Misdiagnosis and Mistreatment of a Rare Case of Intracranial Oncogenic Osteomalacia with an Altered Amino Acid Profile.

Background. Oncogenic osteomalacia (OO), also known as tumor-induced osteomalacia (TIO), is a rare paraneoplastic syndrome caused by mesechymal tumors secreting fibroblast growth factor 23 (FGF23). Common in middle age, these tumors are often disclosed by progressive generalized bone pain and muscle weakness, along with an altered biochemical profile. Despite its characteristic presentation, the disease is often underrecognized with delayed onset of surgical or pharmacological intervention that can have serious repercussions on the patients' health and quality of life. Case presentation. We describe the case of a 65-year-old Caucasian man presenting TIO with intracranial and spinal localizations and Fanconi-like aminoaciduria. The condition was misdiagnosed and mistreated for three years, leading to loss of self-sufficiency and depression. Following proper identification, the spinal mass was excised with complete remission of the functional symptoms. As it was not possible to remove the intracranial lesion, the patient was treated conservatively with calcitriol and phosphorous supplements that granted good metabolic control up to the time of a recent follow-up visit (at 5 years). Conclusions. The finding of an altered amino acid profile, not usually reported in these cases, should prompt clinicians to a wider usage of these molecules as suitable candidates for metabolic diseases. In addition to providing central information, they are easy to obtain and inexpensive to analyze. Such determination could help to speed up the diagnostic process, as a long-lasting history of misdiagnosis and mistreatments can lead primarily to clinical worsening, but also to the use of expensive, useless medications with side effects that contribute to poor patient health.

Bone-related polymorphisms and dental status in older men and women. Results of the longitudinal Pro.V.A. study.

BACKGROUND/PURPOSE: Genetics plays a role in the susceptibility to periodontitis and tooth loss. Several studies examined the involvement of polymorphisms in candidate genes. We hypothesize that bone metabolism-related polymorphisms could be associated with the number of remaining teeth. MATERIALS AND METHODS: Participants in the Pro.V.A. longitudinal Study: 3099 Italians (aged 65+ at baseline), 2196 at follow-up 1 (5yrs), 1641 at follow-up 2 (7yrs) underwent detailed interview and clinical-instrumental examination. Subjects, grouped by remaining teeth number (0, 1-7, 8-19, 20+), were genotyped for six different bone-related polymorphisms: collagen type Iα1 (COL1A1, Sp1, Ss alleles, n = 1068), vitamin D receptor (VDR, Fok I, Ff alleles, n = 300), calcitonin receptor (CALCR, Alu I, CT alleles, n = 1430), estrogen receptor alpha (ESR1, Pvu II and Xba I, Pp and Xx alleles, n = 1335 and n = 1324). RESULTS: COL1A1 associated with dental status: ss carriers had reduced incident tooth loss (p < 0.05). The low frequency of this genotype, 3.6% in the whole population, didn't grant sufficient statistical power to other findings, such as the lower prevalence of edentulism, consistent throughout the study. In men, CC genotype of CALCR was associated with higher tooth loss between follow ups (p < 0.05). Biochemical markers of inflammation didn't differ by genotype. Confounders such as diabetes, neoplasms, and smoking hampered the detrimental effect of S allele in the logistic regression analysis (OR = 0.67, 95% CI 0.4-1.0, p = 0.06). CONCLUSION: The present study, demonstrating an association between tooth loss and COL1A1 and -in men- CALCR, contributes to the identification of genes involved in tooth loss and, possibly, susceptibility to periodontitis.

An efficient, fast, and green procedure to quantify α- and ß-acids and xanthohumol in hops and their derived products.

