Objective
To investigate whether women with systemic sclerosis (SSc) have an increased risk of osteoporosis (OP) and related fractures compared to a high‐risk population with rheumatoid arthritis ...(RA) and also healthy controls, and to determine putative specific OP and fracture risk factors.
Methods
We performed a cross‐sectional study with successive inclusion of age‐matched healthy women and women with SSc and RA. Risk factors for OP and fracture were collected for all patients. Bone mineral density (BMD) was systematically measured at the lumbar spine and total hip region with dual x‐ray absorptiometry.
Results
We included 71 women with SSc, 139 women with RA, and 227 healthy women. The prevalence of OP and fracture was similar in SSc and RA, and was for both diseases higher than in healthy controls (OP: 30% in SSc, 32% in RA, and 11% in controls; fracture: 35% in SSc, 33% in RA, and 10% in controls). Multivariate analysis identified age as a risk factor of OP in SSc. Age and low 25‐hydroxyvitamin D (25OHD) levels were recognized as risk factors of fracture in SSc. In comparison, age and corticosteroid treatment were associated with OP in RA. Multivariate analysis confirmed age, OP, and low 25(OH)D levels as independent risk factors of fractures in RA.
Conclusion
The prevalence of OP and fracture in SSc was increased compared to healthy women and reached the high prevalence associated with RA. Age and vitamin D deficiency were identified as risk factors of fracture in SSc. Therefore, increasing the awareness and performance of BMD measurements together with the vitamin D supply in patients with SSc is warranted.
Parathyroid-related hypercalcemia is due to primary hyperparathyroidism (PHPT) or to familial hypocalciuric hypercalcemia (FHH). PHPT can lead to complications that necessitate parathyroidectomy. FHH ...is a rare genetic disease resembling PHPT; surgery is ineffective. A reliable method for distinguishing FHH from PHPT is needed.
To develop an easy-to-use tool to predict if a patient has PHPT.
Retrospective analysis of two prospective cohorts. Development of an unsupervised risk equation (Pro-FHH).
University hospitals in Paris, France, and Aarhus, Denmark.
Patients (Paris: 65 with FHH, 85 with PHPT; Aarhus: 38 with FHH, 55 with PHPT) were adults with hypercalcemia and PTH concentration within normal range.
Performance of Pro-FHH to predict PHPT.
Pro-FHH takes into account plasma calcium, PTH, and serum osteocalcin concentrations, and calcium-to-creatinine clearance ratio calculated from 24-hour urine collection (24h-CCCR). In the Paris cohort, area under the receiver operating characteristic curve (AUROC) of Pro-FHH was 0.961, higher than that of 24h-CCCR. With a cutoff value of 0.928, Pro-FHH had 100% specificity and 100% positive predictive value for the diagnosis of PHPT; it correctly categorized 51 of 85 patients with PHPT; the remaining 34 were recommended to undergo genetic testing. No patients with FHH were wrongly categorized. In an independent cohort from Aarhus, AUROC of Pro-FHH was 0.951, higher than that of 24h-CCCR.
Pro-FHH effectively predicted whether a patient has PHPT. A prospective trial is necessary to assess its usefulness in a larger population and in patients with elevated PTH concentration.
•18F-fluorocholine PET/CT, cervical ultrasound and 99mTc-MIBI scintigraphy have 76%, 71% and 33% sensitivity, respectively in the detection of abnormal parathyroid glands.•Overall sensitivity of ...cervical ultrasound, 99mTc-MIBI scintigraphy and 18F-fluorocholine PET/CT used as a single set is 94% for the detection of parathyroid lesion(s) in patients with primary hyperparathyroidism.•Cervical ultrasound, 99mTc-MIBI scintigraphy and 18F-fluorocholine PET/CT used as a single set help localize parathyroid lesion(s) in patients with primary hyperparathyroidism before surgery.
The purpose of this study was to assess the diagnostic capabilities of preoperative conventional imaging (99mTc-MIBI scintigraphy, cervical ultrasonography CUS) and 18F-fluorocholine PET/CT (FCH PET/CT) in the detection of hyperfunctioning parathyroid gland in patients with primary hyperparathyroidism (PHPT) used alone or as a single imaging set.
