Radiological diagnosis of prevalent osteoporotic vertebral fracture on radiographs: an interim consensus from a group of experts of the ESSR osteoporosis and metabolism subcommittee.

When a low-energy trauma induces an acute vertebral fracture (VF) with clinical symptoms, a definitive diagnosis of osteoporotic vertebral fracture (OVF) can be made. Beyond that, a "gold" radiographic standard to distinguish osteoporotic from non-osteoporotic VFs does not exist. Fracture-shaped vertebral deformity (FSVD) is defined as a deformity radiographically indistinguishable from vertebral fracture according to the best of the reading radiologist's knowledge. FSVD is not uncommon among young populations with normal bone strength. FSVD among an older population is called osteoporotic-like vertebral fracture (OLVF) when the FSVD is likely to be associated with compromised bone strength. In more severe grade deformities or when a vertebra is collapsed, OVF diagnosis can be made with a relatively high degree of certainty by experienced readers. In "milder" cases, OVF is often diagnosed based on a high probability rather than an absolute diagnosis. After excluding known mimickers, singular vertebral wedging in older women is statistically most likely an OLVF. For older women, three non-adjacent minimal grade OLVF (< 20% height loss), one minimal grade OLVF and one mild OLVF (20-25% height loss), or one OLVF with ≥ 25% height loss, meet the diagnosis of osteoporosis. For older men, a single OLVF with < 40% height loss may be insufficient to suggest the subject is osteoporotic. Common OLVF differential diagnoses include X-ray projection artifacts and scoliosis, acquired and developmental short vertebrae, osteoarthritic wedging, oncological deformities, deformity due to high-energy trauma VF, lateral hyperosteogeny of a vertebral body, Cupid's bow, and expansive endplate, among others.

Revision of the 1994 World Health Organization T-score definition of osteoporosis for use in older East Asian women and men to reconcile it with their lifetime risk of fragility fracture.

The 1994 WHO criterion of a T-score ≤ -2.5 for densitometric osteoporosis was chosen because it results in a prevalence commensurate with the observed lifetime risk of fragility fractures in Caucasian women aged ≥ 50 years. Due to the much lower risk of fragility fracture among East Asians, the application of the conventional WHO criterion to East Asians leads to an over inflated prevalence of osteoporosis, particularly for spine osteoporosis. According to statistical modeling and when a local BMD reference is used, we tentatively recommend the cutpoint values for T-score of femoral neck, total hip, and spine to be approximately -2.7, -2.6, and -3.7 for Hong Kong Chinese women. Using radiographic osteoporotic vertebral fracture as a surrogate clinical endpoint, we empirically demonstrated that a femoral neck T-score of -2.77 for Chinese women was equivalent to -2.60 for Italian women, a spine T-score of -3.75 for Chinese women was equivalent to -2.44 for Italian women, and for Chinese men a femoral neck T-score of -2.77 corresponded to spine T-score of -3.37. For older Chinese men, we tentatively recommend the cutpoint values for T-score of femoral neck, total hip, and spine to be approximately -2.7, -2.6, and -3.2. With the BMD reference published by IKi et al. applied, T-score of femoral neck, total hip, and spine of -2.75, -3.0, and -3.9 for Japanese women will be more in line with the WHO osteoporosis definition. The revised definition of osteoporosis cutpoint T-scores for East Asians will allow a more meaningful international comparison of disease burden.

A comparison of radiographic degeneration features of older Chinese women and older Italian Caucasian women with a focus on thoracic spine.

