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PURPOSE: Craniofacial fibrous dysplasia (CFD) is a subtype of fibrous dysplasia/McCune-Albright syndrome (FD/MAS) characterized by FD lesions in one or more of the skull bones. The orbit is often involved, with facial pain, facial deformity, and increased risk of compressive optic neuropathy as associated clinical manifestations possibly leading to altered illness perceptions and impairments in quality of life(QoL). The aim of this study was to evaluate illness perceptions and QoL in patients with CFD among our FD/MAS cohort. METHODS: One hundred ninety-one patients were included. Illness perceptions and QoL were assessed by using validated questionnaires, that is, the Illness Perceptions Questionnaire-Revised and the Short-Form 36. Patients were first grouped as CFD versus non-CFD, a second selection was based on the presence of "Isolated CFD" versus "CFD+PFD/MAS." Non-CFD patients were grouped as monostotic fibrous dysplasia "MFD" versus polyostotic "PFD/MAS." RESULTS: Patients with isolated CFD attributed less symptoms to their disease compared with patients with CFD+PFD/MAS (p < 0.05). Furthermore, patients with isolated CFD reported better QoL on all domains (except role emotional and mental health) compared with patients with CFD+PFD/MAS (p < 0.05). Patients with isolated CFD also reported better QoL compared with non-CFD groups (on 3 out of 8 subscales) (p < 0.05). CONCLUSIONS: Patients with isolated CFD attribute less symptoms to their disease and report better QoL compared with patients with CFD with extracranial involvement or FD without cranial involvement. These findings indicate that craniofacial involvement alone is not sufficient to cause negative illness perceptions and impairments in QoL. Therefore, it can be postulated that isolated CFD should be considered a unique patient subtype within the spectrum of FD/MAS patients.
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Displasia Fibrosa Ósea , Displasia Fibrosa Poliostótica , Humanos , Calidad de Vida , Cráneo , Encuestas y CuestionariosRESUMEN
Background and purpose - Fibrous dysplasia (FD) is a rare bone disorder associated with pain, deformities, and pathological fractures. The pathophysiological mechanism of FD-related pain remains ill-understood. We evaluated the degree of pain and the potential contributory factors in 2 patient cohorts from Austria and the Netherlands. Patients and methods - 197 patients (16-85 years) with FD (Graz n = 105, Leiden n = 92) completed a survey concerning the presence and severity of pain at their FD site. Sex, age, type of FD, and localization of FD lesions were examined for a relationship with the presence and severity of pain. Results - Of 197 patients from the combined cohort (61% female, mean age 49 (SD 16) years, 76% monostotic) who completed the questionnaires, 91 (46%) reported pain at sites of FD lesions. Severity of pain was higher in patients with lesions of the lower extremities and ribs compared with upper extremity or craniofacial lesions. Severe subtypes of FD (polyostotic/McCune-Albright syndrome) were more often associated with pain, often severe. Interpretation - Our data suggest that almost 50% of patients with FD report pain at FD sites, thus representing a major clinical manifestation of the disorder, importantly also in patients with monostotic lesions. Lesions in lower extremities and ribs were more painful.
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Displasia Fibrosa Ósea/complicaciones , Dolor/etiología , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Austria , Femenino , Displasia Fibrosa Ósea/patología , Humanos , Masculino , Persona de Mediana Edad , Países Bajos , Dimensión del Dolor , Factores de Riesgo , Encuestas y Cuestionarios , Adulto JovenRESUMEN
Low serum 25-hydroxyvitamin D (25OHD) concentrations have been associated with increased cancer risk, but the relative importance of seasonality, i.e. high summer concentrations versus low winter concentrations, is unclear. We investigated this issue in a high risk group: kidney transplant recipients with known increased risk of cancer and low vitamin D statuses. We examined the relationship between registered concentrations of 25OHD binned by quarter and subsequent risk of internal malignancy or cutaneous squamous cell carcinoma in 1112 kidney transplant recipients. Hazard ratios for internal malignancies were significantly increased with lower pre-diagnostic 25OHD concentrations in the first quarter of the year (January-March); a 1.4 fold increase (95%CI 1.1;1.7) per 10 nmol L-1 decrease in 25OHD. Except for women in April-June (1.3 (1.01;1.7) per 10 nmol L-1 decrease) pre-diagnostic 25OHD concentrations in the other quarters were not statistically significantly associated with internal malignancies. Higher 25OHD concentrations tended to be associated with the development of cutaneous squamous cell carcinomas, independent of the time of the year. Our study indicates that low wintertime 25OHD concentrations are associated with an increased risk of internal malignancies and that transplant recipients may benefit from wintertime vitamin D supplementation. Our findings need further corroboration, but suggest that the lowest concentrations of vitamin D, which occur in winter, are important for the risk of internal malignancies.
