/alendronate (i.e., daily subcutaneous teriparatide for 2 years followed by weekly oral alendronate for 8 years) compared with alendronate monotherapy for 10 years among community-dwelling older osteoporotic women with prior clinical or morphometric vertebral fracture in Japan.MethodsUsing a previously validated and updated Markov microsimulation model, we obtained incremental cost-effectiveness ratios (Japanese yen [¥] (or US dollars [$]) per quality-adjusted life year [QALY]) from the perspective of a single payer responsible for both public healthcare and long-term care. We assumed a lifetime horizon with a willingness-to-pay of ¥5million (or $47,500) per QALY in the base case. We modeled the cost of biosimilar teriparatide, which has been available since November 2019 in Japan, assuming the efficacy was the same as that of the brand version.ResultsIn the base case, sequential teriparatide/alendronate was not cost-effective compared with alendronate monotherapy. In deterministic sensitivity analyses, sequential teriparatide/alendronate would become cost-effective with 85%, 50%, and 15% price discounts to teriparatide at ages 70, 75, and 80, respectively, compared to the current biosimilar cost. Otherwise, results were especially sensitive to changes that affected efficacy of teriparatide or alendronate. In probabilistic sensitivity analyses, the probabilities of sequential teriparatide/alendronate being cost-effective were 0%, 1%, and 37% at ages 70, 75, and 80, respectively.ConclusionsAmong high-risk osteoporotic women in Japan, sequential teriparatide/alendronate was not cost-effective compared with alendronate monotherapy, even with the availability of biosimilar teriparatide.

Fractal lacunarity of trabecular bone in vertebral MRI to predict osteoporotic fracture risk in over-fifties women. The LOTO study

BackgroundOsteoporotic fractures are a major cause of morbidity in the elderly. Menopausal women represent the population with the highest risk of early osteoporosis onset, often accompanied by vertebral fractures (VF). Bone mineral density (BMD) is commonly assessed by dual-energy X-ray absorptiometry (DXA) for osteoporosis diagnosis; however, BMD alone does not represent a significant predictor of fracture risk. Bone microarchitecture, instead, arises as a determinant of bone fragility independent of BMD. High-resolution magnetic resonance imaging (MRI) is an effective noninvasive/nonionizing tool for in vivo characterisation of trabecular bone microarchitecture (TBA). We have previously set up an MRI method able to characterise TBA changes in aging and osteoporosis by one parameter, trabecular bone lacunarity parameter β (TBLβ). Fractal lacunarity was used for TBA texture analysis as it describes discontinuity of bone network and size of bone marrow spaces, changes of which increase the risk of bone fracture. This study aims to assess the potential of TBLβ method as a tool for osteoporotic fracture risk.MethodsAn observational, cross-sectional, and prospective study on over-50s women at risk for VF was designed. TBLβ, our index of osteoporotic fracture risk, is the main outcome measure. It was calculated on lumbar vertebra axial images, acquired by 1.5 T MRI spin-echo technique, from 279 osteopenic/osteoporotic women with/without prior VF. Diagnostic power of TBLβ method, by Receiver Operating Characteristics (ROC) curve and other diagnostic accuracy measurements were compared with lumbar spine DXA-BMD.ResultsBaseline results show that TBLβ is able to discriminate patients with/without prevalent VF (p = 0.003). AUC (area under the curve from ROC) is 0.63 for TBLβ, statistically higher (p = 0.012) than BMD one (0.53). Contribution of TBLβ to prevalent VF is statistically higher (p < 0.001) than BMD (sensitivity: 66% vs. 52% respectively; OR: 3.20, p < 0.0001 for TBLβ vs. 1.31, p = 0.297 for BMD). Preliminary 1-year prospective results suggest that TBA contribution to incident VF is even higher (sensitivity: 73% for TBLβ vs. 55% for BMD; RR: 3.00, p = 0.002 for TBLβ vs. 1.31, p = 0.380 for BMD).ConclusionResults from this study further highlight the usefulness of TBLβ as a biomarker of TBA degeneration and an index of osteoporotic fracture risk.

