Circulating MicroRNAs as Biomarkers of Osteoporosis and Fragility Fractures.

CONTEXT: Measurement of circulating microRNAs (miRNAs) as potential biomarkers of fragility fracture risk has recently become a subject of investigation. OBJECTIVE: Measure by next-generation sequencing (NGS), global miRNA expression in serum samples of osteoporotic subjects vs individuals with normal bone mineral density (BMD). DESIGN: Samples were collected from patients with different bone phenotypes and/or fragility fractures who did not receive any antiresorptive and/or bone-forming drug at the time of blood collection. SETTING: Samples and data were collected at 7 medical centers in Italy. PATIENTS: NGS prescreening: 50 osteoporotic patients vs 30 individuals with normal BMD. Droplet digital polymerase chain reaction (ddPCR) validation: 213 patients with different bone phenotypes, including the NGS-analyzed cohort. RESULTS: NGS identified 5 miRNAs (miR-8085, miR-320a-3p, miR-23a-3p, miR-4497, miR-145-5p) differentially expressed in osteoporosis cases without fractures vs controls. ddPCR validation confirmed lower c-miR-23a-3p expression in osteoporotic patients, with or without fracture, than in osteopenic and normal subjects and increased c-miR-320a-3p expression in osteoporotic patients with fracture and lower expression in osteoporotic patients without fracture. ddPCR analysis showed a significantly increased expression of miR-21-5p in osteoporotic patients, with or without fracture, than in osteopenic and normal subjects, not evidenced by the NGS prescreening. DISCUSSION: Our study confirmed levels of c-miR-23a-3p and c-miR-21-5p as able to distinguish osteoporotic patients and subjects with normal BMD. Increased levels of c-miR-320a-3p specifically associated with fractures, independently by BMD, suggesting c-miR-320a-3p as a prognostic indicator of fracture risk in osteoporotic patients, to be confirmed in prospective studies on incident fractures.

Secretin Stimulation Test and Early Diagnosis of Gastrinoma in MEN1 Syndrome: Survey on the MEN1 Florentine Database.

CONTEXT: Multiple endocrine neoplasia type 1 (MEN1) is a rare inherited endocrine cancer syndrome. Multiple gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) affect 30% to 80% of MEN1 patients, with the most common functioning GEP-NET being gastrinoma. Biochemical identification of hypergastrinemia may help to recognize the presence of gastrinomas before they are detectable by instrumental screening, enabling early diagnosis and start of therapy, preferably before tumor progression and metastases occurrence. OBJECTIVE: Evaluate the effectiveness of secretin stimulation test to precociously diagnose the presence of gastrin-secreting tumors. DESIGN: Results of secretin stimulation tests, performed between 1991 and February 2020, were retrospectively analyzed, as aggregate, in a cohort of MEN1 patients with GEP-NETs. SETTING: Data were extracted from the MEN1 Florentine database. PATIENTS: The study included 72 MEN1 patients with GEP-NETs who underwent a secretin stimulation test for the evaluation of gastrin secretion. OUTCOMES: A positive secretin stimulation test was assumed with a difference between basal fasting serum gastrin (FSG) and the maximum stimulated value of gastrin over 120 pg/mL. RESULTS: The secretin stimulation test showed a secretin-induced hypergastrinemia in 27.8% (20/72) of patients with GEP-NETs, and a positive test in 18 cases. The test allowed the identification of a positively stimulated hypergastrinemia in 75.0% (3/4) of patients who presented a basal FSG within the normal range. CONCLUSIONS: Diagnosis of gastrinoma is complex, difficult, and controversial. Results of this study confirm that a positive secretin stimulation test allows early diagnosis of gastrinomas, even in the presence of borderline or normal levels of nonstimulated FSG.

Hypoparathyroidism and pseudohypoparathyroidism in pregnancy: an Italian retrospective observational study.

