A novel mutation in collagen gene COL1A2 associated with transient regional osteoporosis.

A young man was diagnosed with transient regional osteoporosis (TRO). The genetic analysis revealed a novel de novo likely pathogenic variant in COL1A2 gene. Our hypothesis is that TRO may be a possible clinical manifestation of osteogenesis imperfecta due to a reduced bone mass and an impaired trabecular mechanical competence. INTRODUCTION: Transient regional osteoporosis (TRO) is a disease characterized by episodes of pain in the lower limbs involving the hip, knee, ankle or foot. Here, we present a clinical case of a Caucasian 25-year-old man exhibiting TRO. Based on few mild clinical findings suggestive of osteogenesis imperfecta (OI), but without a history of fragility fractures, we performed a genetic assessment to investigate this hypothesis. METHODS: Medical history was obtained from the patient and family members, including biochemical, RMI and DXA assessments. Next-generation sequencing of COL1A1, COL1A2, COL2A1, CASR, CYP19A1, CUL7, CRTAP, KAL1, LEPRE1, LRP5, PPIB and SLC9A3R1, genes involved in juvenile osteoporosis, was performed. RESULTS: We identified a novel de novo heterozygous missense variant, c.488G > A, in exon 11 of the COL1A2 gene (NM_000089.3), resulting in the putative p.Gly163Asp substitution in the N-terminal part of the helical domain of type I collagen. The variant was predicted to be damaging by the in silico prediction tools and the mutation was therefore classified as likely pathogenic. This mutation can affect skeletal health impairing bone mass and trabecular mechanical competence, inducing a disease whose features strictly evoke a TRO. CONCLUSION: The present study describes a novel de novo heterozygous missense variant in COL1A2 gene, possibly inducing a propensity to trabecular microfractures. The recurrent symptomatic bone marrow oedema episodes could be the clinical picture consistent with the hypothesis of an inherited connective tissue disorder giving bone fragility.

Osteoporosis with vertebral fractures in young males, due to bone marrow mastocytosis: a report of two cases.

Male osteoporosis in young patients is an unusual condition, always worth investigating as a possible manifestation of secondary osteoporosis. Mastocytosis is a clonal disorder of mast cells with heterogeneous presentations; when pathologic cells accumulate only in the bone marrow, vertebral fractures and systemic osteoporosis may represent the sole clinical presentation at the onset of the disease. We report on two young male patients who came to our attention because of multiple dorsal and lumbar vertebral fractures, with no other signs of systemic mastocytosis (SM). Lumbar and femoral dual x-ray absorptiometry showed reduced bone mineral density values; biochemical investigations did not report significant anomalies, suggestive of secondary osteoporosis. One of the patients underwent iliac crest bone biopsy, which was not diagnostic. A vertebral intralesional CT-guided bone biopsy was performed in both patients, which allowed the diagnosis of SM. Our experience pointed out that bone biopsy still remains the gold standard for the diagnosis of SM. However, iliac crest biopsy can be not significant because of circumscribed bone marrow involvement: in these cases only intralesional bone biopsy could be diagnostic.

Pleural granuloma mimicking malignancy 42 years after slurry talc injection for primary spontaneous pneumothorax.

BACKGROUND: Talc poudrage is considered a safe pleurodesis technique to improve the results of video-assisted thoracoscopic surgery in cases of primary spontaneous pneumothorax (PSP). METHODS: We report the case of a patient with left pleural pseudo-nodular plaque and a high metabolic rate upon PET scan suspected for malignancy, occurring 42 years after slurry talc injection for conservative treatment of PSP. The patient presented with coughing, chest pain and weight loss. Thoracotomy was required to obtain a diagnosis and perform a complete pleurectomy. RESULTS: Histology was conclusive for pleural talc granuloma. CONCLUSIONS: Indications and possible complications of talc use in young patients with PSP, and the management of possible consequent pleural lesions suspected for malignancy, need to be investigated.

Articular facets syndrome: diagnostic grading and treatment options.