Randomized, controlled trial to assess the safety and efficacy of odanacatib in the treatment of men with osteoporosis.

ODN, a selective oral cathepsin K inhibitor, was in development for osteoporosis treatment. This phase 3, double-blind, randomized, placebo-controlled, 24-month study investigated ODN safety and efficacy in men with osteoporosis. Men with idiopathic osteoporosis or osteoporosis due to hypogonadism and a lumbar spine or hip (total hip [TH], femoral neck [FN], or trochanter) bone mineral density (BMD) T-score of ≤ - 2.5 to ≥ - 4.0 without prior vertebral fracture or ≤ - 1.5 to ≥ - 4.0 with one prior vertebral fracture were randomized (1:1) to once-weekly ODN 50mg or placebo. All received 5600IU vitamin D3 weekly and calcium supplementation as needed (≥ 1200mg daily). The primary efficacy outcome was changed from baseline in lumbar spine BMD versus placebo. Overall, 292 men, mean age 68.8years, were randomly assigned to ODN or placebo. Versus placebo, ODN increased BMD from baseline at the lumbar spine, TH, FN, and trochanter by 5.6%, 2.0%, 1.7%, and 2.1%, respectively (all p < 0.01), and decreased uNTx/Cr (68%, p < 0.001), sCTx (77%, p < 0.001), sP1NP (16%, p = 0.001), and sBSAP (8%, p = 0.019). The between-group bone formation marker decrease peaked at 3months, then returned toward baseline. The safety profile, including cardiovascular events, was similar between groups. Though a promising osteoporosis therapy for men, ODN development was discontinued due to increased risk of stroke in the LOFT phase 3 trial. Clinicaltrials.gov NCT01120600 (registered May 11, 2010).

Prevalent vertebral fractures incur high risk of future fractures in inflammatory myositis.

To assess accrual of new vertebral fractures (VF) in patients with idiopathic inflammatory myositis (IIM) over a period of time. Hundred patients who were previously enrolled for a cross-sectional study on prevalence of asymptomatic VF were telephonically requested to review with repeat spinal radiographs and dual-energy X-ray absorptiometry (DEXA) after 3 years. Radiographs were scored using Genant's semi-quantitative technique. Disease activity and damage were assessed by myositis damage index (MDI) extent of damage and modified MDI for which the osteoporotic fracture item in MDI was removed. VF progressors were compared with non-progressors. Of 31 patients reviewed, 11 had dermatomyositis, 8 polymyositis, and 6 each overlap and anti-synthetase syndrome. Eighteen patients underwent DEXA scan. Seventeen had VF at baseline. At 91.62 patient years of follow-up, total number of VF increased from 27 to 51. Patients who had previous VF had higher risk of developing a new VF when compared with those with no VF (76.5% vs. 14.28%, RR: 5.35). Patients with old VF accrue fractures at a rate of 26.2 per 100 patient years. The number of fractures correlated significantly with age, T scores at the L4 level, and lower third of radius on DEXA, MDI, and modified MDI. Neither conventional nor disease-related variables differed between progressors and non-progressors. Patients with IIM with a prior VF incurred a five times risk of subsequent VF irrespective of disease activity and glucocorticoids. Key Points • Patients with inflammatory myositis are at a high risk of asymptomatic vertebral fractures. • Patients with baseline vertebral fractures incur a high risk of future fractures on follow-up. • Number of fractures is negatively correlated with age, BMD values at lower end of radius, L4, and damage.

