Antonio Del Puente

Fat-free mass and fat mass reference values by dual-energy X-ray absorptiometry (DEXA) in a 20–80 year-old Italian population

BACKGROUND & AIMS To establish reference values for limb composition, fat-free mass (FFM) and fat mass (FM) in Italian adults for gender-specific age brackets 20-80 years old and to assess age-related regional changes in body composition. METHODS A multicenter, retrospective study was conducted on 1571 healthy subjects, 1240 women and 331 men. Regional FFM and FM were measured by dual-energy X-ray absorptiometry. FM was expressed as % of limb weight. RESULTS FFM in men diminished with age in both arms and legs, with reference ranges (25th -75th percentile) of 3.8-4.6 kg and 10.4-12.2 kg, respectively for 20-29 year-olds, and 3.1-3.9 kg and 8.2-10.4 kg for 70-79 year-olds. Womens arm FFM remained stable with aging (reference values 1.7-2.2 kg), decreasing in their legs (6.2-7.2 kg for 20-29 year-olds, 5.5-6.5 kg for 70-79 year-olds). Limb FM% increased with age in both genders: the reference values were 9-15% (arms) and 12-21% (legs) for 20-29 year-old men, and 19-26% and 19-29%, respectively, for 70-79 year-olds; for womens arms, they were 25-36% for 20-29 year-olds and 36-48% for 70-79 year-olds, while their leg FM remained the same with aging, i.e. 32-40%. CONCLUSIONS These data complete the published reference values for whole body composition, enabling physiological or pathological changes in limb composition to be identified in Caucasian populations living in the Mediterranean area.

Genetic Epidemiology of Paget's Disease of Bone in Italy: sequestosome1/p62 Gene Mutational Test and Haplotype Analysis at 5q35 in a Large Representative Series of Sporadic and Familial Italian Cases of Paget's Disease of Bone

Families affected by Paget’s disease of bone frequently harbor mutations in the SQSTM1/p62 gene. In this multicentric study we collected 345 sporadic and 12 familial PDB cases throughout Italy, identifying 12 different mutations, 5 of which are newly reported and 3, D335E, A381V, and Y383X, external to the UBA domain. Subjects with truncating mutations, E396X, showed a significantly younger age at clinical diagnosis, while the Y383X subjects had a higher average number of affected skeletal sites. All the mutants exhibited the CGTG-H2 haplotype. In two pairs and one triad of unrelated Italian PDB families from different Italian regions, we detected a common SQSTM1/p62 mutation for each P392L, M404V, and G425R group. Since the CGTG-H2 haplotype frequency was also high in normal subjects, and genetic influence due to migratory fluxes of different ethnic groups exists in the Italian population, to refine the search for a more geographically specific founder effect, we extended the haplotype analysis in these families using polymorphic microsatellite repeat markers, within and flanking the SQSTM1/p62 locus, from chromosome 5q35, other than the exon 6 and 3′UTR polymorphisms. All mutant carriers from two of the three M404V families and from the G425R families exhibited common extended chromosome 5q35 haplotypes, IT01 and IT02, respectively, which may be reflecting influences of past migrations. This may be helpful in estimating the true rate of de novo mutations. We confirm the data on the existence of both a mutational hotspot at the UBA domain of SQSTM1/p62 and a founder effect in the PDB population.

Prevalence of Sarcopenia Based on Different Diagnostic Criteria Using DEXA and Appendicular Skeletal Muscle Mass Reference Values in an Italian Population Aged 20 to 80