Approximately 80% of the adult population suffers from chronic lumbar pain with episodes of acute back pain. The aetiology of this disorder can be very extensive: degenerative scoliosis, spondiloarthritis, disc hernia, spondylolysis, spondylolisthesis and, in the most serious cases, neoplastic or infectious diseases. For several years, the attention of surgeons was focused on the articular facets syndrome (Lilius et al. in J Bone Joint Surg (Br) 71-B:681-684, 1998), characterised clinically by back pain and selective pressure soreness at the level of the facets involved. The instrumental framework highlights widespread zigoapophysary arthritis and hypertrophy/degeneration of articular facets due to a functional overload. This retrospective study analyses the patients who arrived at our observation and were treated with a neuroablation using a pulsed radiofrequency procedure, after a CT-guided infiltration test with anaesthetic and cortisone. From the data collected, it would seem that this procedure allows a satisfactory remission of the clinical symptoms, leaving the patient free from pain; furthermore, this method can be repeated in time.

VATS for congenital lobar emphysema: a case report.

UNLABELLED: Congenital lobar emphysema (CLE) is a rare congenital lung disease consisting in overinflation of a pulmonary lobe. Adult onset of CLE is therefore unusual, often presented with mild symptoms. The authors report a very uncommon case of congenital segmental emphysema diagnosed in a 21-year-old non-smoking man because of recurrent right pneumothorax. Indication to pulmonary resection was established according to functional limitation, radiological findings of right upper lobe segmental emphysema with corresponding bronchial agenesia, scintigraphic result of extremely reduced ventilation and perfusion of lung emphysematous area and recurrency of pneumothorax. The intervention was carried out by 3-portal video-assisted thoracic surgery (VATS) using single-lung ventilation leading to determine precisely how much lung to resect thanks to the obvious and clear-cut distinction between functioning and non functioning parenchyma of the upper lobe. A stapler wedge resection by VATS was thus obtained, that, as far as the author's knowledge, it is the first case of endoscopic parenchymal sparing resection in CLE. Even though congenital lobar emphysema is rare, clinical awareness of this condition is important for early diagnosis and effective surgical treatment that in this case led to favourable RESULTS: The VATS procedure seems to be an advantageous approach.

Intravenous pamidronate in the treatment of transient osteoporosis of the hip.

The aim of this study was to evaluate the efficacy of intravenous pamidronate in patients with transient osteoporosis of the hip (TOH). Thirteen men and three women (mean age 38.3 years, range 30-49) were recruited. The diagnosis was made by means of radiographs, bone scintigraphy, and magnetic resonance imaging (MRI). Pamidronate (45 mg) was intravenously administered three times, once every third day. The outcome measures included a clinical assessment using a pain visual analog scale (VAS; range 0-100), and the WOMAC functional impairment score (FUI; range 0-100). The bone mineral density (BMD) of the total hip and femoral neck was measured using dual-energy X-ray absorptiometry (DXA). Clinical assessments were made before treatment (T(0)) and 1 month later (T(1)), and the densitometric measurements at T(0), and then after 2 (T(2)) and 4 months (T(4)). A further MRI scan was made 3 months after treatment. In comparison to the unaffected side, there was a significant decrease at T(0) in the BMD of both the total hip (median 16.6%, range 8.5%-29.1%, p < 0.00001) and femoral neck (median 22.5%, range 12.0%-34.2%, p < 0.00001). By T(1), both VAS and FUI had decreased significantly (p < 0.00001). By T(2), the total hip and femoral neck BMD had increased by 10.9% (range 2.7%-23.6%, p < 0.00001) and 12.3% (range 7.8%-26.9%, p < 0.00001), respectively, and all patients were asymptomatic. By T(3), the MRI findings had normalized in all patients and, at T(4), there was a further increase in BMD. None of the patients experienced symptom relapse during the follow-up of 39.5 +/- 17.7 months. These results suggest that a short course of pamidronate is effective in treating TOH, and leads to a prompt and long-lasting recovery.

Evaluation by dual-photon absorptiometry of bone mineral loss in rheumatic children on long-term treatment with corticosteroids.

The introduction of reliable and non-invasive methods of measuring bone mass has allowed investigators to study the bone mass loss (ostopenia) related to rheumatic diseases and corticosteroid therapy. Serial measurements of lumbar bone mineral density (BMD) by dual-photon absorptiometry (DPA) is an effective method of checking bone mineralisation. In children, however, the bone mass is not constant over time, so bone densitometric measurements must take into account not only the net loss but also the missing increase in BMD. In order to study the effects of both chronic rheumatic disease and the long-term administration of corticosteroids in children, as a first step the reference curves of bone mineralisation (mean BMD values and annual % BMD growth rates) were calculated from a control population of 79 children (32 males and 47 females) aged 3 to 20 years. All the subjects involved in the study underwent DPA utilising a Norland Bonestar instrument provided with a 153 Gadolinium source and the average BMD (g/cm2) of the lumbar spine was calculated. As a second step, a transverse study was carried out on a series of 157 children and young adults affected by chronic rheumatic diseases with juvenile onset. As a third step, a longitudinal study on the adverse effect of the chronic administration of corticosteroids on bone mineralisation was carried out on a series of 58 patients affected by chronic rheumatic diseases with juvenile onset who were being treated with long-term corticosteroids. Serial measurements of bone mass should help us to improve our strategies in preventing and counteracting osteopenia due to the chronic administration of corticosteroids also in children.