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Trasplante de Riñón , Neoplasias/diagnóstico , Vitamina D/análogos & derivados , Adolescente , Adulto , Anciano , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/etiología , Niño , Preescolar , Femenino , Humanos , Masculino , Persona de Mediana Edad , Neoplasias/etiología , Modelos de Riesgos Proporcionales , Factores de Riesgo , Estaciones del Año , Receptores de Trasplantes , Vitamina D/sangre , Adulto JovenRESUMEN
BACKGROUND: Fibrous dysplasia of the proximal femur is a progressive, often recurrent condition of bone that can cause skeletal deformity, fractures, and pain [corrected]. Allogeneic cortical strut grafting to minimize the risk of fracture or as part of fracture treatment is a promising treatment option, but evidence is scarce on the intermediate- to long-term results of this procedure and there are no data on factors associated with graft failure. QUESTIONS/PURPOSES: The purposes of this study were (1) to evaluate the revision-free survivorship; (2) radiographic findings; (3) factors associated with failure; and (4) complications associated with cortical strut allograft to prevent or treat fractures of the proximal femur in patients with fibrous dysplasia. METHODS: Between 1980 and 2013 we performed cortical strut allografting in 30 patients for impending or actual fractures of the proximal femur, of whom 28 (93%) were available for followup at a minimum of 2 years (mean, 13 years; range, 4-37 years) and of whom 22 (73%) had also been evaluated within the last 5 years. During that time, the indications for cortical strut allografting were an impending fracture of the proximal femur, persistent pain, or an actual nondisplaced femoral fracture. In patients who presented with a diaphyseal fracture, a fracture with severe dislocation of severe varus deformity, which required an osteotomy, placement of a blade plate was instead performed and these patients are not included here. During that time, for patients with diaphyseal fractures, and in patients with a displaced femoral fracture of the proximal femur, placement of a blade plate without strut grafting was instead performed; these patients are not included here. The primary outcome was the success rate of allogeneic cortical strut grafting surgery as assessed by the absence of revision surgery for a newly sustained fracture, resorption of the graft, or progressive deformity of the proximal femur. The association of possible contributing factors to graft failure such as gender, age at surgery, preoperative fracture, and anchoring distances of the graft in healthy bone was also evaluated using Cox regression analysis. RESULTS: Revision surgery was performed in 13 patients, resulting in a mean survival time of 13 years (Kaplan-Meier 95% confidence interval [CI], 10-16). Radiological resorption of the graft was observed in 15 of 28 patients (54%). However, revision surgery was not performed in all patients who developed graft resorption, because of the absence of a risk for fracture on the basis of the anatomical site of resorption. Identified risk factors for graft failure included preoperative fractures (hazard ratio [HR], 4.5; 95% CI, 1.2-17.2; p = 0.028) and insufficient proximal anchoring of the graft in healthy bone (HR, 6.02; 95% CI, 1.3-27; p = 0.02). One patient sustained a refracture after surgery resulting from an in-hospital fall. The fracture was treated without further surgery, and it healed. CONCLUSIONS: Our findings from this study suggest that cortical strut allografting may be a viable option for treatment of fibrous dysplasia of the proximal femur a without previous pathological fracture. Surgeons should pay particular attention to the proximal fixation point of the allograft to decrease the risk of failure. Patients with a fracture have an increased risk of failure and reoperation and so should be treated with an osteosynthesis. LEVEL OF EVIDENCE: Level IV, therapeutic study.
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Trasplante Óseo/métodos , Fracturas del Fémur/cirugía , Fémur/cirugía , Displasia Fibrosa Ósea/cirugía , Fracturas Espontáneas/cirugía , Adolescente , Adulto , Trasplante Óseo/efectos adversos , Niño , Preescolar , Supervivencia sin Enfermedad , Femenino , Fracturas del Fémur/diagnóstico por imagen , Fémur/diagnóstico por imagen , Displasia Fibrosa Ósea/diagnóstico por imagen , Fracturas Espontáneas/diagnóstico por imagen , Supervivencia de Injerto , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Oseointegración , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Modelos de Riesgos Proporcionales , Reoperación , Estudios Retrospectivos , Factores de Riesgo , Factores de Tiempo , Trasplante Homólogo , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Growth hormone deficiency (GHD) in adulthood may be associated with a decreased bone mineral density (BMD), a decreased bone mineral content (BMC) and an increased fracture risk. Recombinant human GH (rhGH) replacement induces a progressive increase in BMD for up to 5-7 years of treatment. Data on longer follow-up are, however, scarce. METHODS: Two hundred and thirty-adult GHD patients (mean age 47·1 years, 52·6% female), of whom 88% patients had adult-onset (AO) GHD, receiving rhGH replacement for ≥5 years were included in the study. Most patients had multiple pituitary hormone deficiencies. Bone turnover markers, BMC and BMD and T-scores at the lumbar spine and femoral neck were evaluated at baseline, and after 5, 10 and 15 years of rhGH replacement. In addition, clinical fracture incidence was assessed. RESULTS: Mean lumbar spine BMD, lumbar spine BMC and T-scores gradually increased during the first 10 years of rhGH replacement and remained stable thereafter. Largest effects of rhGH supplementation were found in men. In the small subset of patients using bisphosphonates, use of bisphosphonates did not impact additional beneficial effects in the long term. Low baseline BMD positively affected the change in BMD and BMC over time, but there was a negative effect of high GH dose at 1 year on the change in BMD and BMC over time. Clinical fracture incidence during long-term rhGH replacement was 20.1/1000 py. CONCLUSIONS: Fifteen years of rhGH replacement in GHD adults resulted in a sustained increase in BMD values at the lumbar spine, particularly in men, and stabilization of BMD values at the femoral neck. Clinical fracture incidence was suggested not to be increased during long-term rhGH replacement.
