Prevalent Vertebral Fractures Research Articles

Bone health in idiopathic inflammatory myopathies.

To review the extant literature relating to bone health in the idiopathic inflammatory myopathies (IIM) including both adult and juvenile patients. A PubMed search® identified relevant studies from 1966 to 2020 in accordance with PRISMA guidelines. Two independent reviewers screened and extracted the abstracts/full manuscripts, and a third author was consulted in the case of disagreement. We identified 37 articles (3 review articles, 2 RCTs, 9 cross-sectional, 16 cohort and 7 case-control studies). The prevalence of osteopenia (n=7) ranges from 7 to 75% and osteoporosis (n=7) between 13% to 27%. The prevalence of vertebral fractures ranged from 11 to 75%. Systemic inflammation likely contributes to reduced bone mineral density (BMD) in children with IIM but data is currently lacking in adult patients. Association between with impaired BMD and Vitamin D or calcium intake and physical activity has not been demonstrated in IIM. There is no clear consensus regarding the impact of age, menopause or BMI on bone health. Gender, smoking status, disease activity and inflammatory markers are not obvious independent predictors of low BMD. Several studies have demonstrated that glucocorticoids are associated with an increased risk of low BMD. There are no specific guidelines relating to the management of bone health in adult and juvenile patients with IIM. Both adult and juvenile patients with IIM are at high risk of impaired bone health and fracture. The mechanisms behind this are likely multifactorial including systemic inflammation, glucocorticoid treatment, reduced mobility and impaired calcium/vitamin D homeostasis. There are a lack of guidelines and studies relating to the screening, prevention and treatment of impaired bone health in adult and juvenile patients with IIM. Future research is required to understand the complexity of bone health in IIM including to develop much needed disease-specific management recommendations.

Associations between bone attenuation and prevalent vertebral fractures on chest CT scans differ with vertebral fracture locations

SummaryVertebral fracture (VF) locations are bimodally distributed in the spine. The association between VF and bone attenuation (BA) measured on chest CT scans varied according to the location of VFs, indicating that other factors than only BA play a role in the bimodal distribution of VFs.IntroductionVertebral fractures (VFs) are associated with low bone mineral density but are not equally distributed throughout the spine and occur most commonly at T7–T8 and T11–T12 (“cVFs”) and less commonly at T4–T6 and T9–T10 (“lcVF”). We aimed to determine whether associations between bone attenuation (BA) and VFs vary between subjects with cVFs only, with lcVFs only and with both cVFs and lcVFs.MethodsChest CT images of T4–T12 in 1237 smokers with and without COPD were analysed for prevalent VFs according to the method described by Genant (11,133 vertebrae). BA (expressed in Hounsfield units) was measured in all non-fractured vertebrae (available for 10,489 vertebrae). Linear regression was used to compare mean BA, and logistic regression was used to estimate the association of BA with prevalent VFs (adjusted for age and sex).ResultsOn vertebral level, the proportion of cVFs was significantly higher than of lcVF (5.6% vs 2.0%). Compared to subjects without VFs, BA was 15% lower in subjects with cVFs (p < 0.0001), 25% lower in subjects with lcVFs (p < 0.0001) and lowest in subjects with cVFs and lcVFs (− 32%, p < 0.0001). The highest ORs for presence of VFs per − 1SD BA per vertebra were found in subjects with both cVFs and lcVFs (3.8 to 4.6).ConclusionsThe association between VFs and BA differed according to VF location. ORs increased from subjects with cVFs to subjects with lcVFs and were highest in subjects with cVFs and lcVFs, indicating that other factors than only BA play a role in the bimodal VF distribution.Trial registrationClinicaltrials.gov identifier: NCT00292552

Vertebral Fracture Assessment in Postmenopausal Women With Postsurgical Hypoparathyroidism

