Expert opinion on the management of patients with osteoporosis with anabolic drugs in Italy.

OBJECTIVE: Fragility fractures (FF) resulting from osteoporosis pose a significant public health challenge in Italy, with considerable socio-health and economic implications. Despite the availability of safe and effective drugs, osteoporosis remains underdiagnosed and undertreated, leaving over 2 million high-risk Italian women without treatment. This paper aims to identify and propose key improvements in the management of osteoporosis, focusing particularly on the critical issues related to the use of anabolic drugs in secondary prevention, according to the current Italian Medicines Agency (AIFA) Note 79. METHODS: The Expert Panel, composed of nine recognized Italian experts in rheumatology, analyzed current practices, prescribing criteria, and the most recent literature. Three main reasons for revising the indications on pharmacological treatment of osteoporosis were identified: inadequate treatment of osteoporosis, new evidence regarding frontline placement of anabolics in high-risk conditions, and emerging sequential or combined strategies. RESULTS: The proposed improvements include the adoption of the Derived Fracture Risk Assessment algorithm for accurate fracture risk assessment, revision of AIFA Note 79 to reflect current evidence, improved prescribing appropriateness, broader access to anabolic agents, and the provision of sequential therapies with antiresorptives for teriparatide. These changes aim to enhance patient outcomes, streamline healthcare processes, and address the high percentage of undertreated individuals. CONCLUSIONS: This expert opinion emphasizes the importance of the appropriate use of anabolic drugs to reduce FF and associated costs while ensuring the sustainability of the National Health Service. The proposed recommendations are in line with the latest scientific evidence, providing a comprehensive strategy to optimize the management of osteoporosis in Italy. On behalf of the Study Group on Osteoporosis and Skeletal Metabolic Diseases of the Italian Society of Rheumatology.

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.

Secukinumab retention rate is greater in patients with psoriatic arthritis presenting with axial involvement.

Psoriatic arthritis (PsA) is an inflammatory disease characterized by peripheral and axial involvement. Biological disease-modifying antirheumatic drugs (bDMARDs) are the mainstream treatment for PsA and bDMARDs retention rate is a proxy for the drug's overall effectiveness. However, it is unclear whether IL-17 inhibitors can have a higher retention rate than tumor necrosis factor (TNF) inhibitors, in particular in axial or peripheral PsA. A real-life observational study was conducted on bDMARD naïve PsA patients initiating TNF inhibitors or secukinumab. Time-to-switch analysis was carried out with Kaplan-Meyer curves (log-rank test) truncated at 3 years (1095 days). Sub-analyses of Kaplan-Meyer curves between patients presenting with prevalent peripheral PsA or prevalent axial PsA were also conducted. Cox regression models were employed to describe predictors of treatment switch/swap. Data on 269 patients with PsA naïve to bDMARD starting either TNF inhibitors (n=220) or secukinumab (n=48) were retrieved. The overall treatment retention at 1 and 2 years was similar for secukinumab and TNF inhibitors (log-rank test p NS). We found a trend towards significance in the Kaplan-Meyer at 3 years in favor of secukinumab (log-rank test p 0.081). Predominant axial disease was significantly associated with a higher chance of drug survival in secukinumab users (adjusted hazard ratio 0.15, 95% confidence interval = 0.04-0.54) but not in TNF inhibitor users. In this real-life, single-center, study on bDMARD naïve PsA patients, axial involvement was associated with longer survival of secukinumab but not of TNF inhibitors. Drug retention of secukinumab and TNF inhibitors were similar in predominantly peripheral PsA.

Association between exposure to fine particulate matter and osteoporosis: a population-based cohort study.