BACKGROUND: Compared with Caucasians, East Asians have a lower incident of back pain, lower prevalence and severity of osteoporotic vertebral fracture and lumbar spine degeneration. AIM: This study compares radiographic spine degeneration features of older Chinese women (as an example of East Asians) and older Italian women (as an example of Caucasians) with a focus on the thoracic spine. METHODS: From two population-based epidemiological studies conducted in Hong Kong, China and Rome, Italy, 297 pairs (mean age: 73.6 years) age-matched older community women's lateral spine radiographs were sampled. Existence (or absence) of seven degeneration features were assessed including: (1) hyper-kyphosis, (2) disc space narrowing (T3/T4 ~ T11/T12), (3) osteoarthritic (OA) wedging (T4 ~ T12), (4) generalised osteophyte formation (T4 ~ T12); (5) acquired short vertebrae (T4 ~ T12), (6) Schmorl node (T4 - L5), (7) disc calcification (T4-L5). RESULTS: Italian women were more likely to have hyper-kyphosis (53.4% vs 25.6%), disc space narrowing (34.4% vs. 17.2%), OA wedging (6.4% vs. 0.67%), Schmorl node (19.5% vs. 4.4%, all P < 0.001). However, there was no statistically significant difference in osteophyte formation (7.7% vs. 9.4%, P > 0.1) and acquired short vertebrae (8.0% vs. 10.4%, P > 0.1). Disc calcification was uncommon among both Chinese and Italians. DISCUSSION AND CONCLUSION: For the first time, this study documented a lower prevalence of a number of thoracic spine degeneration features among Chinese. This study further affirms the concept of a generally healthier spine in older Chinese relative to older Caucasians. The observed differences may reflect a foundational background influence of genetic predisposition that represents an important line of future research.

Genetic aspects underlying the normocalcemic and hypercalcemic phenotypes of primary hyperparathyroidism.

PURPOSE: Hypercalcemic primary hyperparathyroidism (PHPT) is a common endocrine disorder that has been very well characterized. In contrast, many aspects of normocalcemic primary hyperparathyroidism (NPHPT) such as natural history, organ damage, and management are still matter of debate. In addition, both the pathophysiology and molecular basis of NPHPT are unclear. We investigated whether PHPT and NPHPT patient cohorts share the same pattern of genetic variation in genes known to be involved in calcium and/or bone metabolism. RESEARCH DESIGN AND METHODS: Genotyping for 9 single nucleotide polymorphisms (SNPs) was performed by Real-Time PCR (TaqMan assays) on 27 NPHPT and 31 PHPT patients evaluated in a tertiary referral Center. The data of both groups were compared with 54 in house-controls and 503 subjects from the 1000 Genomes Project. All groups were compared for allele/haplotype frequencies, on a single locus, two loci and multi-locus basis. RESULTS: The NPHPT group differed significantly at SNPs in OPG and ESR1. Also, the NPHPT cohort was peculiar for pairwise associations of genotypes and for the overrepresentation of unusual multilocus genotypes. CONCLUSIONS: Our NPHPT patient set harbored a definitely larger quota of genetic diversity than the other samples. Specific genotypes may help in defining subgroups of NPHPT patients which deserve ad hoc clinical and follow-up studies.

Bone Marrow Adipose Tissue Is Increased in Postmenopausal Women With Postsurgical Hypoparathyroidism.

CONTEXT: Suppression of bone turnover, greater trabecular volume, and normal-high normal all-site bone mineral density (BMD) are hallmarks of postsurgical hypoparathyroidism (HypoPT). Impairment in the trabecular microarchitecture with possible higher risk of vertebral fractures (VF) in women with postmenopausal HypoPT has also been described. Currently, no data on bone marrow adipose tissue (BMAT) are available in HypoPT. OBJECTIVE: To assess BMAT by magnetic resonance imaging (MRI) and proton magnetic resonance spectroscopy (1H-MRS) in postmenopausal women with chronic postsurgical HypoPT. METHODS: This cross-sectional pilot study, conducted at an ambulatory referral center, included 29 postmenopausal women (mean age 66 ± 8.4 years) with postsurgical HypoPT and 31 healthy postmenopausal women (mean age 63 ± 8.5). Lumbar spine MRI was performed and BMAT was measured by applying PRESS sequences on the L3 body. Lumbar spine, femoral neck, and total hip BMD were measured by dual x-ray absorptiometry (DXA); site-matched spine trabecular bone score (TBS) was calculated by TBS iNsight (Medimaps, Switzerland); VF assessment was performed with lateral thoracic and lumbar spine DXA. RESULTS: Fat content (FC) and saturation level (SL%) were higher (P <.0001 and P <.001), while water content (W) was lower in HypoPT compared to controls (P <.0001). FC significantly correlated with years since menopause and body weight (P <.05) in HypoPT, while TBS negatively correlated with FC and SL% (P <.05) and positively with residual lipids (RL) and W (P <.05). CONCLUSION: We demonstrate for the first time that BMAT is increased in postmenopausal women with postsurgical hypoparathyroidism and negatively associated with trabecular microarchitecture.

