RESUMEN
BACKGROUND AND OBJECTIVES: Synovitis acne pustulosis hyperostosis osteitis (SAPHO) is a rare heterogeneous disease of unknown aetiopathology. Externally validated and internationally agreed diagnostic criteria or outcomes and, as a result, prospective randomised controlled trials in SAPHO are absent. Consequently, there is no agreed treatment standard. This study aimed to systematically collate and discuss treatment options in SAPHO. METHODS: Following 'Preferred Reporting Items for Systematic Reviews and Meta-Analyses' guidance, a systematic literature search was conducted using PubMed, Scopus and Web of Science databases. Prospective clinical studies and retrospective case collections discussing management and outcomes in SAPHO involving five or more participants were included. Articles not published in English, studies not reporting defined outcomes, and studies solely relying on patient-reported outcomes were excluded. RESULTS: A total of 28 studies (20 observational, 8 open-label clinical studies) reporting 796 patients of predominantly European ethnicity were included. Reported therapies varied greatly, with many centres using multiple treatments in parallel. Most patients (37.1%) received non-steroidal anti-inflammatory drugs alone or in combination. Bisphosphonates (22.1%), conventional (21.7%) and biological (11.3%) disease-modifying antirheumatic drugs were the next most frequently reported treatments. Reported outcomes varied and delivered mixed results, which complicates comparisons. Bisphosphonates demonstrated the most consistent improvement of osteoarticular symptoms and were associated with transient influenza-like symptoms. Paradoxical skin reactions were reported in patients treated with TNF inhibitors, but no serious adverse events were recorded. Most treatments had limited or mixed effects on cutaneous involvement. A recent study investigating the Janus kinase inhibitor tofacitinib delivered promising results in relation to skin and nail involvement. CONCLUSIONS: No single currently available treatment option sufficiently addresses all SAPHO-associated symptoms. Variable, sometimes descriptive outcomes and the use of treatment combinations complicate conclusions and treatment recommendations. Randomised clinical trials are necessary to generate reliable evidence.
Asunto(s)
Acné Vulgar , Síndrome de Hiperostosis Adquirido , Hiperostosis , Osteítis , Sinovitis , Humanos , Síndrome de Hiperostosis Adquirido/diagnóstico , Síndrome de Hiperostosis Adquirido/tratamiento farmacológico , Síndrome de Hiperostosis Adquirido/etiología , Osteítis/complicaciones , Osteítis/diagnóstico , Osteítis/tratamiento farmacológico , Estudios Retrospectivos , Estudios Prospectivos , Sinovitis/tratamiento farmacológico , Hiperostosis/complicaciones , Hiperostosis/tratamiento farmacológico , Acné Vulgar/complicaciones , Acné Vulgar/tratamiento farmacológico , Difosfonatos/uso terapéuticoRESUMEN
BACKGROUND: Chronic nonbacterial osteomyelitis (CNO) is a rare, and impactful auto-inflammatory bone disease occurring in children and adults. Clinical care for CNO is challenging, as the condition lacks validated classification criteria and evidence-based therapies. This study aimed to map the current diagnostic and therapeutic practices for CNO in adults, as a first step towards a standardized disease definition and future consensus treatment plans. METHODS: A primary survey was spread among global rheumatological/bone networks and 57 experts as identified from literature (May 2022), covering terminology, diagnostic tools (clinical, radiological, biochemical) and treatment steps. A secondary survey (sent to primary survey responders in August 2022) further queried key diagnostic features, treatment motivations, disease activity and treatment response monitoring. RESULTS: 36 and 23 physicians completed the primary and secondary survey respectively. Diagnosis was mainly based on individual physician assessment, in which the combination of chronic relapsing-remitting bone pain with radiologically-proven osteitis/osteomyelitis, sclerosis, hyperostosis and increased isotope uptake on bone scintigraphy were reported indicative of CNO. Physicians appeared more likely to refer to the condition as synovitis, acne, pustulosis, hyperostosis, osteitis (SAPHO) syndrome in the presence of joint and skin pathology. MRI was most frequently performed, and the preferred diagnostic test for 47%. X-rays were second-most frequently used, although considered least informative of all available tools. Typical imaging features reported were hyperostosis, osteitis, osteosclerosis, bone marrow edema, while degeneration, soft tissue calcification, and ankylosis were not regarded characteristic. Inflammation markers and bone markers were generally regarded unhelpful for diagnostic and monitoring purposes and physicians infrequently performed bone biopsies. Management strategies diverged, including indications for treatment, response monitoring and declaration of remission. Step-1 treatment consisted of non-steroidal anti-inflammatory drugs/COX-2 inhibitors (83%). Common step 2-3 treatments were pamidronate, methotrexate, and TNF-a-inhibition (anti-TNFα), the latter two regarded especially convenient to co-target extra-skeletal inflammation in SAPHO syndrome. Overall pamidronate and anti-TNFα and were considered the most effective treatments. CONCLUSIONS: Following from our survey data, adult CNO is a broad and insufficiently characterized disease spectrum, including extra-osseous features. MRI is the favoured imaging diagnostic, and management strategies vary significantly. Overall, pamidronate and anti-TNFα are regarded most successful. The results lay out current practices for adult CNO, which may serve as backbone for a future consensus clinical guideline.