The main precursors of bitter principles of beer are α-acids, followed by ß-acids. Determination of their content in hop cones and their derivatives is an essential part of brewing. HPLC-UV is the preferred technique when a more precise quantification of some specific bitter acids are required. However, current methods do not allow the proper quantification of all the six major α- and ß-acids; furthermore, these multi-step methods generate considerable volumes of chemical waste. In this work, a new UHPLC-UV protocol was developed and compared side-by-side with reference, considering traditional and sustainability parameters. Baseline separations were achieved for the six major bitter acids and xanthohumol, while a greener and faster sample preparation procedure was developed. The new validated procedure could be adopted for quality control of hops and their derivative products with enhanced sample throughput and with a potential gain in the safety of the analyst.

Tryptophan Metabolites, Cytokines, and Fatty Acid Binding Protein 2 in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome.

Patients with Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) differ for triggers, mode of start, associated symptoms, evolution, and biochemical traits. Therefore, serious attempts are underway to partition them into subgroups useful for a personalized medicine approach to the disease. Here, we investigated clinical and biochemical traits in 40 ME/CFS patients and 40 sex- and age-matched healthy controls. Particularly, we analyzed serum levels of some cytokines, Fatty Acid Binding Protein 2 (FAPB-2), tryptophan, and some of its metabolites via serotonin and kynurenine. ME/CFS patients were heterogeneous for genetic background, trigger, start mode, symptoms, and evolution. ME/CFS patients had higher levels of IL-17A (p = 0.018), FABP-2 (p = 0.002), and 3-hydroxykynurenine (p = 0.037) and lower levels of kynurenine (p = 0.012) and serotonin (p = 0.045) than controls. Changes in kynurenine and 3-hydroxykynurenine were associated with increased kynurenic acid/kynurenine and 3-hydroxykynurenine/kynurenine ratios, indirect measures of kynurenine aminotransferases and kynurenine 3-monooxygenase enzymatic activities, respectively. No correlation was found among cytokines, FABP-2, and tryptophan metabolites, suggesting that inflammation, anomalies of the intestinal barrier, and changes of tryptophan metabolism may be independently associated with the pathogenesis of the disease. Interestingly, patients with the start of the disease after infection showed lower levels of kynurenine (p = 0.034) than those not starting after an infection. Changes in tryptophan metabolites and increased IL-17A levels in ME/CFS could both be compatible with anomalies in the sphere of energy metabolism. Overall, clinical traits together with serum biomarkers related to inflammation, intestine function, and tryptophan metabolism deserve to be further considered for the development of personalized medicine strategies for ME/CFS.

Tooth retention predicts good physical performance in older adults.

BACKGROUND: Oral health is closely related to both physical and psychological well-being, as it enables individuals to eat, speak, and socialize. The number of teeth is the most used indicator of oral health. Several reports document a relationship of dental status with a variety of indicators of general health but longitudinal studies employing standardized physical performance tests are infrequent in the scientific literature. SUBJECTS AND METHODS: The Italian elderly participating in the Pro.V.A. longitudinal Study (3099 subjects aged 65+ at baseline, 2196 at the 5-year follow-up 1 and 1641 at the 7-year follow- up 2) underwent detailed interview and extensive clinical and instrumental examination that included validated physical performance measures. Participants were classified into 4 groups according to the number of remaining teeth: 0, 1-7, 8-19, and 20+. To explore the association of the number of remaining teeth with physical function and disability, we performed logistic regression analyses with models progressively adjusted for a wide number of covariates, namely anthropometric (gender, age, BMI), comorbidity (cardio-vascular, osteoarticular, and neurological diseases including depression), muscle strength (assessed for upper and lower limbs), lifestyle (smoking status, alcohol use, leisure time activities) and socioeconomical status (education, income, marital status, loneliness). RESULTS: Dental status correlated with most comorbidities, lifestyle, and socio-economic variables at the univariate analysis at baseline and at follow-ups. A good dental status was significantly associated with better physical functioning and lower disability. The presence of 20+ teeth resulted significantly protective (reference group: 0 teeth) versus mobility-related disability (OR = 0.67), disability (OR = 0.54) and inability to perform heavy duties (OR = 0.62), at follow up 1 and low physical performance score (OR = 0.59) at follow up 2. Conversely, the detrimental effect of edentulism, explored in subjects with or without dentures, was present but not as straightforward. Conclusion. The assessment of a geriatric patient should include an oral evaluation as a good dental status is a crucial component of successful aging.