Conversion of osteoporotic vertebral fracture severity score to osteoporosis T-score equivalent status: a framework and a comparative study of Hong Kong Chinese and Rome Caucasian older women.

We explored how the severity of radiological osteoporotic vertebral fracture (OVF) can be converted to the equivalent T-score values. INTRODUCTION: To perform a study to define what portion of older community women with what severity of radiographic OVF correspond to what low T-score status. METHODS: There were age-matched 301 Italian community women and 301 Chinese community women (sub-group A, age, 73.6 ± 6.1 years). In addition, Chinese sub-groups B and C included 110 community women (age, 68.9 ± 5.5 years) and 101 community women (age: 82.2 ± 4.3 years), respectively. For each vertebra in women, a score of 0, - 0.5, - 1, - 1.5, - 2, - 2.5, and - 3 was assigned for no OVF or OVF of < 20%, ≥ 20 ~ 25%, ≥ 25% ~ 1/3, ≥ 1/3 ~ 40%, ≥ 40%-2/3, and ≥ 2/3 vertebral height loss, respectively, OVFss was defined as the summed score of vertebrae T4 to L5. OVFss and T-scores were ranked from the smallest to the largest values. RESULTS: For the Chinese total group (sub-groups A, B, and C together), OVFss = - 1 corresponded to lowest T-score (lowest T-score of lumbar spine, femoral neck, and total hip) of - 3.4 ~ - 3.2. OVFss ≤ - 1.5 corresponded to femoral neck T-score ≤ - 2.5. OVFss = -1.5 corresponded to a mean femoral neck T-score of - 3.0, - 2.6, and - 2.4, among Chinese sub-groups B, A, and C subjects, respectively. For Italians, all cases with OVFss ≤ - 1 had lowest T-score ≤ - 2.5. For cases with femoral neck T-score = - 2.5, 41.7% had OVFss = - 1.5, and 58.3% had OVFss = - 1. CONCLUSION: For older women, statistically OVFss ≤ - 1 suggests this subject is osteoporotic according to lowest T-score. If using femoral neck T-score, OVFss ≤ - 1.5 qualifies osteoporosis diagnosis.

A software program for automated compressive vertebral fracture detection on elderly women's lateral chest radiograph: Ofeye 1.0.

Background: Because osteoporotic vertebral fracture (OVF) on chest radiographs is commonly missed in radiological reports, we aimed to develop a software program which offers automated detection of compressive vertebral fracture (CVF) on lateral chest radiographs, and which emphasizes CVF detection specificity with a low false positivity rate. Methods: For model training, we retrieved 3,991 spine radiograph cases and 1,979 chest radiograph cases from 16 sources, with among them in total 1,404 cases had OVF. For model testing, we retrieved 542 chest radiograph cases and 162 spine radiograph cases from four independent clinics, with among them 215 cases had OVF. All cases were female subjects, and except for 31 training data cases which were spine trauma cases, all the remaining cases were post-menopausal women. Image data included DICOM (Digital Imaging and Communications in Medicine) format, hard film scanned PNG (Portable Network Graphics) format, DICOM exported PNG format, and PACS (Picture Archiving and Communication System) downloaded resolution reduced DICOM format. OVF classification included: minimal and mild grades with <20% or ≥20-25% vertebral height loss respectively, moderate grade with ≥25-40% vertebral height loss, severe grade with ≥40%-2/3 vertebral height loss, and collapsed grade with ≥2/3 vertebral height loss. The CVF detection base model was mainly composed of convolution layers that include convolution kernels of different sizes, pooling layers, up-sampling layers, feature merging layers, and residual modules. When the model loss function could not be further decreased with additional training, the model was considered to be optimal and termed 'base-model 1.0'. A user-friendly interface was also developed, with the synthesized software termed 'Ofeye 1.0'. Results: Counting cases and with minimal and mild OVFs included, base-model 1.0 demonstrated a specificity of 97.1%, a sensitivity of 86%, and an accuracy of 93.9% for the 704 testing cases. In total, 33 OVFs in 30 cases had a false negative reading, which constituted a false negative rate of 14.0% (30/215) by counting all OVF cases. Eighteen OVFs in 15 cases had OVFs of ≥ moderate grades missed, which constituted a false negative rate of 7.0% (15/215, i.e., sensitivity 93%) if only counting cases with ≥ moderate grade OVFs missed. False positive reading was recorded in 13 vertebrae in 13 cases (one vertebra in each case), which constituted a false positivity rate of 2.7% (13/489). These vertebrae with false positivity labeling could be readily differentiated from a true OVF by a human reader. The software Ofeye 1.0 allows 'batch processing', for example, 100 radiographs can be processed in a single operation. This software can be integrated into hospital PACS, or installed in a standalone personal computer. Conclusions: A user-friendly software program was developed for CVF detection on elderly women's lateral chest radiographs. It has an overall low false positivity rate, and for moderate and severe CVFs an acceptably low false negativity rate. The integration of this software into radiological practice is expected to improve osteoporosis management for elderly women.

