Development of Spinal Enthesopathies in Adults With X-linked Hypophosphatemia.

CONTEXT: Musculoskeletal complications are the main manifestations in adults with X-linked hypophosphatemia (XLH). Enthesopathy significantly impairs quality of life. OBJECTIVE: To identify the risk factors associated with the development and progression of spinal enthesopathies in adults with XLH. DESIGN AND SETTING: We conducted a retrospective study in the French Reference Center for Rare Diseases of the Calcium and Phosphate Metabolism. PATIENTS: Adults XLH patients with 2 EOS® imaging performed at least 2 years apart at the same center between June 2011 and March 2022. The progression of enthesopathies was defined as a new enthesopathy at least 1 intervertebral level in patients with or without presence of enthesopathy at baseline. MAIN OUTCOME MEASURES: Demographic, treatment, PHEX mutation with the progression of enthesopathies. RESULTS: Fifty-one patients (66.7% of women, mean age 42.1 ± 13.4 years) underwent 2 EOS imaging with an average interval of 5.7 (± 2.31) years.Progression of spinal enthesopathies was observed in 27 (52.9%) patients. In univariate analysis, patients with a progression of spinal enthesopathies were significantly older (P < .0005), were significantly older at treatment initiation (P = .02), presented with dental complications (P = .03), received less frequently treatment during childhood with phosphate and/or vitamin D analogs (P = .06), and presented more frequently with hip osteoarthritis (P = .002) at baseline. In multivariate analysis, none of these factors was associated with a progression of spinal enthesopathies. CONCLUSION: This study confirms the high proportion of patients with a progression of spinal enthesopathies. Age seems to be the main factor associated with progression.

Fully automated opportunistic screening of vertebral fractures and osteoporosis on more than 150 000 routine computed tomography scans.

OBJECTIVE: Osteoporosis is underdiagnosed and undertreated, although severe complications of osteoporotic fractures, including vertebral fractures, are well known. This study sought to assess the feasibility and results of an opportunistic screening of vertebral fractures and osteoporosis in a large database of lumbar or abdominal CT scans. MATERIAL AND METHODS: Data were analysed from CT scans obtained in 35 hospitals from patients aged 60 years or older and stored in a Picture Archiving and Communication System in Assistance-Publique-Hôpitaux de Paris, from 2007 to 2013. Dedicated software was used to analyse the presence or absence of at least 1 vertebral fracture (VF), and the radiodensity of the lumbar vertebrae was measured Hounsfield Units (HUs). A simulated T-score was calculated. RESULTS: Data were analysed from 152 268 patients [mean age (S.D.) = 73.2 (9.07) years]. Success rates for VF assessment and HUs measurements were 82 and 87%, respectively. The prevalence of VFs was 24.5% and increased with age. Areas under the receiver operating characteristic curves for the detection of VFs were 0.61 and 0.62 for the mean HUs of the lumbar vertebrae and the L1 HUs, respectively. In patients without VFs, HUs decreased with age, similarly in males and females. The prevalence of osteoporosis (sT-score ≤ -2.5) was 23.8% and 36.5% in patients without and with VFs, respectively. CONCLUSION: It is feasible on a large scale to screen for VFs and osteoporosis during opportunistic screening in patients 60 years or older having lumbar or abdominal CT.

Adherence to and patient's knowledge of self-management of subcutaneous biologic therapy in chronic inflammatory rheumatic diseases: results of a multicentre cross-sectional study.

OBJECTIVES: Non-adherence to biologic therapy is an issue in chronic inflammatory rheumatic diseases (CIRDs) and might be related to poor patient knowledge of the risk of these therapies. Our aim here was to evaluate the level of patient adherence to and knowledge of self-care safety skills for biologic therapy. METHODS: This was a multicentre, cross-sectional study in which out-patients visited an office- or hospital-based rheumatologist. All the patients received subcutaneous biologic therapy for CIRDs. We collected data on: 1. the level of CIRD patient adherence to current subcutaneous biologic therapy using both the self-administered Compliance Questionnaire Rheumatology 5 items (CQR5) and a simple adherence question; 2. patients' knowledge of self-management of biologic therapy by the self-administered BIOSECURE questionnaire; 3. sources of information related to biologic therapy. RESULTS: In all, 285 patients (rheumatoid arthritis, n=103; spondyloarthritis, n=153; psoriatic arthritis, n=25) were enrolled by 19 rheumatologists. The mean (SD) biologic therapy duration was 5.9 (4.9) years. Adherence to the current biologic therapy was high (79.3% and 57.5% according to the CQR5 questionnaire and the adherence question, respectively). Level of knowledge of self-care safety skills (median BIOSECURE score 71) was in the acceptable range. Level of adherence and level of knowledge of self-care safety skills for biologic therapy were not associated. Patients declared that the main sources of information were their rheumatologist (92.6%) and the rheumatology team (30.5%). CONCLUSIONS: According to the patients' estimation, adherence to biologic therapy and the level of knowledge of self-care safety skills related to biologic therapy are acceptable, and these domains are not related (e.g. level of adherence and level of knowledge of risks).