Accuracy and reproducibility of the assessment of the global ejection fraction using 195mAu and a single-crystal digital gamma camera: influence of collimator design.

A sequence of RAO first-pass studies (first with 99mTc and then twice with 195mAu) was performed in 18 normal volunteers and in 12 CAD patients using two different types of collimator for medium energy: a standard collimator (MEMS) and a special high-sensitivity collimator (MEHS). The following data were compared: the peak count rate, the net LV end-diastolic counts and the LVEF. Using MEMS the end-diastolic counts acquired were so low (12% of 99mTc average value) that EF standard deviation had a mean value of 0.061 (range 0.045-0.081). With MEHS the following results were obtained: 1. the peak count rate and LV net end-diastolic counts with 195mAu were 55% and 50% respectively, of 99mTc values; 2. a good correlation was shown between LVEF values either with 99mTc and 195mAu (r = .97), or with 195mAu sequential studies (r = .98).

Transient osteoporosis of the hip: a densitometric study.

Three new cases of transient osteoporosis of the hip are reported. Diagnosis was achieved by plain radiographs, bone scintiscan, magnetic resonance imaging and X-ray absorptiometry of proximal femurs. The densitometry showed at the Ward's triangle a mean reduction of bone mineral density in the affected side of 36%. All subjects were treated with i.v. clodronate for ten consecutive days with a complete recovery of femoral density within 4 months. X-ray absorptiometry allows a quantification of the demineralization process and can be useful in the long term evaluation of this entity.

Effect of lactation on postmenopausal bone mineral density of the lumbar spine.

OBJECTIVE: To investigate the relationship between lactation and bone mineral density (BMD) of the lumbar spine in a cohort of 540 healthy, postmenopausal women. STUDY DESIGN: Women were selected who experienced long-term lactation (n = 155, median 18 months) or short-term lactation (n = 168, median 3 months) or who were parous, nonlactating subjects (n = 217). The groups were homogeneous in age and differed in body mass index, parity and age at menopause. Vertebral BMD was measured by x-ray absorptiometry. RESULTS: No statistically significant difference in BMD was found between groups or after adjusting for body mass index, number of live births and age at menopause. Even when the 86 women with the longest lactation history (median 22 months) were matched with 112 parous women with the same parity who did not lactate, we could not find any significant difference. CONCLUSION: Long-term lactation did not significantly affect postmenopausal vertebral BMD in a cohort of healthy women.

Studies of complement activation in ARDS patients treated by long-term extracorporeal CO2 removal.

To investigate the role of complement activation in the adult respiratory distress syndrome (ARDS) and in the complications of extracorporeal circulation (ECC), several parameters (CH50, C3 split products, C3a, C5a, PMN aggregating activity, carboxypeptidase activity) of the complement profiles of 23 ARDS patients were measured. Twenty patients were treated by long-term extracorporeal support. Before connection to ECC, marked leukocytosis (18,250 +/- 5,950) and significantly high plasma C3a levels (p less than 0.005) were observed. After connection, C3a levels increased further, up to values eight times higher than the basal ones. The WBC count transiently decreased to 41% of prebypass levels after 15 minutes of ECC. At the same time C3 split products appeared and PMN aggregating activity was shown in 52% of the patients. C5a levels remained normal during bypass, even in two samples in which PMN aggregating activity was detected. Later decreases in CH50 titers (p less than 0.001) and carboxypeptidase activity (p less than 0.005) were observed. Complement activation was no longer evident after the 24th hour of bypass. We conclude that there is a low-degree complement activation in ARDS, and ECC is a further strong stimulus for complement activation. This phenomenon appears, however, to be self-limited.

Reproducibility and reliability of first pass radionuclide ventriculography with Au-195m. Validation of Au-195m radionuclide ventriculography.