A total of 51 consecutive patients (6 men, 45 women; mean age, 62 ± 11.6 SD years; age range: 28–86 years) with biochemically confirmed PHPT who underwent CUS, single-tracer dual phase 99mTc-MIBI scintigraphy and FCH PET/CT were retrospectively included. 99mTc-MIBI scintigraphy were performed immediately after CUS and interpreted by the same operators. FCH PET/CT examinations were interpreted independently by two nuclear medicine physicians. An additional reading session integrating the three imaging modalities read in consensus as a combined imaging set was performed.
At surgery, 74 lesions were removed (32 parathyroid adenomas, 38 parathyroid hyperplasia and 4 subnormal glands). Thirty-six patients (71%) had single-gland disease and 15 patients (29%) had multiglandular disease at histopathological analysis. On a patient basis, sensitivity and accuracy of FCH PET/CT, CUS and 99mTc-MIBI scintigraphy for the detection of abnormal parathyroid glands were 76% (95% CI: 63–87%) and 76% (95% CI: 63–87%), 71% (95% CI: 56–83%) and 71% (95% CI: 56–83%), 33% (95% CI: 21–48%) and 33% (95% CI: 21–48%), respectively. The sensitivity of the combined imaging set was 94% (95% CI: 84–99%) and greater than the sensitivity of each individual imaging technique (P ≤ 0.001 for all).
Our results suggest that CUS, 99mTc-MIBI scintigraphy and FCH PET/CT interpreted as a single imaging set could be the ideal practice to precisely localize parathyroid lesion in patients with PHPT before surgery.
To assess the prevalence of autoimmune diseases in first-degree relatives of patients with systemic sclerosis (SSc), and to compare those results with control families in order to identify patterns ...of autoimmune diseases in relatives.
A retrospective case-control postal questionnaire survey was performed in France to recruit patients with SSc belonging to an association of patients with SSc and unrelated age-matched and sex-matched controls. Each participant was asked to self-report on the existence of autoimmune diseases in their first-degree relatives. The prevalence of autoimmune diseases in the families of patients with SSc was compared with the corresponding prevalence in the families of controls.
A total of 121 families out of 373 (32.4%) with a member having SSc reported at least 1 autoimmune disease in 1 or more first-degree relatives. The most frequent autoimmune diseases in SSc families when adjusted for family size were autoimmune thyroid disease (AITD; 4.9%), rheumatoid arthritis (4.1%), psoriasis (3.9%), and type 1 diabetes mellitus (2.9%). Compared with control families, AITD and connective tissue diseases (SSc, systemic lupus erythematosus, or Sjögren's syndrome) were more likely to occur in families with SSc (p = 0.01 and p = 0.01, respectively), with OR of 3.20 (95% CI 1.25-8.18) and 5.20 (95% CI 1.22-21.8). In contrast, inflammatory bowel disease was less likely to occur within families with SSc (p = 0.02, OR 0.29, 95% CI 0.11-0.80). In addition, the coexistence of more than 1 autoimmune disease in the index SSc case was associated with familial aggregation of autoimmune diseases.
Our results show that autoimmune diseases cluster within families of patients with SSc. This supports the notion that these diseases might arise on a shared genetic basis underlying several autoimmune phenotypes.
Abstract Objectives Anterior chest wall pain is a common but little studied feature of spondyloarthritis. The objectives of our study were to assess the prevalence of anterior chest wall pain and to ...describe its clinical characteristics in a cohort of spondyloarthritis patients in a tertiary care center. Methods Study design: retrolective single center observational study in 2010 (COSPA). Consecutive patients with definite spondyloarthritis according to Amor's criteria were included. Data collection: each patient underwent direct interview by a physician. Prevalence of anterior chest wall pain, according to spondyloarthritis subtype and its date of appearance, localization and nature were collected. Results In all, 275 consecutive spondyloarthritis patients were assessed. Among them, 102 patients (37.1%) suffered from spondyloarthritis-associated anterior chest wall pain. It was the first symptom of spondyloarthritis in 3.6% of cases. The prevalence after 5 and 10 years following the diagnosis of spondyloarthritis was 26.0% and 35.5%, respectively. Pain was usually in the upper chest and acute, increased by respiratory movements and movements of the arm; pain during the night was less frequent (41.0%). A flare lasted on average 5 weeks; recurrences were frequent (75%). Non-steroidal anti-inflammatory drugs and anti-tumor necrosis factor agents were reported as effective in 49.3% and 80.0% of cases, respectively. Conclusion Anterior chest wall pain was a frequent manifestation in spondyloarthritis. It occurred early in the disease course, but the risk persisted after disease onset. Better knowledge of the clinical characteristics of this symptom may help physicians for diagnosis and follow-up.