Sperm Count and Hypogonadism as Markers of General Male Health.

BACKGROUND: Some evidence suggests that infertile men, who are at increased risk for hypogonadism, metabolic derangements, and osteoporosis, have higher long-term morbidity and mortality than controls, but data are scarce and not conclusive. OBJECTIVE: We tested whether semen quality and reproductive function could represent a marker of general male health. DESIGN, SETTING, AND PARTICIPANTS: A retrospective study of 5177 individuals from a prospectively collected database of 11516 males of infertile couples who had semen analysis in a tertiary university center. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Of them, 5177 had all data for reproductive hormones, testis ultrasound, and biochemical determinations for glucose and lipid metabolism. Hypogonadism was defined as testosterone <10.5nmol/l and/or luteinizing hormone >9.4 IU/l. Individuals with a total sperm count of <10 million had genetic testing (karyotype, Y chromosome microdeletions, and CFTR gene mutations) and those with hypogonadism underwent dual-energy x-ray absorptiometry for bone mineral density. Descriptive statistics and odds ratio (OR) calculation were used. RESULTS AND LIMITATIONS: Men with a low sperm count (<39 million/ejaculate) are at a high risk of hypogonadism (OR 12.2, 95% confidence interval [CI] 10.2-14.6) and have higher body mass index, waist circumference, systolic pressure, low-density lipoprotein cholesterol, triglycerides, and homeostatic model assessment (HOMA) index; lower high-density lipoprotein cholesterol; and a higher prevalence of metabolic syndrome (OR 1.246, 95 CI 1.005-1.545). All data are worse in men with hypogonadism, but a low sperm count per se is associated with a poor metabolic parameter. Men with hypogonadism have lower bone mineral density and 51% prevalence of osteoporosis/osteopenia. Longitudinal studies are necessary to support these data. CONCLUSIONS: This is the largest study with comprehensive evaluation of semen quality and reproductive function, etiology and risk factor determination, and metabolic, cardiovascular, and osteoporosis risk assessment, performed in men referred for fertility evaluation. A low sperm count is associated with poorer metabolic, cardiovascular, and bone health. Hypogonadism is mainly involved in this association, but a low sperm count in itself is a marker of general health. PATIENT SUMMARY: This large study evaluated semen quality, reproductive function, and metabolic risk in men referred for fertility evaluation, and showed that a man's semen count is a marker of his general health. Men with low sperm counts are more likely than those with normal sperm counts to have greater body fat, higher blood pressure, higher "bad" (low-density lipoprotein) cholesterol and triglycerides, and lower "good" (high-density lipoprotein) cholesterol. They also have a higher frequency of metabolic syndrome and insulin resistance, a condition that can lead to diabetes. Men with low sperm counts had a 12-fold increased risk of hypogonadism or low testosterone levels, and half of them had osteoporosis or low bone mass. Fertility evaluation gives men the unique opportunity for health assessment and disease prevention.

Parathyroidectomy Resolves Tooth Discoloration: A New Presenting Sign of Hyperparathyroidism?

INTRODUCTION: We report the resolution of tooth discoloration following parathyroidectomy in an otherwise asymptomatic woman with primary hyperparathyroidism-associated hypercalcemia. Case Report. A 59-year-old Caucasian woman, diagnosed with primary hyperparathyroidism in 2011, nonsmoker with excellent overall oral health. She complained of tooth discoloration starting in 2013. Pigmentation was particularly evident in the necks of the lower central and lateral incisors (Vita Classical score C2). No bleaching was undertaken. Parathyroidectomy was performed five years after primary hyperparathyroidism diagnosis. Six months later, a reduction in pigmentation was strikingly evident, with incisors scoring A1 and A2. The improvement persisted over time. Tooth value also increased compared to baseline. CONCLUSIONS: This is, to our knowledge, the first report that parathyroidectomy might resolve dental discoloration. This outcome deserves investigation in a meaningful sample size and may eventually prompt the inclusion of dental issues among the consequences of primary hyperparathyroidism.