BACKGROUND: Hypoparathyroidism (HypoPT) or pseudo-hypoparathyroidism (pseudo-HypoPT) during pregnancy may cause maternal and fetal/neonatal complications. In this regard, only a few case reports or case series of pregnant or lactating women have been published. The purpose of this study was to describe clinical and biochemical course, pharmacological management, and potential adverse events during pregnancy and post-partum in pregnant women with HypoPT or pseudo-HypoPT. This was a retrospective, observational, multicenter, study involving nine Italian referral centers for endocrine diseases affiliated with the Italian Society of Endocrinology and involved in "Hypoparathyroidism Working Group". RESULTS: This study identified a cohort of 28 women (followed between 2005 and 2018) with HypoPT (n = 25, 84% postsurgical, 16% idiopathic/autoimmune) and pseudo-HypoPT (n = 3). In HypoPT women, the mean calcium carbonate dose tended to increase gradually from the first to third trimester (+ 12.6%) in pregnancy. This average increase in the third trimester was significantly greater compared to the pre-pregnancy period (p value = 0.03). However, analyzing the individual cases, in 44% the mean calcium dosage remained unchanged throughout gestation. Mean calcitriol doses tended to increase during pregnancy, with a statistically significant increase between the third trimester and the pre-pregnancy period (p value = 0.02). Nevertheless, analyzing the individual cases, in the third trimester most women with HypoPT (64%) maintained the same dosage of calcitriol compared to the first trimester. Both mean calcium carbonate and calcitriol doses tended to decrease from the third trimester to the post-partum six months. Most identified women (~ 70%) did not display maternal complications and (~ 90%) maintained mean serum albumin-corrected total calcium levels within the low-to-mid normal reference range (8.5 ± 0.8 mg/dl) during pregnancy. The main complications related to pregnancy period included: preterm birth (n = 3 HypoPT women), and history of miscarriages (n = 6 HypoPT women and n = 2 pseudo-HypoPT women). CONCLUSION: This study shows that mean serum albumin-corrected total calcium levels were carefully monitored during pregnancy and post-pregnancy, with limited evaluation of other biochemical parameters, such as serum phosphate, 24 h urinary calcium, 25-OH vitamin D, and creatinine clearance. To avoid complications in mothers affected by (HypoPT) or (pseudo-HypoPT) and offspring, intense biochemical, clinical and pharmacological monitoring during pregnancy and breastfeeding is highly recommended.

Mediterranean diet adherence and dietary calcium intake in a group of pregnant women: Results of an Italian survey.

Pregnancy is a delicate phase in woman's life that could become a risk factor for osteoporosis in pregnant women who do not meet recommended nutrient standards, especially for calcium and vitamin D. Mediterranean diet (MD) has been demonstrated to be beneficial for adequate nutrient intake. This article aims to evaluate the MD adherence and dietary calcium intake in a group of pregnant Italian women and to investigate how these are linked to each other and to fast glycemia at first trimester of pregnancy. Two hundred and seventy-nine pregnant women were recruited at the gynecology units of two hospitals in Florence. Socio-demographic, clinical information, and results of the first trimester blood sample analysis were collected. Two questionnaires, validated for evaluation of MD adherence and calcium intake, were administered to the pregnant women. Approximately 60% of the women had a high level of MD adherence, with a mean dietary calcium intake of 870.3 ± 335.3. In women with higher MD adherence level, fast glycemia resulted lower. Calcium intake was lower than Population Rate Intake for the Italian population (1,200 mg/daily) and was positively correlated to MD adherence score. The MD proved to be nutritious, as it was related to a higher calcium intake in this group of Italian women.

Chronic hypoparathyroidism and treatment with teriparatide.

PURPOSE: Chronic hypoparathyroidism is usually treated with calcium and active vitamin D metabolites or analogs, despite the fact that their chronic use can lead to long-term complications. The use of hormone replacement therapy with PTH peptides [teriparatide and rhPTH (1-84)] has therefore been proposed. The main purpose of this study was to investigate the efficacy of teriparatide dose at 20 µg once or twice daily, in order to maintain normocalcemia reducing standard treatment, in adult patients with chronic hypoparathyroidism not well controlled with conventional treatment. METHODS: The study was a Phase III, open-label, non-comparative, clinical investigation (study period: 3 months), at a tertiary care clinical research center. Thirty patients with chronic hypoparathyroidism were screened, and 12 started teriparatide. After the optimization phase (0-4 weeks), calcium and calcitriol supplements were progressively reduced, while teriparatide 20 µg once daily was administered (5-7 weeks), and then could be titrated up to 20 µg twice daily (7-17 weeks). The main outcome measures included serum and urinary biochemical exams and Rand 36-Item Short Form Health Survey. RESULTS: This study showed that teriparatide 20 µg once daily was insufficient to discontinue calcium and calcitriol supplements to maintain normal serum calcium concentrations. Conversely, for more than half of patients treated with teriparatide 20 µg twice daily, calcium and calcitriol administration was avoidable, but in some cases at the expense of serum calcium and phosphate oscillations. CONCLUSIONS: Since intervention trials evaluating the efficacy and safety of teriparatide in hypoparathyroid patients are not yet available, the routine use of this molecule poses some doubts.