Hypoparathyroidism is a rare endocrine disorder whose skeletal features include suppression of bone turnover and greater volume and width of the trabecular compartment. Few and inconsistent data are available on the prevalence of vertebral fractures (VF). To evaluate the prevalence of VF assessed by vertebral fracture assessment (VFA) in postmenopausal women with chronic postsurgical hypoparathyroidism. Cross-sectional study. Ambulatory referral center. Fifty postmenopausal women (mean age 65.4 ± 9 years) with chronic postsurgical hypoparathyroidism and 40 age-matched healthy postmenopausal women (mean age 64.2 ± 8.6). Lumbar spine, femoral neck, and total hip bone mineral density were measured by dual X-ray absorptiometry (Hologic Inc., USA) in all subjects. Site-matched spine trabecular bone score was calculated by TBS iNsight (Medimaps, Switzerland). Assessment of VF was made by VFA (iDXA, Lunar GE, USA) using the semiquantitative method and the algorithm-based qualitative assessment. All-site BMD values were higher in the hypoparathyroid vs the control group. By VFA, we observed a 16% prevalence of VF in hypoparathyroid women vs 7.5% in control subjects. Among those with hypoparathyroidism who fractured, 5 (62.5%) had grade 1 wedge, 2 (25%) had grade 2 wedge, and 1 (12.5%) had grade 2 wedge and grade 2 biconcave VF. In the hypoparathyroid group, 57% with VFs and 32% without VFs had symptoms of hypoparathyroidism. We demonstrate for the first time that in postmenopausal women with chronic postsurgical hypoparathyroidism, VFs are demonstrable by VFA despite normal BMD.

Bone mass and vertebral fractures in South African children on prolonged oral glucocorticoids for chronic non-malignant illnesses

IntroductionWe hypothesized that the prevalence of vertebral fractures would be low and that bone mineral density (BMD) would be less severely affected in a black South African (SA) population treated with glucocorticoids (GCs) than that reported in mainly white populations. MethodsAll children aged 5–17.9 years with chronic non-malignant illnesses who were on GCs (intravenous or oral) for greater than 3 months duration were evaluated. DXA scans were performed using a Hologic Discovery machine (Software version Apex 4.0.2) and the Hologic paediatric reference database. Whole body less head (WBLH) and lumbar spine (LS) bone mineral content (BMC) and density (BMD) Z-scores unadjusted and adjusted for height were calculated using the Zemel equation calculator. ResultsSeventy-two patients (49% with renal, 24% with rheumatic, 14% with neurological, 11% with hepatic and 3% with respiratory conditions; mean age 11.6 ± 3.3 years, 57% boys, 92% SA black) were enrolled. The mean duration of GC treatment was 34.1 (±25.1) months. Mean WBLH and LS height adjusted BMD Z-scores were −1.2 ± 1.5 and −0.9 ± 1.0 respectively. Eleven percent of patients had a LS height adjusted BMD Z-score ≤ −2. The prevalence of vertebral fractures on lateral vertebral fracture assessment (VFA) was 15% (11 of 72 patients). ConclusionThe prevalence of vertebral fractures (15%) in predominantly black children on GCs with chronic non-malignant illnesses is similar to that reported from North America suggesting that routine yearly DXA scans including VFA are warranted in this highly at-risk population.

Risk of bone fractures after the diagnosis of adrenal adenomas: a population-based cohort study.

Several small studies reported increased prevalence and incidence of asymptomatic vertebral fractures in patients with non-functioning adrenal adenomas and adenomas with mild autonomous cortisol secretion. However, the risk of symptomatic fractures at vertebrae, and at other sites remains unknown. Our objective was to determine the prevalence and incidence of symptomatic site-specific fractures in patients with adrenal adenomas. Population-based cohort study, Olmsted County, Minnesota, USA, 1995-2017. Participants were the patients with adrenal adenoma and age/sex-matched referent subjects. Patients with overt hormone excess were excluded. Main outcomes measures were prevalence and incidence of bone fractures. Of 1004 patients with adrenal adenomas, 582 (58%) were women, and median age at diagnosis was 63 years (20-96). At the time of diagnosis, patients had a higher prevalence of previous fractures than referent subjects (any fracture: 47.9% vs 41.3%, P = 0.003, vertebral fracture: 6.4% vs 3.6%, P = 0.004, combined osteoporotic sites: 16.6% vs 13.3%, P = 0.04). Median duration of follow-up was 6.8 years (range: 0-21.9 years). After adjusting for age, sex, BMI, tobacco use, prior history of fracture, and common causes of secondary osteoporosis, patients with adenoma had hazard ratio of 1.27 (95% CI: 1.07-1.52) for developing a new fracture during follow up when compared to referent subjects. Patients with adrenal adenomas have higher prevalence of fractures at the time of diagnosis and increased risk to develop new fractures when compared to referent subjects.

Associations of clinically recognized vs unrecognized vertebral fracture with mortality.