Long-term environmental air pollution exposure was associated with osteoporosis' risk in a cohort of women at high risk of fracture. Cortical sites seemed to be more susceptible to the exposure's effect. INTRODUCTION: Environmental air pollution has been associated with disruption of bone health at a molecular level. Particulate matter (PM) exposure can simultaneously stimulate bone resorption and halt bone formation. The primary aim of the present study is to describe the association between long-term exposure to PM and osteoporosis in a large cohort of women at high risk of fracture. METHODS: Clinical, demographic, and densitometric data were extracted from the DeFRAcalc79 dataset, which gathers data on women at risk for osteoporosis. Data on the monitoring of PM10 and PM2.5 concentrations were retrieved from the Italian institute of environment protection and research (Istituto Superiore per la Protezione e la Ricerca Ambientale, ISPRA). Generalized linear models with robust estimators were employed to determine the relationship between BMD and PM long-term exposure. RESULTS: A total 59,950 women from 110 Italian provinces were included in the study. PM 2.5 exposure was negatively associated with T-score levels at the femoral neck (ß -0.005, 95 CI -0.007 to -0.003) and lumbar spine (ß -0.003, 95% CI -0.006 to -0.001). Chronic exposure to PM2.5 above 25 µg/m3 was associated with a 16% higher risk of having osteoporotic T-score at any site (aOR 1.161, 95% CI 1.105 to 1.220), and exposure to PM10 above 30 µg/m3 was associated with a 15% higher risk of having osteoporotic T-score at any site (aOR 1.148, 95% CI 1.098 to 1.200). CONCLUSION: Long-term exposure to air pollution was associated with higher risk of osteoporosis. Femoral neck site seemed to be more susceptible to the detrimental effect of PM exposure than lumbar spine site. KEY MESSAGE: Exposure to air pollution is associated with osteoporosis, mainly at femoral site.

Efficacy of mud plus bath therapy as compared to bath therapy in osteoarthritis of hands and knees: a pilot single-blinded randomized controlled trial.

The primary objective of this study was to assess the efficacy of mud plus bath therapy in comparison to bath therapy alone in hand and knee osteoarthritis (HOA and KOA). We conducted a single-blinded randomized controlled trial (RCT). Patients were randomly assigned to either mud plus bath therapy (group 1) or balneotherapy (group 2). The primary outcome was a change in AUSCAN questionnaire for HOA and in WOMAC for KOA at month 12. Evaluations were performed at baseline (B), immediately after the interventions (week 2, W2) and after 3 (M3), 6 (M6), 9 (M9) and 12 (M12) months. 37 patients with KOA and 52 with HOA were randomized in the study. In HOA patients, AUSCAN pain improved more in group 1 compared to group 2 at M3, M6 and M12 (p<0.001, p=0.001 and p=0.038, respectively). AUSCAN stiffness improved more in group 1 at M3 (p=0.001). AUSCAN function improved more at M3, M6, M9 and M12 (p=0.001, p=0.001, p=0.014 and p=0.018, respectively). Regarding, KOA, WOMAC function decreased more prominently in group 1 compared to group 2 at M9 (p=0.007). The absolute values of WOMAC function at M6 and M9 were lower in group 1 compared to group 2 (p=0.029 and p=0.001, respectively). WOMAC pain absolute values were lower in group 1 at W2 (p=0.044) and at M9 (p=0.08). We conducted a RCT on the efficacy of mud plus balneotherapy over balneotherapy alone in HOA and KOA. We found that mud plus balneotherapy was more effective than balneotherapy alone on clinical outcomes of HOA. Differences in clinical outcomes of KOA were not significant, yet numerically higher.

Vitamin D and disease severity in coronavirus disease 19 (COVID-19).

The role of 25-OH-vitamin D in the assessment of coronavirus disease 19 (COVID-19) has not been investigated. We sought to investigate the prevalence of 25-OH-vitamin D deficiency among COVID-19 patients, and to determine the associations between 25-OH-vitamin D status and the severity of the disease. We have conducted a retrospective observational study of COVID-19 patients admitted to the University of Verona Hospital Trust. Demographic, clinical and biochemical parameters were collected at hospital admission, and serum 25-OH-vitamin D levels were measured. The following outcomes were assessed: arterial partial oxygen pressure (PaO2); C-reactive protein (CRP); length of hospitalization; requirement of oxygen therapy; non-invasive ventilation (NIV); mechanical ventilation; and death. Among 61 patients enrolled, 72.1% was 25-OH-vitamin D deficient (<20 ng/mL) and 57.4% had 25-OHvitamin D <15 ng/mL. Patients with arterial PaO2 <60 mmHg had significantly lower mean 25-OH-vitamin D levels compared to patients with PaO2 ≥60 mmHg (13.3 ng/mL vs 20.4 ng/mL respectively, p=0.03). Vitamin D deficiency was associated with 3-fold higher risk of having arterial pO2 <60 mmHg. 25-OH-vitamin D deficiency was associated with increased CRP and dyspnea. 25-OH-vitamin D deficiency was associated with more severe systemic inflammatory response and respiratory failure in COVID-19 patients.

Different fracture risk profile in patients treated with anti-osteoporotic drugs in real-life.