Quality of life in Italian patients with Multiple endocrine neoplasia type 1 (MEN 1): results of an extensive survey.

BACKGROUND: MEN1 is a complex, rare, syndrome inherited in an autosomal dominant tract and characterized by the development of multiple neuroendocrine tumors, requiring lifelong surveillance and multiple medical and surgical therapies throughout the patient's life. For all these reasons, a diagnosis of MEN1 can be a psychological shock for the patient, as well as his/her relatives, more so than the diagnosis of a single tumor. In the last two decades, clinicians have started to consider the emotional, psychological, relational, and social aspects of their patients' lives. The data collected in the present analyses highlight the unique features of MEN1 syndrome, and aim to evaluate the Quality of Life in the patients and their relatives. In this study, a comprehensive survey of various aspects of Health-Related Quality of Life was performed in a large series of Italian MEN1 patients, by administering five of the most common targeted questionnaires. RESULTS: The results of the study showed that our patients, despite having a complex multi-tumor syndrome, were moderately optimistic (50%), and this corresponds with a normal Quality of Life. This positive response is strictly correlated with the fact that the patients are cared for at a dedicated Referral Center, receiving personalized care and constant follow-up, which gives them reassurance regarding the high quality of management of the disorder. CONCLUSIONS: The possibility of having access to a clinical Referral Center for their complex rare disease, together with the support of a dedicated patient association, has been demonstrated to be the ideal model for the management of post-diagnosis shock, and contributes to the preservation of a good Health-Related Quality of Life for MEN1 patients.

Calcium Intake in Bone Health: A Focus on Calcium-Rich Mineral Waters.

Calcium is an essential element that plays numerous biological functions in the human body, of which one of the most important is skeleton mineralization. Bone is a mineralized connective tissue in which calcium represents the major component, conferring bone strength and structure. Proper dietary calcium intake is important for bone development and metabolism, and its requirement can vary throughout life. The mineral composition of drinking water is becoming relevant in the modulation of calcium homeostasis. In fact, calcium present in mineral drinking waters is an important quantitative source of calcium intake. This, together with its excellent bioavailability, contributes to the maintenance of the bone health. This article aims to examine studies that assessed the bioavailability of the calcium contained in calcium-rich mineral waters and their impact on bone health, including original data collected in a recent study in humans.

Correction to: Multiple endocrine neoplasia type 1: analysis of germline MEN1 mutations in the Italian multicenter MEN1 patient database.

The original version of this article unfortunately contained a mistake in Table 2. The table 2 was truncated in the original publication. The full table 2 is given below.

Multiple endocrine neoplasia type 1: analysis of germline MEN1 mutations in the Italian multicenter MEN1 patient database.

PURPOSE: Multiple endocrine neoplasia type 1 (MEN1) is caused by germline inactivating mutations of the MEN1 gene. Currently, no direct genotype-phenotype correlation is identified. We aim to analyze MEN1 mutation site and features, and possible correlations between the mutation type and/or the affected menin functional domain and clinical presentation in patients from the Italian multicenter MEN1 database, one of the largest worldwide MEN1 mutation series published to date. METHODS: The study included the analysis of MEN1 mutation profile in 410 MEN1 patients [370 familial cases from 123 different pedigrees (48 still asymptomatic at the time of this study) and 40 single cases]. RESULTS: We identified 99 different mutations: 41 frameshift [small intra-exon deletions (28) or insertions (13)], 13 nonsense, 26 missense and 11 splicing site mutations, 4 in-frame small deletions, and 4 intragenic large deletions spanning more than one exon. One family had two different inactivating MEN1 mutations on the same allele. Gastro-entero-pancreatic tumors resulted more frequent in patients with a nonsense mutation, and thoracic neuroendocrine tumors in individuals bearing a splicing-site mutation. CONCLUSIONS: Our data regarding mutation type frequency and distribution are in accordance with previously published data: MEN1 mutations are scattered through the entire coding region, and truncating mutations are the most common in MEN1 syndrome. A specific direct correlation between MEN1 genotype and clinical phenotype was not found in all our families, and wide intra-familial clinical variability and variable disease penetrance were both confirmed, suggesting a role for modifying, still undetermined, factors, explaining the variable MEN1 tumorigenesis.

