Presentation of hypoparathyroidism in Italy: a nationwide register-based study.

PURPOSE: We sought to assess the clinical presentation of hypoparathyroidism (HypoPT) in Italy. METHODS: We performed a nationwide study retrieving data from the hospital discharge ICD-9 codes database of the Italian Health Ministry, from 2007 through 2017. The codes corresponding to diagnosis of cardiovascular disease, cancer, infection, renal failure, psychiatric disease, upper airway tract infection and pneumonia, seizures, nephrolithiasis, cognitive impairment, cerebral calcifications, skin disorders, fracture, and cataract were retrieved when associated with the diagnosis of HypoPT (252.1). We excluded codes corresponding to diagnoses of cancer of the neck region. In-hospital mortality rate was calculated. We retrieved the same data from an age- and sex-matched non-HypoPT control population. RESULTS: Fourteen thousand five hundred seventy-nine hospitalizations for HypoPT and controls were analyzed. Hospitalization for cardiovascular disease, cancer, infection, renal failure, seizures, nephrolithiasis, cerebral calcifications (p < 0.0001), and cognitive impairment (p < 0.05) were more common in HypoPT compared to controls. Mean age of HypoPT with cardiovascular disease, cancer, and renal failure was younger compared to controls (p < 0.0001). The OR of hospitalization for cardiovascular disease, cancer, renal failure, seizures (OR 2, 40, 48  and 1.6, respectively), and nephrolithiasis (OR 1.6) were significant in HypoPT compared to non-HypoPT. The OR of hospitalization for infection and cognitive impairment were significant only in HypoPT women (OR 1.3 and 2.3, respectively). In-hospital mortality rate was lower in HypoPT vs controls (0.5% and 3.7%; p < 0.0001). CONCLUSION: Hospitalizations for cardiovascular disease, cancer, and renal failure are more prevalent and occur at a younger age in HypoPT vs non-HypoPT. Hospitalizations for seizures and nephrolithiasis are frequent in HypoPT; those for infection and cognitive impairment are more common in HypoPT women.

A practical approach for anabolic treatment of bone fragility with romosozumab.

BACKGROUND: Romosozumab, a fully humanized anti-sclerostin-antibody, is a bone-builder stimulating osteoblasts and inhibiting osteoclast by activation of the canonical Wnt-beta catenin signaling. This unique mechanism of action has the potential to address unmet needs in osteoporosis management. METHODS: The multifaceted practical clinical issues related to romosozumab are discussed, especially focusing on the rationale of employing a sclerostin inhibitor to target bone fragility as first line or second line treatment in post-menopausal osteoporosis and in males at increased risk of fractures. RESULTS: Four randomized clinical trials with several post-hoc analyses and more than ten observational studies have consistently demonstrated that romosozumab is effective in rapidly increasing bone mineral density (BMD) and decreasing risk of vertebral, non-vertebral and hip fractures in post-menopausal women at very-high risk of fractures. In male osteoporosis, only data on BMD are available. Noteworthy, romosozumab was shown to be more effective and rapid than teriparatide in improving BMD, bone structure and strength at the hip, especially in women already treated with anti-resorptive drugs. Interestingly, even if romosozumab displays best results in treatment-naïve patients, its favourable effects on BMD were observed even in women previously treated with teriparatide or denosumab, although to a lesser extent. CONCLUSIONS: Based on the available evidence, romosozumab could be proposed as ideal drug in several clinical settings, such as non-fractured post-menopausal women at very-high risk of fractures, patients with recent hip fracture, patients non responder to bisphosphonates and short-term denosumab therapy.

Twenty-four hour Holter ECG in normocalcemic and hypercalcemic patients with hyperparathyroidism.