Zoledronic acid for the treatment of pregnancy-associated femoral head necrosis: A case report.

INTRODUCTION: The management of pregnancy-associated femoral necrosis is controversial. Conservative management may eventually lead to hip replacement. CASE: A 40-year-old woman developed necrosis of the left hip during her first pregnancy. Treatment with zoledronic acid three months after delivery resulted in rapid reduction of the necrotic area. The patient's second pregnancy shortly afterwards had no complications. A magnetic resonance scan three years later documented complete resolution. CONCLUSION: Femoral head necrosis should be suspected in the differential diagnosis of pain in pregnancy. Zoledronic acid given in the early stages prevented progression to hip arthritis in this case.

Assessment of bone mineral density in patients with cirrhosis treated with third-generation nucleos(t)ide analogues: comparison between tenofovir and entecavir.

BACKGROUND AND AIM: Tenofovir and entecavir are nowadays the first-line treatment in hepatitis B virus (HBV)-related cirrhosis. Both drugs were shown to be effective in HBV suppression and well tolerated. The effects of tenofovir on bone mineral density (BMD), however, were shown to worsen the rate of osteoporosis, which is already a common feature in cirrhosis. In contrast, entecavir seems to have no effect on mineral metabolism. The aim of our study was to compare the effects of nucleos(t)ide analogs on bone density in HBV-related cirrhosis. PATIENTS AND METHODS: Fourty-eight patients were treated with tenofovir and 22 patients were treated with entecavir, and were followed prospectively from 2008 to 2013. To evaluate BMD, laboratory examinations, dual-X-ray absorptiometry, and Fracture Risk Assessment Tool were assessed. RESULTS: During the study, no difference was found between the two groups in the plasmatic concentration of calcium, phosphate, vitamin D, parathyroid hormone, or creatinine. Dual-X-ray absorptiometry showed no difference in the T-score and Fracture Risk Assessment Tool showed no significant difference in the 10-year risk of osteoporotic fractures in the two groups. On univariate and multivariate analyses, the only predictors of osteoporosis development were the prognostic scores of liver disease and BMI. CONCLUSION: Both tenofovir and entecavir are effective in treating HBV in cirrhotic patients. The known effects of tenofovir on BMD do not worsen osteoporotic fractures risk compared with entecavir in these patients.

The effect of childcare activities on cognitive status and depression in older adults: gender differences in a 4.4-year longitudinal study.

OBJECTIVES: Although involvement in childcare activities seems to promote better physical and mental health in older adults, its impact on cognitive status and depression has not yet been fully elucidated. We aimed to analyze the association between engagement in childcare activities and cognitive and psychological status over a 4.4-year period in community-dwelling older adults. METHODS: Two thousand one hundred four subjects older than 65 years without severe cognitive impairment at baseline were categorized according to the frequency of their involvement in childcare activities (everyday, occasionally, never). The participants' cognitive status and depressive symptoms were evaluated at baseline and after 4.4 years. RESULTS: During the follow-up, 269 (12.8%) new cases of cognitive impairment and 229 (10.9%) new cases of depression were registered. Men engaged in childcare showed an almost 20% lower risk of cognitive impairment and cognitive decline. Women demonstrated similar results, except for those occasionally involved in childcare, who had a higher risk of cognitive decline compared with women who never engaged in it. The risk of developing depression was reduced in men involved daily (OR = 0.44, 95% CI: 0.30-0.62, p < 0.0001) and occasionally in childcare, who also demonstrated a lower risk of exacerbating depressive symptoms compared with subjects who never involved in it. The onset of depression was reduced in women occasionally engaged in childcare (OR = 0.68, 95% CI: 0.56-0.82, p < 0.0001), but not significantly in those daily involved in it. CONCLUSIONS: Involvement of older adults in childcare activities seems to lower the risk of cognitive impairment in both genders and to prevent onset or worsening of depression particularly in older men. Copyright © 2017 John Wiley & Sons, Ltd.