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Huesos/efectos de los fármacos , Terapia de Reemplazo de Hormonas , Hormona de Crecimiento Humana/deficiencia , Hormona de Crecimiento Humana/uso terapéutico , Hipopituitarismo/tratamiento farmacológico , Adulto , Densidad Ósea/efectos de los fármacos , Remodelación Ósea/efectos de los fármacos , Huesos/metabolismo , Estudios de Cohortes , Femenino , Cuello Femoral , Humanos , Hipopituitarismo/metabolismo , Vértebras Lumbares , Masculino , Persona de Mediana Edad , Proteínas Recombinantes/uso terapéuticoRESUMEN
Osteitis of the sternocostoclavicular (SCC) region, referred to as sternocostoclavicular hyperostosis (SCCH), is the clinical expression of chronic non-bacterial osteitis (CNO) in adults with this rare chronic auto-inflammatory disorder of the axial skeleton. The diagnosis is based on distinctive computerized tomography (CT) features of sclerosis and hyperostosis of the SCC region, and local increases in osteoid formation visualized by high radiopharmacon uptake on skeletal scintigraphy but clear radiologic diagnostic criteria are lacking. In a cross-sectional study, CT scans and whole-body skeletal scintigraphy images obtained in 169 patients seen at the Center for Bone Quality of the Leiden University Medical Center between 2008 and 2018 with a suspected diagnosis of CNO of the SCC region were re-evaluated by 2 skeletal radiologists and 2 nuclear physicians. The diagnosis was confirmed in 118 (70%) predominantly female patients (n = 103, 89.2%); median age at first symptoms 45 years (range 20-73). The diagnosis was excluded in the remaining 51 "non-CNO" patients. Increased radiopharmacon uptake at the SCC region was observed in 82% CNO patients, with the manubrium sterni having the highest predictive ability to discriminate on both imaging modalities. The prevalence of sclerosis of the clavicles, manubrium and first ribs was significantly higher in CNO patients (P < 0.001). Hyperostosis was not observed in non-CNO patients. 46 CNO versus only 2 non-CNO patients had costoclavicular ligament calcification. Our findings identify CT scan features of sclerosis and hyperostosis of manubrium sterni, medial end of clavicles and first ribs, and calcification of costoclavicular ligaments, associated with increased tracer uptake on skeletal scintigraphy at the SCC region, specifically manubrium sterni, as well-defined imaging diagnostic criteria for adult CNO. Pitfalls encountered in the diagnosis of CNO are highlighted. These defined imaging diagnostic criteria for adult CNO should facilitate the diagnosis of this rare auto-inflammatory bone disease across the spectrum of its early to late stages.
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There is no universally accepted definition for rare diseases: in Europe a disease is considered to be rare when affecting fewer than 1 in 2000 people. European Reference Networks (ERNs) have been the concrete response to address the unmet needs of rare disease patients and many pan-European issues in the field, reducing inequities, and significantly increasing accessibility to high-quality healthcare across Europe. ERNs are virtual networks, involving centres and patient representatives with the general scope to facilitate discussion on complex cases requiring highly specialised competences and trained expertise. ERN BOND - the European Reference Network on rare BONe Diseases - is one of these 24 approved networks with the specific ongoing mission to implement measures facilitating multidisciplinary, holistic, continuous, patient-centred, and participative care provision to patients, and supporting them in the full realisation of their fundamental human rights. ERN BOND includes in 2023 a total of 53 centres of expertise from 20 European countries. Its governing structure installed in March 2017 includes decision-making, operative and consultative committees, which comprise experts in the field and patient representatives ensuring patient's voice and perspectives are taken into account. Over the years, ERN BOND has worked hard to achieve its mission and valuably contribute to the advancement of diagnosis, management, treatment, and research in rare diseases. The network activities are mainly related to (i) the provision of care which collectively involves averagely 2800 patients diagnosed per year, (ii) the development of education for and training of the healthcare personnel consisting until now in the realisation of 7 thematic workshops and 19 webinars, (iii) the dissemination and exchange and spread of knowledge via network's website (https://ernbond.eu/), social media channels, and newsletters, (iv) the management of related data through a disease registry currently mapping over 2300 cases and recording over 600 reported cases, and (v) the enhancement of research which now include two clinical trials endorsed by the network. ERN BOND represents therefore an unprecedented move to improve the healthcare management of patients suffering from rare bone diseases through European collaborations. This network, through the support from the European Health Programme, will continue to pursue its efforts to achieve its goals, always maintaining the patients and their families at the centre of healthcare services.