Lower Prevalence and Severity of Degenerative Changes in the Lumbar Spine in Elderly Hong Kong Chinese Compared With Age-Matched Italian Caucasian Women.

STUDY DESIGN: Cross-sectional observational study. OBJECTIVE: The aim was to compare the prevalence and severity of radiographic lumbar spine degeneration between elderly Hong Kong Chinese and elderly Italian Caucasian women. SUMMARY OF BACKGROUND DATA: Rates of symptomatic low back pain and osteoporotic vertebral fracture have been shown to be lower in Asian and Chinese populations compared with Caucasians, but ethnic differences in spinal degeneration are less established. METHODS: Lumbar spine lateral radiographs of 566 age-matched (mean: 73.6 yr; range: 65-87 yr) female subjects from two population-based epidemiological studies from Hong Kong (n=283) and Rome, Italy (n=283) were reviewed. Grading of degeneration categories: disk height loss (none, <30%, 30%-60%, >60%), osteophyte formation (not present, minimal, small, large), endplate sclerosis (none, mild, moderate, severe), and antero/retrolisthesis (none, <25%, 25%-50%, >50%) was performed for vertebral levels from L1/2 to L5/S1 (five levels). Each category was assigned a score (0, 1, 2, 3) at individual vertebral level according to severity. The total degeneration score was obtained by adding scores for all categories across the vertebral levels. RESULTS: Italian subjects [total score (mean±SD): 7.0±5.5] had a higher severity of overall degenerative changes compared with Hong Kong subjects (5.7±4.4), P <0.01. Italian subjects had higher scores for individual findings of disk height loss (Italian, 3.6±2.8 vs. Hong Kong 2.5±2.1, P <0.01); antero/retrolisthesis (Italian 0.3±0.7 vs. Hong Kong 0.2±0.4, P =0.01); and endplate sclerosis (Italian 1.0±1.2 vs. Hong Kong 0.6±1.0, P <0.01). At each individual level from L1/2 to L5/S1, total degeneration scores were higher in Italian than Hong Kong subjects ( P <0.01-0.04). CONCLUSION: Degenerative changes in the lumbar spine are less prevalent and less severe in elderly Hong Kong Chinese women than in age-matched Italian Caucasian women. The observed differences may reflect a foundational background influence of genetic predisposition that requires further studies.

Much lower prevalence and severity of radiographic osteoporotic vertebral fracture in elderly Hong Kong Chinese women than in age-matched Rome Caucasian women: a cross-sectional study.