Poor Physical Performance Predicts Future Onset of Depression in Elderly People: Progetto Veneto Anziani Longitudinal Study.

BACKGROUND: Reduced physical performance is predictive of deleterious outcomes in older adults. Data considering objective physical performance and incident depression are sparse. OBJECTIVE: The objective of this study was to investigate during a 4-year study whether objective physical performance can predict incident depression among older adults who do not have depression at the baseline. DESIGN: This was a longitudinal study. METHODS: From 3,099 older people initially enrolled in the Progetto Veneto Anziani study, 970 participants without depression at the baseline were included (mean age = 72.5 years; 54.6% women). Physical performance measures included the Short Physical Performance Battery, 4-m gait speed, Five-Times Sit-to-Stand test, leg extension and flexion, handgrip strength, and 6-minute walk test, categorized in sex-specific tertiles. Depression was classified on the basis of the Geriatric Depression Scale and a diagnosis from a geriatric psychiatrist. Area under the curve and logistic regression analyses were conducted. RESULTS: At the baseline, participants developing depression during the follow-up (n = 207) scored significantly worse across all physical performance measures than those who did not develop depression. The area under the curve and predictive power were similar for all of the physical performance tests assessed. In the logistic regression analysis, after adjustment for 14 potential confounders, worse physical performance across all tests increased the risk of depression. Participants in the lowest tertile of the Short Physical Performance Battery were at notable odds of developing depression (odds ratio = 1.79; 95% CI = 1.18-2.71). The association between poor physical performance and depression was typically stronger in women than in men, except for 4-m gait speed. LIMITATIONS: No gold standard was used for a depression diagnosis; oxidative stress and inflammatory markers were not included; and there was a high rate of missing data at the follow-up. CONCLUSIONS: Low physical performance appeared to be an independent predictor of depression over a 4-year follow-up in a sample of elderly people.

Anthropometric parameters and the incidence of atrial fibrillation in older people: the PRO.V.A study.

BACKGROUND: Atrial fibrillation (AF) has been associated with body size and central obesity, but the impact of different anthropometric measures in this relationship has been inadequately investigated. HYPOTHESIS: In this study, we examined the association between baseline anthropometric parameters with the incidence of AF in older people, hypothesizing that body size could impact the onset of AF more than fat distribution. METHODS: Our study included 1764 participants with a mean age of 74.3 ± 6.9 years and no AF at baseline. Body mass index (BMI), body height, body surface area (BSA), waist and hip circumference, waist-to-stature ratio, waist-to-hip ratio, and mid-upper arm circumference (MUAC) were measured by trained physicians. AF was assessed after a 4.4-year follow-up. RESULTS: There were 115 new cases of AF observed after the follow-up. Taking lower values of these measures for reference, the adjusted AF risk was 2.42 (95% confidence interval [CI]:1.88-3.12) for the highest stature quartile, 1.36 (95% CI:1.15-1.62) for BMI ≥30 kg/m2 , 2.12 (95% CI:1.73-2.59) for the highest BSA quartile, 1.38 (95% CI: 1.21-1.56) for higher MUAC, and 1.39 (95% CI: 1.23-1.58, P < 0.0001) for higher hip circumference values. Central obesity did not seem to relevantly predict the onset of AF in our sample. Stature revealed the strongest impact on the onset of AF (5% higher risk of developing AF per 1 cm increase in height). CONCLUSIONS: Body size, particularly tall stature and obesity, but not fat distribution, seems to be associated with the risk of AF in the elderly.