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Enfermedades Óseas , Enfermedades Raras , Humanos , Enfermedades Raras/diagnóstico , Enfermedades Raras/terapia , Europa (Continente)RESUMEN
Context: Testicular germ cell tumour (TGCT) survivors are potentially at risk of developing osteoporosis, because of increased risk for disturbed bone remodelling associated with hypogonadism and anti-cancer treatment. A number of studies show bone loss and increased fracture risk in TGCT survivors, but data are scarce. There are no clinical guidelines or recommendations issued to address skeletal health in this group of patients potentially at high risk for osteoporosis. Objective: To conduct a systematic review of available literature addressing bone health in TGCT patients. Subgroup analysis was performed to identify risk factors for bone loss and increased fracture risk. Evidence Acquisition: Relevant databases, including MEDLINE, Embase and the Cochrane Library, including all English written comparative studies addressing bone health in TGCT patients, were searched up to December 2021 and a narrative synthesis was undertaken. Risk of bias (RoB) was assessed using Cochrane ROBINS-I tool. Evidence Synthesis: Ten studies (eight cross-sectional and two longitudinal), recruiting a total of 1997 unique TGCT patients, were identified and included in the analysis. Bone health was reported in various ways in different studies, and subgroups were defined heterogeneously, resulting in a widely varying prevalence of osteoporosis of up to 73.2% of patients. Six studies reported low BMD associated with higher luteinizing hormone levels and one study showed a correlation between follow up duration and bone loss. Conclusions: TGCT survivors are at risk of developing osteoporosis and sustaining fragility fractures. Chemotherapy, pituitary-gonadal axis dysfunction and ageing are key risk factors, although available data are scarce. With increasing survival of TGCT patients, a clear unmet need has been identified to systematically evaluate and monitor skeletal health in larger numbers of survivors in order to develop best clinical practice guidelines to manage the insidious but potentially preventable and treatable skeletal complications of TGCT.
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Sternocostoclavicular hyperostosis (SCCH), the main clinical manifestation of chronic non-bacterial osteomyelitis (CNO) in adults, is associated with various degrees of chronic pain and restricted shoulder girdle function. We evaluated the impact of CNO/SCCH on quality of life (QoL) and its determinants in 136 adult patients with this rare auto-inflammatory bone disorder using the Short Form 36, Brief Pain Inventory, Brief Illness Perception, Utrecht Coping List, and Shoulder Rating questionnaires. Data were compared with those of the general Dutch population, patients with chronic pain, fibrous dysplasia, or osteoarthritis. Eighty-six (64%) predominantly female (85%) patients with completed questionnaires were included in the study. Sixty-four (75%) had isolated CNO/SCCH. Mean delay in diagnosis was 3.0 ± 5.5 (SD) years, 90% had variable pain, and 84% limited shoulder function. Compared to healthy and chronically diseased reference populations, CNO/SCCH patients demonstrated significant impairments in almost all aspects of QoL, maladaptive illness perceptions, and ineffective coping strategies. For patients with >5-year delay in diagnosis, higher pain scores and limited shoulder function were identified as determinants for impaired QoL. Patients with CNO/SCCH reported significant impairments in QoL associated with clinical and psychological determinants. Clinical measures such as shortening delay in diagnosis, effective pain management, and psychosocial interventions targeting these factors should help minimize the negative impact of CNO/SCCH on QoL.