INTRODUCTION: Many earlier studies reported that East Asians and Caucasians have similar radiographic osteoporotic vertebral fracture (OVF) prevalence. Since elderly Chinese's osteoporotic hip fracture prevalence is half (or less than half) of that of their age-match Caucasians, we hypothesize that elderly Chinese's OVF prevalence could be only half, or even less than half, of that of their age-match Caucasians. MATERIALS: Age-matched (mean: 74.1 years; range: 65-87 years) elderly women's radiographs (T4-L5) were from two OVF population-based epidemiological studies conducted in Hong Kong (n = 200) and in Rome (n = 200). All radiographs were double read by one reader in Hong Kong and one reader in Rome. Radiological osteoporotic vertebral deformity (ROVD) classification included no ROVD (grade 0), and ROVDs with < 20%, 20 ~ 25%, ≥ 25% ~ 1/3, ≥ 1/3 ~ 40%, ≥ 40% ~ 2/3, and ≥ 2/3 height loss (grade 1 ~ 6) as well as endplate/cortex fracture (ECF). Spinal deformity index (SDI) was calculated with each vertebra assigned a score of 0, 0.5, 1, 1.5, 2, 2.5, and 3 for no ROVD or ROVDs grade 1 ~ 6. RESULTS: Seventy-seven (38.5%) Chinese subjects and 123 Italian subjects (61.5%) had ROVD respectively (p < 0.0001). Chinese subjects had ECF in 52 (26%) cases involving 100 vertebrae, while Italian subjects had ECF in 93 (47%) cases involving 230 vertebrae. ROVDs in Italian subjects tended to be more severe (total and mean SDI: 454.5 and 3.71 for Italian, and 212 and 2.72 for Chinese, p < 0.05), more likely to be multiple, more likely to have severe and collapsed grades. The slope of the relationship between age vs. SDI was steeper for the Italian subjects than for the Chinese subjects, suggesting ROVD severity developed faster for aging Italian subjects. A trend suggested earlier onset of ROVD among Italian. CONCLUSION: OVFs in Chinese women tend to be less common, less severe, and less likely to have multiple fractures.

Osteomalacia and Vitamin D Status: A Clinical Update 2020.

Historically, rickets and osteomalacia have been synonymous with vitamin D deficiency dating back to the 17th century. The term osteomalacia, which literally means soft bone, was traditionally applied to characteristic radiologically or histologically documented skeletal disease and not just to clinical or biochemical abnormalities. Osteomalacia results from impaired mineralization of bone that can manifest in several types, which differ from one another by the relationships of osteoid (ie, unmineralized bone matrix) thickness both with osteoid surface and mineral apposition rate. Osteomalacia related to vitamin D deficiency evolves in three stages. The initial stage is characterized by normal serum levels of calcium and phosphate and elevated alkaline phosphatase, PTH, and 1,25-dihydroxyvitamin D [1,25(OH)2D]-the latter a consequence of increased PTH. In the second stage, serum calcium and often phosphate levels usually decline, and both serum PTH and alkaline phosphatase values increase further. However, serum 1,25(OH)2D returns to normal or low values depending on the concentration of its substrate, 25-hydroxyvitamin D (25OHD; the best available index of vitamin D nutrition) and the degree of PTH elevation. In the final stage, hypocalcemia and hypophosphatemia are invariably low with further exacerbation of secondary hyperparathyroidism. The exact,or even an approximate, prevalence of osteomalacia caused by vitamin D deficiency is difficult to estimate, most likely it is underrecognized or misdiagnosed as osteoporosis. Signs and symptoms include diffuse bone, muscle weakness, and characteristic fracture pattern, often referred to as pseudofractures, involving ribs, scapulae, pubic rami, proximal femurs, and codfish-type vertebrae. The goal of therapy of vitamin D-deficiency osteomalacia is to alleviate symptoms, promote fracture healing, restore bone strength, and improve quality of life while correcting biochemical abnormalities. There is a need for better understanding of the epidemiology of osteomalacia. Simplified tools validated by concurrent bone histology should be developed to help clinicians promptly diagnose osteomalacia. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Vertebral Fracture Assessment in Postmenopausal Women With Postsurgical Hypoparathyroidism.

CONTEXT: 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). OBJECTIVE: To evaluate the prevalence of VF assessed by vertebral fracture assessment (VFA) in postmenopausal women with chronic postsurgical hypoparathyroidism. DESIGN: Cross-sectional study. SETTING: Ambulatory referral center. PATIENTS OR OTHER PARTICIPANTS: 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). MAIN OUTCOME MEASURES: 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. RESULTS: 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. CONCLUSION: We demonstrate for the first time that in postmenopausal women with chronic postsurgical hypoparathyroidism, VFs are demonstrable by VFA despite normal BMD.

Imaging technologies in the differential diagnosis and follow-up of brown tumor in primary hyperparathyroidism: Case report and review of the literature.

Brown tumors are osteolytic lesions associated with hyperparathyroidism (HPT). They may involve various skeletal segments, but rarely the cranio-facial bones. We report a case of a young boy with a swelling of the jaw secondary to a brown tumor presenting as the first manifestation of primary HPT (PHPT). He was found to have brown tumor located in the skull, as well. Different imaging technologies were employed for the diagnosis and follow-up after parathyroidectomy. We enclose a review of the literature on the employment of such imaging technologies in the differential diagnosis of osteolytic lesions. A multidisciplinary approach comprising clinical, laboratory and imaging findings is essential for the differential diagnosis of brown tumor in PHPT.