Our purpose was to contrast mortality associated with clinically undiagnosed prevalent vertebral fracture recognized on densitometric vertebral fracture assessment (VFA) and prior clinically diagnosed vertebral fracture. Between 2010 and 2016, 9679 men and women (mean age [SD] 76 [6.9] years, 93% women) with central site bone density T-score≤-1.5 had VFA images obtained at the time of bone densitometry. Vertebrae between T4 and L4 inclusive were evaluated for prevalent vertebral fracture on these images. Participants were categorized into three mutually exclusive groups; those with no vertebral fracture on VFA and no prior clinically diagnosed vertebral fracture (n=7983), those with a definite vertebral fracture on VFA but no vertebral fracture clinically diagnosed before the index VFA date (n=1376), and those with a prior clinically diagnosed vertebral fracture (n=320). We ascertained mortality after the index VFA date using Manitoba provincial vital statistics files over a mean 2.8 (SD 1.7) years. We used Cox proportional hazards models to estimate the hazard ratios (HR) and 95% confidence intervals (C.I.) of prevalent vertebral fractures with mortality adjusted for multiple covariates. Adjusted for age and sex, those with clinically undiagnosed vertebral fracture on VFA had an HR of 1.22 (95% C.I. 1.00 to 1.50) for mortality, and those with a prior clinically diagnosed vertebral fracture had an HR of 1.78 (95% C.I. 1.27 to 2.50) for mortality compared to those with no prevalent vertebral fracture. After further adjustment for comorbidity score, current smoking, and other causes of mortality, these associations were slightly attenuated (HRs 1.18 [95% C.I. 0.95 to 1.45] and of 1.70 [95% C.I. 1.21 to 2.40], respectively). Stratified by elapsed years since diagnosis, clinical vertebral fractures were associated with excess mortality for up to 10years after their occurrence. Clinically undiagnosed prevalent vertebral fracture detected on densitometric VFA images are weakly associated with subsequent mortality adjusted for age and sex, but not after accounting for other causes of mortality. Clinical vertebral fractures are associated with increased mortality for ten years after their diagnosis, even after accounting for other causes of mortality.

Automatic opportunistic osteoporosis screening in routine CT: improved prediction of patients with prevalent vertebral fractures compared to DXA

ObjectivesTo compare spinal bone measures derived from automatic and manual assessment in routine CT with dual energy X-ray absorptiometry (DXA) in their association with prevalent osteoporotic vertebral fractures using our fully automated framework (https://anduin.bonescreen.de) to assess various bone measures in clinical CT.MethodsWe included 192 patients (141 women, 51 men; age 70.2 ± 9.7 years) who had lumbar DXA and CT available (within 1 year). Automatic assessment of spinal bone measures in CT included segmentation of vertebrae using a convolutional neural network (CNN), reduction to the vertebral body, and extraction of bone mineral content (BMC), trabecular and integral volumetric bone mineral density (vBMD), and CT-based areal BMD (aBMD) using asynchronous calibration. Moreover, trabecular bone was manually sampled (manual vBMD).ResultsA total of 148 patients (77%) had vertebral fractures and significantly lower values in all bone measures compared to patients without fractures (p ≤ 0.001). Except for BMC, all CT-based measures performed significantly better as predictors for vertebral fractures compared to DXA (e.g., AUC = 0.885 for trabecular vBMD and AUC = 0.86 for integral vBMD vs. AUC = 0.668 for DXA aBMD, respectively; both p < 0.001). Age- and sex-adjusted associations with fracture status were strongest for manual vBMD (OR = 7.3, [95%] CI 3.8–14.3) followed by automatically assessed trabecular vBMD (OR = 6.9, CI 3.5–13.4) and integral vBMD (OR = 4.3, CI 2.5–7.6). Diagnostic cutoffs of integral vBMD for osteoporosis (< 160 mg/cm3) or low bone mass (160 ≤ BMD < 190 mg/cm3) had sensitivity (84%/41%) and specificity (78%/95%) similar to trabecular vBMD.ConclusionsFully automatic osteoporosis screening in routine CT of the spine is feasible. CT-based measures can better identify individuals with reduced bone mass who suffered from vertebral fractures than DXA.Key Points• Opportunistic osteoporosis screening of spinal bone measures derived from clinical routine CT is feasible in a fully automatic fashion using a deep learning-driven framework (https://anduin.bonescreen.de).• Manually sampled volumetric BMD (vBMD) and automatically assessed trabecular and integral vBMD were the best predictors for prevalent vertebral fractures.• Except for bone mineral content, all CT-based bone measures performed significantly better than DXA-based measures.• We introduce diagnostic thresholds of integral vBMD for osteoporosis (< 160 mg/cm3) and low bone mass (160 ≤ BMD < 190 mg/cm3) with almost equal sensitivity and specificity compared to conventional thresholds of quantitative CT as proposed by the American College of Radiology (osteoporosis < 80 mg/cm3).

