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Analisa-se as diversas funções das ondas de choque referente à dose, intensidade, tempo de aplicação e a seleção dos pacientes aptos, ou seja, as indicações, contra indicações e suas complicações. Necessita-se aperfeiçoar métodos de aplicação das ondas de choque em espasticidade de maneira segura e coerente. Selecionam-se 23 casos, idade entre 20 a 76 anos. Divididos em dois grupos diferentes. Grupo 1: Composto por 10 indivíduos normais, utiliza-se dosagem elevadas. Dose: 0.050mj/mm² a 0,060mj/mm². Grupo 2: Composto por 13 indivíduos com espasticidade, utiliza-se as mesmas dosagens elevadas do primeiro grupo para verificar a resistência da pele frente a dosagem. As mensurações compararam os momentos antes e após as aplicações utilizando a escala de Ashworth modificada, goniometria digital, acelerômetro e a inspeção na pele para verificar sinais de hematomas ou petéquias. Ao analisar a média, antes das aplicações o grau de flexão do cotovelo era (37,2) e após as aplicações a flexão do cotovelo evoluiu para (61,0) ficando o cotovelo mais livre e maleável. A segunda articulação que refletiu melhora foi a abdução do ombro. A abdução que apresentava (40,2) passou a apresentar (49,6) graus. A aceleração máxima melhorou comparando os momentos antes e após as aplicações de ondas de choque (0,97-1,27). Não se observa petéquias, eritema e hematomas frente ao equipamento. No final demonstra-se uma tabela com as dosagens e ciclos e energia segura. Conclusão: Houve decréscimo da espasticidade em todas as avaliações. A tolerância dos pacientes ao equipamento foi observada satisfatoriamente nesse estudo.

Objectif L’hypophosphatemie genetique lie a l’X (XLH), due aux mutations du gene PHEX, s’accompagne d’une production excessive de Fibroblast Growth Factor 23 (FGF-23), ayant pour consequence une fuite urinaire de phosphate avec des anomalies de la mineralisation osseuse. Les etudes epidemiologiques suggerent un lien entre FGF-23, obesite et syndrome metabolique. Toutefois, le retentissement metabolique du XLH n’a pas ete evalue. Methodes Etude prospective (CNIL2171036v0) comparant la prevalence du surpoids et de l’obesite chez des patients XLH adultes aux donnees de la population francaise. La tolerance au glucose et l’insulinosecretion ont ete evaluees par une hyperglycemie provoquee par voie orale (HGPO) et comparees aux resultats obtenus chez des temoins apparies sur l’âge, le sexe et l’IMC. Resultats Cent treize patients XLH (85F/28H), âge median 35,5 ans, porteurs de mutation PHEX, ont ete evalues. Leur IMC median etait de 25 kg/m2. Trente-huit (35,5 %, 29F) patients etaient en surpoids et 22 (20,5 %, 16F) patients etaient obeses. La prevalence de l’obesite en comparaison a la population generale etait plus importante chez les patients XLH (+ 20 %, 95 % CI [+6; + 33], p = 0,013), en particulier chez les sujets jeunes. Quatre (3,8 %) patients avaient un diabete et 10 (10,3 %) etaient classes comme intolerants au glucose lors de l’HGPO. Les aires sous la courbe de glycemie et d’insulinemie de 82 patients XLH et de 82 temoins etaient comparables. Discussion Les patients XLH ont un risque eleve de surcharge ponderale par rapport a la population francaise, sans retentissement sur le metabolisme glucidique.