In this retrospective study, we intended to investigate the baseline fracture risk profile in patients who started treatment with different anti-osteoporotic medications. We analyzed retrospectively the fracture risk calculated with DeFRA, a validated FRAX derived tool, in women who started an anti-osteoporotic treatment from 2010 to 2017. We analyzed baseline data of 12,024 post-menopausal women aged over 50 years. Teriparatide initiators had a baseline 10-year risk of major osteoporotic fracture of 82.1% with a Standard Deviation (SD) of 66.5%. Denosumab initiators and zoledronic acid initiators had a greater 10-year baseline risk of fracture (54.3%, SD 46.5% and 47.0%, SD 42.0 respectively) than patients initiated on alendronate (24.9%, SD 34.6%) and patients initiated on risedronate (23.9%, SD 24.1%). Using DeFRA, a FRAX™ derived tool, we showed significantly different fracture risk profiles in women who were started on various therapeutic agents for the treatment of osteoporosis in routine clinical practice.

Risk of fragility fractures in obesity and diabetes: a retrospective analysis on a nation-wide cohort.

This study aims to investigate the role of obesity and diabetes on bone health in a nation-wide cohort of women with high risk of fracture. INTRODUCTION: The role of obesity and diabetes on fracture risk is yet poorly understood. Body mass index (BMI) and bone mineral density (BMD) are strongly correlated; however, patients with elevated BMI are not protected against fractures, configuring the obesity paradox. A similar controversial association has been also found in diabetic patients. Herein, we present a retrospective analysis on 59,950 women. METHODS: Using a new web-based fracture risk-assessment tool, we have collected demographic (including BMI), densitometric, and clinical data (including history of vertebral or hip and non-vertebral, non-hip fractures, presence of comorbidities). We performed a propensity score generation with 1:1 matching for patients in the obese (BMI ≥ 30) and non-obese (BMI < 30) groups, in the diabetics and non-diabetics. Propensity score estimates were estimated using a logistic regression model derived from the clinical variables: age, lumbar spine T-score, and femoral neck T-score. RESULTS: We found an association between diabetes and fractures of any kind (OR 1.3, 95% CI 1.1-1.4 and 1.3, 95% CI 1.2-1.5 for vertebral or hip fractures and non-vertebral, non-hip fractures, respectively). Obesity, on the other hand, was significantly associated only with non-vertebral, non-hip fractures (OR 1.3, 95% CI 1.1-1.6). To estimate the individual effect of obesity and diabetes on bone health, we ran sensitivity analyses which included obese non-diabetic patients and non-obese diabetic patients, respectively. CONCLUSIONS: Non-obese diabetics had the highest risk of vertebral or hip fracture, whereas obese non-diabetics predominantly had non-vertebral, non-hip fracture's risk. These results should raise awareness in clinical practice when evaluating diabetic and/or obese patients.

Concentric left ventricular remodelling is associated with subclinical systolic dysfunction in patients with psoriatic arthritis.

Objectives: Subclinical left ventricular (LV) abnormalities have been reported in echocardiographic studies of patients with psoriatic arthritis (PsA). Left ventricular systolic dysfunction (LVSD) often coexists with concentric LV remodelling, an unfavourable prognostic factor that is commonly found in patients at high cardiovascular risk. However, it is unclear whether PsA is associated with concentric LV remodelling. This cross-sectional study assesses the prevalence of and factors associated with concentric LV remodelling in a cohort of patients with PsA, and tests the hypothesis that concentric LV remodelling is a major determinant of LVSD in PsA. Method: We evaluated 101 adults attending an outpatient clinic with PsA diagnosed according to the ClASsification criteria for Psoriatic ARthritis (CASPAR). All patients were free of cardiovascular disease. Patients with PsA were compared with 101 controls matched for age, gender, body mass index, hypertension, and diabetes. Echocardiography was performed: concentric LV remodelling was defined if the relative wall thickness was > 0.43; stress-corrected mid-wall shortening was used as an index of LVSD and considered impaired if < 86.5%. Results: Concentric LV remodelling was found in 58% of patients with PsA and 18% of controls (p < 0.001). LVSD was found in a significantly higher proportion of patients with PsA (56%, p < 0.001) than controls. The presence of PsA yielded a 10-fold higher probability of having LVSD [odds ratio (OR) 9.6, 95% confidence interval (CI) 4.2-21.9, p < 0.0001]. In patients with PsA, concentric LV remodelling increased the risk of LVSD four-fold (OR 3.7, 95% CI 1.3-10.2, p = 0.013). Conclusion: Most asymptomatic patients with PsA have concentric LV remodelling, which is closely associated with subclinical LVSD.