P1446DIFFUSE IDIOPATHIC SKELETAL HYPEROSTOSIS IN PATIENTS UNDERGOING MAINTENANCE HEMODIALYSIS

Abstract Background and Aims Diffuse idiopathic skeletal hyperostosis (DISH) is an idiopathic degenerative disease characterized by ossification of spinal ligaments and entheses, especially in the anterior longitudinal ligament. The ankylosed spine is prone to fracture with minor trauma and may result in spinal cord injury. It is usually asymptomatic and often diagnosed incidentally by computed tomography or other imaging methods. Several reports have revealed DISH as a risk factor for stroke, cardiovascular disease, and metabolic disorders, such as diabetes mellitus, hyperinsulinemia, obesity, dyslipidemia, and hyperuricemia. However, there are few reports of DISH in patients with end stage kidney disease (ESKD) requiring hemodialysis. Epidemiology, etiology and risk factors of DISH in patients with ESKD are unknown. We aimed to examine the prevalence and predictors of DISH in maintenance hemodialysis patients. Method This was a case-control study using patients who received maintenance hemodialysis in our hospital in December 2018. The prevalence of DISH at enrollment was evaluated according to Resnick and Niwayama criteria by computed tomography (CT). The criteria is defined as follows: (1) Flowing ossification along the anterolateral aspect of at least four contiguous vertebral bodies, (2) Relative preservation of intervertebral disc height in the involved segment, (3) Absence of apophyseal joint bony ankylosis and sacroiliac joint erosion. We excluded patients who could not receive chest CT or with a history of thoracic spine surgery. Fisher exact tests were used to evaluate the relationships between categorical variables, and Kruskal-Wallis or Mann-Whitney U tests were used to evaluate continuous variables. We performed logistic regression analyses to identify variables that had a statistically significant association with DISH, as measured by the estimated odds ratio (OR) with the 95% confidence interval (CI). Results A total of 395 consecutive patients were treated with maintenance hemodialysis in our hospital in December 2018. After excluding 4 patients who could not receive chest CT and 2 patients with a history of thoracic spine surgery, the remaining 389 patients were analyzed. The median age was 70 years, and 61.2% of patients were men. One hundred and twenty-three (31.6%) patients were diagnosed with DISH. We assigned them to the DISH group and other 266 patients to the control group. The patients with DISH were significantly more likely to have advanced age, male sex, high body weight, high bone mineral density, prior vertebral fracture, and diabetic nephropathy. Multivariate analysis showed that having DISH was significantly associated with advanced age (OR 1.06, 95%CI 1.03-1.09, P&amp;lt;0.001), high bone mineral density (OR1.02, 95%CI 1.00-1.03, P=0.03), prior vertebral fracture (OR3.22, 95%CI 1.23-8.41, P=0.017), diabetic nephropathy (OR 2.00, 1.03-3.90, P=0.041). Conclusion The prevalence of DISH in maintenance hemodialysis patients was high. Advanced age, male sex, high body weight, high bone mineral density, prior vertebral fracture, and diabetic nephropathy were identified as a risk factor for DISH. Physicians involved in hemodialysis treatment should be aware of the existence of DISH as one of the comorbidities in the elderly ESKD patients.

Cost-Effectiveness of Sequential Teriparatide/Alendronate Versus Alendronate-Alone Strategies in High-Risk Osteoporotic Women in the US: Analyzing the Impact of Generic/Biosimilar Teriparatide.

ABSTRACTTeriparatide, currently only available in brand form in the United States, is a costly drug approved for the treatment of postmenopausal osteoporotic women who are at high risk of fracture. Because market exclusivity for brand teriparatide expired in August 2019 in the US, we sought to understand the potential health economic impact of the availability of generic or biosimilar (generic/biosimilar) teriparatide. We examined the cost‐effectiveness of daily teriparatide for 2 years followed by weekly alendronate for 10 years (ie, sequential teriparatide/alendronate) compared with alendronate alone for 10 years in community‐dwelling white osteoporotic women with prior vertebral fracture at ages 65, 70, 75, and 80. Using an updated version of previously validated Markov microsimulation models, we obtained incremental cost‐effectiveness ratios (ICERs) (dollars [$] per quality‐adjusted life year [QALY]) with a willingness‐to‐pay (WTP) of $150,000 per QALY from a societal perspective with a lifelong time horizon. In the base case, we estimated the annual cost of teriparatide to be $20,161, based on the assumption of 10% brand usage (at a cost of $27,618) and 90% generic/biosimilar usage (priced 30% lower than brand). The ICERs of sequential teriparatide/alendronate compared with alendronate alone were greater than $280,000 per QALY at all ages examined. In deterministic sensitivity analyses, results were sensitive to teriparatide's cost, with the cost of a generic/biosimilar product needing to be 65% to 85% lower than brand for sequential teriparatide/alendronate to be cost‐effective. In probabilistic sensitivity analyses, under the assumption that the annual cost of teriparatide was $20,161, the probabilities of sequential teriparatide/alendronate being cost‐effective were less than 4% at a WTP of $150,000 per QALY. In conclusion, among community‐dwelling older osteoporotic women with prior vertebral fracture in the US, even with the potential availability of generic/biosimilar teriparatide, sequential teriparatide/alendronate would not be cost‐effective unless the cost of generic/biosimilar teriparatide were heavily discounted with respect to the current brand cost. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Long-term persistence in patients with osteoporosis receiving denosumab in routine practice: 36-month non-interventional, observational study.