Low-dose diclofenac in patients with fragility fractures.

Most osteoporotic patients complain of back pain one year after a fragility vertebral fracture and the frequency of chronic back pain increases with increasing age. The use of the lowest effective dose of an analgesic which is able to control symptoms seems to be a possible solution in order to limit potential side effects in multi-treated elderly patients. Non-steroidal anti-inflammatory drugs (NSAIDs) have a proven efficacy in the treatment of back pain associated with fragility vertebral fractures and diclofenac is available at low-dose subcutaneous injective formulation. This is the rational of ImPAVeDic study, acronym of Improvement of back Pain Associated with fragility Vertebral fractures with low-dose Diclofenac, an observational study that will be performed in a group of 50 elderly (≥ 65 years), male and female osteoporotic patients with symptomatic fragility vertebral fractures. The objective of the study is to evaluate the improvement of back pain in the study population treated with low-dose diclofenac and regularly monitored for 2-6 months. Visual Analogic Scale (VAS) and Numerical Rating Scale (NRS) will be used for pain monitoring. The reduction of the risk of occurrence of drug side effects can favour the optimization of elderly patients' care.

Calcium intake, bone mineral density, and fragility fractures: evidence from an Italian outpatient population.

This study was performed in 1000 adult Italian subjects to focus on the effects of dietary calcium intake on bone health. A higher fracture risk appears to be associated with a reduced calcium intake. An adequate daily calcium intake is recommended to counteract osteoporotic fractures. PURPOSE: The principal aim of the present study was to focus on the effects of dietary calcium intake on bone mineral density (BMD) and fragility fractures in a representative sample of an adult Italian outpatient population. METHODS: The study group consisted of 1000 consecutive adult Italian subjects [838 women (F) and 162 men (M)] referred to the Bone Metabolic Diseases Unit for the evaluation of their bone metabolism. Daily dietary calcium intake was assessed using a specific food frequency questionnaire (FFQ). Other evaluations included fracture risk, lumbar and femoral BMD, heel ultrasound, fragility fractures, plasma concentration of parathyroid hormone ([PTH]) and 25-hydroxy-vitamin D ([25(OH)D]), and urinary calcium. RESULTS: Only 10.4% of the subjects (n = 104; 71 F and 33 M) had a daily calcium intake adequate for adults (≥1000 mg/day). No correlation was found between calcium intake and BMD. The transition from a daily dietary calcium intake <400 mg/day to a daily dietary calcium intake ≥400 mg/day was associated with a reduced fracture probability ratio at any site [from 42 to 21% (p < 0.05)]. Subjects with one or more vertebral fractures had a significantly lower dietary calcium intake (<400 mg/day) than did subjects without vertebral fractures, and they practiced physical activity only occasionally (p = 0.030). CONCLUSIONS: Daily dietary calcium intake is lower than the recommended daily intake in an Italian ambulatory population, and a higher fracture risk appears to be associated with a reduced calcium intake. An age-adequate daily calcium intake, combined with regular physical activity, is strongly recommended in order to counteract fragility fractures.

Multiple endocrine neoplasia syndrome type 1: institution, management, and data analysis of a nationwide multicenter patient database.

OBJECTIVE: The aim of this study was to integrate European epidemiological data on patients with multiple endocrine neoplasia type 1 by creating an Italian registry of this syndrome, including clinical and genetic characteristics and therapeutic management. METHODS: Clinical, familial and genetic data of patients with multiple endocrine neoplasia type 1, diagnosed, treated, and followed-up for a mean time of 11.3 years, in 14 Italian referral endocrinological centers, were collected, over a 3-year course (2011-2013), to build a national electronic database. RESULTS: The Italian multiple endocrine neoplasia type 1 database includes 475 patients (271 women and 204 men), of whom 383 patients (80.6%) were classified as familial cases (from 136 different pedigrees), and 92 (19.4%) patients were sporadic cases. A MEN1 mutation was identified in 92.6% of familial cases and in 48.9% of sporadic cases. Four hundred thirty-six patients were symptomatic, presenting primary hyperparathyroidism, gastroenteropancreatic neuroendocrine tumors and pituitary tumors in 93, 53, and 41% of cases, respectively. Thirty-nine subjects, belonging to affected pedigrees positive for a MEN1 mutation, were asymptomatic at clinical and biochemical screening. Age at diagnosis of multiple endocrine neoplasia type 1 probands was similar for both familial and simplex cases (mean age 47.2 ± 15.3 years). In familial cases, diagnosis of multiple endocrine neoplasia type 1 in relatives of affected probands was made more than 10 years in advance (mean age at diagnosis 36.5 ± 17.6 years). CONCLUSIONS: The analysis of Italian registry of multiple endocrine neoplasia type 1 patients revealed that clinical features of Italian multiple endocrine neoplasia type 1 patients are similar to those of other western countries, and confirmed that the genetic test allowed multiple endocrine neoplasia type 1 diagnosis 10 years earlier than biochemical or clinical diagnosis.