Vitamin D supplementation: much ado about nothing.

The scientific interest and the number of papers dealing with vitamin D supplementation has greatly grown in the last decades. Unfortunately, expert consensus on many clinical aspects of this topic is still lacking. In addition, data coming from recent clinical trials and meta-analyses seem to strongly put into doubt the real benefit of vitamin D supplementation, on both skeletal and extra-skeletal outcomes. This is further confusing since they seem to completely contradict the considerable body of evidence provided from previous epidemiological studies. This paper aims to analyze these new data in order to shed light onto the debated issues.

Correction to: Bone metabolism in patients with anorexia nervosa and amenorrhoea.

Unfortunately, the sixth author name was incorrectly spelled as "S. Fassio" instead of "A. Fassio" in the original publication.

Radiological features of knee joint synovial chondromatosis.

Synovial chondromatosis (SC) is a rare condition with a very variable clinical presentation, thus making the diagnosis not immediate. We report a case of massive primary SC of the knee, properly evaluated with X-rays, ultrasonography and magnetic resonance imaging and successfully treated with an arthroscopic approach.

Changes in Dkk-1, sclerostin, and RANKL serum levels following discontinuation of long-term denosumab treatment in postmenopausal women.

PURPOSE: The positive effects of denosumab (DMAb) on bone mineral density (BMD) are quickly reversible after its discontinuation. We investigated whether this rebound was associated with dysregulation of the Wnt canonical pathway and/or by the increase in the receptor-activator of nuclear factor-kappa B ligand (RANKL) serum levels. METHODS: The study included patients (n = 15) with postmenopausal osteoporosis to whom DMAb was administered for 78 months and then discontinued. We collected BMD data at baseline/month 0 (M0), M60, M84 (6 months after last DMAb administration, coinciding when the next DMAb dose would typically be due), and after 3 and 12 months of follow-up (FU-M3 and FU-M12, respectively). Serum C-terminal telopeptide of type 1 collagen (CTX-I), Dickkopf-1 (Dkk-1), and sclerostin were measured at M0, M60, M84, FU-M3, and FU-M12. Serum N-terminal propeptide of type 1 procollagen (PINP) and RANKL were dosed at M60, M84, FU-M3, and FU-12. RESULTS: We found a significant decrease in the T-score at all sites at FU-M12, when compared to M84 (-0.51 ±â€¯0.91 at the lumbar spine; -0.72 ±â€¯0.33 at the total hip; and -0.42 ±â€¯0.27 at the femoral neck, p < 0.05). After DMAb discontinuation (M84 vs FU M12) CTX-I, PINP increased already at FU-M3 (+0.921 ±â€¯0.482 ng/mL, +126.60 ±â€¯30.36 ng/mL, respectively, p < 0.01), RANKL increased at FU-M12 (+0.041 ±â€¯0.062 ng/mL, p < 0.05), while Dkk-1 and sclerostin decreased at FU-M12 (-10.90 ±â€¯11.80 and - 13.00 ±â€¯10.52 pmol/L, respectively, p < 0.01). No changes in BMD or any of the markers were found between M60 and M84. CONCLUSIONS: RANKL serum levels progressively increased after discontinuation of long-term DMAb while Dkk-1 and sclerostin serum levels decreased. The increase in RANKL serum levels supports the hypothesis of a sudden loss of inhibition of the resting osteoclast line after DMAb clearance, with a hyperactivation of these cells. Our results suggest that the changes in serum Wnt inhibitors after DMAb suspension might represent a mere feedback response to the increased bone turnover.

Inhibition of tumor necrosis factor-alpha (TNF-alpha) in patients with early rheumatoid arthritis results in acute changes of bone modulators.