Low incidence of vertebral fractures in early spondyloarthritis: 5-year prospective data of the DESIR cohort.

OBJECTIVES: An increased risk of vertebral fractures (VFs) has been reported in spondyloarthritis (SpA). Our hypothesis is that the prevalence of VFs is lower than reported in previous studies, especially in early SpA. This study aimed at assessing the incidence of radiographical VFs over 5 years in early axial SpA. METHODS: The DESIR (DEvenir des Spondylarthropathies Indifférenciées Récentes) cohort, which included patients with inflammatory back pain highly suggestive of axial SpA, is the basis of this study. All radiographs of the DESIR cohort had been assessed at a central facility, by one investigator specialised in the field of the diagnosis of VFs according to Genant's method. We assessed the prevalence and incidence of VFs and vertebral deformities at baseline and over 5 years. RESULTS: Five-year X-rays were available for 432 patients (mean age 34.3±8.7 years, 53% women). Diagnosis of VF was doubtful and needed adjudication for 19 patients (4.4%). 13 patients had prevalent VFs (3.0%) which were located at the thoracic spine (12 were grade 1). At 5 years, five patients had an incident VF (1.15%); seven vertebrae were fractured, mostly located at the thoracic spine (n=6/7), and of grade 1 (n=6/7). CONCLUSION: In the DESIR cohort, a population of early SpA, we found a low prevalence and incidence of VFs (3.0% and 1.15 %), respectively. This confirms our hypothesis that the actual prevalence and incidence of VFvertebral fracture in SpA is lower than that reported in the previous studies.

Difficulties in the diagnosis of vertebral fracture in men: agreement between doctors.

UNLABELLED: The agreement for vertebral fracture (VF) diagnosis in men, between doctors is poor. OBJECTIVES: To assess the agreement for VF diagnosis, in men, on standard radiographs, between experts, before and after consensual workshop and establishing an algorithm. METHODS: The agreement between thirteen experimented rheumatologists has been calculated in thirty osteoporotic men. Then, the group discussed in a workshop and 28 other radiograph sets of osteoporotic men with follow-up radiographs and incident confirmed VF, have been reviewed. The experts identified and hierarchised 18 pathological features of vertebral deformation and established an algorithm of VF diagnosis. Eleven experts have realized a second reading of the first set of radiographs. We compared the agreement between the 2 readings without and with the algorithm. RESULTS: After consensus and the use of the algorithm the results are: number of fractured patients (with at least 1 VF) according to the experts varies from 13 to 26 patients out of 30 (13 to 28 during the first reading). The agreement between the experts at the patient level is 75% (70% at the first reading). Among the 390 vertebrae analyzed by the experts, the number of VF detected varies from 18 to 59 (18 to 98 at the first reading). The agreement between the experts at the vertebral level is 92% (89% at the first reading). The algorithm allows a good improvement of the agreement, especially for 8 of the 11 experts. Discrepancies for the VF diagnosis between experts exist. The algorithm improves the agreement.

Increase in bone density in patients with spondyloarthritis during anti-tumor necrosis factor therapy: 6-year followup study.