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Parathyroid carcinoma is associated with mutations in the HRPT2/CDC73 gene and with decreased parafibromin and calcium-sensing receptor (CASR) expression, but in some cases establishing an unequivocal diagnosis remains a challenge. The aim of our study was to evaluate the prognostic value of CASR and parafibromin expression and of HRPT2/CDC73 mutations in patients with an established diagnosis of parathyroid carcinoma. Data on survival and disease-free survival were obtained from hospital records of 23 patients with an established diagnosis of parathyroid carcinoma in whom CASR and parafibromin expression and HRPT2/CDC73 mutation analyses were available from paraffin-embedded pathological specimens. Kaplan-Meier curves were used for survival analysis. Downregulation of CASR expression, global loss of parafibromin staining and a HRPT2/CDC73 mutation were, respectively, found in 7 (30%), 13 (59%) and 4 (17%) patients, and were associated with, respectively, 16-fold, 4-fold and 7-fold increased risk of developing local or distant metastasis. These findings suggest that although downregulation of CASR expression, global loss of parafibromin staining and mutations in the HRPT2/CDC73 gene are tools of proven value to assist in establishing a diagnosis of parathyroid carcinoma, their absence does not exclude it. Notwithstanding, we demonstrate a significant added value of these markers as strong determinants of increased malignant potential and thus as negative prognostic markers in this malignancy.
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Adenocarcinoma/diagnóstico , Regulación hacia Abajo/genética , Mutación , Neoplasias de las Paratiroides/diagnóstico , Receptores Sensibles al Calcio/genética , Proteínas Supresoras de Tumor/genética , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/mortalidad , Adulto , Anciano , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/mortalidad , Países Bajos/epidemiología , Neoplasias de las Paratiroides/genética , Neoplasias de las Paratiroides/metabolismo , Neoplasias de las Paratiroides/mortalidad , Paratiroidectomía , Pronóstico , Receptores Sensibles al Calcio/metabolismo , Tasa de Supervivencia , Proteínas Supresoras de Tumor/metabolismoRESUMEN
BACKGROUND: In primary hyperparathyroidism (PHPT) the predictive value of technetium 99m sestamibi single emission computed tomography (Tc99m-MIBI-SPECT) for localizing pathological parathyroid glands before a first parathyroidectomy (PTx) is 83-100%. Data are scarce in patients undergoing reoperative parathyroidectomy for persistent hyperparathyroidism. The aim of the present study was to determine the value of Tc99m-MIBI-SPECT in localizing residual hyperactive parathyroid tissue in patients with persistent primary hyperparathyroidism (PHPT) after initial excision of one or more pathological glands. METHOD: We retrospectively evaluated the localizing accuracy of Tc99m-MIBI-SPECT scans in 19 consecutive patients with persistent PHPT who had a scan before reoperative parathyroidectomy. We used as controls 23 patients with sporadic PHPT who had a scan before initial surgery. RESULTS: In patients with persistent PHPT, Tc99m-MIBI-SPECT accurately localized a pathological parathyroid gland in 33% of cases before reoperative parathyroidectomy, compared to 61% before first PTx for sporadic PHPT. The Tc99m-MIBI-SPECT scan accurately localized intra-thyroidal glands in 2 of 7 cases and a mediastinal gland in 1 of 3 cases either before initial or reoperative parathyroidectomy. CONCLUSIONS: Our data suggest that the accuracy of Tc99m-MIBI-SPECT in localizing residual hyperactive glands is significantly lower before reoperative parathyroidectomy for persistent PHPT than before initial surgery for sporadic PHPT. These findings should be taken in consideration in the preoperative workup of patients with persistent primary hyperparathyroidism.
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Hiperparatiroidismo Primario/diagnóstico por imagen , Radiofármacos , Tecnecio Tc 99m Sestamibi , Tomografía Computarizada de Emisión de Fotón Único/métodos , Análisis de Varianza , Distribución de Chi-Cuadrado , Femenino , Humanos , Hiperparatiroidismo Primario/cirugía , Masculino , Persona de Mediana Edad , Paratiroidectomía , Valor Predictivo de las Pruebas , Reoperación , Estudios RetrospectivosRESUMEN
X-linked hypophosphatemia (XLH) is a rare inheritable disorder of phosphate handling due to loss of function mutations of the PHEX gene, associated with increased production of FGF23 and impaired bone mineralization. In children, the disease's most common manifestations are bowing deformities of the lower limbs, short stature, and spontaneous dental abscesses. In adults, these are osteomalacia, insufficiency fractures, and enthesopathies associated with bone and joint pain. The XLH patient's journey with the disease may be difficult, reflecting concerns and experiences globally common to all patients with rare genetic diseases. Delays in diagnosis often preclude an optimal treatment outcome. Under-treatment is common as treating physicians, particularly those not familiar with the disease, tend to err on the side of caution, often choosing safety over efficacy. Physical abnormalities, pain, diminished function, and impaired mobility tend not only to isolate the XLH patient from his peers but also to have a significant psychological effect, eventually leading to significant impairment in quality of life. Significant advances in understanding the pathophysiology of XLH, the availability of a very comprehensive Evidence-based Guideline for the diagnosis and management of XLH, and the successful development of an effective and safe disease-specific novel therapy for XLH, have paved the way for a significant improvement in the management of this rare disorder of phosphate metabolism, heralding a significant improvement in the disease's outcome measures. Additional data from long-term observational studies and randomized controlled trials are eagerly awaited to consolidate these promising developments in the field of this rare disease.