Background X-linked hypophosphatemic rickets (XLHR) is due to mutations in PHEX leading to unregulated production of FGF23 and hypophosphatemia. XLHR is characterized by leg bowing of variable severity. Phosphate supplements and oral vitamin analogs, partially or, in some cases, fully restore the limb straightness. Surgery is the alternative for severe or residual limb deformities. Objective To retrospectively assess the results of surgical limb correction in XLHR (osteotomies and bone alignment except for 3 transient hemiepiphysiodesis). Methods We analyzed the incidence of recurrence and post-surgical complications in 49 XLHR patients (29F, 20M) (mean age at diagnosis 6.0 years (± 7.1)). Results At first surgery, the mean age was 13.4 years (± 5.0). Recurrence was observed in 14/49 (29%) patients. The number of additional operations significantly decreased with age (2.0 (± 0.9), 1.7 (± 1.0) and 1.2 (± 0.4) in children 15 years; P Conclusion We report a large series of surgical procedures in XLHR. Our results confirm that phosphate supplements and vitamin D analog therapy is the first line of treatment to correct leg bowing. Surgery before puberty is associated with a high risk of recurrence of the limb deformity. Such procedures should only be recommended, following multidisciplinary discussions, in patients with severe distortion leading to mechanical joint and ligament complications, or for residual deformities once growth plates have fused.

Background/Aims: Hypoparathyroidism associated with malabsorption can be particularly challenging to manage due to limited and erratic intestinal absorption of calcium and vitamin D analogues, resulting in episodes of hypo- or hypercalcaemia. We evaluated the role of continuous subcutaneous recombinant parathyroid hormone (rhPTH 1–34) infusion (CSPI) in children with hypoparathyroidism associated with intestinal malabsorption resistant to conventional therapy. Method: Four patients (8–13 years of age), with symptomatic hypocalcaemia resistant to conventional therapy, were started on CSPI (follow-up 3–8 years) in two paediatric endocrinology units in Europe. Results: Serum calcium normalized within 48 h of commencing treatment in all 4 patients. An average rhPTH 1–34 dose of 0.4 µg/kg/day resulted in a substantial reduction in symptomatic hypocalcaemia and hypo-/hypercalcaemia-related hospital admissions. An increased alkaline phosphatase activity was noted in the first 6 months on CSPI, indicating an increase in bone turnover. In 2 patients with elevated urinary calcium excretion before CSPI, this normalized in the first year on treatment. No significant side effects were noticed in the short or long term, with patient-reported preference of CSPI over conventional treatment. Conclusion: CSPI is a promising and effective treatment option for managing hypocalcaemia and hyperphosphataemia in children with hypoparathyroidism associated with intestinal malabsorption.

In this essay, we explicate the internal logic of contemporary terrorist acts and our society’s responses, to denaturalize the label and meanings we give to “terrorism.” We argue that contemporary terrorism communicates intimidation, fear, and anxiety through the ritualization and mediatization of terrorist attacks. Mediatization refers to the strategic coercion of imperative media coverage of the attacks, and ritualization refers to the focus on sacred life structures in both terrorist attacks and remedial responses. In combining ritualization and mediatization, terrorism aims to introduce maximal chaos through unexpected disruption of the sacred and taken-for-granted in everyday life in the community of the attack and wherever media coverage can reach. The fear and anxiety induced by disrupted life rhythms, including normal media flows, and the compelling footage of the disruption lead to ritualized reactions which both restore and transform the social order beyond the moment of the attack.