Hyperuricemia, Cardiovascular Profile, and Comorbidity in Older Men and Women: The Pro.V.A. Study.

Hyperuricemia (HU) is growing worldwide and associates with several medical conditions in the elderly. However, data about older people and possible gender differences are sparse. The aim of this study was to compare HU prevalence rates and association with relevant medical disorders in elderly subjects of both sexes. Pro.V.A. is a survey of 3099 individuals aged 65+, focusing on chronic diseases and disability. Uric acid (UA) levels were dichotomized using 6.0 mg/dL (females) and 7.0 mg/dL (males), and multivariate logistic regression models were used to estimate odds ratios (ORs) between HU and single comorbidity. HU prevalence was 21.5% in females and 15.8% in males. HU was associated with most anthropometric and laboratory variables in women, but not in men. After adjustment for age, body mass index, and renal function, HU was independently associated with the presence of cardiovascular diseases in both sexes. In women, HU was associated with hand osteoarthritis (OR = 1.52; 95%CI: 1.12-2.08) and edentulism (OR = 1.31; 95%CI: 1.01-1.71), while resulted protective for osteoporosis (OR = 0.69; 95%CI: 0.53-0.91). In men, HU was significantly related with knee osteoarthritis (OR = 1.72; 95%CI: 1.06-2.79) and chronic obstructive pulmonary disease (OR = 1.60; 95%CI: 1.04-2.45). The presence of ≥4 comorbidities was a stronger determinant of HU in men (OR = 2.54; 95%CI: 1.21-5.37) than in women (ns). Patterns of age-dependent UA increase are markedly different in men and women. HU prevalence is substantial and its association with other diseases is gender specific, connoting a peculiar clinical profile.

A Comparison of Objective Physical Performance Tests and Future Mortality in the Elderly People.

Background: Physical performance is an important predictor of mortality, but little is known on the comparative prognostic utility of different objective physical performance tests in community-dwelling older adults. We compared the prognostic usefulness of several objective physical performance tests on mortality, adjusting our analyses for potential confounders. Methods: Among 3,099 older community-dwelling participants included in the Progetto Veneto Anziani study, 2,096 were followed for a mean of 4.4 years. Physical performance tests measured were Short Physical Performance Battery (SPPB), 4-meter gait speed, chair stands time, leg extension and flexion, handgrip strength, and 6-Minute Walking Test (6MWT), treated as continuous variables and categorized in gender-specific quartiles. The main outcome was mortality assessed with death certificates. Results: Participants who died during the follow-up (n = 327) scored significantly worse in all physical performance tests measured at baseline than those who survived (n = 1,769). Using a Harrell's C-index, the highest C-index was observed for 6MWT in men (C-index = 0.735; 95% confidence interval [CI]: 0.701-0.770, p < .0001) and SPPB in women (C-index = 0.781; 95% CI: 0.740-0.822, p = .0009). However, in both genders, only SPPB, 4-meter walking speed, and 6MWT are significant predictors of mortality. Analyses using sex-specific quartiles substantially confirmed these findings. Conclusions: Slow gait speed, 6MWT, and SPPB are significant predictors for mortality in community-dwelling older men and women. Physicians should consider using these tests to identify elderly individuals who are at higher risk of death to improve clinical decision making.

Results of an Observational Cohort Study of Hyperuricemia as a Predictor of Poor Physical Performance in the Elderly.