Do proximal hip geometry, trabecular microarchitecture, and prevalent vertebral fractures differ in postmenopausal women with type 2 diabetes mellitus? A cross-sectional study from a teaching hospital in southern India.

There is limited information with regard to bone health in Indian postmenopausal women with type 2 diabetes. We studied the bone mineral density (BMD), trabecular bone score (TBS), prevalent vertebral fractures (VF), proximal hip geometry, and bone mineral biochemistry in ambulatory postmenopausal women with and without type 2 diabetes mellitus (T2DM). This was a cross-sectional study conducted at a tertiary care center. BMD, TBS, prevalent vertebral fractures, and hip structural analysis (HSA) were assessed using a dual-energy X-ray absorptiometry (DXA) scanner. Bone mineral biochemical profiles were also studied. A total of 202 ambulatory postmenopausal women known to have type 2 diabetes mellitus with mean (SD) age of 65.6 (5.2) years and 200 age and BMI matched non-diabetic controls with mean (SD) age of 64.9 (4.7) years were recruited from the local community. Although the prevalence of lumbar spine osteoporosis was significantly lower among cases (30.7%) as compared to controls (42.9%), the prevalence of degraded bone microarchitecture (TBS < 1.200) was significantly higher among cases (51%) than in controls (23.5%); P < 0.001. Prevalent vertebral fractures were not significantly different in cases and controls. The various geometric indices of the proximal hip were significantly impaired in subjects with diabetes as compared to controls. This study may highlight the utility of the trabecular bone score and hip structural analysis in subjects with diabetes, where the bone mineral density tends to be paradoxically high, and may not adequately predict fracture risk.

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.

Vertebral fracture: epidemiology, impact and use of DXA vertebral fracture assessment in fracture liaison services

SummaryVertebral fractures are independent risk factors for vertebral and nonvertebral fractures. Since vertebral fractures are often missed, the relatively new introduction of vertebral fracture assessment (VFA) for imaging of the lateral spine during DXA-measurement of the spine and hips may contribute to detect vertebral fractures. We advocate performing a VFA in all patients with a recent fracture visiting a fracture liaison service (FLS). Fracture liaison services (FLS) are important service models for delivering secondary fracture prevention for older adults presenting with a fragility fracture. While commonly age, clinical risk factors (including fracture site and number of prior fracture) and BMD play a crucial role in determining fracture risk and indications for treatment with antiosteoporosis medications, prevalent vertebral fractures usually remain undetected. However, vertebral fractures are important independent risk factors for future vertebral and nonvertebral fractures. A development of the DXA technology, vertebral fracture assessment (VFA), allows for assessment of the lateral spine during the regular DXA bone mineral density measurement of the lumbar spine and hips. Recent approaches to the stratification of antiosteoporosis medication type according to baseline fracture risk, and differences by age in the indication for treatment by prior fracture mean that additional information from VFA may influence initiation and type of treatment. Furthermore, knowledge of baseline vertebral fractures allows reliable definition of incident vertebral fracture events during treatment, which may modify the approach to therapy. In this manuscript, we will discuss the epidemiology and clinical significance of vertebral fractures, the different methods of detecting vertebral fractures, and the rationale for, and implications of, use of VFA routinely in FLS.Summary points• Vertebral fracture assessment is a tool available on modern DXA instruments and has proven ability to detect vertebral fractures, the majority of which occur without a fall and without the signs and symptoms of an acute fracture.• Most osteoporosis guidelines internationally suggest that treatment with antiosteoporosis medications should be considered for older individuals (e.g., 65 years +) with a recent low trauma fracture without the need for DXA.• Younger individuals postfracture may be risk-assessed on the basis of FRAX® probability including DXA and associated treatment thresholds.• Future fracture risk is markedly influenced by both site, number, severity, and recency of prior fracture; awareness of baseline vertebral fractures facilitates definition of true incident vertebral fracture events occurring during antiosteoporosis treatment.• Detection of previously clinically silent vertebral fractures, defining site of prior fracture, might alter treatment decisions in younger or older FLS patients, consistent with recent IOF-ESCEO guidance on baseline-risk-stratified therapy, and provides a reliable baseline from which to define new, potentially therapy-altering, vertebral fracture events.