Introduction Les pseudohypoparathyroidies et l’acrodysostose sont des maladies metaboliques caracterisees par une resistance a l’hormone parathyroidienne, causee par des defauts moleculaires sur la voie de signalisation d’AMP cyclique. D’autres recepteurs hormonaux couples aux proteines G empruntent cette voie, notamment les recepteurs des gonadotrophines. Cependant, l’existence d’une resistance aux gonadotrophines chez ces patients reste incertaine. Notre objectif est de caracteriser la fonction testiculaire des hommes atteints de pseudohypoparathyroidie et d’acrodysostose. Patients Les hommes âges d’au moins 16 ans, suivis au CRMR du Calcium, avec un diagnostic genetique confirme de PHP1A (mutations inactivatrices ou deletions de GNAS), PHP1B (anomalies de methylation du locus GNAS) ou d’acrodysostose (mutations de PRKAR1A ou de PDE4D) ont ete inclus. Resultats Nous avons evalue 32 patients : 10 PHP1A, 18 PHP1B et 4 acrodysostoses. L’echographie testiculaire retrouve une diminution du volume testiculaire chez les patients PHP1A par rapport aux patients PHP1B (6,9 mL [4,8 ;13,1] versus 13,4 mL [9 ;20], p = 0,005). Les concentrations plasmatiques de testosterone, d’inhibine B et des gonadotrophines sont comparables et majoritairement dans les valeurs normales. Chez 2 patients avec acrodysostose, l’echographie a retrouve une agenesie deferentielle en absence de mutation de CFTR2. En conclusion, les patients avec PHP1A presentent une hypotrophie testiculaire, probablement liee a l’atteinte de la spermatogenese (en cours d’evaluation). L’empreinte parentale du locus GNAS semble s’appliquer sur l’epithelium spermatogenique, mais pas a la cellule de Sertoli ni a la cellule de Leydig. L’acrodysostose est associee a des anomalies du developpement des canaux deferents, absentes dans la pseudohypoparathyroidie.

X-linked hypophosphatemia (XLH), due to a PHEX gene mutation, is the most common genetic form of rickets and osteomalacia. Manifestations in children consist of rickets, lower-limb bone deformities, bone pain, failure to thrive, dental abscesses, and/or craniostenosis. Adults may present with persistent bone pain, early osteoarthritis, hairline fractures and Looser zones, enthesopathy, and/or periodontitis. Regardless of whether the patient is an infant, child, adolescent or adult, an early diagnosis followed by optimal treatment is crucial to control the clinical manifestations, prevent complications, and improve quality of life. Treatment options include active vitamin D analogs and phosphate supplementation to correct the 1.25(OH)2 vitamin D deficiency and to compensate for the renal phosphate wasting, respectively. The recently introduced FGF23 antagonist burosumab is designed to restore renal phosphate reabsorption by the proximal tubule and to stimulate endogenous calcitriol production. In Europe, burosumab is licensed for use in pediatric patients older than 1 year who have XLH. This review discusses the diagnosis and treatment of XLH and describes the indications of the various available treatments.

Introduction Some metabolic bone disorders may result in the premature closure of one or more calvarial sutures during childhood, potentially leading to a cranioencephalic disproportion. The aim of this paper is to review the characteristics and consequences of craniosynostosis associated with metabolic disorder. Material and methods A review of the literature on metabolic forms of craniosynostosis was performed. Results The most common forms of craniosynostosis associated with metabolic bone disorder were isolated sagittal suture fusion with or without scaphocephaly, and sagittal suture fusion associated with coronal suture fusion (oxycephaly) or also with lambdoid suture fusion (pansynostosis). Synostosis may be well-tolerated, but in some subjects results in neurodevelopmental and functional impairment that is sometimes severe. Conclusion The impact of metabolic synostosis is very variable, depending on the specific underlying metabolic disease, with a large spectrum of morphological and functional consequences. Diagnosis should be early and management should be carried out by a multidisciplinary team with expertise in both rare skeletal disorders and craniosynostosis. The impact of emergent medical therapies recently developed for some of these diseases will be assessed by systematic coherent follow-up of international registries.