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Raquitismo Hipofosfatémico Familiar/psicología , Costo de Enfermedad , Raquitismo Hipofosfatémico Familiar/complicaciones , Raquitismo Hipofosfatémico Familiar/terapia , Factor-23 de Crecimiento de Fibroblastos , Humanos , Mutación/genética , Calidad de VidaRESUMEN
Vascular Calcification (VC), low bone mass and fragility fractures are frequently observed in ageing subjects. Although this clinical observation could be the mere coincidence of frequent age-dependent disorders, clinical and experimental data suggest that VC and bone loss could share pathophysiological mechanisms. Indeed, VC is an active process of calcium and phosphate precipitation that involves the transition of the vascular smooth muscle cells (VSMCs) into osteoblast-like cells. Among the molecules involved in this process, parathyroid hormone (PTH) plays a key role acting through several mechanisms which includes the regulation of the RANK/RANKL/OPG system and the Wnt/ß-catenin pathway, the main pathways for bone resorption and bone formation, respectively. Furthermore, some microRNAs have been implicated as common regulators of bone metabolism, VC, left ventricle hypertrophy and myocardial fibrosis. Elucidating the common mechanisms between ageing; VC and bone loss could help to better understand the potential effects of osteoporosis drugs on the CV system.
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Envejecimiento/fisiología , Osteoporosis/fisiopatología , Calcificación Vascular/fisiopatología , Resorción Ósea/fisiopatología , Humanos , Osteogénesis/fisiologíaRESUMEN
BACKGROUND: Sternocostoclavicular hyperostosis (SCCH) is a rare, debilitating, chronic inflammatory disorder of the anterior chest wall due to a chronic sterile osteomyelitis of unknown origin. SCCH is largely underdiagnosed and often misdiagnosed. In individual cases it can remain unrecognized for years. The purpose of this study is twofold. Firstly, to evaluate the psychological condition of SCCH patients, both in the sometimes quite extended pre-diagnostic period between first manifestations and confirmed diagnosis of the disease, and in the current situation. Secondly, to investigate the relationships between the pre-diagnostic and the current psychological conditions of confirmed SCCH patients. METHODS: Structured interviews were held with 52 confirmed SCCH patients. Questionnaires were included to assess posttraumatic stress symptoms, social support, aspects of pain, illness perceptions, self-reported health status, and quality of life. RESULTS: SCCH patients reported stronger posttraumatic stress symptoms, more unfavorable illness perceptions, lower health status, and poorer quality of life than healthy individuals and patients with other diseases or traumatic experiences. Psychological distress in the pre-diagnostic period was associated with unfavorable conditions in the current situation. CONCLUSION: SCCH is an illness with serious psychological consequences. Psychological monitoring of patients with unexplained complaints is recommended as long as a diagnosis has not been reached.
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Costo de Enfermedad , Hiperostosis Esternocostoclavicular/psicología , Calidad de Vida/psicología , Enfermedades Raras/psicología , Trastornos por Estrés Postraumático/etiología , Adulto , Edad de Inicio , Anciano , Femenino , Estado de Salud , Humanos , Hiperostosis Esternocostoclavicular/diagnóstico , Masculino , Persona de Mediana Edad , Países Bajos , Enfermedades Raras/diagnóstico , Factores Socioeconómicos , Encuestas y Cuestionarios , Adulto JovenRESUMEN
The current gold standard for the diagnosis of osteoporosis and the prediction of fracture risk is the measurement of bone mineral density (BMD) using dual energy x-ray absorptiometry (DXA). A low BMD is clearly associated with increased fracture risk, but BMD is not the only determinant of bone strength, particularly in secondary osteoporosis and metabolic bone disorders in which components other than BMD are affected and DXA often underestimates true fracture risk. Material properties of bone which significantly contribute to bone strength have become evaluable in vivo with the impact microindentation (IMI) technique using the OsteoProbe® device. The question arises whether this new tool is of added value in the evaluation of bone fragility. To this effect, we conducted a systematic review of all clinical studies using IMI in vivo in humans also addressing practical aspects of the technique and differences in study design, which may impact outcome. Search data generated 38 studies showing that IMI can identify patients with primary osteoporosis and fractures, patients with secondary osteoporosis due to various underlying systemic disorders, and scarce longitudinal data also show that this tool can detect changes in bone material strength index (BMSi), following bone-modifying therapy including use of corticosteroids. However, this main outcome parameter was not always concordant between studies. This systematic review also identified a number of factors that impact on BMSi outcome. These include subject- and disease-related factors such as the relationship between BMSi and age, geographical region and the presence of fractures, and technique- and operator-related factors. Taken together, findings from this systematic review confirm the added value of IMI for the evaluation and follow-up of elements of bone fragility, particularly in secondary osteoporosis. Notwithstanding, the high variability of BMSi outcome between studies calls for age-dependent reference values, and for the harmonization of study protocols. Prospective multicenter trials using standard operating procedures are required to establish the value of IMI in the prediction of future fracture risk, before this technique is introduced in routine clinical practice.