Prevalence of osteoporosis in the Italian population and main risk factors: results of BoneTour Campaign.

BACKGROUND: BoneTour is a campaign conducted throughout the Italian territory for the assessment of Italian people bone status and for the prevention of osteoporosis. METHODS: A total of 7305 sequential subjects of both sexes were screened, collecting clinical data through the FRAX™ questionnaire, and measuring heel bone stiffness by Quantitative Ultrasonography (QUS). The 10-year risk for hip and major osteoporotic fractures was calculated taking into account personal or family history of fragility fracture, smoking, alcohol abuse, rheumatoid arthritis, prolonged steroids assumption. Additional risk factors were evaluated, including early menopause, poor sunlight exposure, low dietary calcium intake, physical inactivity, number of pregnancies, months of lactation, tobacco cigarettes smoked per year, specific causes of secondary osteoporosis. Through a correlation study, the influence of each factor on the development of osteoporosis was analyzed. RESULTS: As many as 18 % of women suffer from osteoporosis, as defined by QUS T-score. The calculation of FRAX™ confirmed the weight of the already known risk factors. The correlation study revealed the significance of some additional factors, such as hyperthyroidism, nephrolithiasis, Crohn disease, ulcerative colitis, celiac disease, poor sun exposure, and oophorectomy before age 50. CONCLUSIONS: The high prevalence of secondary osteoporosis in the Italian population clearly indicates the importance of additional risk factors not yet included in the FRAX™ algorithm, for which preventive measures should be considered. Screening campaigns may allow both early diagnosis and access to treatment.

Hip Protectors: Are They Worth it?

Hip fractures are one of the most serious conditions in frail elderly subjects, greatly increasing morbidity and mortality, and decreasing healthy life years. Since their first introduction on the market, hip protectors have been revealed to be a potential preventive measure for hip fractures, in addition to other well-known recognized medical interventions and rehabilitation procedures. However, randomized controlled trials have given contradictory results regarding their efficacy. Moreover, little data are available on the cost effectiveness of hip protectors. Adherence is a major problem in assessing the effectiveness of hip protectors in preventing fractures. Indeed, there is a lack of general consensus on a standard definition and quantitative objective estimation of adherence to hip protectors, along with still scarce evidence on specific interventions on how to ameliorate it. From what is known so far, it seems reasonable to advise the use of hip protectors in aged care facilities, since recent pooled analyses have suggested their efficacy in this setting. The introduction of sensors combined with hip protectors will probably address this issue, both for monitoring and optimizing compliance, especially in elderly people. In the meantime, new, well-designed studies following specific guidelines are strongly encouraged and needed. In particular, studies in community-dwelling elderly individuals at high risk of first or further fragility fractures are required. The optimization of the tested devices in a preclinical setting according to international standard biomechanical testing is necessary.

CYP19 and ESR1 gene polymorphisms: response of the bone mineral density in post-menopausal women to hormonal replacement therapy.