Growing body of scientific evidence points to link between fibroblast growth factor-23 (FGF-23) and unfavourable metabolic profile (obesity, insulin resistance, hyperglycemia) and all-cause mortality in general population with normal kidney function. On the other hand, there is little information about metabolic profile in situations characterized by pathophysiologically high FGF-23 such as chronic kidney disease and X-linked hypophosphatemia (XLH). The aim of the present longitudinal observational study was to investigate anthropometric parameters of obesity and metabolic profile on large cohort of children with XLH. Methods: Among 263 XLH-patients registered in our centre we selected 168 children of 5-20 years (108 girls/60 boys). Total period of FU was divided in five sub-periods according age (group 0: birth, N=168; group 1: 5-7 years, N=122; group 2: 7-10 years, N=86; group 3: 10-15 years, N=89; group 4: 15-20 years, N=49). Anthropometric parameters (weight, height, BMI) were collected from birth (group 0) and for every point of FU (group 1-4). In each group, subjects were classified based on International Obesity Taskforce (IOTF) cut off values of BMI for age and sex as overweight or obese (IOTF 25-30 or ≥30 kg/m2, respectively). Metabolic parameters (total cholesterol, triglycerides, HDL, LDL, fasting glycemia and insulinemia, HOMA-IR) were measured at one point of FU in some patients (N=40). Results: In each group of FU (1,2,3,4) almost 1/3 of patients were classified as overweight or obese (29.5% vs 29.4% vs 28.1% vs 36.7%, respectively). Even without reaching statistical significance (p=0.75), there was a tendency of higher number of overweight or obese patients in group 4 (15-20 years) (36.7%) compared to group 1,2,3, which was explained by gender differences (higher number of overweight or obese girls compared to boys (42.4% vs 25%, respectively, p=0.35). There were no differences in BMI z-score (SDS) and BMI-IOTF between groups 1,2,3,4 during FU (BMI-SDS: 0.9±1.1 vs 0.7±1.0 vs 0.6±1.1 vs 0.6±0.9, respectively, p=0.45; BMI-IOTF: 23.5±4.4 vs 23.5±4.1 vs 23.7±4.2 vs 24.3±3.6, respectively, p=0.72). As regard other metabolic parameters, only 1 patient was diagnosed with diabetes mellitus at age 10. No other alterations were found. In each group of FU, no correlation was found between FGF-23 and BMI, total cholesterol, triglycerides, HDL, LDL, fasting glycemia, insulinemia, HOMA-IR. In conclusion, 1/3 of XLH children have phenotypically unfavourable metabolic profile expressed as overweight or obesity which is higher compared to general paediatric population. This phenomenon has increasing tendency after puberty, especially in girls, and requires strict follow-up of BMI in XLH patients. In order to understand the further development of metabolic parameters, the studies on adult XLH population are needed.

Context Parathormone (PTH) resistance is characterized by hypocalcaemia, hyperphosphatemia, and elevated PTH in the absence of vitamin D deficiency. Pseudohypoparathyroidism type 1A [PHP1A, or inactivating parathormone (PTH)/PTHrp signaling disorder 2, according to the new classification (iPPSD2)], is caused by mutations in the maternal GNAS allele. Objective To assess PTH resistance over time in 20 patients affected by iPPSD2 (PHP1A), diagnosed because of family history, ectopic ossification, or short stature, and carrying a GNAS mutation. Methods We gathered retrospective data for calcium, phosphate, thyrotropin (TSH), and PTH levels at regular intervals. PTH infusion testing (teriparatide) was performed in 1 patient. Results Patients were diagnosed at a mean age of 3.9 years and had a mean follow-up of 2 years. TSH resistance was already present at diagnosis in all patients (TSH, 13.3 ± 9.0 mIU/L). Over time, PTH levels increased (179 to 306 pg/mL; P < 0.05), and calcium levels decreased (2.31 to 2.21 mmol/L; P < 0.05), but phosphate levels did not decrease with age as expected for healthy individuals. One patient born with ectopic ossifications showed an increase in cyclic adenosine monophosphate upon PTH infusion, similar to that of controls, at 7 months of age, but an impaired response at 4 years of age. Conclusions In patients with iPPSD2 (PHP1A), PTH resistance and hypocalcemia develop over time. These findings highlight the importance of screening for maternal GNAS mutations in the presence of ectopic ossifications or family history, even in the absence of PTH resistance and hypocalcemia. The follow-up of these patients should include regular assessments of calcium, phosphate, and PTH levels.