Asunto(s)
Síndrome de Hiperostosis Adquirido , Hiperostosis , Osteítis , Osteomielitis , Niño , Adulto , Humanos , Osteítis/diagnóstico , Osteítis/tratamiento farmacológico , Pamidronato/uso terapéutico , Osteomielitis/diagnóstico , Osteomielitis/tratamiento farmacológico , Osteomielitis/patología , Hiperostosis/tratamiento farmacológico , InflamaciónRESUMEN
Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare autoimmune inflammatory disease characterized by osteoarticular and dermatological manifestations. The most common osteoarticular manifestations involve the anterior chest wall, axial skeleton, and long bones. Cranial bone involvement is less reported in SAPHO syndrome. We herein present three cases of SAPHO syndrome with cranial bone involvement, and review the previous literature on similar manifestations. It was revealed that SAPHO syndrome could lead to cranial bone involvement, which could involve the dura mater, leading to hypertrophic pachymeningitis, but the outcome is usually good. Janus kinase inhibitors may be a potential treatment option.
Asunto(s)
Acné Vulgar , Síndrome de Hiperostosis Adquirido , Hiperostosis , Osteítis , Sinovitis , Humanos , Síndrome de Hiperostosis Adquirido/complicaciones , Síndrome de Hiperostosis Adquirido/diagnóstico , Síndrome de Hiperostosis Adquirido/tratamiento farmacológico , Osteítis/diagnóstico por imagen , Osteítis/tratamiento farmacológico , Hiperostosis/diagnóstico por imagen , Hiperostosis/tratamiento farmacológico , Acné Vulgar/diagnóstico , Acné Vulgar/tratamiento farmacológico , Enfermedades RarasRESUMEN
We report a case of isolated lesions of the thoracic spine attributed to synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. A 55-year-old woman who suffered from 6 months of back pain had vertebral osteomyelitis on magnetic resonance imaging (MRI). There were no laboratory findings suggestive of infection, malignancy, or autoimmune disease. Radiography, computed tomography (CT), and MRI of the thoracic spine showed mixed lesions of sclerosis and erosion, whereas bone scintigraphy did not show accumulation at any site except the thoracic spine. No lesions in the anterior chest wall or sacroiliac joints were apparent from CT and MRI. No lesions other than at the thoracic spine were observed. As the isolated lesions of the thoracic spine were considered not to have resulted from infection, malignancy, or autoimmune disease, the patient was referred to our department for differential diagnosis. Given that isolated sterile hyperostosis/osteitis among adults is included in the modified diagnostic criteria for SAPHO syndrome, we suspected that the mixed lesions of sclerosis and erosion of the thoracic spine in this case may reflect SAPHO syndrome with chronic non-bacterial osteitis (CNO) of the thoracic spine. Treatment with non-steroidal anti-inflammatory drugs (NSAIDs) was initiated and led to alleviation of her back pain, although the thoracic spine lesions remained on the 6-month MRI. Based on the CNO of the thoracic spine and the rapid response to NSAIDs, the final diagnosis was SAPHO syndrome with isolated lesions of the thoracic spine.