The study objective was to describe long-term persistence with denosumab among patients treated for osteoporosis in a real-world setting. We also sought to examine patient characteristics predictive of persistence. Lastly, this study attempted to place the results in context by conducting a literature review of published persistence data for denosumab. This retrospective, non-interventional study analyzed 1158 patients from a specialty community private practice to assess patient persistence with denosumab in routine care. Persistence was defined as receiving seven denosumab injections, using an 8-week permissible gap, over 36months. Non-persistent patients were further investigated retrospectively to identify reasons for discontinuation, when available. Demographic analysis showed a population of 1158 patients with mean age 68.4years old and baseline T-score - 2.7; nearly half of which experienced a prior osteoporosis-related fracture. In a Kaplan-Meier survival analysis, 36-month persistence overall was 50.7%. Net persistence, as defined by receiving seven injections in the allowable time frame, was 64.2% of the cohort. In a multivariate analysis, prior vertebral fractures and recent osteoporosis therapy were associated with higher persistence; age greater than 75years was associated with non-persistence. Reasons for discontinuation were available in 91.6% of non-persistent patients and categorized to include the ten most common explanations. This study to our knowledge represents the longest continuous observational period providing data on denosumab persistence in a real-world setting. The total persistence noted is quite robust when compared to bisphosphonates and is within the upper range of prior published studies of denosumab with shorter observation periods.

Accurate and Efficient Plate and Rod Microfinite Element Models for Whole Bone Segments Based on High-Resolution Peripheral Computed Tomography

The high-resolution peripheral quantitative computed tomography (HR-pQCT) provides unprecedented visualization of bone microstructure and the basis for constructing patient-specific microfinite element (μFE) models. Based on HR-pQCT images, we have developed a plate-and-rod μFE (PR μFE) method for whole bone segments using individual trabecula segmentation (ITS) and an adaptive cortical meshing technique. In contrast to the conventional voxel approach, the complex microarchitecture of the trabecular compartment is simplified into shell and beam elements based on the trabecular plate-and-rod configuration. In comparison to voxel-based μFE models of μCT and measurements from mechanical testing, the computational and experimental gold standards, nonlinear analyses of stiffness and yield strength using the HR-pQCT-based PR μFE models demonstrated high correlation and accuracy. These results indicated that the combination of segmented trabecular plate-rod morphology and adjusted cortical mesh adequately captures mechanics of the whole bone segment. Meanwhile, the PR μFE modeling approach reduced model size by nearly 300-fold and shortened computation time for nonlinear analysis from days to within hours, permitting broader clinical application of HR-pQCT-based nonlinear μFE modeling. Furthermore, the presented approach was tested using a subset of radius and tibia HR-pQCT scans of patients with prior vertebral fracture in a previously published study. Results indicated that yield strength for radius and tibia whole bone segments predicted by the PR μFE model was effective in discriminating vertebral fracture subjects from nonfractured controls. In conclusion, the PR μFE model of HR-pQCT images accurately predicted mechanics for whole bone segments and can serve as a valuable clinical tool to evaluate musculoskeletal diseases.

Cost-effectiveness Analysis of Sequential Treatment of Abaloparatide Followed by Alendronate Versus Teriparatide Followed by Alendronate in Postmenopausal Women With Osteoporosis in the United States.

