Giovanni Iolascon

Osteoporosis in beta-thalassaemia major patients: analysis of the genetic background.

Regular blood transfusions from infancy until adulthood in β‐thalassaemia major patients have substituted severe bone deformities with less marked skeletal lesions as osteoporosis. Osteoporosis is characterized by low bone mass and disruption of bone architecture, resulting in reduced bone strength and increased risk of fractures. Genetic factors have an important role in determining bone mineral density (BMD). We have investigated the possible association between BMD and two polymorphisms in 135 β‐thalassaemic patients: (i) a substitution G→Τ in a regulatory region of the COLIA1 gene encoding for the major protein of bone (type 1 collagen), and (ii) a one‐base deletion in intron 4 (713–8del C) of transforming growth factor beta 1 (TGF‐β1) gene. We have found a remarkable incidence (90%) of osteopenia and osteoporosis among regularly transfused patients. Bone mass was lower in men than in women (P = 0·0023), with a more prevalent osteopenia/osteoporosis of the spine in men than in women (P = 0·001). The sample was stratified on the basis of BMD expressed as Z‐score, i.e. normal, osteopenic and osteoporotic patients, and genotype frequencies of each group were evaluated. TGF‐β1 polymorphism failed to demonstrate a statistical difference in BMD groups. However, subjects with heterozygous or homozygous polymorphism of the COLIA1 gene showed a lower BMD than subjects without the sequence variation (P = 0·012). The differences among genotypes were still present when the BMD was analysed as adjusted Z‐score and when men and women were analysed separately (P = 0·022 and 0·004 respectively), with men more severely affected. Analysis of COLIA1 polymorphism could help to identify those thalassaemic patients at risk of osteoporosis and fractures.

Incidence and costs of hip fractures vs strokes and acute myocardial infarction in Italy: comparative analysis based on national hospitalization records

Objectives As osteoporotic fractures are becoming a major health care problem in countries characterized by an increasing number of older adults, in this study we aimed to compare the incidence and costs of hip fragility fractures in Italian elderly people versus those of major cardiovascular diseases (strokes and acute myocardial infarctions [AMI]) occurring in the whole adult population. Methods We analyzed hospitalization records maintained at the national level by the Italian Ministry of Health for the diagnosis of hip fractures (ICD-9-CM codes 820–821), AMI (code 410), hemorrhagic (codes 430, 431, 432) and ischemic strokes (codes 433–434), and TIA (code 435) between 2001–2005. Cost analyses were based on diagnosis-related groups. Results The incidence of hip fractures in elderly people has increased (+12.9% between 2001 and 2005), as well as that of AMI (+20.2%) and strokes (hemorrhagic: +9.6%; ischemic: +14.7) occurring in the whole adult population; conversely, hospitalization due to TIA decreased by a rate of 13.6% between 2001 and 2005. In 2005, the hospital costs across the national health care system that were associated with hip fragility fractures in the elderly were comparable to those of strokes (both hemorrhagic and ischemic), which occurred in the whole Italian adult population. Moreover, these costs were higher than those generated by AMI and TIA. Rehabilitation costs following strokes reached about 3 billion Euros in 2005, but rehabilitative costs of hip fractures and AMI were comparable (about 530 million Euros in 2005). Conclusion The burden of hip fragility fractures in Italy is comparable to that of AMI and strokes.

Socioeconomic burden of total joint arthroplasty for symptomatic hip and knee osteoarthritis in the Italian population: a 5-year analysis based on hospitalization records

To assess the burden of total joint arthroplasties (TJAs) performed for symptomatic hip and knee osteoarthritis (OA) in the Italian population.