PURPOSE: To investigate the occurrence of arrhythmias in patients with normocalcemic (NC) primary hyperparathyroidism (PHPT) compared to both hypercalcemic PHPT patients and control subjects by means of 24-h Holter ECG. METHODS: Thirteen NCPHPT postmenopausal patients were enrolled and age-matched with 13 hypercalcemic PHPT patients and 13 controls. Every subject underwent basal ECG, 24-h Holter ECG and mineral metabolism biochemical evaluation. RESULTS: PHPT patients had higher mean serum calcium levels compared to both NCPHPT and controls; there was no difference in mean serum calcium levels between NCPHPT and controls. Both NCPHPT and PHPT patients had significantly higher mean PTH levels compared with controls. There were no differences in ECG parameters between the three groups, except for QTc interval. PHPT patients had normal QTc interval values, but significantly shorter mean values compared with those of controls and NCPHPT patients. During 24-h Holter ECG recording, 100% of PHPT patients had supraventricular premature beats (SVPBs), compared to 46% of NCPHPT (p = 0.005) and to 53% of controls (p = 0.01). PHPT patients experienced ventricular premature beats (VPBs) (69.2%) vs 15% of NCPHPT patients (p = 0.01) and 23% of controls (p = 0.04). There was no difference between NCPHPT and controls subjects concerning occurrence of both VPBs and SVPBs. CONCLUSIONS: NCPHPT patients did not experience an increased occurrence of arrhythmias compared to controls, while PHPT patients showed an increased occurrence compared to both controls and NCPHPT. Our findings are most probably related to the short QTc interval caused by hypercalcemia observed in PHPT patients, but not in NCPHPT.

Study of the link between hemotopoietic and skeletal systems in patients attending a referral center for osteoporosis.

PURPOSE: To investigate the link between hematopoietic and skeletal tissues in patients with fragility fractures. METHODS: We retrospectively analyzed the medical records of women older than 40 years who attended the Bone Disease Unit of "Sapienza" University of Rome for their first visit for osteoporosis from January 2020 to June 2022. RESULTS: Fragility fractures were found in 61.8% of the sample. In particular, vertebral fractures in 35.5%, femoral fractures in 6.3%, Colles fractures in 16.5% and non-vertebral non-hip in 42.5%. Fractured patients were significantly older compared to non-fractured, had lower mean values of lumbar spine (p = 0.01), and femoral neck BMD (p = 0.007). A red blood cell distribution width (RDW) value higher than 15% was observed four times more in those with fractures compared to non-fractured patients (8.9% vs 2%, p = 0.01) and was associated with vertebral fracture after adjusting for age, BMI, menopause, nutritional status, smoking, osteoporosis and anemia (OR = 4.1, 95% CI 1.6-11.4, p = 0.003). Hematocrit was negatively associated with hip fracture also adjusting for age, BMI, menopause, nutritional status, smoking, osteoporosis (p = 0.025). CONCLUSION: Our study demonstrates that RDW values were significantly associated with vertebral fracture and hematocrit with hip fracture. Since both parameters are included in the initial evaluation of patients with suspected bone fragility, our results should push doctors to look at these values with no incremental cost for national health services.

Bone quality in endocrine diseases: determinants and clinical relevance.

PURPOSE: Bone is one of the main targets of hormones and endocrine diseases are frequent causes of secondary osteoporosis and fractures in real-world clinical practice. However, diagnosis of skeletal fragility and prediction of fractures in this setting could be a challenge, since the skeletal alterations induced by endocrine disorders are not generally captured by dual-energy X-ray absorptiometry (DXA) measurement of bone mineral density (BMD), that is the gold standard for diagnosis of osteoporosis in the general population. The aim of this paper is to review the existing evidence related to bone quality features in endocrine diseases, proposing assessment with new techniques in the future. METHODS: A comprehensive search within electronic databases was performed to collect reports of bone quality in primary hyperparathyroidism, hypoparathyroidism, hyperthyroidism, hypercortisolism, growth hormone deficiency, acromegaly, male hypogonadism and diabetes mellitus. RESULTS: Using invasive and non-invasive techniques, such as high-resolution peripheral quantitative computed tomography or DXA measurement of trabecular bone score (TBS), several studies consistently reported altered bone quality as predominant determinant of fragility fractures in subjects affected by chronic endocrine disorders. CONCLUSIONS: Assessment of skeletal fragility in endocrine diseases might take advantage from the use of techniques to detect perturbation in bone architecture with the aim of best identifying patients at high risk of fractures.

Higher serum levels of a cathepsin K-generated periostin fragment are associated with fractures in postmenopausal women with primary hyperparathyroidism: a pilot study.