OBJECTIVES: Sex steroids are important regulators of bone physiology and play an essential role in the maintenance of bone health throughout the life. Hormonal replacement therapy (HRT) is a treatment commonly used to relieve symptoms and some undesirable consequences of menopause such as osteoporosis. Osteoporosis, characterized by the loss of bone mass and deterioration of microarchitecture with a consequent higher risk of fragility fractures, is under genetic influence. A tetranucleotide (TTTA)n microsatellite repeat polymorphism, at intron 4 of the CYP19 (aromatase) gene, has been previously associated with higher lumbar spine bone mineral density (LS-BMD) and lower risk of spine fracture in postmenopausal women. Moreover, the ERα encoded by the ESR1 gene is another important candidate for the regulation of bone mass of menopause. Moreover prospective analysis from >18.000 subjects at the GENOMOS study indicated that XX homozygotes genotype had a reduced risk of fracture independently from BMD. In the present study, we investigated in postmenopausal Italian women, at baseline and after 1 year of HRT, whether ESR1 and CYP19 gene polymorphisms could affect BMD through different statistical models. METHODS: This study has been performed on 100 post-menopausal Italian women, from a larger group of 250. The study group was administred HRT and LS-BMD was measured at baseline and after 1 year of therapy. Genetic analysis evaluating ESR1 and CYP19 gene polymorphisms was performed. RESULTS: Generalized Linear Models (GLMs) test showed that women with normal LS-BMD at the baseline had a major statistically significant BMD increase of 0.1426 gr/cm(2) (p= 0.0001) with respect to the osteoporotic patients. In addition, subjects with genotype 1 and 2 of CYP19 gene had a lower modification in LS-BMD after 1 year of HRT (0.0837 gr/cm(2) and 0,076 g/cm(2); p=0.0470 and 0,0547 respectively) when compared to genotype 3. No influences of the aromatase genotypes were observed in the variable difference using both Anova and GLMs test. Regarding the ESR1 gene polymorphism, the LS-BMD after 1 year of HRT was influenced by the diagnosis at the baseline and height and ERα genotypes were able to influence difference with statistical significant results with both test. CONCLUSIONS: In the present study, we have demonstrated that CYP19 gene polymorphism is able to influence the effect of 1 year HRT on LS-BMD with no influence on pre-/ and post-/HRT LS-BMD differences. Although ESR1 gene polymorphism is not able to influence the LS-BMD after 1 year HRT, it influences the observed modifications during the year of therapy. These data underlie the complexity of the genetics of the bone mass and its importance in influencing the response to HRT.

Is calcium signaling relevant for long bone growth?

BACKGROUND: Neonatal severe hyperparathyroidism (NSHPT) is a rare autosomal recessive disorder of calcium homeostasis, more often induced by homozygous inactivating mutations of the calcium-sensing receptor gene. This rare syndrome can be lethal if total parathyroidectomy is not performed within the first weeks of life. CLINICAL REPORT: We report the clinical case of a male patient, son of consanguineous hypercalcemic parents, with clinical and biochemical features of NSHPT, followed until the age of 21 years. The patient underwent total parathyroidectomy, and then, due to the low compliance to calcium and calcitriol supplementation, an attempt was made with recombinant human parathyroid hormone [rhPTH (1-84)]. The patient did not reach the predicted height with an increased ratio of the upper and lower segments. CONCLUSIONS: While this case is unique for the length of follow-up, the continuous and detailed description of NSHPT after total parathyroidectomy in its adult phenotype, and the treatment of hypoparathyroidism with rhPTH (1-84). Following this first description of a statural defect due to shortening of long bones in NSHPT, future investigations will attempt to uncover the role of calcium signaling in growth plate cartilage in humans.

Connections between the outcomes of osteoporotic hip fractures and depression, delirium or dementia in elderly patients: rationale and preliminary data from the CODE study.

BACKGROUND: osteoporosis, depression and other neuro-psychiatric disorders are very common after 50 years of age. Although these conditions recognize several and specific etiologic factors, they however appear to share physiologic, environmental processes and risk factors which may explain their possible association. METHODS: we have built up a specific research project (the CODE study, Connections between the outcomes of osteoporotic hip fractures and depression, delirium or dementia in elderly patients), and carried out a preliminary survey on 55 hip fractured elderly patients (42 women, mean age 85 years old and 13 men, mean age 82 years old), hospitalized at SS. Annunziata hospital in Florence from July to September 2010. RESULTS: there was a significant difference (p=0.010) in the functional recovery after surgery (as measured by Cumulated Ambulation Score, CAS) between depressed and non-depressed subjects (n=38), with a worse recovery and a lower CAS score in depressed patients (n=17). We also observed a higher prevalence of depression in the osteoporotic-fragile elderly people (69,1% of total sample). CONCLUSION: our preliminary survey has validated the suitability of the CODE study protocol in assessing connections between outcomes of osteoporotic hip fractures and depression in elderly patients, fostering the extension of the study (and suggesting also the inclusion of delirium and dementia) within a multicentric prospective study aimed to provide specific information and guidelines for osteoporotic fractured patients with concomitant depression or other neuro-psychiatric disorders.