OBJECTIVE: To assess the effects on bone mineral density (BMD) of prolonged anti-tumor necrosis factor (anti-TNF) therapy in patients with spondyloarthritis (SpA); to compare the BMD changes to those observed in SpA patients not treated with anti-TNF; and to identify the predictors of these changes. METHODS: Fifty-nine patients with SpA according to the European Spondylarthropathy Study Group criteria who were treated with anti-TNF therapy for at least 4 years were included. Thirty-four patients with SpA from an international longitudinal observational study (OASIS cohort) were used as a control group. Lumbar spine and hip BMD were measured by dual-energy x-ray absorptiometry at baseline, after 1 year, and after at least 4 years. RESULTS: Over an average 6.5 years' followup, the increase in BMD was 11.8% (± 12.8%) at the lumbar spine (p < 0.0001) and 3.6% (± 9.3%) at the great trochanter (p = 0.0001) in patients treated with anti-TNF. At the lumbar spine, the increase was similar in patients with and those without syndesmophytes. BMD changes were significantly higher in the anti-TNF group than in the control group at lumbar spine (p < 0.0001), at femoral neck (p = 0.002), and at trochanter (p = 0.011), but not at total hip (p = 0.062). Multivariate analysis showed that the predictors of lumbar spine BMD changes in the total population were the use of anti-TNF (p < 0.0001) and, in the anti-TNF therapy group, the 1-year lumbar spine BMD change (p = 0.007). CONCLUSION: This study shows that prolonged anti-TNF therapy increases lumbar spine and trochanter BMD. This effect should be taken into account before introducing antiosteoporotic treatment in these patients.

Lumbar disc degeneration in osteoporotic men: prevalence and assessment of the relation with presence of vertebral fracture.

OBJECTIVE: The relationship between osteoarthritis (OA) and osteoporosis (OP) remains controversial. An inverse relationship between spine OA and the presence of prevalent vertebral fractures has been shown in osteoporotic women. Our objective was to assess this relationship in osteoporotic men. METHODS: All the patients had OP based on densitometric data and were aged ≥ 65 years. Spine radiographs were performed according to a standardized procedure. Vertebral fractures were assessed from T4 to L4 by a semiquantitative method. Disc degenerative changes were assessed by the presence and severity of osteophytes and disc narrowing at levels T12-L1 to L5-S1. Logistic regression was used to study the relationship between the presence of vertebral fracture and lumbar disc degeneration. RESULTS: The study included 261 osteoporotic men. The prevalence of vertebral fractures was 26.4% (69/261). At least 1 osteophyte was found in 91.6% (239/261) of patients, and at least 1 disc space narrowing in 63.5% (165/260). The prevalence of at least 1 osteophyte and/or at least 1 disc space narrowing was similar in patients with and those without vertebral fracture. No relationship was found between the presence and/or the severity of osteophytes and disc narrowings and the presence of prevalent vertebral radiographic fractures. CONCLUSION: In osteoporotic men, the prevalence of lumbar spine degeneration is high. There is no relationship between lumbar disc degeneration and the presence of vertebral fracture in osteoporotic men.

Identification of rheumatoid arthritis patients with vertebral fractures using bone mineral density and trabecular bone score.

The aim of this study was to test bone mineral density (BMD), trabecular bone score (TBS), and their combination, for detection of rheumatoid arthritis (RA) patients with vertebral fractures (VFs). One hundred eighty-five women aged 56.0 ± 13.5 yr, with RA since 15.5 ± 9.9 yr were studied. Lumbar spine, total hip, and femoral neck BMD were assessed by dual-energy X-ray absorptiometry (DXA). TBS was calculated from anteroposterior image of lumbar spine BMD. VFs from T4 to L4 were evaluated using Vertebral Fracture Assessment software on DXA device. The proportions of patients with VF and T-scores ≤-2.5 were only 24.2%, 21.2%, and 33.3% at lumbar spine, total hip, and femoral neck, respectively. T-scores were significantly lower in patients with VF than in patients without VF, the largest difference being observed at femoral neck (p=0.0001). TBS was significantly lower in patients with VF vs without VF (p=0.0001). The areas under the curves were 0.621, 0.704, 0.703, 0.719, and 0.727 for lumbar spine BMD, TBS, lumbar spine BMD+TBS, total hip BMD, and femoral neck BMD, respectively. The threshold of 1.173 for TBS had the best sensitivity (63%) and specificity (74%). TBS measured at the lumbar spine has a better discrimination value than lumbar spine BMD, and similar to femoral neck BMD, for prediction of presence of VF in patients with RA. In RA subjects with osteopenia, the proportion of patients with VF was higher in the lowest tertile of TBS when compared with the highest tertile. In this population, at low risk according to BMD, TBS could help to detect patients with VF.

Prospective assessment of thoracic kyphosis in postmenopausal women with osteoporosis.