Asunto(s)
Acné Vulgar , Síndrome de Hiperostosis Adquirido , Enfermedades Autoinmunes , Hiperostosis , Osteítis , Sinovitis , Pared Torácica , Adulto , Femenino , Humanos , Persona de Mediana Edad , Síndrome de Hiperostosis Adquirido/complicaciones , Síndrome de Hiperostosis Adquirido/diagnóstico , Osteítis/diagnóstico , Osteítis/etiología , Esclerosis , Hiperostosis/tratamiento farmacológico , Sinovitis/diagnóstico , Sinovitis/tratamiento farmacológico , Acné Vulgar/diagnóstico , Dolor de Espalda/tratamiento farmacológico , Antiinflamatorios no Esteroideos/uso terapéuticoRESUMEN
For disorders of keratinization, topical treatment alone may be ineffective, and systemic retinoid therapy may be indicated. Treatment with systemic retinoids (acitretin, isotretinoin and alitretinoin) has been shown to be effective in reducing disease severity; however, potentially rare adverse effects (AEs) may occur, including hyperostotic skeletal changes. The true prevalence of this AE in adult patients administered life-long therapy is unknown. We identified 3 of 127 (2.4%) patients (with ichthyosis or Darier disease) who had been prescribed isotretinoin with or without acitretin, and who developed radiological signs and clinical symptoms of hyperostosis and ligamentous ossification. This clinical review highlights the significance of retinoid-induced skeletal hyperostosis in patients prescribed long-term, high-dose retinoid therapy for disorders of keratinization. Patients commencing systemic retinoid therapy, particularly women of childbearing age, should be counselled about this important and potentially serious AE, especially if long-term treatment is indicated.
Asunto(s)
Hiperostosis , Ictiosis , Adulto , Humanos , Femenino , Acitretina/efectos adversos , Isotretinoína/uso terapéutico , Alitretinoína/efectos adversos , Hiperostosis/inducido químicamente , Hiperostosis/tratamiento farmacológico , Ictiosis/tratamiento farmacológicoRESUMEN
ABSTRACT: Synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome is a rare chronic disease with marked clinical and radiological heterogeneity. It is characterized by a combination of dermatological and osteoarticular manifestations. The treatment of SAPHO syndrome is not yet codified. It includes several therapeutic options such as anti-inflammatory drugs, bisphosphonates, antibiotics, conventional disease-modifying antirheumatic drugs, and biological treatment.This article aims to provide an updated review of the different pharmacological options for SAPHO syndrome. We also propose a therapeutic algorithm for the management of this disease.
Asunto(s)
Acné Vulgar , Síndrome de Hiperostosis Adquirido , Hiperostosis , Osteítis , Sinovitis , Acné Vulgar/diagnóstico , Acné Vulgar/tratamiento farmacológico , Síndrome de Hiperostosis Adquirido/diagnóstico , Síndrome de Hiperostosis Adquirido/tratamiento farmacológico , Algoritmos , Humanos , Hiperostosis/diagnóstico , Hiperostosis/tratamiento farmacológico , Hiperostosis/etiología , Osteítis/diagnóstico , Osteítis/tratamiento farmacológico , Osteítis/etiologíaRESUMEN
OBJECTIVE: This study aimed to investigate the efficacy and safety of Tripterygium wilfordii Hook F. (TwHF) in the treatment of osteoarticular lesions in synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. METHODS: Eligible SAPHO patients were recruited to this single-center trial to receive 12-week TwHF treatment. Two dose groups (1.0-mg/kg/day group and 1.5-mg/kg/day group) were designed and patients were allocated (1:1) to these two groups. The primary endpoint was the change from baseline in Ankylosing Spondylitis Disease Activity Score on the basis of C-reactive protein level (ASDAS) at week 12. RESULTS: All the 30 included patients completed the trial. At week 12, both dose groups showed significant change from baseline in ASDAS (1.0-mg/kg/day group: - 1.34 (1.10), p = 0.000; 1.5-mg/kg/day group: - 1.53 (1.19), p = 0.000). Similar improvement was also found in the Visual Analogue Scale in global osteoarticular pain, Bath Ankylosing Spondylitis Disease Activity Index, and other efficacy measures. The results showed a fast-acting characteristic of TwHF that the maximum efficacy was achieved within the first 2-4 weeks and maintained at a stable level for the rest of the study. No significant differences were observed between the two dose groups under the current sample size. TwHF was well tolerated that no severe adverse events or irregular menstruation were recorded, except for one patient who developed severe alanine aminotransferase elevation at the last follow-up and has stopped the TwHF treatment after the 12-week follow-up. CONCLUSIONS: TwHF should be considered for the treatment of osteoarticular lesions in SAPHO syndrome in clinical practice because of significant efficacy, reliable safety, and high socioeconomic value. TRIAL REGISTRATION: ChiCTR1900025912 Key points ⢠This is the first clinical trial to evaluate Tripterygium wilfordii Hook F. (TwHF) in the treatment of synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome. ⢠Twelve-week TwHF treatment in both dose groups designed (1.0-mg/kg/day group and 1.5-mg/kg/day group) was well tolerated and could lead to significant disease remission of SAPHO syndrome. ⢠No significant differences were observed between the two dose groups under the current sample size. ⢠TwHF should be considered for the treatment of osteoarticular lesions in SAPHO syndrome in clinical practice because of significant efficacy, reliable safety, and high socioeconomic value.
