Osteochondromas in fibrodysplasia ossificans progressiva: a widespread trait with a streaking but overlooked appearance when arising at femoral bone end.

Metaphyseal bony outgrowths are a well-recognized feature of fibrodysplasia ossificans progressiva (FOP) phenotype, but its genuine frequency, topographic distribution, morphological aspect, and potential implications are not fully established. To better ascertain the frequency and characteristics of osteocartilaginous exostoses in FOP disease, we conducted a cross-sectional radiological study based on all the traceable cases identified in a previous comprehensive national research. Metaphyseal exostoses were present in all the 17 cases of FOP studied. Although most often arising from the distal femoral (where metaphyseal exostoses adopt a peculiar not yet reported appearance) and proximal tibial bones, we have found that they are not restricted to these areas, but rather can be seen scattered at a variety of other skeletal sites. Using nuclear magnetic resonance imaging, we show that these exophytic outgrowths are true osteochondromas. As a whole, these results are in agreement with data coming from the literature review. Our study confirms the presence of metaphyseal osteochondromas as a very frequent trait of FOP phenotype and an outstanding feature of its anomalous skeletal developmental component. In line with recent evidences, this might imply that dysregulation of BMP signaling, in addition to promoting exuberant heterotopic ossification, could induce aberrant chondrogenesis and osteochondroma formation. Unveiling the molecular links between these physiopathological pathways could help to illuminate the mechanisms that govern bone morphogenesis.

Dermatomiositis asociada a linfoma no-Hodgkin folicular / Follicular non-Hodgkin lymphoma-associated dermatomyositis

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Monostotic Paget's disease of the femur: a diagnostic challenge and an overlooked risk.

BACKGROUND: Although radiological diagnosis of Paget's disease of bone (PD) is usually straightforward, monostotic cases may potentially raise specific problems which lead to performing invasive procedures. Therefore, the purpose of this study is to ascertain whether or not monostotic femoral Paget's disease (MFPD) presentation poses particular diagnostic difficulties which prompt excessive use of excisional biopsies. METHODS: We retrospectively reviewed the medical records of 24 MFPD patients identified from a series of 412 patients; their clinical features were compared with those of the remaining 164 monostotic cases and the radiological images were systematically assessed. RESULTS: When compared with the remaining monostotic cases, MFPD patients were more prone to having normal alkaline phosphatase levels (31.8% vs. 16.4%; 0.08) and a significantly higher percentage of patients have PD symptoms (75% vs. 51%; 0.02) and complain of bone pain (73.9% vs. 40.8%; 0.003). Six (25%) MFPD patients evidenced a fracture over the pagetic lesion. This incidence is higher than that of the monostotic cases of other locations (8.4%; p=0.02). The existence of PD lesion was not recognised initially in 10 cases and an excisional bone biopsy was performed in 7 (29%). One patient subsequently experienced a fracture through the biopsy site and another two experienced worsening of their previous bone pain. CONCLUSION: The femur is a relatively common monostotic PD location which often causes diagnostic confusion, prompting a bone biopsy in many cases. Careful assessment of this lesion by X-ray examination may help attain an early appropriate diagnosis and avoidance of unnecessary surgical morbidity.

Fibrodysplasia ossificans progressiva in Spain: epidemiological, clinical, and genetic aspects.