Background: The US Food and Drug Administration has recently approved abaloparatide (ABL) for treatment of women with postmenopausal osteoporosis (PMO) at high risk of fracture. With increasing health care spending and drug prices, it is important to quantify the value of newly available treatment options for PMO. Objective: To determine cost-effectiveness of ABL compared with teriparatide (TPTD) for treatment of women with PMO in the United States. Methods: A discrete-event simulation (DES) model was developed to assess cost-effectiveness of ABL from the US health care perspective. The model included three 18-month treatment strategies with either placebo (PBO), TPTD, or ABL, all followed by additional 5-year treatment with alendronate (ALN). High-risk patients were defined as women with PMO ⩾65 years old with a prior vertebral fracture. Baseline clinical event rates, risk reductions, and patient characteristics were based on the Abaloparatide Comparator Trial in Vertebral Endpoints (ACTIVE) trial. Results: Over a 10-year period, the DES model yielded average total discounted per-patient costs of $10 212, $46 783, and $26 837 and quality-adjusted life-years (QALYs) of 6.742, 6.781, and 6.792 for PBO/ALN, TPTD/ALN, and ABL/ALN, respectively. Compared with TPTD/ALN, ABL/ALN accrued higher QALYs at lower cost and produced an incremental cost-effectiveness ratio (ICER) of $333 266/QALY relative to PBO/ALN. In high-risk women, ABL/ALN also had more QALYs and less cost over TPTD/ALN and yielded an ICER of $188 891/QALY relative to PBO/ALN. Conclusion and Relevance: ABL is a dominant treatment strategy over TPTD. In women with PMO at high risk of fracture, ABL is an alternative cost-effective treatment.

Real-world effectiveness of teriparatide on fracture reduction in patients with osteoporosis and comorbidities or risk factors for fractures: Integrated analysis of 4 prospective observational studies.

Teriparatide significantly reduces fracture rates in clinical trials; however, those study populations were relatively restricted and included too few patients to analyze fracture outcomes within clinically important patient subgroups. We assessed fracture outcomes in subgroups of osteoporosis patients from 4 real-world teriparatide observational studies. Patients received teriparatide 20 μg/day for up to 24 months. Fracture rates were compared between 0 to 6 months versus >6 months using a piecewise exponential model for first fracture. Analyses included incident clinical vertebral fractures (CVF) and nonvertebral fractures (NVF), and clinical fractures (CVF and NVF) by subgroups of gender, age <75 or ≥75 years, diabetes, prior bisphosphonates use, rheumatoid arthritis (RA), glucocorticoid use, prior hip, and prior vertebral fracture. The population included 8828 patients (8117 women, 92%) with mean (SD) age 71 (10.6) years and teriparatide treatment duration 17.4 (8.6) months. Overall, CVF, NVF, clinical fracture, and hip fracture rates decreased by 62%, 43%, 50%, and 56%, respectively (all p < .005) for >6 months versus 0 to 6 months. Subgroup analyses all showed significantly decreased rates after >6 months except for NVF reduction in males (n = 710, fracture rate low during months 0 to 6) and in patients using glucocorticoids, and CVF in patients with prior hip fracture. The effects of teriparatide on CVF, NVF, and clinical fractures over time were statistically consistent in all subgroups except age for CVF (p = .074, patients <75 years of age responded better), and diabetes for clinical fractures (p = .046, patients with diabetes responded better), although all of these subgroups experienced significant reductions over time. Glucocorticoids, prior bisphosphonate, and prior vertebral fracture were associated with increased CVF, NVF, and clinical fracture rates; RA, prior hip fracture and female gender were associated with higher NVF and clinical fracture rates; increased age was associated with higher CVF and clinical fracture rates. Data from 4 real-world observational studies showed statistically significant reductions during teriparatide treatment in rates of CVF, NVF, and clinical fractures in clinically relevant patient subgroups. These results should be interpreted in the context of the non-controlled design of the source studies.

Vertebral Fractures After Discontinuation of Denosumab: A Post Hoc Analysis of the Randomized Placebo-Controlled FREEDOM Trial and Its Extension.