The only difference between fractured and non-fractured postmenopausal women with PHPT of same sex, age, and BMI was a significantly mean higher serum k-periostin level. K-periostin value was associated with fracture at any site (odds ratio 1.044, 95% CI 1.005-1.091, p = 0.03). INTRODUCTION: To assess serum k-periostin fragment levels in patients with primary hyperparathyroidism (PHPT), fractured and non-fractured matched for sex, age, and body mass index. METHODS: Twenty-five Caucasian fractured postmenopausal women with PHPT (group Fx) and 25 PHPT non-fractured (group NFx) were enrolled. Each patient underwent DXA scan at lumbar, hip, and forearm, spine X-ray, and biochemical evaluation of calcium metabolism. For k-periostin analyses, we utilized a specific ELISA test that detects CatK-generated fragment levels in the bloodstream. RESULTS: We found no difference in mean BMD and bone turnover marker values between Fx and NFx groups. Prevalence of osteoporosis was not significantly different in Fx vs NFx (72% vs 60%, p = 0.55). Among Fx, 16% reported multiple fractures, 28% morphometric vertebral fractures, 4% femoral fractures, 28% non-vertebral non-femoral fractures, and 8% wrist fractures. The only detectable difference between Fx and NFx group was a significantly mean higher k-periostin serum level (46.2 ± 21.4 vs 34.7 ± 13.5 ng/ml, p = 0.02). K-periostin was associated with fracture at any site (odds ratio 1.044, 95% CI 1.005-1.091, p = 0.03). No difference in mean k-periostin values was found between patients with vertebral fracture vs those with non-vertebral fracture, and between those with multiple fractures vs those with single fracture. CONCLUSION: Serum k-periostin is significantly associated with fracture in PHPT. If confirmed by further studies, k-periostin could be considered a new marker of bone fragility in PHPT, independently of BMD.

Lumbar spine bone mineral density and trabecular bone score-adjusted FRAX, but not FRAX without bone mineral density, identify subclinical carotid atherosclerosis.

PURPOSE: Osteoporosis and atherosclerosis share common risk factors. Aim of this study was to test if FRAX (which is an algorithm that can identify subjects at risk of fracture), without or with BMD values, also adjusted for trabecular bone score (TBS) was able to identify subclinical atherosclerosis, evaluated by measurement of carotid intima media thickness (cIMT ≥ 0.9 mm) as compared to DXA values. METHODS: Ninety postmenopausal women underwent DXA measurement and cIMT evaluation. For each patient, the FRAX algorithm for major osteoporotic fracture (M) and for hip fracture (H) without BMD was computed, together with FRAX with BMD and TBS-adjusted FRAX. Serum levels of osteoprotegerin, sRANKL, and interleukin-6 were also measured. RESULTS: There were no differences in anthropometric parameters and cardiovascular risk factors between subjects with cIMT ≥ 0.9 mm (35% of subjects, group A) compared to those with cIMT < 0.9 mm (group B). The prevalence of osteoporosis and FRAX BMD, TBS-adjusted FRAX both for M and H were higher in group A compared to group B. The best ROC curves to identify subjects with a cIMT ≥ 0.9 mm were: lumbar spine T-score, with a threshold of - 2.5 SD (area under the curve, AUC 0.64; p = 0.02) with a sensibility of 50% and a specificity of 76%; TBS-adjusted FRAX H with a sensibility of 50% and a specificity of 72% (AUC 0.64; p = 0.01 with a threshold of 3%). Interleukin-6 positively correlated with FRAX BMD H and M. CONCLUSIONS: FRAX without BMD does not identify subclinical carotid atherosclerosis, while lumbar spine T-score and TBS-adjusted FRAX H similarly detected it with higher specificity for T-score.

Diagnostic pathway of the biopsy-naïve patient suspected for prostate cancer: Real-life scenario when multiparametric Magnetic Resonance Imaging is not centralized.