We aimed to investigate the epidemiological determinants, clinical features, and genetic pattern of FOP in our country by evaluating the entire population of patients identified according to a combination of methods. To achieve this, 24 individuals were confirmed as FOP cases, 17 of whom were alive at the end of 2011 (point prevalence=0.36 × 10(-6)). The gender distribution (male/female ratio=13/11) and the concurrent range of ages (from 4 to 53 years; mean ± SD: 30.2 ± 13.8) are in agreement with similar reports. Twenty-one (87.5%) had characteristic congenital malformations of the big toe, and short thumbs were found in 65.2% of cases. In addition, other skeletal malformations such us fusion of the posterior elements of the cervical spine (89.0%), knee osteochondromas (71%), scoliosis (54.5%), and short and broad femoral neck (52.6%) were observed. All had developed mature ossicles of heterotopic bone in typical anatomic and temporal patterns, ranging in number from 1 to 17 (9.5 ± 3.9). Age at appearance of first ossifying lesion varied from 3 months to 15 years. Mean age at diagnosis was 7.3 ± 5.1 years and the average delay in reaching the correct diagnosis after the onset of heterotopic ossification was 2.7 years (range=0-12 years). Biopsy of the pre-osseous lesions was performed in 11 of 20 (55.0%), providing no useful information for the diagnosis of FOP. Seven of 18 (38.9%) reported some hearing loss, and 5 (27.8%) experienced diffuse thinning of the hair or were bald. No patient had relatives with a typical FOP clinical picture. Fourteen of the 16 cases which were genetically investigated displayed the single heterozygous mutation c.617G>A in exon 4 of the ACVR1 gene. One of the two patients who did not present with the canonical ACVR1 mutation showed a heterozygous mutation c.774G>C in exon 5 leading to the substitution of Arginine 258 with a serine. The other patient had a heterozygous c.774G>T substitution in exon 5 leading to the same amino acid change (p.Arg258Ser). These two patients had only nonspecific abnormalities of the great toe, lacked the typical anatomic and developmental pattern of heterotopic ossification, and shared a trend toward uncommon clinical features. These results provide new insight on the epidemiological and clinical traits of FOP, reinforcing the notion of its worldwide homogeneity. The molecular characterization of ACVR1 sequence variation will contribute to the understanding of the genetic profile of this devastating disease in different geographical areas.

Further evidence supporting a genetic background for Paget's disease of bone in Spain.

The aim of this paper is to investigate heritable factors that might be related to the recognised genetic susceptibility for developing Paget's disease of bone (PD). This was a hospital-based, case-control study of a systematically selected group of PD patients and a group of controls drawn from the same health setting. In these populations we assessed surname pattern, parental consanguinity and constitutional physical traits. In a separate case-control analysis, genetically-based features and pathological traits of interest for genetic inference in 43 demonstrated familial cases were then compared to those in 24 sporadic cases. Results showed coincidence of three or four surnames (Odds Ratio [OR] = 5.6; 95% CI = 1.7-18.5), degree of parental consanguinity (OR = 4.1; 95% CI = 2.1-1.8), and green or blue eye colour (OR = 1.5; 95% CI = 1.1-2.1) were significantly associated with PD. Comparison of proven familial and sporadic PD cases showed that the former had a stronger association with Monckeberg-type vascular calcifications (32% vs. 4%; p = 0.02), percentage of skeleton affected (13.1 vs. 9.0), and green and blue eye colour (82% vs. 25%; p = 0.006), with Monckeberg-type vascular calcifications being the main variable of interest (OR = 30.9; 95% CI = 12.75-347.00) in the multivariate analysis. In conclusion, heritable factors are crucial in the pathogenesis of PD and, in line with other data sources, might account for the ethnic predisposition observed in different countries.

Hiperparatiroidismo secundario en el cáncer de próstata metastásico. A propósito de un caso / No disponible

Las metástasis óseas son frecuentes en el cáncer de próstata. En ellas predomina la actividad formadora de hueso de los osteoblastos sobre la resortiva de los osteoclastos, por ello en las pruebas de imagen se visualizan como lesiones de predominio esclerótico. Cuando son generalizadas, mediante la gammagrafía ósea de cuerpo completo puede obtenerse una imagen conocida como patrón "superscan". En algunos casos resulta muy similar a la producida por ciertas enfermedades metabólicas óseas. Se ha descrito el desarrollo de hipocalcemia asociada a estas metástasis Que resultaría del aumento del depósito de calcio y fósforo plasmático en las lesiones óseas. Secundariamente, las glándulas paratiroides aumentarían la producción de parathormona (PTH) en un intento de compensar esa hipocalcemia. Se presenta el caso de un paciente que desarrolló este síndrome, hacemos revisión de la literatura y discutimos la posible asociación del hiperparatiroidismo hipocalcémico y la captación en "superscan de tipo metabólico". Así mismo, insistimos en la importancia de su diagnóstico y en el posible tratamiento específico con intención paliativa (AU)