Inhibition of the RANKL with denosumab has no effect on circulating markers of atherosclerosis in women with postmenopausal osteoporosis: a pilot study.

PURPOSE: We evaluated the early effect of denosumab on circulating markers of atherosclerosis in women with postmenopausal osteoporosis. METHODS: Denosumab (60 mg) was administered subcutaneously every 6 months (m) in 27 women (mean age 75 ± 5 years) with postmenopausal osteoporosis and high cardiovascular risk for a total of 24 m. Zoledronic acid was administered in 6 age-matched women as a single intravenous dose. Serum levels of vascular cell adhesion protein 1 (VCAM-1), intercellular adhesion molecule 1 (ICAM-1), E and P selectin, CD-40 ligand (CD40L), interleukin-6 (IL-6), matrix metalloproteinase (MMP) 1 and 9, monocyte chemoattractant protein-1 (MCP-1), fibrinogen (FBG), and high sensitivity C-reactive protein (hs-CRP) were measured at baseline, 15 days (d), 2, 6 and 12 m after dosing. In the denosumab group, observation was extended to 24 m as secondary endpoint. RESULTS: Serum ICAM-1 levels showed significant increase in the zoledronic acid group (+18 ± 0.1%; p < 0.01) at 12 m. In the denosumab group, we observed a significant increase in serum CD40L (+2 ± 0.8%; p < 0.001), MMP-1 (+11 ± 0.4%, p < 0.02), and MMP-9 (+39.4 ± 0.8%, p < 0.01) at 24 m. There was a significant increase in serum FBG and hs-CRP in both groups at 12 m (denosumab:+2.2 ± 0.2% and +50.3 ± 1.6%; zoledronic acid: +9.4 ± 0.1 and +81.8 ± 0.8%; p < 0.01). No significant between-group differences were found. CONCLUSIONS: 24-m treatment with denosumab has no effect on the circulating markers of atherosclerosis in women with postmenopausal osteoporosis. Fluctuation of serum ICAM-1, CD40L, MMPs, FBG and hs-CRP can be ascribed to perturbation of immunological mechanisms stimulated by denosumab and zoledronic acid.

Diagnosis and grading of radiographic osteoporotic vertebral deformity by general radiologists after a brief self-learning period.

BACKGROUND: The expanded semi-quantitative (eSQ) osteoporotic vertebral deformity (OVD) classification has minimal, mild, moderate, moderately-severe, severe, and collapsed grades with <20%, 20-25%, >25%-1/3, >1/3-40%, >40%-2/3, >2/3 vertebral height loss respectively. This study evaluates the performance of using this grading criterion by radiology readers who did not have former training in OVD assessment. METHODS: Spine radiographs of 44 elderly women with 278 normal appearing vertebrae and 65 OVDs were selected, with two senior readers agreed the reference reading. Three readers from Italy and three readers from China were invited to evaluate these radiographs after reading five reference articles including one detailing eSQ criteria with illustrative examples. Before the second round of reading, the readers were asked to read an additional explanatory document. For the readers in Italy an additional on-line demonstration was given on how to measure vertebral height loss in another five cases of OVD. Two Chinese readers had a third round of reading after a 90 minutes' on-line lecture. RESULTS: The final absolute agreement rate with the reference reading (i.e., exactly the same grading as the reference) ranged between 46.2% to 68.2% for the six readers, and the final relative agreement (with one eSQ grade difference allowed) ranged between 78.5% to 92.5%. The >1 grade disagreement rate was all below 11%, and mostly below 7%. The missed OVD were mostly minimal grade. The rate for missing a ≥ mild OVD was <4.5%, and false positive rate was generally <1.4% among the final reading. If the minimal grade was removed and the remaining gradings were converted to Genant's semi-quantitative (GSQ) grading, the mean kappa values against the reference reading for SQ grades-1,2,3 were 0.813, 0.814, and 0.916 respectively. CONCLUSIONS: This study demonstrates good performance of the six learner readers for assessing radiographic after a brief self-learning period.