Objective: X-linked hypophosphatemic rickets (XLH) is the most common form of inheritable rickets. Rickets treatment is monitored by assessing alkaline phosphatase (ALP) levels, clinical features, and radiographs. Our objectives were to describe the magnetic resonance imaging (MRI) features of XLH and to assess correlations with disease activity. Study Design: Twenty-seven XLH patients (median age 9.2 years) were included in this prospective single-center observational study. XLH activity was assessed using height, leg bowing, dental abscess history, and serum ALP levels. We looked for correlations between MRI features and markers of disease activity. Results: On MRI, the median maximum width of the physis was 5.6 mm (range 4.8–7.8; normal 1.5 mm in all of the patients. The appearance of the zone of provisional calcification was abnormal on 21 MRI images (78%), Harris lines were present on 24 (89%), and bone marrow signal abnormalities were present on 16 (59%). ALP levels correlated with the maximum physeal widening and with the transverse extent of the widening. Conclusions: MRI of the knee provides precise rickets patterns that are correlated with ALP, an established biochemical marker of the disease, avoiding X-ray exposure and providing surrogate quantitative markers of disease activity.

X-linked hypophosphatemia (XLH) is a rare genetic skeletal disease where increased phosphate wasting in the kidney leads to hypophosphatemia and prevents normal mineralization of bone and dentin. Here, we examined the periodontal status of 34 adults with XLH and separated them according to the treatment they received for hypophosphatemia. We observed that periodontitis frequency and severity were increased in adults with XLH and that the severity varied according to the hypophosphatemia treatment. Patients who benefited from an early and continuous vitamin D and phosphate supplementation during their childhood presented less periodontal attachment loss than patients with late or incomplete supplementation. Continued hypophosphatemia treatment during adulthood further improved the periodontal health. Extracted teeth from patients with late or incomplete supplementation showed a strong acellular cementum hypoplasia when compared with age-matched healthy controls. These results show that XLH disturbs not only bone and dentin formation but also cementum and that the constitutional defect of the attachment apparatus is associated with attachment loss.

ObjectiveAdults with X-linked hypophosphatemia (XLH) may suffer from skeletal symptoms leading to functional disability. No data on their quality of life (QoL) have been reported so far. Our objectives were to evaluate the QoL and its determinants in XLH adults.Patients and methodsWe conducted a prospective study in XLH adults, who consulted for musculoskeletal symptoms between 2013 and 2014. We assessed their QoL using HAQ, RAPID3 and SF36, and analysed the variables associated with low QoL. We compared their QoL to that of patients affected with axial spondyloarthritis (ax-SpA) (paired on age and gender), a rheumatologic disorder with a known low QoL.ResultsFifty-two XLH adults (37 women (71.1%); mean age 41.8±13.3 years) were included; 44 (84.6%) patients had an altered QoL. Increased age and presence of structural lesions were significantly associated with worse QoL (HAQ, RAPID3) (PP=0.038). Treatment with phosphate supplements and vitamin D in XLH adults were significantly associated with a better SF36-mental component score (OR=0.14 (0.03–0.57), P=0.007 and OR=0.26 (0.07–0.98), P=0.047 respectively). QoL was significantly worse in XLH than in ax-SpA adults (VAS pain, SF36-PCS, RAPID3) (PConclusionOur study showed i) QoL of XLH adults is altered and significantly worse than that of ax-SpA patients (VAS pain, SF36-PCS and RAPID3), ii) structural lesions and especially enthesopathies are associated with a worse QoL and iii) treatment using phosphate supplements and/or vitamin D is associated with a better mental health score.