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 association between overweight/obesity and vertebral fractures in older adults: a meta-analysis of observational studies.

Recent investigations suggest that the influence of overweight/obesity on fracture risks is site-specific, while conflicting data were reported related to vertebral fracture. This meta-analysis was performed to qualitatively assess the relationship between overweight/obesity and the risk of vertebral fracture. MEDLINE, Web of Science, Embase, and Cochrane were searched for relevant observational articles assessing the vertebral fracture risk of the overweight or obese population compared to normal population. Two independent reviewers conducted data extraction and quality assessment. Relative risks (RR) and 95% confidence intervals (CI) were pooled using a random effect model. Eleven studies including 1,078,094 participants were extracted from 1645 records. Pooled RR showed that decreased risk of vertebral fractures was observed in the overweight older adults (RR: 1.16; 95% CI: 1.07-1.26; I2: 51.8%), but not in the obese populations (RR: 0.98; 95% CI: 0.82-1.17; I2: 92.1%). In the subgroup analysis, we found a significant inverse association between overweight and risk of vertebral fracture in women (RR: 0.92; 95% CI: 0.85-1.00; I2: 0.0%), non-Asian areas (RR: 0.89; 95% CI: 0.80-0.99; I2: 40.7%), sample size > 2000 (RR: 0.87; 95% CI: 0.80-0.94; I2: 4.9%), and quality score > 7 (RR: 0.87; 95% CI: 0.79-0.95; I2: 21.9%). Furthermore, pooled studies of sample size > 2000 (RR: 0.66; 95% CI: 0.76, 0.89; I2: 52.1%) and quality score > 7 (RR: 0.75; 95% CI: 0.62, 0.91; I2: 68.1%) showed that the people with obesity had a significantly lower prevalence of vertebral fracture. Overweight aged adults tend to have a lower vertebral fracture risk. When gender and ethnicity were taken into consideration, the inverse relationship between overweight and vertebral fracture risk were only observed in female and non-Asian populations. Besides, there is insufficient data to conclude the relationship between obesity and the risk of vertebral fractures, and thus, further studies are needed.

Comparison of the NOF and NOGG guidelines for spinal radiographic examination in postmenopausal Chinese women.

To compare the National Osteoporosis Foundation (NOF) and the UK National Osteoporosis Guideline Group (NOGG) guidelines for the detection of vertebral fractures in postmenopausal Chinese women. A cross-sectional study on 255 community-dwelling postmenopausal women was conducted in Hunan province in 2017. Demographic and clinical characteristics and risk factors were recorded through questionnaires. Height and weight were measured using standard methods, and bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry. Vertebral fractures were diagnosed by radiography using semi-quantitative morphometry. The prevalence of vertebral fractures was 9.4%. Women with vertebral fractures were significantly older and shorter, had higher years-since menopause and height loss values and lower BMD and T-scores at the femoral neck and total hip, and were more likely to have a history of previous fractures. The sensitivity and specificity of the NOF guidelines were 91.7% and 39.8%, respectively, while the NOGG guidelines had lower sensitivity (87.5%) and specificity (32.5%). However, a higher percentage had indications for radiography in the 50-64 years age group according to the NOGG guidelines, while a higher percentage had indications for radiography in the ≥ 65 year group according to the NOF guidelines. The NOF guidelines were better than the NOGG guidelines for spinal radiography examination in the Chinese postmenopausal women.

Prevalence and risk factors of morphometric vertebral fracture in apparently healthy osteopenic postmenopausal Thai women.