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Huesos/patología , Equipos y Suministros , Fracturas Óseas/diagnóstico , Microtecnología , Manejo de Especímenes , Absorciometría de Fotón , Biopsia con Aguja/instrumentación , Biopsia con Aguja/métodos , Densidad Ósea , Enfermedades Óseas Metabólicas/diagnóstico , Enfermedades Óseas Metabólicas/patología , Fracturas Óseas/patología , Humanos , Microtecnología/instrumentación , Microtecnología/métodos , Osteoporosis/diagnóstico , Osteoporosis/patología , Fracturas Osteoporóticas/diagnóstico , Fracturas Osteoporóticas/patología , Valor Predictivo de las Pruebas , Factores de Riesgo , Manejo de Especímenes/instrumentación , Manejo de Especímenes/métodosRESUMEN
Patients affected by pseudohypoparathyroidism (PHP) or related disorders are characterized by physical findings that may include brachydactyly, a short stature, a stocky build, early-onset obesity, ectopic ossifications, and neurodevelopmental deficits, as well as hormonal resistance most prominently to parathyroid hormone (PTH). In addition to these alterations, patients may develop other hormonal resistances, leading to overt or subclinical hypothyroidism, hypogonadism and growth hormone (GH) deficiency, impaired growth without measurable evidence for hormonal abnormalities, type 2 diabetes, and skeletal issues with potentially severe limitation of mobility. PHP and related disorders are primarily clinical diagnoses. Given the variability of the clinical, radiological, and biochemical presentation, establishment of the molecular diagnosis is of critical importance for patients. It facilitates management, including prevention of complications, screening and treatment of endocrine deficits, supportive measures, and appropriate genetic counselling. Based on the first international consensus statement for these disorders, this article provides an updated and ready-to-use tool to help physicians and patients outlining relevant interventions and their timing. A life-long coordinated and multidisciplinary approach is recommended, starting as far as possible in early infancy and continuing throughout adulthood with an appropriate and timely transition from pediatric to adult care.
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Diabetes Mellitus Tipo 2 , Enanismo Hipofisario , Hipotiroidismo , Seudohipoparatiroidismo , Transición a la Atención de Adultos , Adulto , Niño , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/terapia , Enanismo Hipofisario/diagnóstico , Enanismo Hipofisario/terapia , Humanos , Hipotiroidismo/diagnóstico , Hipotiroidismo/terapia , Guías de Práctica Clínica como Asunto , Seudohipoparatiroidismo/diagnóstico , Seudohipoparatiroidismo/terapiaRESUMEN
In osteoporosis, disruption of bone remodelling leads to bone loss, microarchitectural damage and increased fracture risk, and the goal of any treatment for osteoporosis is to decrease this fracture risk. Available anti-resorptive and anabolic agents effectively achieve this goal by either suppressing or stimulating the activation frequency of bone remodelling units, and by improving the biomechanical properties of bone by a number of different mechanisms. Strontium ranelate represents a novel approach in the management of osteoporosis with proven anti-fracture efficacy. Two putative mechanisms have been proposed for the unique dual mode of action of strontium ranelate, rebalancing bone turnover in favour of bone formation: activation of the calcium- or other cation-sensing receptor, and increase in the expression of osteoprotegerin (OPG), coupled with a decrease in RANK ligand expression by the osteoblasts. In addition to these cellular changes, micro-CT analysis of bone biopsies from strontium ranelate-treated patients demonstrate improvement in intrinsic bone tissue quality as evidenced by increased trabecular number, decreased trabecular separation, lower structure model index and increased cortical thickness, associated with a shift in trabecular structure from rod-to plate-like configuration compared with controls. This review examines the evidence for the ability of strontium ranelate to improve bone microarchitecture in osteoporosis and explores the cellular and microstructural changes by which its anti-fracture efficacy may be achieved. No attempt is made at comparing the effects of strontium ranelate on bone microarchitecture with that of other anti-resorptive or anabolic osteoporosis agents.