We attempt to assess quantitatively thoracic kyphosis and its influence on incident fractures and quality of life over three years in postmenopausal women with osteoporosis and the effect of strontium ranelate on thoracic kyphosis progression. This study was performed on women with postmenopausal osteoporosis from the Spinal Osteoporosis Therapeutic Intervention (SOTI) and Treatment of Peripheral Osteoporosis (TROPOS) studies. Vertebral fractures were assessed on lateral thoracic radiographs performed at baseline and at three years according to standardized procedure. Kyphosis index (KI, %), was defined as the percentage ratio between the maximum depth of thoracic curvature and the height measured from the T4 to the T12 vertebrae. Baseline characteristics of the 3218 patients (1594 strontium ranelate, 1624 placebo) were mean age 73.3 years, spine bone mineral density (BMD) T-score (L2-4) -3.1, femoral neck T-score -3.0, and KI 25.4%. In the placebo group, patients with the highest baseline KI experienced significantly more vertebral fractures than those with medium KIs [relative risk (RR) = 1.53; 95% confidence interval (CI) 1.19-1.96, p < .001) or the lowest KIs (RR = 1.70, 95%CI 1.32-2.21, p < .001), even after adjusting for the presence of prevalent fractures, age, body mass index (BMI), and BMD. There was no difference in the risk of nonvertebral fractures according to baseline KI. Three-year changes in quality-of-life physical scores reflected significantly better status for patients in the lowest tertile of KI compared with those in the highest at baseline. Over three years, the KI increased for all patients, indicating worsening of thoracic kyphosis, whatever the presence of prevalent or incident vertebral fractures. This KI progression was lower in the strontium ranelate group than in the placebo group. Thoracic kyphosis is a risk factor for vertebral fractures over three years and influences physical capacity changes in postmenopausal women with osteoporosis. Thoracic kyphosis progression over three years is lower in a subgroup of strontium ranelate-treated patients compared with placebo-treated patients.

Radiographic methods for evaluating osteoporotic vertebral fractures.

UNLABELLED: Reproducible methods for the radiological assessment of osteoporotic vertebral fractures, defined based on accurate criteria, are needed in everyday practice and in therapeutic trials and epidemiological studies. OBJECTIVES: To describe and to evaluate methods for osteoporotic vertebral fracture assessment based on standard radiographs or dual-energy X-ray absorptiometry (DXA) and to determine the role for each method in clinical practice, therapeutic trials, and epidemiological studies. METHODS: A review written by a rheumatologist based on his clinical experience and on a literature review was submitted to four experts. Studies in English or French published between 1975 and February 2008 were retrieved from Medline using the keywords vertebral fracture, osteoporosis, vertebral deformity, and vertebral fracture assessment. RESULTS: One hundred forty-nine articles were selected and read in their full-text version. There was no consensus regarding the definition of osteoporotic vertebral fractures. The following methods were evaluated: visual assessment, Genant's semi-quantitative assessment, Jiang's algorithm-based qualitative method, morphometric radiography, and DXA of the spine. In everyday practice, Genant's semi-quantitative assessment on standard radiographs may provide useful information on the severity and prognosis of osteoporosis. DXA done for bone mineral density measurement may detect vertebral fractures in asymptomatic patients. Assessment of standard radiographs remains the reference standard for diagnosing vertebral fractures in patients with suggestive symptoms (e.g., pain in the thoracic or lumbar spine, height loss, or thoracic kyphosis). For therapeutic trials and epidemiological studies, Genant's semi-quantitative assessment used by a trained and experienced observer is the preferred method, based on its good reproducibility and ability to differentiate fractures from other deformities. However, thousands of radiographs may be needed, making routine interpretation by an expert impractical. A visual semi-quantitative method may be used to separate normal radiographs from radiographs showing possible or obvious fractures, which can then be read by an expert. Alternatively, radiomorphometric indices can be determined on digitized radiographs in combination with a semi-quantitative assessment, with discordant cases being reviewed by an expert. We do not recommend Jiang's method at present, as it is still undergoing validation.

Practice patterns in outpatient rheumatology: a pilot evaluation of medical file content.

OBJECTIVES: High-quality medical records that contain detailed data on the patient and disease are essential to high-quality patient care. RHEVER is a network of hospital- and office-based rheumatologists created in 1999 to pursue a number of objectives, including the development of recommendations about items that should be recorded routinely at each patient visit. Subsequently, one of the RHEVER members investigated whether these recommendations were followed by RHEVER participants at a teaching hospital. METHODS: A cross-section of paper-based outpatient files at the rheumatology clinic of the Cochin Teaching Hospital, Paris, France, was studied. The sample comprised 50 files taken at random and 30 files of patients with rheumatoid arthritis. RESULTS: In the 50 unselected files, the reason for the visit was consistently provided, but the diagnosis was variably recorded and decisions about investigations and treatments were not always described. Of the 30 files in patients with rheumatoid arthritis, 75% contained the full set of recommended clinical items. CONCLUSION: This pilot study establishes the feasibility of practice pattern evaluation by rheumatologists. A similar study should be conducted among office-based RHEVER participants. Follow-up investigations are needed to evaluate the impact of medical record evaluations on quality of care.