European women's preference for osteoporosis treatment: influence of clinical effectiveness and dosing frequency*

ABSTRACT Objective: To determine participant preference for weekly versus monthly bisphosphonate therapy for osteoporosis after being informed about differences in fracture efficacy. Design: 20‐minute, semi-structured, face-to-face or telephone interviews. Two bisphosphonate choices were presented on the basis of block randomization: weekly therapy with proven efficacy to reduce fracture risk at the spine and hip, or monthly therapy with proven efficacy to reduce fracture risk at the spine but not the hip. Subjects: Women from the UK, Germany, France, Spain and Italy, with postmenopausal osteoporosis and aged ≥ 55 years. Fifty percent were currently taking a weekly bisphosphonate; 50% had no history of taking any bisphosphonate. Measures: An efficacy rating scale and an intention-to-use rating scale were developed for this study. The primary endpoint was preference for weekly or monthly therapy. Reasons for preference were recorded. Results: A preference was recorded for 1248 women (1253 were recruited). More women preferred weekly to monthly therapy (82% vs. 18%, respectively; p < 0.001). Among women who preferred weekly therapy, efficacy was the most commonly cited reason (65%). Ninety-two percent of the total cohort rated the efficacy of the weekly therapy as ‘excellent/good’ versus 38% for monthly ( p < 0.001). Sixty-nine percent intended to use weekly bisphosphonates compared with 34% for monthly ( p < 0.001). Conclusions: When informed about differences in fracture efficacy in weekly and monthly bisphosphonates, a significantly greater proportion (82%) of women preferred a weekly bisphosphonate with proven fracture efficacy at the spine and hip over a monthly bisphosphonate with proven fracture efficacy only at the spine.

Neridronate improves bone mineral density and reduces back pain in β‐thalassaemia patients with osteoporosis: results from a phase 2, randomized, parallel‐arm, open‐label study

Neridronate is a third generation bisphosphonate with established efficacy in metabolic bone disease. In this randomized, open‐label study, 118 adults with β‐thalassaemia and bone mineral density (BMD) Z scores ≤−2·0 were randomized 1:1–500 mg calcium with 400 international unis (iu) vitamin D daily or 500 mg calcium with 400 iu vitamin D daily plus neridronate 100 mg intravenously every 90 d. Significant increases in BMD at the lumbar spine and total hip were noted in the neridronate group at 6 and 12 months from baseline (P < 0·001), and values were significantly higher than the control group at both time intervals. Neridronate also significantly decreased serum bone alkaline phosphatase and C‐telopeptide of collagen type 1 levels from as early as 3 months (P = 0·04 and P < 0·001, respectively), reaching significantly lower values at 12 months compared with the control group (P < 0·05). Reductions in back pain and analgesic use were also evident, starting 3 months from commencing treatment. Treatment was well tolerated by all patients. In this largest randomized trial in thalassaemia‐induced osteoporosis to date, neridronate was safe and effective in reducing bone resorption and increasing BMD. The associated reduction in back pain and improved quality of life will encourage adherence to therapy. (Clinicaltrials.gov identifier NCT01140321.)

Development and validation of the Italian version of the Spinal Cord Independence Measure III

Purpose. To provide a translation and cultural adaptation of the Spinal Cord Independence Measure version III scale for Italy (i-SCIM3) and to validate this version of the scale. Method. i-SCIM3 was developed involving a forward–backward translation and administered to patients with spinal cord lesions (SCL) admitted to two centers. Two raters for each center evaluated patients at admission and discharge. Psychometric testing included reliability by internal consistency (Cronbachs α) and test–retest reliability. The validity of i-SCIM3 was assessed by comparing it with the Italian version of Functional Independence Measure™ (FIM™). Results. One hundred three adult patients with SCL (84 males) with a mean age of 50.33 ± 15.35 years were recruited. Seventy-four patients were paraplegic and 29 patients were tetraplegic. The median time elapsed between the two evaluations was 77.5 days (interquartile range, 53–144 days). Internal consistency, inter-rater reliability, and test–retest reliability were satisfactory overall, showing values higher than 0.90. The validity of i-SCIM3 was confirmed by the close correlation with FIM results both at admission and discharge (r = 0.91, p < 0.01). The sensitivity to change of i-SCIM3 was similar to that of FIM. Conclusion. i-SCIM3 was found to be a consistent, reliable, and valid scale for use in the clinical setting. It is the first validated scale in Italian for patients with SCL.