OBJECTIVE: Hyperuricemia is frequent in older people and associated with several medical conditions. The relationship between hyperuricemia and physical performance is limited. We aimed to investigate the association between hyperuricemia and physical performance over a 4.4-year followup in the elderly. METHODS: A total of 1,904 community-dwelling older participants were followed for a mean of 4.4 years. Hyperuricemia at baseline was defined using serum uric acid concentrations ≥6 and ≥7 mg/dl for women and men, respectively. Objective physical performance tests measured included the Short Physical Performance Battery (SPPB), 4-meter gait speed, chair-stands time, leg extension and flexion, handgrip strength, and the 6-minute walking test. RESULTS: At baseline, participants with hyperuricemia (n = 98 men, 232 women) scored significantly worse in all the tests investigated. After adjusting for 19 covariates, men with hyperuricemia at baseline had an increased risk of having poor SPPB scores at followup (odds ratio [OR] 1.44 [95% confidence interval (95% CI) 1.21-1.72]; P < 0.0001), poor chair-stands time (OR 1.40 [95% CI 1.18-1.6]; P < 0.0001), poor leg extension (OR 1.47 [95% CI 1.21-1.7]; P < 0.0001), and poor handgrip strength (OR 1.54 [95% CI 1.24-1.90]; P < 0.0001). Among women, hyperuricemia was associated with an increased risk of having poor scores in all the SPPB items and in leg flexion (OR 1.26 [95% CI 1.08-1.49]; P = 0.03). CONCLUSION: Hyperuricemia seems to be significantly associated with poor physical performance in older people, over a followup of 4.4 years. The relationship appears to be more consistent in men than in women. Further longitudinal research is required to better understand the relationships and potential biologic pathways.

Factors Influencing Transitions Between Frailty States in Elderly Adults: The Progetto Veneto Anziani Longitudinal Study.

OBJECTIVES: To investigate frailty state transitions in a cohort of older Italian adults to identify factors exacerbating or improving frailty conditions. DESIGN: Population-based longitudinal study with mean follow-up of 4.4 years. SETTING: Community. PARTICIPANTS: Individuals enrolled in the Progetto Veneto Anziani (Pro.V.A.) (N = 2,925; n = 1,179 male, n = 1,746 female; mean age 74.4 ± 7.3). MEASUREMENTS: Frailty was identified at baseline and follow-up based on the presence of at least three Fried criteria; prefrailty was defined as the presence of one or two Fried criteria. Anthropometric, socioeconomic, and clinical characteristics were assessed at baseline in a personal interview and clinical examination using validated scales and medical history. RESULTS: During the study period, 1,114 (38.1%) subjects retained their baseline frailty status, 1,066 (36.4%) had a transition in frailty status, and the remainder of the sample died. Older age, female sex, obesity, cardiovascular disease, osteoarthritis, smoking, loss of vision, low levels of self-sufficiency and physical performance, cognitive impairment, hypovitaminosis D, hyperuricemia, and polypharmacy were associated with increasing frailty and greater mortality. Conversely, overweight, low to moderate drinking, high educational level, and living alone were associated with decreasing frailty. CONCLUSIONS: Frailty was confirmed as a dynamic syndrome, with socioeconomic and clinical factors that could be targets of preventive actions influencing transitions to better or worse frailty status.

Pain Increases the Risk of Developing Frailty in Older Adults with Osteoarthritis.

Objective: While osteoarthritis (OA)-related pain increases the risk of physical inactivity, disability, and falls, less is known about whether pain increases the risk of frailty. We investigated if people with OA reporting pain are more likely to develop frailty than people with OA without pain. Design: Population-based prospective cohort study with a follow-up of 4.4 years. Setting: Community. Subjects: The subjects were 1,775 older men and women with osteoarthritis, enrolled in the Progetto Veneto Anziani. Methods: Pain was ascertained according to medical records, symptoms/signs, and use of analgesics. Participants were considered frail if they met three out of five criteria of Fried's Index. Results: Cross-sectional analysis at baseline demonstrated that after adjusting for potential confounders (age, gender, anthropometric and demographic data, comorbidities), people with OA and pain (n = 568) were significantly more likely to have frailty compared with those with OA without pain (n = 1,207; hand OA, OR = 1.86, 95% CI = 1.65-2.09; hip OA, OR = 1.62, 95% CI = 1.44-1.83; knee OA, OR = 1.42, 95% CI = 1.26-1.60; all p < 0.0001). Prospective analysis of 1,152 nonfrail subjects at baseline demonstrated that 19.9% developed incident frailty. A fully-adjusted logistic regression analysis demonstrated that lower limb OA-related pain was associated with an increased risk of developing frailty compared with people with OA and no pain. Conclusions: Pain related to OA might be an important factor influencing the relationship between OA and the development of frailty.