To determine the prevalence of and risk factors for morphometric vertebral fracture (VF) in apparently healthy postmenopausal women with osteopenia. This cross-sectional study included 490 postmenopausal Thai women with osteopenia. All had no known history of low-trauma fracture, no underlying diseases, or history of taking medications that affect bone metabolism. Morphometric VFs were assessed by thoracolumbar spine x-rays, using the Genant semiquantitative method, and interpreted independently by three radiologists. Mean age of participants was 59.9 ± 7.8 years and mean body mass index was 24.3 ± 3.4 kg/m2. Morphometric VFs were present in 29% (142/490) of women (grade 1: 62.0%, grade 2: 19.3%, and grade 3: 18.7%). Of these, 4.9% were aged 50 years or less, 40.1% were aged 50-59 years, 38% were aged 60-69 years, and 16.9% were aged over 70 years. Age and the Fracture Risk Assessment Tool (FRAX) scores for hip and major osteoporotic fracture, with or without bone mineral density, were positively correlated with VF. No differences in fracture prevalence among those with various degrees of osteopenia. Applying the current guidelines for VF screening results in discoveries of less than a half of osteopenic women who have had morphometric VF. Almost one third of apparently healthy postmenopausal women with osteopenia had morphometric VF. Advancing age and greater FRAX scores were associated with higher prevalence of morphometric VF.

Current and Future Burden of Hip and Vertebral Fractures in Asia.

The increase in the incidence of hip fractures over time disappeared in Northern European and North American Caucasians after 2000, while an increase was observed in Asian countries including Japan until 2010. However, a decrease in the incidence was observed after 2010. The prevalence of vertebral fractures in Asians, Europeans, and American Caucasians is similar, and the incidences of clinical and morphometric vertebral fractures are higher in Asians compared with European Caucasians. The decrease in the incidence of vertebral fractures over time has been observed in Japan. Although the stabilization or decrease over time in the incidence of hip and vertebral fractures have been observed, the number of patients with these fractures is expected to increase rapidly with increases in the elderly population. Multidisciplinary measures to prevent fragility fractures are an urgent issue in Asia at this time. This narrative review outlines the recent trends in incidence and future burdens of hip fracture and vertebral fracture in Asia.

Impact of bone mineral density in reducing fracture risk in patients receiving alendronate plus alfacalcidol therapy

BackgroudChanges in bone mineral density (BMD) are a potential surrogate marker for fracture endpoints in clinical trials. However little is known whether the increase in BMD in response to combination treatment with alendronate plus alfacalcidol is associated with fracture risk reduction. We aimed to evaluate the impact of BMD on fracture risk in osteoporosis patients, using the data from the randomized clinical trial comparing alendronate plus alfacalcidol with alendronate alone. MethodsWe selected 412 patients with two or more prevalent vertebral fractures and who had BMD measurements at baseline and after 6, 12, and/or 24 months out of 2022 patients from the database of the Japanese Osteoporosis Intervention Trial. Patients in this subset who received combination treatment with alendronate plus alfacalcidol had shown a lower risk of fracture than patients treated with alendronate alone. We used Poisson regression model analysis to calculate the proportion of treatment effect (PTE) that was attributable to BMD increases in patients receiving combination treatment. ResultsThe highest PTE attributable to changes in BMD was 1.2% in patients with a BMD increase of 3% or more in the lumbar spine. For BMD measurements of the radius, the highest PTE was 2.8% with a BMD increase of 0% or more. For BMD measurements of the metacarpal bone, the highest PTE was 1.2% with a BMD increase of 3% or more. In patients with a BMD greater than or equal to 70% of the young adult mean in the lumbar spine, the PTE attributable to BMD was 0.2%. In patients with a BMD greater than or equal to 70% of the young adult mean in the radius, the PTE attributable to BMD was 0.3%. ConclusionsThe additional effects of alfacalcidol in reducing fracture risk do not likely result from increased BMD; other mechanisms remain a possibility.

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.

Pentosidine and carboxymethyl-lysine associate differently with prevalent osteoporotic vertebral fracture and various bone markers

Pentosidine (PEN) and carboxymethyl-lysine (CML) are well-recognized advanced glycation end products (AGEs). However, how these AGEs affect the pathophysiology of osteoporosis and osteoporotic fractures remains controversial. This cross-sectional study aimed to investigate the associations of PEN and CML with bone markers, bone mineral density (BMD), and osteoporotic fractures in postmenopausal women from the Nagano Cohort Study. A total of 444 Japanese postmenopausal outpatients (mean ± standard deviation age: 69.8 ± 10.2 years) were enrolled after the exclusion of patients with acute or severe illness or secondary osteoporosis. The relationships among urinary PEN and serum CML levels, various bone markers, lumbar and hip BMD, and prevalent vertebral and long-bone fractures were evaluated. PEN associated significantly with prevalent vertebral fracture after adjustment for other confounders (odds ratio [OR] 1.59, 95% confidence interval [CI] 1.22–2.07; P < 0.001), but not with lumbar BMD. In contrast, a significant negative correlation was found between CML and lumbar BMD (r = − 0.180; P < 0.001), and this relationship was significant after adjustment for confounders (OR 0.84, 95% CI 0.76–0.93; P < 0.01). Although patients with prevalent vertebral fracture had significantly higher CML levels, the association between CML and prevalent vertebral fracture did not reach significance in the multivariate regression model. Both PEN and CML may play important roles in bone health for postmenopausal women, possibly via different mechanisms.