Denosumab reduces bone resorption and vertebral and nonvertebral fracture risk. Denosumab discontinuation increases bone turnover markers 3 months after a scheduled dose is omitted, reaching above-baseline levels by 6 months, and decreases bone mineral density (BMD) to baseline levels by 12 months. We analyzed the risk of new or worsening vertebral fractures, especially multiple vertebral fractures, in participants who discontinued denosumab during the FREEDOM study or its Extension. Participants received ≥2 doses of denosumab or placebo Q6M, discontinued treatment, and stayed in the study ≥7 months after the last dose. Of 1001 participants who discontinued denosumab during FREEDOM or Extension, the vertebral fracture rate increased from 1.2 per 100 participant-years during the on-treatment period to 7.1, similar to participants who received and then discontinued placebo (n = 470; 8.5 per 100 participant-years). Among participants with ≥1 off-treatment vertebral fracture, the proportion with multiple (>1) was larger among those who discontinued denosumab (60.7%) than placebo (38.7%; p = 0.049), corresponding to a 3.4% and 2.2% risk of multiple vertebral fractures, respectively. The odds (95% confidence interval) of developing multiple vertebral fractures after stopping denosumab were 3.9 (2.1-7. 2) times higher in those with prior vertebral fractures, sustained before or during treatment, than those without, and 1.6 (1.3-1.9) times higher with each additional year of off-treatment follow-up; among participants with available off-treatment total hip (TH) BMD measurements, the odds were 1.2 (1.1-1.3) times higher per 1% annualized TH BMD loss. The rates (per 100 participant-years) of nonvertebral fractures during the off-treatment period were similar (2.8, denosumab; 3.8, placebo). The vertebral fracture rate increased upon denosumab discontinuation to the level observed in untreated participants. A majority of participants who sustained a vertebral fracture after discontinuing denosumab had multiple vertebral fractures, with greatest risk in participants with a prior vertebral fracture. Therefore, patients who discontinue denosumab should rapidly transition to an alternative antiresorptive treatment. Clinicaltrails.gov: NCT00089791 (FREEDOM) and NCT00523341 (Extension). © 2017 American Society for Bone and Mineral Research.

Patients with prior vertebral or hip fractures treated with teriparatide in the Direct Assessment of Nonvertebral Fractures in Community Experience (DANCE) observational study

In patients in the Direct Assessment of Nonvertebral Fractures in Community Experience (DANCE) observational study with and without a prior vertebral or hip fracture, the incidence of nonvertebral fractures was lower with >6 months of teriparatide treatment than during the first 6 months. Clinical evidence on the effect of teriparatide in patients with prior fracture is limited. In the DANCE observational study, the incidence of nonvertebral fragility fractures (NVFX) decreased significantly in patients receiving teriparatide for >6 months (6-24 months) versus >0 to ≤6 months (reference period). We performed a post hoc analysis to assess the effect of teriparatide 20 μg/day in patients who entered DANCE with prior vertebral or hip fractures. The incidence of patients experiencing a NVFX for four 6-month intervals during and after treatment was compared with the reference period. Overall, 4085 patients received ≥1 dose of teriparatide. Of 3720 with sufficient data for efficacy analysis, 692 had prior vertebral fracture, including 179 with previous kyphoplasty/vertebroplasty; 290 had prior hip fracture. These patients were older, and those with prior vertebral fractures had more comorbid conditions at baseline than those without prior vertebral fractures. The incidence of patients experiencing NVFX declined over time in all patient groups. The fracture incidence rate declined 49 and 46%, respectively, in patients with and without prior vertebral fracture and was 63 and 46% lower in patients with previous kyphoplasty/vertebroplasty and without prior vertebral fracture. NVFX declined 43 and 48% in patients with and without prior hip fracture. The reduced incidence over time was consistent in the subgroups (all interaction p values >0.05). Patients with prior fracture were more likely to experience serious adverse events. The incidence of NVFX decreased over time in patients receiving teriparatide in DANCE regardless of prior fracture status.