Bone metastases are common in prostate cancer. Osteoblast-related bone formation predominates over the activity of resorptive osteoclasts, and this is why sclerotic bone lesions are seen with imaging tests. When generalized, a full-body bone scan known as a "superscan" pattern may be obtained. In some cases, it is very similar to that produced by certain metabolic bone diseases. Hypocalcemia has been described in association with these images, which result from an increased deposition of plasma calcium and phosphorus in bone lesions. Secondarily, the parathyroid glands increase PTH production in an attempt to balance hypocalcemia. We report the case of a patient who developed this syndrome, review the literature, and discuss the potential association of hyperparathyroidism, hypocalcemia, and "superscan" pattern. We also emphasize the importance of diagnosis, and potential specific treatment with palliative intent (AU)

Factores que determinan la duración de la respuesta al tratamiento con tiludronato en una cohorte de pacientes con enfermedad de Paget / Factors determining duration of response to tiludronate in a cohort of patients with Paget's disease

Fundamento: Investigar la influencia de los factores que determinan la duración de la respuesta al tiludronato en la enfermedad de Paget. Pacientes y métodos: Se ha seguido a intervalos regulares, desde abril de 1993 hasta mayo de 2003, a todos los pacientes (n = 26) incluidos en un ensayo clínico sobre eficacia y bioequivalencia del tiludronato en la enfermedad de Paget. Cada paciente tomó 400 mg/día por vía oral durante 90 ñ 6 días. Diecisiete (65 por ciento) eran varones y 9 (35 por ciento) mujeres, y la media de edad ñ desviación estándar (DE) era 60,3 ñ 9,8 años. La evolución de la probabilidad de recaída bioquímica se investigó mediante la prueba de Kaplan-Meier. Para determinar qué variables predicen mejor la duración de la respuesta, y en qué medida, se realizó análisis de modelos de riesgo proporcional (regresión de Cox).Resultados: Sólo uno de los 26 pacientes incluidos en el ensayo clínico presentó resistencia inicial al tratamiento con tiludronato. De los restantes, en 19 se normalizaron las cifras de fosfatasa alcalina y 6 tuvieron una respuesta superior al 50 por ciento de los valores basales, aunque no alcanzaron la remisión completa. Nueve de los 19 pacientes en que se normalizaron las cifras de fosfatasa alcalina han permanecido durante los 10 años de seguimiento libres de recaída, por lo que no han precisado de nuevos ciclos. Los 16 restantes han presentado recaída, y han recibido uno o varios ciclos posteriores, con una media ñ DE de 1,43 ñ 0,68 ciclos por paciente. No se observaron efectos secundarios importantes ni alteraciones analíticas relevantes que indicaran toxicidad en los 49 ciclos administrados. El tiempo medio hasta la primera recaída fue de 53,5 meses y de 36 meses hasta la segunda. El porcentaje máximo de reducción de fosfatasa alcalina (media ñ DE) tras el segundo ciclo fue del 55,3 ñ 12,9 por ciento. Los pacientes con recaída muestran una mayor extensión de las lesiones óseas (11,68 ñ 7,4 frente a 5,33 ñ 0,7; p = 0,003) y una fosfatasa alcalina más elevada (1.446 ñ 810 frente a 849 ñ 255; p = 0,01). La concentración basal de fosfatasa alcalina y las concentraciones mínima y máxima de tiludronato al mes de comenzar el tratamiento son las que predicen con mayor fiabilidad la probabilidad de recaída. Conclusiones: El tiludronato suprime de manera eficaz a largo plazo la actividad bioquímica de la enfermedad de Paget. La concentración mínima o valle de tiludronato en plasma es el mejor predictor de la duración de la respuesta (AU)

Mujer con osteoporosis con dolor en región ilíaca / Woman with osteoporosis and pain in the iliac region

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