Joint Associations of Prevalent Radiographic Vertebral Fracture and Abdominal Aortic Calcification With Incident Hip, Major Osteoporotic, and Clinical Vertebral Fractures.

Prevalent vertebral fractures (PVFx) and abdominal aortic calcification (AAC) are both associated with incident fractures and can be ascertained on the same lateral spine images, but their joint association with incident fractures is unclear. Our objective was to estimate the individual and joint associations of PVFx and AAC with incident major osteoporotic, hip, and clinical vertebral fractures in 5365 older men enrolled in the Osteoporotic Fractures in Men (MrOS) Study, using Cox proportional hazards and Fine and Gray subdistribution hazards models to account for competing mortality. PVFx (Genant SQ grade 2 or 3) and 24-point AAC score were ascertained on baseline lateral spine radiographs. Self-reports of incident fractures were solicited every 4 months and confirmed by review of clinical radiographic reports. Compared with men without PVFx and AAC-24 score 0 or 1, the subdistribution hazard ratio (SHR) for incident major osteoporotic fracture was 1.38 (95% confidence interval [CI] 1.13-1.69) among men with AAC-24 score ≥2 alone, 1.71 (95% CI 1.37-2.14) for men with PVFx alone, and 2.35 (95% CI 1.75-3.16) for men with both risk factors, after accounting for conventional risk factors and competing mortality. Wald statistics showed improved prediction model performance by including both risk factors compared with including only AAC (chi-square=17.3, p < .001) or including only PVFx (chi-square=8.5, p=.036). Older men with both PVFx and a high level of AAC are at higher risk of incident major osteoporotic fracture than men with either risk factor alone. Assessing prevalent radiographic vertebral fracture and AAC on the same lateral spine images may improve prediction of older men who will have an incident major osteoporotic fracture, even after accounting for traditional fracture risk factors and competing mortality. © 2021 American Society for Bone and Mineral Research (ASBMR).

The Accuracy of Incident Vertebral Fracture Detection in Children Using Targeted Case-Finding Approaches.

Vertebral fractures are clinically important sequelae of a wide array of pediatric diseases. In this study, we examined the accuracy of case-finding strategies for detecting incident vertebral fractures (IVF) over 2 years in glucocorticoid-treated children (n=343) with leukemia, rheumatic disorders, or nephrotic syndrome. Two clinical situations were addressed: the prevalent vertebral fracture (PVF) scenario (when baseline PVF status was known), which assessed the utility of PVF and low lumbar spine bone mineral density (LS BMD; Z-score <-1.4), and the non-PVF scenario (when PVF status was unknown), which evaluated low LS BMD and back pain. LS BMD was measured by dual-energy X-ray absorptiometry, vertebral fractures were quantified on spine radiographs using the modified Genant semiquantitative method, and back pain was assessed by patient report. Forty-four patients (12.8%) had IVF. In the PVF scenario, both low LS BMD and PVF were significant predictors of IVF. Using PVF to determine which patients should have radiographs, 11% would undergo radiography (95% confidence interval [CI] 8-15) with 46% of IVF (95% CI 30-61) detected. Sensitivity would be higher with a strategy of PVF or low LS BMD at baseline (73%; 95% CI 57-85) but would require radiographs in 37% of children (95% CI 32-42). In the non-PVF scenario, the strategy of low LS BMD and back pain produced the highest specificity of any non-PVF model at 87% (95% CI 83-91), the greatest overall accuracy at 82% (95% CI 78-86), and the lowest radiography rate at 17% (95% CI 14-22). Low LS BMD or back pain in the non-PVF scenario produced the highest sensitivity at 82% (95% CI 67-92), but required radiographs in 65% (95% CI 60-70). These results provide guidance for targeting spine radiography in children at risk for IVF. © 2021 American Society for Bone and Mineral Research (ASBMR).