Os et hyperparathyroïdie primaire Cormier, Catherine; Koumakis, Eugénie
Revue du rhumatisme,
March 2021, 2021-03-00, Volume:
88, Issue:
2
Journal Article
Open access
•L’hyperparathyroïdie primaire est une maladie due à une sécrétion excessive et inappropriée d’hormone parathyroïdienne ayant pour conséquence une hypercalcémie et compliquée d’atteinte osseuse.•Le ...diagnostic de certitude est biologique.•Les formes normocalcémiques ont un retentissement osseux aussi important que les formes hypercalcémiques.•Le traitement de référence est chirurgical, seul traitement épargnant les fractures.•En cas de contre-indication à la chirurgie, les bisphosphonates sont possibles sans démonstration d’épargne fracturaire.
L’hyperparathyroïdie primaire (HPP) est une maladie due à une sécrétion excessive et inappropriée d’hormone parathyroïdienne ayant pour conséquence une hypercalcémie. Elle est le plus souvent diagnostiquée fortuitement devant une hypercalcémie ou bien devant une complication, soit une ostéoporose, soit plus rarement une complication rénale avec lithiase. La présentation clinique est le reflet de l’hypercalcémie et de l’atteinte de plusieurs organes, principalement le système cardiovasculaire, l’os et le rein. La majorité des patients ayant une HPP sont cependant asymptomatiques. Le diagnostic est biologique, facile quand il y a augmentation de la calcémie et de l’hormone parathyroïdienne, plus difficile quand un de ces deux paramètres est normal. On ne retiendra le diagnostic d’HPP normocalcémique qu’après avoir écarté toutes les causes d’hyperparathyroïdie secondaire. L’imagerie parathyroïdienne ne fait pas le diagnostic, mais elle guide le chirurgien et écarte une anomalie thyroïdienne associée. Le traitement de référence est chirurgical, son indication repose sur la présence ou un risque de complications, c’est le seul traitement qui épargne les fractures. Les traitements médicaux n’ont que des effets limités sur les complications, ils sont réservés aux contre-indications à la chirurgie. Après chirurgie parathyroïdienne, on évitera l’utilisation des bisphosphonates qui semblent empêcher l’épargne fracturaire de la parathyroïdectomie. En l’absence d’indication opératoire, une surveillance biologique, osseuse et rénale sera établie.
Pregnancy and breastfeeding are associated with bone density loss. Fracture occurrence during pregnancy and post-partum, and its determinants, remain poorly known in Osteogenesis Imperfecta (OI). The ...aim of this study was to characterize fractures that occurred during pregnancy and post-partum in OI patients.