OBJECTIVE To identify the mean values and percentiles for ASMM (appendicular skeletal muscle mass) and the prevalence of sarcopenia, in terms of muscle mass reduction, using different cutoffs in a European population. DESIGN A retrospective analysis on the dataset from a multicenter study on apparently healthy Italian adults conducted between 1999 and 2002. A significant muscle mass loss, necessary to diagnose sarcopenia, was defined in 3 different ways: (1) by subtracting 2 SDs from the mean ASMM index (ASMMI) of a young adult population (20-39 year-olds), as in the Rosetta study and the NHANES survey; (2) by calculating the 15th percentile of the distribution of our young population, corresponding to about 1 SD below the mean ASMMI; (3) by calculating the 20th percentile of the distribution of the ASMMI (as in the Health ABC study) of an elderly population. SETTING Five centers for the diagnosis and treatment of osteoporosis in various parts of the country (Padova, Verona, Parma, Roma, Napoli). PARTICIPANTS Participants were 1535 volunteers (1208 women and 327 men) aged 20 to 80 years, drawn from among staff members, university students, lay people contacted by word of mouth, and patients presenting spontaneously for osteoporosis screening. MEASUREMENTS Body weight and height were measured for all participants. Body composition was assessed by DEXA, and the ASMMI was calculated as the ASMM divided by body height in meters squared. RESULTS Both mens and womens lean mass in the arms and ASMM were highest in the young group and became lower in older age. In men, the ASMMI dropped gradually from age 20 to 29 to age 60 to 69, then remained stable in the oldest group. In women, the ASMMI gradually increased from age 20 to 29 to age 60 to 69, then dropped among the 70- to 80-year-olds. Based on the 15th percentile of the ASMMI for our young adult reference population, the cutoffs for sarcopenia were 7.59 kg/m(2) in men and 5.47 kg/m(2) in women; if the 20th percentile of the ASMMI in our elderly subjects (>65 years) was considered, the cutoffs were 7.64 kg/m(2) in men and 5.78 kg/m(2) in women. Applying the different diagnostic criteria to the those older than 65, the prevalence of sarcopenia ranged from 0% to about 20% in both genders. CONCLUSION The 15th percentile (or 1 SD below the mean) of the ASMMI of our young adults, and the 20th percentile of this index for an elderly reference population proved more effective in identifying cases of sarcopenia than subtracting 2 SD from the mean ASMMI of a young adult population.

New developments in magnetic resonance imaging of the nail unit.

The evolution of dedicated magnetic resonance imaging (MRI) musculoskeletal equipment allows new sequences and better images of the nail unit. The use of MRI has modified the imaging strategies used in treating inflammatory arthritis. In the case of psoriatic arthritis (PsA), the MRI study of the nail unit identifies nail involvement, which appears as an initial lesion for the induction of distal phalanx damage and consequently of distal interphalangeal joint arthritis. All patients with psoriasis, even in the absence of a clinically evident onychopathy, show characteristic MRI changes in the nail. This evidence could have a practical diagnostic value, because MRI study of the nail could document diagnosis in patients with undifferentiated spondyloarthropathies who have a barely evident psoriasis. We discuss the advantages and problems related to the use of low-field and high-field MRI in the study of the nail unit of patients with PsA.

Magnetic resonance imaging of nail unit in psoriatic arthritis.

The use of magnetic resonance imaging (MRI) has modified the imaging strategies of inflammatory arthritides. In psoriatic arthritis (PsA), MRI study of the nail unit identifies nail involvement that appears as the initial lesion for induction of distal phalanx damage and consequently of distal interphalangeal joint arthritis. All psoriatic patients, also in the absence of a clinically evident onychopathy, show characteristic MRI changes of the nail. This evidence could have practical diagnostic value because MRI study of the nail could document diagnosis in patients with undifferentiated spondyloarthropathies who have barely evident psoriasis. We discuss the advantages and problems related to the use of low- and high-field MRI in the study of the nail unit of patients with PsA.

Osteoporosis and Psoriatic Arthritis

Osteoporosis (OP) is a skeletal disorder characterized by compromised bone strength that predisposes to an increased risk of fracture. The prevalence of OP in the general population is very high as established in several studies, and OP represents one of the possible aspects of bone involvement in arthritis. In psoriatic arthritis this involvement is particularly complex because it affects not only mechanisms of bone loss but also of bone formation. We will discuss these aspects and the available epidemiological data.

Psoriatic arthritis and TNF inhibitors: advances on effectiveness and toxicity

Over the last decade, due to the high expectations that biologic drugs like anti-TNF are raising, the appropriate identification of patients eligible for these treatments has been conditioned by numerous ordinary aspects, mainly represented by previous or ongoing comorbidities and related therapies, and chronic infections or recurrence of acute infections. Additionally, in the last years, due to close monitoring by experienced clinicians, remarkable changes have been also obtained in the field of safety. Another question mark refers to the management of psoriatic arthritis systemic manifestations, in which the impact of biologic therapy is not enough explored.