OBJECTIVE: Dicckopf-1 (Dkk-1) is a potent inhibitor of the Wnt canonical pathway. In rheumatoid arthritis (RA), Dkk-1 is upregulated by tumor necrosis factor-α (TNF). Certolizumab pegol (CMZ) is a biologic TNF-inhibitor (TNFi) effective in RA and slows radiographic progression. Data on the immediate effects (≤1-8 weeks) of TNFi on Wnt modulators are lacking. This study investigated the acute influence of TNFi treatment on Wnt modulators (Dkk-1 and sclerostin) and bone turnover markers (BTM), including intact N-terminal propeptide of collagen type I (PINP) and C-terminal telopeptide of type I collagen (CTX-I). METHODS: This longitudinal, uncontrolled study involved female RA patients with inadequate response to conventional methotrexate who underwent treatment with CMZ. ESR, Dkk-1, sclerostin, BTM, parathyroid hormone (PTH), and 25OH-vitamin D levels were evaluated at baseline, week 1, week 4, and week 8. Radiographs of the hands and feet were obtained at baseline and the total and erosion scores were assessed using the Simple Erosion Narrowing Score method (SENS). RESULTS: Seventeen patients were enrolled. Dkk-1 and CTX-I significantly decreased after one week of treatment with CMZ (-49.1 ±â€¯17.1% and -25.0 ±â€¯20.6%, respectively, p < 0.01), whereas PINP increased (+43.2 ±â€¯31.5%, p < 0.01). These changes persisted at week 4 and 8. CONCLUSIONS: Our study showed that TNF-alpha inhibition with CMZ promptly results in a rapid decline of serum Dkk-1 levels, alongside decreased bone resorption and increased bone formation.

Association between non-alcoholic fatty liver disease and bone turnover biomarkers in post-menopausal women with type 2 diabetes.

AIM: Information is lacking on the association between non-alcoholic fatty liver disease (NAFLD) and bone mineral density (BMD) or circulating bone turnover biomarkers in post-menopausal women with type 2 diabetes (T2DM). METHODS: We recruited 77 white post-menopausal women with T2DM, who consecutively attended our diabetes outpatient service during a 3-month period. Liver ultrasonography and transient elastography (Fibroscan®) were used for diagnosing and staging NAFLD. A dual energy X-ray absorptiometry, and serum levels of 25-hydroxyvitamin D3 [25(OH)D], parathyroid hormone and multiple bone turnover biomarkers (periostin, sclerostin, dickkopf-related protein-1 [DKK-1], C-terminal telopeptide of type 1 collagen [sCTX], procollagen type 1 N-terminal propeptide [P1NP], receptor activator of nuclear factor-kB ligand [RANKL]) were also measured. RESULTS: Overall, 10 patients had NAFLD with clinically significant fibrosis (i.e., liver stiffness measurement > 7 kPa), 52 had NAFLD without fibrosis and 15 patients were free from steatosis. Although the three patient groups had comparable values of BMD, after adjustment for age, waist circumference, HOMA-insulin resistance and serum 25(OH)D levels, patients with NAFLD and significant fibrosis had significantly higher sclerostin levels (54.1 ± 16.4 vs. 36.1 ± 11.9 vs. 42.3 ± 14.7 pmol/L) and lower levels of serum DKK-1 (26.6 ± 17.8 vs. 49.0 ± 22.4 vs. 42.9 ± 19.4 pmol/L), RANKL (0.04 ± 0.03 vs. 0.08 ± 0.06 vs. 0.11 ± 0.06 pmol/L) and sCTX (0.16 ± 0.09 vs. 0.29 ± 0.17 vs. 0.40 ± 0.28 ng/mL) compared to other groups. Serum periostin and P1NP levels did not significantly differ between the groups. CONCLUSION: In post-menopausal women with T2DM, the presence of NAFLD and clinically significant fibrosis was strongly associated with a low bone turnover, which may reflect the presence of qualitative bone abnormalities.

Radiofrequency echographic multispectrometry compared with dual X-ray absorptiometry for osteoporosis diagnosis on lumbar spine and femoral neck.