Asunto(s)
Acné Vulgar , Síndrome de Hiperostosis Adquirido , Hiperostosis , Osteítis , Sinovitis , Acné Vulgar/tratamiento farmacológico , Síndrome de Hiperostosis Adquirido/tratamiento farmacológico , Femenino , Humanos , Hiperostosis/tratamiento farmacológico , Osteítis/tratamiento farmacológico , TripterygiumRESUMEN
SAPHO (synovitis-acne-pustulosis-hyperostosis-osteitis) syndrome is a chronic inflammatory disease involving multiple organs such as skin and bones. At present, its etiology and pathogenesis are still unclear. Due to the variety of clinical manifestations and the small number of SAPHO syndrome involving the mandible, accurate diagnosis is difficult for oral and maxillofacial surgeons. Here, the authors report that a male patient with SAPHO syndrome involving the maxillofacial skin and mandible, followed for 3 years. We used Tc-MDP (technetium-99 conjugated with methylene disphosphonate) (commercially known as Yunke) to treat this disease and achieved significant clinical treatment. This suggests that Tc-MDP can be used as a bisphosphonate to treat SAPHO syndrome.
Asunto(s)
Síndrome de Hiperostosis Adquirido/tratamiento farmacológico , Enfermedades Mandibulares/tratamiento farmacológico , Medronato de Tecnecio Tc 99m/uso terapéutico , Acné Vulgar/tratamiento farmacológico , Adulto , Enfermedad Crónica , Humanos , Hiperostosis/tratamiento farmacológico , Masculino , Osteítis/tratamiento farmacológico , Sinovitis/tratamiento farmacológicoAsunto(s)
Analgésicos/uso terapéutico , Ingle/diagnóstico por imagen , Hiperostosis/diagnóstico por imagen , Hueso Púbico/patología , Reposo en Cama , Niño , Ingle/fisiopatología , Humanos , Hiperostosis/tratamiento farmacológico , Imagen por Resonancia Magnética/métodos , Masculino , Dolor Musculoesquelético/diagnóstico , Dolor Musculoesquelético/etiología , Hueso Púbico/diagnóstico por imagen , Enfermedades Raras , Medición de Riesgo , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
The WNT pathway has become an attractive target for skeletal therapies. High-bone-mass phenotypes in patients with loss-of-function mutations in the LRP5/6 inhibitor Sost (sclerosteosis), or in its downstream enhancer region (van Buchem disease), highlight the utility of targeting Sost/sclerostin to improve bone properties. Sclerostin-neutralizing antibody is highly osteoanabolic in animal models and in human clinical trials, but antibody-based inhibition of another potent LRP5/6 antagonist, Dkk1, is largely inefficacious for building bone in the unperturbed adult skeleton. Here, we show that conditional deletion of Dkk1 from bone also has negligible effects on bone mass. Dkk1 inhibition increases Sost expression, suggesting a potential compensatory mechanism that might explain why Dkk1 suppression lacks anabolic action. To test this concept, we deleted Sost from osteocytes in, or administered sclerostin neutralizing antibody to, mice with a Dkk1-deficient skeleton. A robust anabolic response to Dkk1 deletion was manifest only when Sost/sclerostin was impaired. Whole-body DXA scans, µCT measurements of the femur and spine, histomorphometric measures of femoral bone formation rates, and biomechanical properties of whole bones confirmed the anabolic potential of Dkk1 inhibition in the absence of sclerostin. Further, combined administration of sclerostin and Dkk1 antibody in WT mice produced a synergistic effect on bone gain that greatly exceeded individual or additive effects of the therapies, confirming the therapeutic potential of inhibiting multiple WNT antagonists for skeletal health. In conclusion, the osteoanabolic effects of Dkk1 inhibition can be realized if sclerostin upregulation is prevented. Anabolic therapies for patients with low bone mass might benefit from a strategy that accounts for the compensatory milieu of WNT inhibitors in bone tissue.