Prevalence of Thyroid Autoimmunity in Patients with Spondyloarthropathies

Objective. To evaluate the prevalence of chronic autoimmune thyroiditis or Hashimoto’s thyroiditis (HT) in a group of patients with spondyloarthritis (SpA). Methods. We evaluated serum levels of thyroid-stimulating hormone, free triiodothyronine, and free thyroxine, and titers of antithyroglobulin and antithyroid peroxidase (anti-TPO) antibodies in 357 consecutive patients with SpA. We also recruited 318 healthy age-matched controls. Ultrasonography of the thyroid gland was performed in all subjects and rheumatic activity was evaluated. Results. Indices of thyroid autoimmunity were significantly more frequent in patients with SpA than in controls (24.09% vs 10.69%, respectively; p < 0.05). In the SpA group, a higher prevalence of HT was found in patients with an active disease than in those with low-moderate disease levels. Also in the SpA group, patients with a disease duration > 2 years had a higher prevalence of HT and anti-TPO antibodies positivity than patients with a disease duration ≤ 2 years. Ultrasonography detected a significantly higher frequency of thyroid nodules and hypoechoic pattern in patients with SpA than in controls. Among patients with SpA, HT and anti-TPO antibodies positivity were significantly more frequent in patients with peripheral involvement (68.6%) than in patients with axial involvement (31.4%; p < 0.05). Conclusion. Our study shows a significantly higher prevalence of thyroid autoimmunity in patients with SpA as compared to controls. Thyroiditis occurs more frequently in patients with longer disease duration and active rheumatic disease. We suggest that thyroid function tests be part of the clinical evaluation in patients with SpA.

The influence of gluten free diet on quantitative ultrasound of proximal phalanxes in children and adolescents with type 1 diabetes mellitus and celiac disease

A reduced bone mineral density has been reported in patients with untreated celiac disease (CD) as well as in patients with poorly controlled type 1 diabetes mellitus (T1DM). The aim of this study was to evaluate the bone mineral status by phalangeal quantitative ultrasound in 52 children and adolescents with both diseases (mean age 13.3+/-4.9 years). As a control group 50 patients with T1DM and no CD (age 12.2+/-4.0 years) were studied. The following bone parameters, amplitude-dependent speed of sound (AD-SoS) and bone transmission time (BTT) were considered and expressed as z score. Compliance to gluten free diet and long term glycemic control (mean of four determinations of HbA1c in the last year) were also assessed. The lowest mean AD-SoS z score values were found in patients with T1DM and CD, who reported transgressions to gluten free diet and exhibited positivity for serum anti-tissue transglutaminase antibodies (tTG) and/or endomysial antibodies (EmA), compared with patients with occasional transgressions but negative for anti-tTG and/or -EmA, patients strictly adherent to the diet, and patients who suffered only from diabetes (ANOVA p=0.021). No difference was found between patients with diabetes alone and patients with both diseases strictly adherent to gluten free diet. Prevalence of osteopenia (z AD-SoS values <-2 SD) was higher in patients with T1DM and CD and poor compliance to the diet (45.5%) compared with patients with T1DM (8%) or patients with both diseases strictly compliant to diet (12.9%) (p=0.015). A negative correlation between Ad-SoS z score and HbA1c (r -0.236, p=0.036) was found when patients with T1DM and patients with T1DM and CD, who strictly adhere to the diet, were pooled. In conclusion the quality of bone as assessed by phalangeal ultrasound in patients with T1DM and CD, who strictly adhere to gluten free diet, is similar to that found in T1DM patients. A higher prevalence of osteopenia is present in patients with both diseases who reported habitual transgressions to gluten free diet. The gluten free diet, as well as the optimization of glycemic control, plays an important role in preventing the osteopenic status caused by the clustering of these two chronic diseases.

Current evidence in the field of the management with TNF-α inhibitors in psoriatic arthritis and concomitant hepatitis C virus infection

Introduction: Psoriatic arthritis (PsA) is a chronic inflammatory condition involving the spine, enthesis and peripheral joints, which is associated with psoriasis. PsA therapy varies from use of NSAIDs to disease-modifying anti-rheumatic agents (DMARDs). However, their use can represent a limitation in patients with concomitant hepatitis C virus (HCV) infection. In the last few decades, anti-TNF-α therapy has opened new horizons in the treatment of PsA. Hence, the purpose of this review is to explore the efficacy and safety of anti-TNF-α agents in PsA and concomitant HCV infection. Areas covered: We reviewed the available medical literature to find all cases of PsA and concomitant HCV infection treated with TNF-α inhibitors. We found a total of 38 cases of patients with PsA and concomitant HCV infection in therapy with anti-TNF-α agents. Expert opinion: The available literature, summarized in this review, still remains very limited. Data suggest that therapy with the anti-TNF-α agents, mainly etanercept and adalimumab, at least with short-term use, would appear efficacious and reasonably safe in the management of PsA patients with concomitant HCV infection. With regard to infliximab, efficacy and safety have been scarcely explored, whereas in the case of golimumab and certolizumab no report was found, may be due to their recent introduction on the market.