Au-195m is a radio-isotope with an ultra-short half-life with which multiple sequential evaluations of ventricular function can be made. In order to evaluate the reliability and reproducibility of analyses of overall and regional ventricular function by radio-isotope ventriculography with Au-195m we studied 10 healthy volunteers and 12 patients with coronary artery disease. Each subject underwent 4 first-pass studies: 1 with Tc-99m and, 10 minutes later, 3 with Au-195m (2 basal studies separated by 3-5 minutes interval and, 10 minutes later, 1 after s.l. nitroglycerin administration). Regional wall motion was analyzed and ejection fraction and peak count rate were determined in each test. Our study showed that the ejection fraction obtained with Au-195m was reproducible (r = 0.98) and correlated well with the ejection fraction determined by using Tc-99m (r = 0.98). The values of the peak count rate obtained with Tc-99m were higher than those obtained with Au-195m. Due to the specially designed collimator and the technical characteristics of the gamma-camera we used, we were able to record sufficiently high count-rates to evaluate regional wall motion, and this analysis was also found to be reliable and reproducible. After s.l. nitroglycerin administration, normal volunteers showed a significant increase of ejection fraction in comparison with basal acquisitions (p less than 0.05), while a wide range of responses was observed in the group of patients with coronary artery disease. We conclude that radio-isotope ventriculography with Au-195m is reliable and reproducible and could be a valid method of monitoring rapid variations induced in overall and regional left ventricular function.

[Isolated muscular sarcoidosis mimicking a tumoral lesion]. / Manifestazione isolata di sarcoidosi muscolare simulante una lesione tumorale.

We report a case of a woman with a palpable painful nodule on her left leg. MR and CT showed a lesion that could be described as a neoplasm. Excisonal biopsy revealed a noncaseating granuloma. The woman presented the nodular type of muscular isolated sarcoidosis. Further the disease involved the lungs; this confirmed the accurate diagnosis of sarcoidosis. Sarcoidosis is a chronic, multisystem granulomatous disease of unknown etiology. Muscle involvement is frequent, but often asymptomatic. There are three forms of muscular sarcoidosis: only the nodular type can be recognized by technical imaging. MR and ultrasound are the best methods to attempt the diagnosis of nodular muscular sarcoidosis; nevertheless, the lesion must have a standardized behaviour because it can mimic a malignant neoform. In this case, biopsy is the only tool to identify the disease.

[Planning of a prospective study with a biological bank]. / Progettazione di uno studio prospettico con banca biologica.

This present work aims to give a critical description of the organization and operative aspects of project ORDET (prospective study on diet and hormones in the aetiology of breast cancer). A number of problems which could arise when carrying-out a prospective study are described: they concern participant recruitment, laboratory organization, planning of a biological bank plus relative security checks in order to ensure full workability and personnel standardization in questionnaire administration and anthropometrical measurements. The methods adopted by ORDET, or at least some of them, could be useful for those engaged in the planning phase of a similarly designed project using a biological bank.

[Bone mass in males. A comparison between dual-photon densitometry of the lumbar spine and the whole body]. / La massa ossea nei maschi. Confronto tra densitometria a doppio raggio fotonico della colonna lombare e whole body.

In order to evaluate the validity of a new method for measuring the whole body mineral content in diagnosing senile osteoporosis we studied 3 groups of male subjects: the first one composed by 40 young healthy subjects (mean age 24.7 years), the second composed by 40 normal patients (mean age 51.3 years); the 3rd group consisted of 26 elderly patients affected with typical osteoporotic fractures (mean age 77 years). All of them underwent a measurement of the spine as well as whole body mineral content performed with a dual photon absorptiometer. The measurements showed a decreasing in mineral content in the second versus the first group but a high correlation coefficient between spine and WB measurements characterized both groups; a striking decrease of it (r = 0.22) was found in the 3rd group. The relative unreliability of the spine measurement in elderly is probably due to the age-linked anatomical alteration. We therefore conclude that WB measurement must be considered the method of choice for the detection of senile osteoporosis.

[Percutaneous radio-frequency ablation of osteoid osteoma: technique and preliminary results]. / Termocoagulazione percutanea degli osteomi osteoidi mediante radiofrequenza: tecnica e risultati preliminari.