Vertebral fracture risk reduction with strontium ranelate in women with postmenopausal osteoporosis is independent of baseline risk factors.

UNLABELLED: Strontium ranelate (2 g/day) was studied in 5082 postmenopausal women. A reduction in incident vertebral fracture risk by 40% was shown after 3 years. This effect was independent of age, initial BMD, and prevalent vertebral fractures. INTRODUCTION: Strontium ranelate is an orally active treatment able to decrease the risk of vertebral and hip fractures in osteoporotic postmenopausal women. The aim of this study was to assess the efficacy of strontium ranelate according to the main determinants of vertebral fracture risk: age, baseline BMD, prevalent fractures, family history of osteoporosis, baseline BMI, and addiction to smoking. MATERIALS AND METHODS: We pooled data of two large multinational randomized double-blind studies with a population of 5082 (2536 receiving strontium ranelate 2 g/day and 2546 receiving a placebo), 74 years of age on average, and a 3-year follow-up. An intention-to-treat principle was used, as well as a Cox model for comparison and relative risks. RESULTS: The treatment decreased the risk of both vertebral (relative risk [RR] = 0.60 [0.53-0.69] p < 0.001) and nonvertebral (RR = 0.85 [0.74-0.99] p = 0.03) fractures. The decrease in risk of vertebral fractures was 37% (p = 0.003) in women <70 years, 42% (p < 0.001) for those 70-80 years of age, and 32% (p = 0.013) for those > or = 80 years. The RR of vertebral fracture was 0.28 (0.07-0.99) in osteopenic and 0.61 (0.53-0.70) in osteoporotic women, and baseline BMD was not a determinant of efficacy. The incidence of vertebral fractures in the placebo group increased with the number of prevalent vertebral fractures, but this was not a determinant of the effect of strontium ranelate. In 2605 patients, the risk of experiencing a first vertebral fracture was reduced by 48% (p < 0.001). The risk of experiencing a second vertebral fracture was reduced by 45% (p < 0.001; 1100 patients). Moreover, the risk of experiencing more than two vertebral fractures was reduced by 33% (p < 0.001; 1365 patients). Family history of osteoporosis, baseline BMI, and addiction to smoking were not determinants of efficacy. CONCLUSIONS: This study shows that a 3-year treatment with strontium ranelate leads to antivertebral fracture efficacy in postmenopausal women independently of baseline osteoporotic risk factors.

Bone mineral measurements in mice: comparison of two devices.

Animal models are widely used to explore the pathogenesis and management of osteoporosis. Mice are increasingly being used in animal models. We have evaluated the precision, accuracy, and ability to monitor changes in bone mineral measurements of mice with the Piximus and Hologic QDR 2000 devices. One hundred and twenty-two C57/BL6 mice were used in this study; 70 of them were put on a low calcium diet and followed prospectively for 14 wk. They were measured using both devices at baseline and at wk 14. Using the Piximus, we measured the whole body, the tibia, and two caudal vertebrae. Using the Hologic, we measured the tibia, which we divided into three equal parts. The remaining mice were used to evaluate the precision and accuracy of the measurement. The accuracy, which was determined only for the Hologic device, revealed a mean difference between the in vivo bone mineral content (BMC) and the ash weight of 0.1 mg. The precision, evaluated from the coefficient of variation (%) and the Smallest Detectable Difference (SDD, in absolute values) was good for both devices, confirming their ability to detect small differences in longitudinal studies: as little as 0.004 g for the BMC of the total tibia on both devices, and 0.003 g/cm2 for whole body bone mineral density (BMD) on the Piximus. The BMC found using the two devices was comparable, whereas the BMD obtained on the Hologic device was nearly double that found using the Piximus. The comparison of the results by Bland and Altman's method showed that the difference between the results was not dependent on the magnitude of the measurement. We concluded that bone density and bone-density changes in mice can be measured precisely in vivo using the Hologic and Piximus devices; the latter being able to measure the whole body BMD with good precision.