INTRODUCTION: We aimed to compare the pathway including multi-parametric Magnetic Resonance Imaging (mpMRI) versus the one without mpMRI in detection of prostate cancer (PCa) when mpMRI is not centralized. MATERIALS: January 2019-March 2020: prospective data collection of trans-perineal prostate biopsies. Group A: biopsy-naïve patients who underwent mpMRI (at any institution) versus Group B: patients who did not. Within Group A, patients were stratified into those with negative mpMRI (mpMRI-, PIRADS v2.1=1-3, with PSA density <0.15 if PIRADS 3) who underwent standard biopsy (SB), versus those with positive mpMRI (mpMRI+, when PIRADS 3-5, with PSA density>0.15 if PIRADS 3) who underwent cognitive fusion biopsy. RESULTS: Two hundred and eighty one biopsies were analyzed. 153 patients underwent mpMRI (Group A). 98 mpMRI+ underwent fusion biopsy; 55 mpMRI- underwent SB. 128 Group B patients underwent SB. Overall PCa detection rate was 52.3% vs. 48.4% (Group A vs. B, P=0.5). Non-clinically-significant PCa was detected in 7.8 vs. 13.3% (Group A vs. B, P=0.1). Among the 98 mpMRI+ Group A patients only 2 had non clinically-significant disease. In 55 mpMRI- patients who underwent SB, 10 (18.2%) had clinically-significant PCa. Prostate volume predicted detection of PCa. In Group B, age and PSA predicted PCa. Sensitivity of mpMRI was 75.0% for all PCa, 85.3% for clinically-significant PCa. CONCLUSION: Higher detection of PCa and lower detection of non-clinically-significant PCa favored mpMRI pathway. A consistent number of clinically-significant PCa was diagnosed after a mpMRI-. Thus, in real-life scenario, mpMRI- does not obviate indication to biopsy when mpMRI is not centralized. LEVEL OF EVIDENCE: 3.

Long-term bone mineral density changes after surgical cure of patients with tumor-induced osteomalacia.

This paper reports our personal experience filling the gap regarding changes of bone mineral density after surgical treatment in patient suffering from tumor-induced osteomalacia. INTRODUCTION: No systematic data are available regarding long-term bone mineral density (BMD) changes after surgical cure of patients with tumor-induced osteomalacia. METHODS: From October 2001 through April 2018, we studied 10 consecutive patients (mean age ± SD, 45.5 ± 13.8 years; 5 males and 5 females) with tumor-induced osteomalacia. We evaluated BMD when initially presented at our Center and after surgical removal of the tumor. RESULTS: Basal BMD and corresponding Z-score values (mean values ± SD) measured by DXA were as follows: L1-L4 = 0.692 ± 0.15 g/cm2, Z-score = - 2.80 ± 1.60; femur neck 0.447 ± 0.10 g/cm2, Z-score = - 2.66 ± 0.93; total femur = 0.450 ± 0.08 g/cm2, Z-score = -3.04 ± 0.85). Furthermore, Trabecular Bone Score (TBS) was evaluated in three patients (basal values, 0.990 ± 0.32). Seven patients were intermittently followed after surgical excision of the tumor while supplemented with cholecalciferol and calcium salts; the remaining three were lost to follow-up. There was a striking increase of BMD values that peaked at 26.7 ± 6.50 months: L1-L4 = 1.289 ± 0.247 g/cm2, p < 0.001, Z-score + 1.75 ± 1.42; femur neck = 0.890 ± 0.235 g/cm2, p = 0.028, Z-score = + 0.50 ± 1.40; total femur = 0.834 ± 0.150 g/cm2, p = 0.005, Z-score = - 0.74 ± 1.14. In patients with the greatest bone involvement at lumbar site, there was a striking increase of an average 1.5% (p < 0.01) in respect to baseline Z-score value for each additional month of observation during the first 2-3 years post-surgery. An improvement of trabecular microarchitecture was also documented (TBS, 1.255 ± 0.16). CONCLUSION: This is the first case series documenting an impressive increase of BMD at both lumbar and femoral sites, together with an improvement of trabecular microarchitecture as documented by TBS. This is the consequence of huge mineralization of the large amount of osteoid tissue after resolution of the disease.

Vitamin D screening.

At present, there is no need and no sufficient evidence to support universal screening for vitamin D status. There are four categories of subjects in whom there is no requirement for screening, since a number of studies indicate beneficial effects of vitamin D supplementation; these are represented by children and adolescents, pregnant women, patients taking bone active drugs and subjects with documented hypovitaminosis D. In the remaining subjects, the utilization of adequate questionnaires will target with sufficient sensitivity and specificity those with hypovitaminosis D. These must be first supplemented and, at a later time, serum 25(OH)D assay should be requested to confirm attainment of sufficiency, independently of the threshold chosen. This strategy will cut costs deriving from both widespread use of vitamin D assays and vitamin D supplementation.

Patients' reasons for adhering to long-term alendronate therapy.