PURPOSE: To report our personal experience with the percutaneous technique for in situ destruction of osteoid osteoma using radio-frequency ablation. MATERIAL AND METHODS: From January 2000 to January 2001 we performed 16 radio-frequency ablations in 15 patients. All candidates for treatment had previously undergone clinical and radiologic examinations to confirm features typical of osteoid osteoma. After administration of spinal anesthetic, procedures were performed with CT-guidance, using a Kirschner wire introduced into the localized lesion, and a guiding cannula. A hole was first cut into the bone with a cutter, then a few biopsy specimens were obtained with a Jamshidi needle. Finally, we introduced a small radio-frequency electrode into the bone, through the biopsy track. Sufficient current was used to heat the electrode tip to 85-90 degrees C with consequent thermal necrosis of the tissue. The healing was continued for 6 minutes. RESULTS: All patients well tolerated the percutaneous procedure and only 1 underwent a second, successful radio-frequency ablation. In all cases, pain relief was noted to occur very rapidly and all patients could bear full weight on the treated extremity within 24 hours after the procedure. No late complications attributable to the ablation were noted, except for a small eschar next to the puncture site. DISCUSSION AND CONCLUSIONS: The results of the present study suggest that percutaneous ablation is preferred to operative excision because it generally requires shorter hospital stay and is not associated with complications. Furthermore, in our experience, pain relief was noted to occur very rapidly in 100% of cases. In agreement with the literature data, our results show that CT-guided percutaneous radio-frequency ablation can actually replace operative excision in the treatment of osteoid osteoma as it achieves the same clinical outcomes with significantly lower costs.

Is the metatarsal fracture in postmenopausal women an osteoporotic fracture? A cross-sectional study on 113 cases.

To evaluate whether metatarsal fracture in postmenopausal women can be related to osteoporosis, a sample of 113 postmenopausal women with metatarsal fracture due to minor trauma were recruited. Demographic and clinical data were compared with a control group of 339 healthy age-matched women and with a sample of 224 women with wrist fracture. In all women, bone mineral density (BMD) was measured at the lumbar spine by dual-energy X-ray absorptiometry. The average age of the metatarsal fracture group was slightly lower than that of the wrist fracture group (56.9 vs 58.4 years). Women with metatarsal and wrist fracture had a significantly higher age at menarche, lower age at menopause and lower body mass index when compared with controls. In both fracture groups BMD was significantly lower compared with controls. In stepwise logistic regression models, factors associated with metatarsal fracture risk were age at menopause (odds ratio [OR] 0.86; 95% confidence interval [CI] 0.81-0.92) and BMD (OR per -1 SD 2.44; CI 1.92-3.11). Factors associated with wrist fracture risk included age at menopause (OR 0.89; CI 0.84-0.93) and BMD (OR per -1 SD 2.65; CI 2.17-3.24). The similarities existing in risk factors and their estimates between a well-recognized osteoporotic fracture such as wrist fracture and metatarsal fracture, support the hypothesis that the latter can be included among osteoporotic fractures.

Prevalence of osteoporosis by educational level in a cohort of postmenopausal women.

To evaluate whether the prevalence of osteoporosis and related risk factors might be influenced by the level of education, as has been demonstrated for many other chronic diseases, 6160 postmenopausal women at their first densitometric referral were interviewed about reproductive variables, past and current use of estrogens, prevalence of chronic diseases, and lifestyle factors such as calcium intake, physical activity, smoking and overweight. This sample was stratified by years of formal education. Densitometric evaluation was performed by dual-energy X-ray absorptiometry. Age at menarche, past exposure to oral contraceptives, use of hormone replacement therapy, prevalence of chronic diseases, physical activity, overweight and smoking showed significant trends according to the years of education. The prevalence of osteoporosis showed an inverse relationship with level of education, ranging from 18.3% for the most educated to 27.8% for the least educated women. Multiple logistic regression analysis demonstrated a predictive role toward osteoporosis by age, age at menarche and menopause, hormone replacement therapy, calcium intake, physical activity and body mass index. Using the lowest educational level as reference category, increases in educational status were associated with a significantly reduced risk for osteoporosis (OR = 0.76, 95% CI 0.65-0.90 for 6-8 years of schooling; OR = 0.68, 95% CI 0.57-0.82 for 9 years or more). This study shows differences in the prevalence of osteoporosis among educational classes and the protective role played by increases in formal education. If these results are confirmed in other population studies, public health intervention programs will have to consider the socioeconomic and cultural background of the population strata that run a greater risk of osteoporosis.