Low Hemoglobin Levels and Risk of Developing Depression in the Elderly: Results From the Prospective PRO.V.A. Study.

OBJECTIVE: Low hemoglobin negatively affects health in the elderly, but research about the association with risk for depression is limited. We investigated the association between baseline hemoglobin concentrations and incident depression in a cohort of nondepressed elderly individuals. METHODS: As part of the Northern Italian Progetto Veneto Anziani (PRO.V.A.) study, randomly drawn, community-dwelling subjects aged ≥ 65 years underwent prospective clinical and laboratory assessments between October 1995 and December 2002. The association between baseline hemoglobin and depression was assessed with adjusted Cox regression analyses. Baseline serum hemoglobin concentrations were further categorized in gender-specific tertiles; anemia was defined as serum hemoglobin < 13 g/dL for men and < 12 g/dL for women. Moreover, hemoglobin concentration was measured at follow-up, and changes in concentration from baseline to follow-up were investigated. Depression was defined by a score of ≥ 11/30 on the validated Geriatric Depression Scale and confirmed by psychogeriatric specialists. RESULTS: Among 1,303 elderly individuals (566 men, 737 women) without depression at baseline, 294 subjects (177 women, 117 men; global incidence rate = 50 [95% confidence interval (CI), 0-170] per 1,000 patient years) developed depression during 4.4 years of follow-up. Low baseline serum hemoglobin concentration was most strongly associated with incident depression at follow-up in men (hazard ratio [HR] = 1.39; 95% CI, 1.12-1.69; P = .002), but not in women (P = .50). Men with the lowest baseline tertile hemoglobin concentration (HR = 1.68; 95% CI, = 1.02-3.08; P = .04) or with anemia (HR = 2.02; 95% CI, = 1.13-3.64; P = .02) had greater risk of depression, whereas findings were nonsignificant for women. Low follow-up hemoglobin concentration in men was less strongly associated with incident depression (HR = 1.15; 95% CI, 1.01-1.33; P = .05), as were the lowest endpoint tertile hemoglobin concentration (P = .03) and presence of anemia (P = .05). CONCLUSIONS: Low baseline hemoglobin strongly predicted incident depression in older men, but not in women.​.

Use of Zoledronic Acid in Paediatric Craniofacial Fibrous Dysplasia.

We describe a case of a paediatric patient affected by mandibular fibrous dysplasia (FD) with severe and chronic pain who was successfully treated with zoledronic acid (ZOL): a third-generation bisphosphonate. Further research is needed to assess its safety and efficacy as a treatment option for FD in the paediatric population.

Hypovitaminosis D predicts the onset of orthostatic hypotension in older adults.

A number of small cross sectional studies have demonstrated that hypovitaminosis D (represented by low 25 hydroxyvitamin D (25OHD) levels) is associated with orthostatic hypotension (OH). We investigated if hypovitaminosis D is associated with the onset of OH in older adults over a follow-up of 4.4 years. 25OHD was categorized using sex-specific quartiles; OH was defined as a drop of ≤20 mm Hg in systolic or ≤10 mm Hg in diastolic blood pressure <3 minutes of standing. Among 1308 elderly without OH at baseline, using an adjusted logistic regression analysis and taking those with higher baseline serum 25OHD as reference, there was a significant increase in the onset of OH in those with lower serum 25OHD levels. The association was significant only in women when we stratified by sex. In conclusion, hypovitaminosis D predicts the onset of OH in older adults, particularly in women.