Resume L’hypophosphatemie liee a l’X (XLH), due a une mutation du gene PHEX, est la forme la plus frequente de rachitisme et osteomalacie genetiques. Chez l’enfant, elle se manifeste par des signes de rachitisme, des deformations osseuses des membres inferieurs, des douleurs osseuses, un retard de croissance, des abces dentaires et/ou une craniostenose. Chez l’adulte, le diagnostic peut etre fait devant des douleurs osseuses persistantes, un diagnostic d’arthrose precoce, des fissures et des pseudo-fractures, des enthesopathies et/ou des anomalies parodontales. Le diagnostic precoce et la prise en charge optimisee des patients, nourrissons, enfants, adolescents et adultes, sont des elements indispensables au traitement des manifestations cliniques, a la prevention des complications et a l’amelioration de la qualite de vie des patients. Les traitements possibles sont l’association d’analogues actifs de la vitamine D et de supplements de phosphate, qui visent a compenser la perte renale de phosphate, et le deficit en 1,25(OH)2 vitamine D, ainsi que le burosumab, un anticorps anti-FGF23, qui vise a restaurer la reabsorption renale du phosphate dans le tubule proximal et stimuler la synthese endogene du calcitriol. En Europe, le burosumab peut etre utilise chez l’enfant de plus d’un an ayant un XLH. Le diagnostic du XLH, le traitement, les indications des differents traitements sont abordees dans cette revue.

Background X-linked hypophosphatemia (XLH) is a rare genetic disease (incidence 1/20 000) due to mutations in the PHEX gene. The genetic defects is associated with high level of FGF23 leading to impaired renal phosphate reabsorption and 1,25(OH)vitaminD synthesis. Most patients are diagnosed at walking age because of lower limb deformities and rickets. In adulthood, patients complain of musculoskeletal pain in relation to bone lesions (pseudofractures, osteomalacia) and joint involvement but also ossification of entheses. The latter is a strong determinant of the altered quality of life in this population. Objectives The aim of this work was to describe the structural bone and joint involvement of the entire skeleton in a large cohort of adult patients with XLH. Methods The study was prospectively conducted in symptomatic adult XLH patients in the context of the systematic evaluation at the French reference centre for rare diseases of calcium and phosphate metabolism. 81 of the 136 patients included between June 2011 and December 2017 had full body x-rays performed with the EOS low-radiation system. Two trained readers performed a standardised analysis of radiographs with a reading grid including the collection of ossifications of the anterior and lateral vertebral ligament, iliac crests, ischial sites, cotyles and achilles tendons; osteophytes on the spine and hip osteoarthritis; and sacroiliac joint aspect. Results Of the 81 patients, 55 are women (68%), mean age 42.4±13.6 years, diagnosed on average at the age of 11 years. 63 (78%) patients were treated during childhood with phosphate and/or vitamin D supplementation. At the time of study, 41 (50.6%) were still upon phosphate supplements and/or vitamin D analogues, 32 (40%) were taking analgesics, although 65 (80%) suffered from pain (71% articular pain, 22% bone pain and 20% enthesitic pain). Of the 81 patients, 71 (88%) presented with structural damage including 44 (63%) with syndesmophytes or ossifications. The average number of syndesmophytes/ossifications was 4,1±2,6 per patient in this subgroup. Most of them were localised at the cervical spine (82%) and the lumbar spine (62%). In addition, these ossifications were fine in 59% (syndesmophytes-like) and coarse in 41%. The other localizations were the ischial region (40%), iliac crests (37%) and the cotyles (90%). Calcanei were visible on 52 radiographs and showed coarse ossifications for 22 of them (42%). 46 patients (65%) had already hip osteoarthritis and 26 (37%) had at least one osteophyte on the spine mainly on the thoracic spine (58%). We found complete ankylosis of sacro-iliac joints in 12 patients (17%). Conclusions This observational study shows that 88% of adult XLH patients have structural damages and at least one ossification on the spine and/or on peri-articular joint (specially on the cotyles). Of importance, these ossifications were as frequent and as severe in patients not treated with phosphate and vitamin D analogues than in untreated patients. Knowing that this disease can be misdiagnosed and eventually diagnosed only at the adult age, attention must be paid to ossification of the entheses, in particular of the common anterior vertebral ligament and Achilles tendons. The mechanisms of formation of these enthesopathies remain to be determined. Disclosure of Interest None declared