Identification of Subclinical Lung Involvement in ACPA-Positive Subjects through Functional Assessment and Serum Biomarkers.

Lung involvement is related to the natural history of anti-citrullinated proteins antibodies (ACPA)-positive rheumatoid arthritis (RA), both during the pathogenesis of the disease and as a site of disease-related injury. Increasing evidence suggests that there is a subclinical, early lung involvement during the course of the disease, even before the onset of articular manifestations, which can potentially progress to a symptomatic interstitial lung disease. To date, reliable, non-invasive markers of subclinical lung involvement are still lacking in clinical practice. The aim of this study is to evaluate the diagnostic potential of functional assessment and serum biomarkers in the identification of subclinical lung involvement in ACPA-positive subjects. Fifty ACPA-positive subjects with or without confirmed diagnosis of RA (2010 ARC-EULAR criteria) were consecutively enrolled. Each subject underwent clinical evaluation, pulmonary function testing (PFT) with assessment of diffusion lung capacity for carbon monoxide (DLCO), cardiopulmonary exercise testing (CPET), surfactant protein D (SPD) serum levels dosage and high-resolution computed tomography (HRCT) of the chest. The cohort was composed of 21 ACPA-positive subjects without arthritis (ND), 10 early (disease duration < 6 months, treatment-naïve) RA (ERA) and 17 long-standing (disease duration < 36 months, on treatment) RA (LSRA). LSRA patients had a significantly higher frequency of overall HRCT abnormalities compared to the other groups (p = 0.001). SPD serum levels were significantly higher in ACPA-positive subjects compared with healthy controls (158.5 ± 132.3 ng/mL vs 61.27 ± 34.11 ng/mL; p < 0.0001) and showed an increasing trend from ND subjects to LSRD patients (p = 0.004). Patients with HRCT abnormalities showed significantly lower values of DLCO (74.19 ± 13.2% pred. vs 131.7 ± 93% pred.; p = 0.009), evidence of ventilatory inefficiency at CPET and significantly higher SPD serum levels compared with subjects with no HRCT abnormalities (213.5 ± 157.2 ng/mL vs 117.7 ± 157.3 ng/mL; p = 0.018). Abnormal CPET responses and higher SPD levels were also associated with specific radiological findings. Impaired DLCO and increased SPD serum levels were independently associated with the presence of HRCT abnormalities. Subclinical lung abnormalities occur early in RA-associated autoimmunity. The presence of subclinical HRCT abnormalities is associated with several functional abnormalities and increased SPD serum levels of SPD. Functional evaluation through PFT and CPET, together with SPD assessment, may have a diagnostic potential in ACPA-positive subjects, contributing to the identification of those patients to be referred to HRCT scan.

Semi-quantitative grading and extended semi-quantitative grading for osteoporotic vertebral deformity: a radiographic image database for education and calibration.

The Genant's semi-quantitative (GSQ) criteria is currently the most used approach in epidemiology studies and clinical trials for osteoporotic vertebral deformity (OVD) evaluation with radiograph. The qualitative diagnosis with radiological knowledge helps to minimize false positive readings. However, unless there is a face-to-face training with experienced readers, it can be difficult to apply GSQ criteria by only reading the text description of Genant et al. (in 1993), even for a musculoskeletal radiologist. We propose an expanded semi-quantitative (eSQ) OVD classification with the following features: (I) GSQ grade-0.5 is noted as minimal grade (eSQ grade-1) for OVDs with height loss <20%; (II) GSQ mild grade (grade-1) is the same as eSQ mild grade (grade-2); (III) GSQ moderate grade (grade-2) is subdivided into eSQ grade-3 (moderate, >25%-1/3 height loss) and eSQ grade-4 (moderately-severe, >1/3-40% height loss); (IV) GSQ severe grade is subdivided into eSQ grade-5 (severe, >40%-2/3 height loss) and eSQ grade-6 (collapsed, with >2/3 height loss). We advocate to estimate vertebral height loss with adjacent vertebral heights as the reference (rather than using individual vertebra's posterior height as the reference). This article presents radiographs of 36 cases with OVD, together with gradings using GSQ criteria and eSQ criteria. The examples in this article can serve as teaching material or calibration database for readers who will use GSQ criteria or eSQ criteria. Our approach for quantitative measurement is explained graphically.