Asunto(s)
Anabolizantes/administración & dosificación , Glicoproteínas/antagonistas & inhibidores , Hiperostosis/tratamiento farmacológico , Osteogénesis/efectos de los fármacos , Sindactilia/tratamiento farmacológico , Vía de Señalización Wnt/efectos de los fármacos , Proteínas Adaptadoras Transductoras de Señales , Animales , Anticuerpos Neutralizantes/administración & dosificación , Proteínas Morfogenéticas Óseas/genética , Modelos Animales de Enfermedad , Femenino , Fémur/citología , Fémur/diagnóstico por imagen , Fémur/patología , Marcadores Genéticos/genética , Glicoproteínas/genética , Glicoproteínas/metabolismo , Humanos , Hiperostosis/diagnóstico por imagen , Hiperostosis/genética , Hiperostosis/patología , Péptidos y Proteínas de Señalización Intercelular/genética , Mutación con Pérdida de Función , Masculino , Ratones , Osteocitos , Columna Vertebral/citología , Columna Vertebral/diagnóstico por imagen , Columna Vertebral/patología , Sindactilia/diagnóstico por imagen , Sindactilia/genética , Sindactilia/patología , Resultado del Tratamiento , Regulación hacia Arriba/efectos de los fármacos , Microtomografía por Rayos XRESUMEN
BACKGROUND: Mutations in the human progressive ankylosis gene (ANKH; Mus musculus ortholog Ank) have been identified as cause for craniometaphyseal dysplasia (CMD), characterized by progressive thickening of craniofacial bones and flared metaphyses of long bones. We previously reported a knock-in (KI) mouse model (Ank KI/KI) for CMD and showed transiently lower serum phosphate (Pi) as well as significantly higher mRNA levels of fibroblast growth factor 23 (Fgf23) in Ank KI/KI mice. FGF23 is secreted by bone and acts in kidney to promote Pi wasting which leads to lower serum Pi levels. Here, we examined whether increasing the Pi level can partially rescue the CMD-like skeletal phenotype by feeding Ank +/+ and Ank KI/KI mice with high Pi (1.7 %) diet from birth for 6 weeks. We studied the Pi metabolism in Ank KI/KI mice and CMD patients by examining the Pi regulators FGF23 and parathyroid hormone (PTH). RESULTS: High Pi diet did not correct CMD-like features, including massive jawbone, increased endosteal and periosteal perimeters and extensive trabeculation of femurs in Ank KI/KI mice shown by computed microtomography (µCT). This unexpected negative result is, however, consistent with normal serum/plasma levels of the intact/active form of FGF23 and PTH in Ank KI/KI mice and in CMD patients. In addition, FGF23 protein expression was unexpectedly normal in Ank KI/KI femoral cortical bone as shown by immunohistochemistry despite increased mRNA levels for Fgf23. Renal expression of genes involved in the FGF23 bone-kidney axis, including mFgfr1, mKlotho, mNpt2a, mCyp24a1 and m1αOHase, were comparable between Ank +/+ and Ank KI/KI mice as shown by quantitative real-time PCR. Different from normal FGF23 and PTH, serum 25-hydroxyvitamin D was significantly lower in Ank KI/KI mice and vitamin D insufficiency was found in four out of seven CMD patients. CONCLUSIONS: Our data suggests that FGF23 signaling and Pi metabolism are not significantly affected in CMD and transiently low Pi level is not a major contributor to CMD.