Ten years of hip fractures in Italy: For the first time a decreasing trend in elderly women

AIM To evaluate the hospitalization rate of femoral neck fractures in the elderly Italian population over ten years. METHODS We analyzed national hospitalizations records collected at central level by the Ministry of Health from 2000 to 2009. Age- and sex-specific rates of fractures occurred at femoral neck in people ≥ 65 years old. We performed a sub-analysis over a three-year period (2007-2009), presenting data per five-year age groups, in order to evaluate the incidence of the hip fracture in the oldest population. RESULTS We estimated a total of 839008 hospitalizations due to femoral neck fractures between 2000 and 2009 in people ≥ 65, with an overall increase of 29.8% over 10 years. The incidence per 10000 inhabitants remarkably increased in people ≥ 75, passing from 158.5 to 166.8 (+5.2%) and from 72.6 to 77.5 (+6.8%) over the ten-year period in women and men, respectively. The oldest age group (people > 85 years old) accounted for more than 42% of total hospital admissions in 2009 (n = 39000), despite representing only 2.5% of the Italian population. Particularly, women aged > 85 accounted for 30.8% of total fractures, although they represented just 1.8% of the general population. The results of this analysis indicate that the incidence of hip fractures progressively increased from 2000 to 2009, but a reduction can be observed for the first time in women ≤ 75 (-7.9% between 2004 and 2009). CONCLUSION Incidence of hip fractures in Italy are continuously increasing, although women aged 65-74 years old started showing a decreasing trend.

Mechanobiology of bone

Bone is a tissue that dynamically adapts mass and architecture to the mechanical loads that occur in daily life in a world with gravity. Bone architecture and mass are influenced by the applied tension peak, whereas the bone formation rate is modulated by the stimulus frequency. In bone tissue, osteocytes govern the detection of mechanical afferents and their transformation into biochemical messages, therefore these cells can be considered a mechanosensor that directs osteogenesis to where it is most needed to increase bone strength. The stimulation of osteocytes occurs with several modalities: shear stress and stretch, extracellular pressure modifications, strains, variations of electric field in and around osteocytes lacunae. The osteocyte network, under physiological conditions, activates osteoclastogenesis and suppresses osteoblast function enhancing bone resorption and inhibiting bone formation. In the unloaded condition, the functions of the osteocyte network are augmented, whereas exercise could decrease inhibitory effects on bone mass by reducing both osteoclastogenesis and inhibition on osteoblast function.

Management of Bone Disease in Gaucher Disease Type 1: Clinical Practice

Gaucher disease is a rare autosomal recessive disorder of glycosphingolipid metabolism resulting from deficient activity of the lysosomal enzyme beta-glucocerebrosidase that causes accumulation of glucosylceramide in tissue macrophage with damage to hematological, visceral, and skeletal organ systems. Severity and progression may vary independently among these domains, necessitating individualized therapy. Skeletal involvement is highly prevalent and often associated with intense pain, impaired mobility, and reduced quality of life. Enzyme replacement therapy improves parameters in all affected domains, but skeletal involvement requires longer treatment and higher dosages to obtain significant results. Despite numerous papers on bone complications in patients with Gaucher disease, there are no specific indications on how to assess properly bone involvement in such condition, the frequency of assessment, the use of markers for osteoblast and osteoclast activity, or the administration of bisphosphonates or other symptomatic drugs in adult and pediatric patients. Starting from a re-evaluation of cases with bone involvement, we have identified some common errors in the diagnostic approach and management. The aim of this paper was to propose a methodological and critical approach to the diagnosis, follow-up and treatment of bone disease in patients with Gaucher disease type 1.

Incidence of breast cancer in Italy: mastectomies and quadrantectomies performed between 2000 and 2005.

ObjectivesWe aimed to determine the incidence of womens breast cancer in Italy without using statistical approximations.MethodsWe analyzed the national hospitalizations database at the Ministry of Health to calculate the number of major surgeries in Italian women (mastectomies and quadrantectomies) due to breast cancer between 2000 and 2005, overall and by age groups (<44, 45–64, 65–74 and ≥ 75 years old).ResultsOver the six years examined, an overall number of 100,745 mastectomies and 168,147 quadrantectomies were performed. A total of 41,608 major surgeries due to breast cancer were performed in the year 2000 and this number rose to 47,200 in 2005, with a 13.4% increase over six years.Conclusionby analyzing the hospitalizations database concerning major breast surgery, incidence of breast cancer in Italy was found to be 26.5% higher than the official estimations which have been computed using statistical models (namely 47,200 vs. 37,300 cases in year 2005).