We aimed to determine patients' reasons for continuing alendronate therapy over 5 years by administering a questionnaire. Bone mineral density, fractures, drugs, Charlson comorbidity index, and lifestyle factors were also considered. Education and awareness of the disease appeared highly associated with good alendronate adherence while worsening health status with discontinuation. INTRODUCTION: Aim of this study was to investigate patients' reasons for adhering to long-term alendronate therapy (more than 5 years), as data is not available in the current literature regarding the reasons behind long-term adherence. METHODS: We studied 204 long-term adherent alendronate users: 65 postmenopausal outpatients still adherent (group C, years on treatment = 8.70 ± 1.31) were compared to 139 age-matched patients who discontinued therapy (group S, years on treatment = 8.64 ± 1.43). We evaluated main biochemical parameters, BMD values, fractures, and Charlson comorbidity index (CCI). A questionnaire was administered to analyze the reasons for long-term adherence. RESULTS: There were no significant differences between groups concerning baseline DXA values, number of fractures, and CCI. A higher education level was observed in group C (C 54% vs S 35% of patients, p = 0.001). At the time of interview, there was a significantly higher number of patients with a CCI of two in group S compared to the beginning of treatment (56% vs 43%, p = 0.04), together with a higher number of patients taking more than 3 drugs (22% vs 11%, p = 0.01) compared to basal evaluation. Forty-seven percent of patients reported new diseases during the treatment as the main reason for stopping alendronate. A multivariate, stepwise logistic regression analysis showed that awareness of the disease was highly associated with adherence (OR = 0.20; 95% CI 0.045-0.93, p = 0.04) followed by higher education (OR = 0.526, 95% CI 0.345-0.801, p = 0.003). Worsening of CCI was associated with discontinuation (OR = 2.75, 95% CI 1.033-7.324, p = 0.04). CONCLUSIONS: Education and disease awareness are associated with long-term alendronate adherence while competing health problems negatively impact adherence.

The epidemiology of osteoporosis in Italian postmenopausal women according to the National Bone Health Alliance (NBHA) diagnostic criteria: a multicenter cohort study.

PURPOSE: The study was aimed at evaluating the prevalence of osteoporosis, defined by BMD and the National Bone Health Alliance (NBHA) criteria, and the prevalence of clinical risk factors for fractures in Italian postmenopausal women. METHODS: This is a cross-sectional, multicenter, cohort study evaluating 3247 postmenopausal women aged ≥ 50 and older in different areas of Italy in the period 2012-2014. All the participants were evaluated as far as anthropometrics; questionnaires for FRAX® and DeFRA calculation were administered and bone mineral density was measured at lumbar spine, femoral neck and total hip by DXA. RESULTS: The prevalence of osteoporosis, as assessed by BMD and NBHA criteria was 36.6 and 57%, respectively. Mean ± SD values of FRAX® and DeFRA were: 10.2 ± 7.3 and 11 ± 9.4 for major fractures, and 3.3 ± 4.9 and 3.9 ± 5.9 for hip fractures, respectively. Among clinical risk factors for fracture, the presence of previous fracture, particularly non-spine/non-hip fracture, parental history of hip fracture and current smoking were the most commonly observed. CONCLUSIONS: Our study showed that more that the half of postmenopausal women aged 50 and older in Italy has osteoporosis on the basis of the NBHA criteria. There is a relevant high risk of femur fracture, as assessed by the FRAX® and DeFRA and previous fracture, parental history of hip fracture and current smoking are the most common risk factors. The data should be considered particularly in relation to the need to increase prevention strategies on modifiable risk factors and therapeutic intervention.

Clinical presentation and management of patients with primary hyperparathyroidism in Italy.

PURPOSE: Evaluation of the phenotype of primary hyperparathyroidism (PHPT), adherence to International Guidelines for parathyroidectomy (PTx), and rate of surgical cure. METHOD: From January 2014-January 2016, we performed a prospective, multicenter study in patients with newly diagnosed PHPT. Biochemical and instrumental data were collected at baseline and during 1-year follow-up. RESULTS: Over the first year we enrolled 604 patients (age 61 ± 14 years), mostly women (83%), referred for further evaluation and treatment advice. Five hundred sixty-six patients had sporadic PHPT (93.7%, age 63 ± 13  years), the remaining 38 (6.3%, age 41 ± 17  years) had familial PHPT. The majority of patients (59%) were asymptomatic. Surgery was advised in 281 (46.5%). Follow-up data were available in 345 patients. Eighty-seven of 158 (55.1%) symptomatic patients underwent PTx. Sixty-five (53.7%) of 121 asymptomatic patients with at least one criterion for surgery underwent PTx and 56 (46.3%) were followed without surgery. Negative parathyroid imaging studies predicted a conservative approach [symptomatic PHPT: OR 18.0 (95% CI 4.2-81.0) P < 0.001; asymptomatic PHPT: OR 10.8, (95% CI 3.1-37.15) P < 0.001). PTx was also performed in 16 of 66 (25.7%) asymptomatic patients without surgical criteria. Young age, serum calcium concentration, 24 h urinary calcium, positive parathyroid imaging (either ultrasound or MIBI scan positive in 75% vs. 16.7%, P = 0.001) were predictors of parathyroid surgery. Almost all (94%) of patients were cured by PTx. CONCLUSIONS: Italian endocrinologists do not follow guidelines for the management of PHPT. Negative parathyroid imaging studies are strong predictors of a non-surgical approach. PTx is successful in almost all patients.