We conducted a retrospective multicentric study including a total of 50 previously pregnant OI women from 10 Bone Centers in France. Among these patients, 12 (24%) patients experienced fractures during pregnancy or in the 6 months following delivery, and 38 (76%) did not experience any fracture. The most frequent localizations were: proximal femur (25%), spine (25%), distal femur (12.5%), and pelvis (12.5%). Fractures during pregnancy occurred during the third trimester and post-partum fractures occurred with a mean delay of 2 months following delivery. No fractures occurred during childbirth. We next compared the 12 patients with pregnancy or post-partum fractures with the 38 patients without fractures. Mean age at pregnancy was 32.7 ± 3.1 years-old in the fractured group, vs 29.3 ± 5.0 years-old in the non-fractured group (p = 0.002). Breastfeeding was reported in 85.7% of patients in the fractured group, vs 47.1% in the non-fractured group (p = 0.03). All patients with post-partum fractures were breastfeeding. Bone mineral density was significantly lower in patients with pregnancy-related fractures compared with other patients: spine Z-score - 2.9 ± 1.6DS vs - 1.5 ± 1.7DS (p = 0.03), and total hip Z-score - 2.0 ± 0.7DS vs - 0.5 ± 1.4DS (p = 0.04). At least one osteoporosis-inducing risk factor or disease other than OI was identified in 81.8% vs 58.6% of fractured vs non-fractured patients (not significant). Fracture during pregnancy or post-partum was not associated with the severity of OI. Bisphosphonates before pregnancy were reported in 16.7% and 21.1% of patients with pregnancy-related fractures and non-fractured patients, respectively (not significant).
OI management during pregnancy and post-partum should aim for optimal control of modifiable osteoporosis risk factors, particularly in patients with low BMD. Breastfeeding should be avoided.
The liver plays a central role in whole-body lipid and glucose homeostasis. Increasing dietary fat intake results in increased hepatic fat deposition, which is associated with a risk for development ...of insulin resistance and type 2 diabetes. In this study, we demonstrate a role for the phosphate inorganic transporter 1 (PiT1/SLC20A1) in regulating metabolism. Specific knockout of Pit1 in hepatocytes significantly improved glucose tolerance and insulin sensitivity, enhanced insulin signaling, and decreased hepatic lipogenesis. We identified USP7 as a PiT1 binding partner and demonstrated that Pit1 deletion inhibited USP7/IRS1 dissociation upon insulin stimulation. This prevented IRS1 ubiquitination and its subsequent proteasomal degradation. As a consequence, delayed insulin negative feedback loop and sustained insulin signaling were observed. Moreover, PiT1-deficient mice were protected against high-fat-diet-induced obesity and diabetes. Our findings indicate that PiT1 has potential as a therapeutic target in the context of metabolic syndrome, obesity, and diabetes.
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•Hepatocyte-specific Pit1-KO protects against HFD-induced obesity and diabetes•Pit1 deletion delayed an insulin negative feedback loop, sustaining insulin signaling•USP7 is a PiT1 binding partner•Pit1 deletion inhibited USP7/IRS1 dissociation upon insulin stimulation
Forand et al. show that PiT1, through regulation of the USP7/IRS1 interaction, modulates the insulin negative feedback loop. Disruption of PiT1 in hepatocytes protects mice against HFD-induced obesity and diabetes, suggesting that it may be therapeutically targeted to treat metabolic syndrome.
Introduction Systemic sclerosis (SSc)-related pulmonary arterial hypertension (PAH) has emerged as a major mortality prognostic factor. Mutations of transforming growth factor beta (TGFβ) receptor ...genes strongly contribute to idiopathic and familial PAH. Objective To explore the genetic bases of SSc–PAH, we combined direct sequencing and genotyping of candidate genes encoding TGFβ receptor family members. Materials and methods TGFβ receptor genes, BMPR2, ALK1, TGFR2 and ENG, were sequenced in 10 SSc–PAH patients, nine SSc and seven controls. In addition, 22 single-nucleotide polymorphisms (SNP) of these four candidate genes were tested for association in a first set of 824 French Caucasian SSc patients (including 54 SSc–PAH) and 939 controls. The replication set consisted of 1516 European SSc (including 219 SSc–PAH) and 3129 controls from the European League Against Rheumatism Scleroderma Trials and Research group network. Results No mutation was identified by direct sequencing. However, two repertoried SNP, ENG rs35400405 and ALK1 rs2277382, were found in SSc–PAH patients only. The genotyping of 22 SNP including the latter showed that only rs2277382 was associated with SSc–PAH (p=0.0066, OR 2.13, 95% CI 1.24 to 3.65). Nevertheless, this was not replicated with the following result in combined analysis: p=0.123, OR 0.79, 95% CI 0.59 to 1.07. Conclusions This study demonstrates the lack of association between these TGFβ receptor gene polymorphisms and SSc–PAH using both sequencing and genotyping methods.
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