Asunto(s)
Enfermedades del Desarrollo Óseo/tratamiento farmacológico , Huesos/patología , Anomalías Craneofaciales/tratamiento farmacológico , Dieta , Suplementos Dietéticos , Hiperostosis/tratamiento farmacológico , Hipertelorismo/tratamiento farmacológico , Fosfatos/uso terapéutico , Adolescente , Animales , Peso Corporal/efectos de los fármacos , Enfermedades del Desarrollo Óseo/sangre , Enfermedades del Desarrollo Óseo/genética , Huesos/diagnóstico por imagen , Huesos/efectos de los fármacos , Niño , Anomalías Craneofaciales/sangre , Anomalías Craneofaciales/genética , Modelos Animales de Enfermedad , Femenino , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Humanos , Hiperostosis/sangre , Hiperostosis/genética , Hipertelorismo/sangre , Hipertelorismo/genética , Riñón/efectos de los fármacos , Riñón/metabolismo , Masculino , Ratones Endogámicos C57BL , Persona de Mediana Edad , Tamaño de los Órganos/efectos de los fármacos , Hormona Paratiroidea/sangre , Fenotipo , Fosfatos/farmacología , Vitamina D/análogos & derivados , Vitamina D/sangre , Microtomografía por Rayos XRESUMEN
Several decades ago, a clinical condition that included severe bone overgrowth was described in a few patients in South Africa. The autosomal-recessive disease that later was named sclerosteosis was found to be caused by a mutation in the SOTS gene causing a lack of the protein sclerostin. This protein is produced by osteocytes and exerts its effect as an inhibitor of bone formation by blocking the Wnt signaling pathway. By the use of a monoclonal antibody that can block sclerostin a novel therapeutic pathway for rebuilding bone has been described. Preclinical studies have shown increased bone mass following subcutaneously administered anti-sclerostin antibody in animals with induced postmenopausal osteoporosis as well as in intact male rats and non-human primates. In a phase II study the efficacy and safety of an anti-sclerostin antibody, romosozumab, has been evaluated in 419 postmenopausal women for 12 months. 70, 140 or 210 mg was given subcutaneously monthly or every three months and compared to 70 mg of oral alendronate given once a week or 20 µg of teriparatide subcutaneously once daily. All dose levels of romosozumab were associated with significant increase in BMD with the most pronounced gain in the group receiving 210 mg where lumbar spine BMD increased with 11.3% from baseline. The BMD for the placebo group decreased by 0.1% while the alendronate group increased 4.1% and the teriparatide increased 7.1%. Biochemical markers revealed a transitory increase in the bone formation marker P1NP while no change in the bone resorption marker ß-CTX. In comparison, teriparatide resulted in an increase for both P1NP and ß-CTX for the complete study period. Even though the rapid gain in BMD is promising when considering a treatment option for osteoporosis and other conditions with bone loss, there are so far no published studies on whether anti-sclerostin can reduce the number of fractures. Wnt signaling might also play an important role in fracture healing with substances that causes an upregulation of the Wnt pathway producing enhancement of the fracture healing process. Healing of experimental fractures in various animal models have shown improvement following subcutaneously administered anti-sclerostin antibody. While there are no published reports on the potential effect of systemically administered anti-sclerostin antibodies on fracture healing in humans.
Asunto(s)
Anticuerpos Monoclonales Humanizados/farmacología , Anticuerpos Monoclonales/farmacología , Conservadores de la Densidad Ósea/farmacología , Densidad Ósea/efectos de los fármacos , Proteínas Morfogenéticas Óseas/antagonistas & inhibidores , Fracturas Óseas/patología , Hiperostosis/patología , Vértebras Lumbares/patología , Osteoporosis Posmenopáusica/tratamiento farmacológico , Sindactilia/patología , Proteínas Adaptadoras Transductoras de Señales , Animales , Biomarcadores/metabolismo , Remodelación Ósea , Modelos Animales de Enfermedad , Femenino , Fracturas Óseas/tratamiento farmacológico , Marcadores Genéticos , Haplorrinos , Humanos , Hiperostosis/tratamiento farmacológico , Masculino , Ratones , Osteoporosis Posmenopáusica/metabolismo , Osteoporosis Posmenopáusica/patología , Sindactilia/tratamiento farmacológicoRESUMEN
Sclerostin is a cysteine-knot glycoprotein product of the SOST gene, predominately expressed by osteocytes, that is a regulator of osteoblastic bone formation. When sclerostin binds to its low-density lipoprotein receptor-related proteins 5 and 6 on the cell membrane of osteoblasts, it inhibits canonical Wnt/ß-catenin signaling and reduces osteoblastic bone formation. Sclerostin was first identified in the study of two rare autosomal recessive disorders, sclerosteosis and van Buchem disease, which are associated with absent or reduced levels of sclerostin. Although homozygote patients with these disorders have serious adverse clinical consequences due to excessive bone growth, heterozygote patients have a normal phenotype, high bone mass, and very low risk of fractures. This has led to the concept that downregulation of sclerostin might be effective in the treatment of osteoporosis. Several humanized monoclonal antibodies to sclerostin, including romosozumab and blosozumab, are now in clinical development. Preliminary data show that these agents result in a transient increase in bone formation markers, a sustained decrease in bone resorption markers, and a robust increase in bone mineral density. If any of these agents are found to reduce fracture risk with a favorable safety profile, it will expand the options for osteoanabolic therapy for patients at high risk for fractures.