Asunto(s)
Conservadores de la Densidad Ósea/farmacología , Huesos/efectos de los fármacos , Compuestos Organometálicos/farmacología , Osteoporosis/patología , Tiofenos/farmacología , Animales , Densidad Ósea/efectos de los fármacos , Conservadores de la Densidad Ósea/uso terapéutico , Remodelación Ósea/efectos de los fármacos , Huesos/fisiopatología , Modelos Animales de Enfermedad , Humanos , Compuestos Organometálicos/uso terapéutico , Osteoporosis/tratamiento farmacológico , Osteoporosis/fisiopatología , Ratas , Tiofenos/uso terapéuticoRESUMEN
CONTEXT: Fibrous dysplasia/McCune-Albright syndrome (FD/MAS) is a rare bone disorder commonly treated with bisphosphonates, but clinical and biochemical responses may be incomplete. OBJECTIVE: To evaluate the efficacy and tolerability of the receptor activator of nuclear factor-κB ligand inhibitor denosumab in the treatment of patients with FD/MAS refractory to bisphosphonate therapy. DESIGN: Case series. SETTING: Academic center of expertise for rare bone diseases. PATIENTS: Data were collected from 12 consecutive patients with FD/MAS with persistent pain and increased biochemical markers of bone turnover (BTMs) after long-term treatment with bisphosphonates (median, 8.8 years) and were treated with subcutaneous denosumab 60 mg at 3- or 6-month intervals with a follow-up for at least 12 months. MAIN OUTCOME(S): Sustained reduction of BTMs and bone pain. RESULTS: A 60 mg dose of denosumab once every 3 months, but not once every 6 months, induced a sustained reduction of BTMs. After a median treatment period of 15.5 months (range, 12 to 19) serum alkaline phosphatase activity and propeptide of type 1 procollagen levels were respectively reduced from 212 ± 39.4 IU/L to 79 ± 6.0 IU/L (P = 0.004) and from 346.2 ± 111.1 ng/mL to 55.7 ± 16.6 ng/mL (P = 0.023) and normalized in 70% and 75% of patients, respectively. Although not quantitavely measured, 10 patients reported a reduction in bone pain of whom 6 reported complete elimination of pain. Treatment with denosumab was well tolerated. CONCLUSION: Our results indicate that 60 mg of denosumab every 3 months is a promising, well-tolerated treatment of most patients with FD/MAS refractory to bisphosphonate therapy. These results together with those of previously published case reports provide the necessary background for the design of a larger, controlled study.
Asunto(s)
Denosumab/administración & dosificación , Denosumab/efectos adversos , Difosfonatos/uso terapéutico , Sustitución de Medicamentos , Displasia Fibrosa Poliostótica/tratamiento farmacológico , Adulto , Anciano , Biomarcadores/sangre , Conservadores de la Densidad Ósea/uso terapéutico , Remodelación Ósea/efectos de los fármacos , Estudios de Cohortes , Colágeno Tipo I/sangre , Resistencia a Medicamentos/efectos de los fármacos , Sustitución de Medicamentos/estadística & datos numéricos , Femenino , Displasia Fibrosa Poliostótica/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Mazabraud syndrome is a rare disorder, characterized by the presence of fibrous dysplasia (FD) with associated intramuscular myxomas. Data are scarce on the prevalence, clinical features, and natural history of this disorder and outcomes. In this multicenter study, we evaluated a series of patients from 6 European centers. METHODS: All centers affiliated with the European Musculo-Skeletal Oncology Society (EMSOS) were invited to include data on all patients with Mazabraud syndrome who were seen between 1980 and 2015. The study investigated the prevalence of Mazabraud syndrome, the type, severity, and localization of FD lesions in relation to myxomas, the histopathology of myxomas, and results of GNAS-mutation analysis, when available. RESULTS: Thirty-two patients (22 female) from 6 centers were included. The prevalence of Mazabraud syndrome was 2.2% in the combined cohort of 1,446 patients with FD, and the syndrome was diagnosed at a mean of 10.1 years after diagnosis of FD. The myxomas were predominantly localized in the upper leg. Excision was performed in 20 patients, recurrence occurred in 6 of these patients (30%) at a median of 8.5 years (range, 1.9 to 16.0 years), and revision surgery was necessary in 5 (25%). High cellularity of myxomas was associated with recurrence (p < 0.05). A GNAS mutation was identified in the myxoma tissue of 5 (83%) of 6 patients with GNAS-mutation analysis. CONCLUSIONS: This study is the first, to our knowledge, to provide data on the prevalence of Mazabraud syndrome in a relatively large cohort. Although the outcomes of surgical resection were good, a quarter of the patients required revision surgery despite clear resection margins. High cellularity of myxomas was associated with recurrence. GNAS mutations were identified in 83% (5 of 6), emphasizing the shared origin of FD and myxomas. Our data show that patients with FD who have disproportionate complaints, irrespective of FD type, extent, or severity, should be investigated for the possible presence of myxomas. LEVEL OF EVIDENCE: Prognostic Level IV. See Instructions for Authors for a complete description of levels of evidence.