An innovative, non-ionizing technique to diagnose osteoporosis on lumbar spine and femoral neck was evaluated through a multicenter study involving 1914 women. The proposed method showed significant agreement with reference gold standard method and, therefore, a potential for early osteoporosis diagnoses and possibly improved patient management. INTRODUCTION: To assess precision (i.e., short term intra-operator precision) and diagnostic accuracy of an innovative non-ionizing technique, REMS (Radiofrequency Echographic Multi Spectrometry), in comparison with the clinical gold standard reference DXA (dual X-ray absorptiometry), through an observational multicenter clinical study. METHODS: In a multicenter cross-sectional observational study, a total of 1914 postmenopausal women (51-70 years) underwent spinal (n = 1553) and/or femoral (n = 1637) DXA, according to their medical prescription, and echographic scan of the same anatomical sites performed with the REMS approach. All the medical reports (DXA and REMS) were carefully checked to identify possible errors that could have caused inaccurate measurements: erroneous REMS reports were excluded, whereas erroneous DXA reports were re-analyzed where possible and otherwise excluded before assessing REMS accuracy. REMS precision was independently assessed. RESULTS: In the spinal group, quality assessment on medical reports produced the exclusion of 280 patients because of REMS errors and 78 patients because of DXA errors, whereas 296 DXA reports were re-analyzed and corrected. Analogously, in the femoral group there were 205 exclusions for REMS errors, 59 exclusions for DXA errors, and 217 re-analyzed DXA reports. In the resulting dataset (n = 1195 for spine, n = 1373 for femur) REMS outcome showed a good agreement with DXA: the average difference in bone mineral density (BMD, bias ± 2SD) was -0.004 ± 0.088 g/cm2 for spine and - 0.006 ± 0.076 g/cm2 for femur. Linear regression showed also that the two methods were well correlated: standard error of the estimate (SEE) was 5.3% for spine and 5.8% for femur. REMS precision, expressed as RMS-CV, was 0.38% for spine and 0.32% for femur. CONCLUSIONS: The REMS approach can be used for non-ionizing osteoporosis diagnosis directly on lumbar spine and femoral neck with a good level of accuracy and precision. However, a more rigorous operator training is needed to limit the erroneous acquisitions and to ensure the full clinical practicability.

Malnutrition and sarcopenia in a large cohort of patients with systemic sclerosis.

Systemic sclerosis (SSc) is an autoimmune disease which may lead to malnutrition. Previous studies have defined it with different criteria. No thorough evaluations of sarcopenia in SSc are available. The aim of the present study was to assess the prevalence and the potential association of malnutrition and sarcopenia in a large cohort of SSc cases. A total of 141 SSc consecutive outpatients were enrolled. Body composition was analyzed by densitometry. Malnutrition was defined according to recently published ESPEN criteria, whereas sarcopenia was diagnosed in patients with reduced skeletal muscle index. Malnutrition was diagnosed in 9.2% of patients (95% CI, 4.4-14.0%). Malnourished patients had worse gastrointestinal symptoms according to UCLA SCTC GIT 2.0 questionnaire (p = 0.007), lower physical activity (p = 0.028), longer disease duration (p = 0.019), worse predicted DLCO/VA and FVC (p = 0.009, respectively), worse disease severity according to Medsger severity score (p < 0.001), lower hemoglobin (p = 0.023), and fat-free mass (p < 0.001) and were more often sarcopenic (p < 0.001). In multivariate analysis, only FVC (p = 0.006) and disease severity (p = 0.003), in particular for the lungs (p = 0.013), were confirmed to be worse in malnourished patients. Sarcopenia was diagnosed in 29\140 patients (20.7%; 95% CI, 14.0-27.4%); 11\29 were also malnourished. In multivariate analysis, sarcopenic patients had longer disease duration (p = 0.049), worse DLCO/VA (p = 0.002), and lung (p = 0.006) and skin (p = 0.014) involvement. In SSc, malnutrition defined with ESPEN criteria was found to be lower than previously reported. Sarcopenia was found to be somewhat common. Lung involvement was significantly associated with nutritional status and may not be explained only by muscle weakness.

Bone metabolism in patients with anorexia nervosa and amenorrhoea.

PURPOSE: Aim of this study is focusing on bone metabolism in AN patients with amenorrhoea and related estrogen deficiency effects. METHODS: AN patients were compared both with healthy females and with postmenopausal women (reference model for estrogen deficiency). The study sample included 81 females with AN. Laboratory tests [25-OH vitamin D, bone turnover markers, intact parathyroid hormone, sclerostin (SOST) and dickkopf-related protein (DKK1)] and dual energy X-ray absorptiometry (DXA) were taken into account. RESULTS: AN patients had higher levels of C-terminal telopeptide of type I collagen (CTX) than both control groups. AN adolescents had CTX higher than AN young adults. In postmenopausal women, intact N-propeptide of type I collagen was higher if compared with each other group. In AN groups, Dickkopf-related protein 1 was significantly lower than the two control groups. No differences were found in sclerostin except in adolescents. In AN adolescents, DXA values at femoral sites were higher than in AN young adults and a positive correlation was found with body weight (p < 0.01) and with fat mass evaluated using DXA (p < 0.01). CONCLUSIONS: AN women with amenorrhoea have an increased bone resorption like postmenopausal women but bone formation is depressed. The consequent remodeling uncoupling is considerably more severe than that occurring after menopause.