Asunto(s)
Proteínas Morfogenéticas Óseas/fisiología , Huesos/fisiología , Marcadores Genéticos/fisiología , Proteínas Adaptadoras Transductoras de Señales , Animales , Anticuerpos Monoclonales/efectos adversos , Anticuerpos Monoclonales/uso terapéutico , Densidad Ósea/genética , Proteínas Morfogenéticas Óseas/antagonistas & inhibidores , Proteínas Morfogenéticas Óseas/inmunología , Marcadores Genéticos/inmunología , Salud , Humanos , Hiperostosis/tratamiento farmacológico , Hiperostosis/genética , Osteocondrodisplasias/tratamiento farmacológico , Osteocondrodisplasias/genética , Osteoporosis/tratamiento farmacológico , Osteoporosis/genética , Sindactilia/tratamiento farmacológico , Sindactilia/genéticaRESUMEN
BACKGROUND: The objective of this work was to determine the role of nasal sound analysis using a software called Odiosoft-Rhino (OR) in evaluation of nasal erectile elements as a cause of nasal obstruction. Comparisons of nasal resistance, amplitude of the nasal sound frequency spectra, and visual analogue score (VAS) were made. METHODS: Nasal endoscopy, VAS, rhinomanometry (RMM), and OR were performed on 64 patients with inferior turbinate hypertrophy but without any other nasal problems, both untreated and 15 minutes after the application of topical decongestants (TDs). Results were compared and any correlation was investigated. RESULTS: For inspiration, the OR intervals for both sides at all 5 frequency intervals changes significantly with decongestion, except for the left side at 0.5 to 1 kHz. For expiration, the OR intervals for both sides changed significantly for 0.2 to 0.5 KHz and 2 to 4 kHz, but not for the other 3 frequency intervals. VAS correlated well with physical examination, both inspiratory and expiratory RMM, and 2 to 4 kHz inspiratory and expiratory nasal sound on both sides both before and after TD application. The 2 to 4 kHz inspiratory and expiratory nasal sound on both sides correlated well with inspiratory and expiratory RMM on both sides both before and after TD application. CONCLUSION: OR is an efficient and reliable method to evaluate the role of the erectile components in nasal patency in the absence of allergy or septal deviation. It is practical and may be used in routine clinical practice.
Asunto(s)
Hiperostosis/diagnóstico , Obstrucción Nasal/diagnóstico , Tabique Nasal/diagnóstico por imagen , Cornetes Nasales/diagnóstico por imagen , Adulto , Endoscopía/métodos , Femenino , Humanos , Hiperostosis/tratamiento farmacológico , Imidazoles/administración & dosificación , Masculino , Descongestionantes Nasales/administración & dosificación , Obstrucción Nasal/tratamiento farmacológico , Tabique Nasal/efectos de los fármacos , Tabique Nasal/patología , Variaciones Dependientes del Observador , Reproducibilidad de los Resultados , Rinomanometría/métodos , Programas Informáticos , Espectrografía del Sonido/métodos , Cornetes Nasales/efectos de los fármacos , Cornetes Nasales/patología , Ultrasonografía , Adulto JovenRESUMEN
In the 1990s there was a tremendous mood of optimism among pharmaceutical scientists that identification of disease-associated variations in the human genome would result in a surge of new drug targets (the 'gene-to-drug' mantra). To date the expected deluge of new drugs has not arrived. However, a small number of drugs arising directly from the study of rare human disorders showing Mendelian inheritance are now entering late stage clinical trials. Here we describe the advantages of this approach and discuss the background and early clinical trial findings with antibodies directed at a target identified in this way.
Asunto(s)
Anticuerpos/uso terapéutico , Conservadores de la Densidad Ósea/uso terapéutico , Proteínas Morfogenéticas Óseas/genética , Descubrimiento de Drogas , Marcadores Genéticos/genética , Hiperostosis/tratamiento farmacológico , Terapia Molecular Dirigida , Mutación , Osteoporosis/tratamiento farmacológico , Sindactilia/tratamiento farmacológico , Proteínas Adaptadoras Transductoras de Señales , Animales , Anticuerpos/farmacología , Conservadores de la Densidad Ósea/farmacología , Proteínas Morfogenéticas Óseas/antagonistas & inhibidores , Proteínas Morfogenéticas Óseas/inmunología , Marcadores Genéticos/inmunología , Predisposición Genética a la Enfermedad , Humanos , Hiperostosis/genética , Hiperostosis/metabolismo , Osteoporosis/genética , Osteoporosis/metabolismo , Fenotipo , Sindactilia/genética , Sindactilia/metabolismo , Resultado del TratamientoRESUMEN
Inactivating mutations of the SOST gene cause a reduction in sclerostin levels and are associated with high bone mass. The clinical phenotypes, sclerosteosis and van Buchem's disease, were described in 1950s. Much later, it was learned that both diseases are due to loss-of-function mutations in the SOST gene. As a regulator of an important osteoanabolic pathway, Wnt, inactivation of SOST leads to a stimulation of the pathway it regulates. The high bone mass in patients with either sclerosteosis or van Buchem's disease is associated with unusual skeletal strength; they do not fracture. Knowledge of this molecule and its actions led rather quickly to the development of anti-sclerostin antibodies that lead to marked increases in bone mass in both animals and human subjects. Blocking sclerostin action with anti-sclerostin antibodies is a promising new therapeutic approach to osteoanabolic therapy of osteoporosis.