Correction of vitamin D status by calcidiol: pharmacokinetic profile, safety, and biochemical effects on bone and mineral metabolism of daily and weekly dosage regimens.

RATIONALE: Calcidiol can be employed to correct vitamin D deficiency. MAIN RESULTS: Calcidiol administered at daily and weekly regimens over a period of 3 months was able to successfully raise 25-hydroxyvitamin D levels without altering other markers related to bone and mineral metabolism. SIGNIFICANCE: Calcidiol supplementation is effective and safe. INTRODUCTION: The correction of vitamin D status is necessary to maintain an optimal mineral and skeletal homeostasis. Despite cholecalciferol (vitamin D3) is the most commonly used drug for vitamin D supplementation, the more hydrophilic compound calcidiol (25-hydroxyvitamin D3) can be employed at daily, weekly, and monthly regimens to reach in the short term the target levels of serum 25-hydroxyvitamin D [25(OH)D]. In the administration of different doses of calcidiol pharmacokinetic study (ADDI-D study), the efficacy and safety of daily and weekly dosages of calcidiol were tested. METHODS: A total of 87 Caucasian, community-dwelling, postmenopausal women, aged 55 years or older, with vitamin D inadequacy (serum 25(OH)D levels <30 ng/ml, with mean 25(OH)D below 20 ng/ml, namely 16.5 ± 7.5 ng/ml) were randomized to receive three different dosages of calcidiol: 20 µg/day, 40 µg/day, and 125 µg/week for 3 months. The attained level of serum 25(OH)D was selected as primary endpoint to assess efficacy, while other parameters of mineral metabolism, (serum calcium, parathyroid hormone, phosphate, FGF23, urinary calcium, and markers of bone turnover) were assessed as secondary endpoints to establish safety. RESULTS: In all the three groups, serum 25(OH)D values significantly and promptly rose and plateaued above the 30 ng/ml threshold remaining within safety interval after 14 days of treatment, with similar efficacy for the similar daily and weekly dose regimens. The different dosages were also equally effective in controlling secondary hyperparathyroidism. No significant changes in calcium and phosphate metabolism and in bone turnover markers were observed for any of the treatments, confirming the safety of this compound. CONCLUSIONS: The results of this study demonstrate the short- and mid-term efficacy and safety on core parameters of mineral metabolism of different daily or weekly dosages of calcidiol when used to treat vitamin D inadequacy or deficiency in postmenopausal women. Further studies are needed to assess falls as primary outcome of calcidiol supplementation.

The effect of parathyroid hormone (1-84) treatment on serum bone morphogenetic protein 4 and vascular endothelial growth factor in postmenopausal women with established osteoporosis.