Asunto(s)
Proteínas Morfogenéticas Óseas/farmacología , Proteínas Morfogenéticas Óseas/uso terapéutico , Huesos/metabolismo , Hiperostosis/tratamiento farmacológico , Osteosclerosis/tratamiento farmacológico , Vía de Señalización Wnt/efectos de los fármacos , Proteínas Adaptadoras Transductoras de Señales , Animales , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/uso terapéutico , Proteínas Morfogenéticas Óseas/antagonistas & inhibidores , Modelos Animales de Enfermedad , Relación Dosis-Respuesta a Droga , Marcadores Genéticos , Humanos , Hiperostosis/fisiopatología , Ratones , Ratones Noqueados , Osteosclerosis/fisiopatología , Vía de Señalización Wnt/fisiologíaRESUMEN
We report the case of a 57-year-old woman with hyperostosis around the bilateral acetabulum associated with untreated secondary hypoparathyroidism. She presented with gait disturbance and inability to walk. Radiographs showed abnormal ossification around her hips. We resected the ossifications to improve joint function. One year after surgery, radiographs showed no recurrence of ossification. When radiographs show excessive hyperostosis, it is important to exclude presence of metabolic bone disease.
Asunto(s)
Acetábulo/diagnóstico por imagen , Articulación de la Cadera/diagnóstico por imagen , Hiperostosis/complicaciones , Hipoparatiroidismo/complicaciones , Acetábulo/cirugía , Conservadores de la Densidad Ósea/uso terapéutico , Femenino , Trastornos Neurológicos de la Marcha/complicaciones , Trastornos Neurológicos de la Marcha/diagnóstico por imagen , Trastornos Neurológicos de la Marcha/tratamiento farmacológico , Articulación de la Cadera/cirugía , Humanos , Hidroxicolecalciferoles/uso terapéutico , Hiperostosis/diagnóstico por imagen , Hiperostosis/tratamiento farmacológico , Hipoparatiroidismo/diagnóstico por imagen , Hipoparatiroidismo/tratamiento farmacológico , Persona de Mediana Edad , Calambre Muscular/complicaciones , Calambre Muscular/tratamiento farmacológico , Radiografía , Resultado del TratamientoRESUMEN
OBJECTIVES: This study aims to evaluate the effect of combining the confidingly preferred modality of radiofrequency (RF) application with intranasal corticosteroid spray treatment on the efficacy of RF and on the number of sessions in patients with hypertrophy of inferior turbinate. PATIENTS AND METHODS: Fifty patients (37 males, 13 females; mean age 42.9 years; range 15 to 74 years) who admitted with the complaint of nasal obstruction and were detected to have hypertrophied inferior turbinate by nasal endoscopy were enrolled in the study. The patients were divided into two groups, each consisting of 25 patients. Before the treatment, the severity of nasal obstruction was evaluated and scored by a visual analogue scale (VAS). Radiofrequency was applied to every patient. Control group received no medical treatment following RF application. Drug group received mometasone furoate nasal spray (MFNS) at a dose of 200 mcg once daily into both nasal passages for eight weeks following surgery. All patients were asked to return for a control visit at week eight after treatment. Radiofrequency application was repeated in patients who continued to have complaints of nasal blockage. At the end of treatment, patients were reevaluated and VAS scores were recorded. RESULTS: The improvement in VAS scores following treatment was statistically significant in both groups (p<0.05). When the two groups were compared, there was no statistical difference between the two groups before treatment; however there was an improvement in the post-treatment corticostreoid group (p<0.05). The mean session number was calculated to be 1.16 in the control group and 1.08 in the corticosteroid treatment group. The difference between the two groups was not statistically significant (p>0.05). CONCLUSION: We recommend the use of intranasal corticosteroids with RF applications to increase the efficacy of radiofrequency.