PURPOSE: To investigate the effect of 18 months' parathyroid hormone 1-84 (PTH 1-84) treatment on serum levels of bone morphogenetic protein 4 (BMP4) and vascular endothelial growth factor (VEGF), in postmenopausal women with established osteoporosis. METHODS: Thirty-seven postmenopausal women with osteoporosis (mean age 72.9 ± 8.1 years old) and 23 healthy controls (mean age 68.9 ± 9.9 years old) were enrolled. Patients were treated with daily subcutaneous injections of PTH (1-84) 100 mcg for 18 months, plus calcium 1 gr and vitamin D 800 IU per os daily. Blood samples were taken every 6 months during the study. RESULTS: At baseline, there were no differences considering anthropometric parameters, co-morbidities, current medications used between patients and controls. Mean serum VEGF levels were significantly higher in osteoporotic patients compared to controls (436.7 ± 259.7 vs. 260.3 ± 184.3 pg/ml, p = 0.006), while there were no differences in mean serum values of BMP4 (5.3 ± 1.7 vs. 5.7 ± 1.6 pg/ml, p = 0.40). Serum VEGF levels increased by approximately 20% after 12 months of PTH (1-84) treatment compared to baseline (p = 0.03) and by 22% after 18 months (p = 0.01). A significant increase of 10% in mean serum BMP4 levels was observed after 18 months of PTH (1-84) treatment compared to baseline (p = 0.02). In the control group we found no differences after 18 months compared to baseline in BMP4 (5.7 ± 1.6 vs. 6.0 ± 1.5 pg/ml, p = 0.53) and VEGF (260.3 ± 184.3 vs. 257.4 ± 107.1 pg/ml, p = 0.94). CONCLUSIONS: PTH (1-84) treatment increased serum levels of VEGF and BMP4 in postmenopausal women with severe osteoporosis.

MR appearance of parathyroid adenomas at 3 T in patients with primary hyperparathyroidism: what radiologists need to know for pre-operative localization.

OBJECTIVES: To identify frequent MRI features of parathyroid adenomas (PTAs) in patients with primary hyperparathyroidism (PHPT) using a fast protocol with a 3 T magnet. METHODS: Thirty-eight patients with PHPT underwent a 3 T-MR. All patients had positive US and Tc-99 sestamibi, for a total number of 46 PTAs. T2-weighted IDEAL-FSE and T1 IDEAL-sequences, before and after contrast, were performed. Five features of PTAs were recognised: hyperintensity, homogeneous or "marbled" appearance and elongated morphology on T2-sequences; cleavage plane from thyroid gland on T2-outphase; rapid enhancement in post-contrast T1. Image quality for T2-weighted IDEAL FSE and usefulness for IDEAL post-contrast T1-weighted and T2-outphase sequences were also graded. RESULTS: PTAs were hyperintense in T2-sequences in 44/46 (95.7%), "marbled" in 30/46 (65.2%) and elongated in 38/46 (82.6%) patients. Cleavage plane was observed in 36/46 (78.3%), and rapid enhancement in 20/46 (43.5%) patients. T2-sequences showed both excellent fat suppression and image quality (average scores of 3.2 and 3.1). T2-outphase images demonstrated to be quite useful (score 2.8), whereas, post-contrast T1 images showed a lower degree of utility (score 2.4). CONCLUSIONS: A fast protocol with 3.0-T MRI, recognising most common features of PTAs, may be used as a second-line method in the preoperative detection of PTAs. KEY POINTS: 3 T MRI protocol based on T2-weighted IDEAL FSE sequences was used. T2-hyperintensity and elongated morphology are common features of PTAs. 3 T MRI could be used in the preoperative detection of PTAs.

Dermo Beta Brachytherapy with 188Re in extramammary Paget's disease.

AIM: Extramammary Paget's disease (EMPD) is a rare neoplastic pathology involving the vulva, scrotum, and perianal areas, and it is characterized by a slow and insidious course. EMPD may also be associated with internal malignancy, and its clinical presentation features long-standing pruritic lesions, eczema-like, refractory to any therapy. The pathogenesis is unclear, and univocal standardization of treatment is yet to be determined. As regard to the patients who suffer from it, women are more often affected than men. The therapeutic approach depends on the extent of involvement; wide surgical excision is the first choice among treatments, but other forms of therapy, alone or in combination, include imiquimod 5%, photodynamic therapy, Mohs surgery as well as external beam radiotherapy and Brachytherapy. In the present paper a new therapeutic alternative is proposed: Dermo-Beta-Brachytherapy (DBBT) with 188Re. METHODS: Five patients with EMPD, one secondary and four primary cases, have been treated by Brachytherapy with DBBT. This therapy has been successfully used for non-melanocytic skin tumors and basically consists in the topical application of a specially designed, tailor-made mould containing a radioactive beta-emitting isotope, rhenium-188. RESULTS: The patients healed completely, after one session in one case and after two sessions in four cases, with 34 months mean follow-up. CONCLUSION: Brachyterapy could represent a new alternative therapy, instead than invasive treatments as surgery and conventional radiotherapy, capable to treat EMPD independently of its extension, with aesthetic and functional satisfactory results.