Long-term effects of COVID-19 pandemic on physical activity and eating behaviour of the Italian population: a longitudinal study.

BACKGROUND: Restrictive measures due to the Covid-19 pandemic strongly impacted lifestyle and daily behaviour. The purpose of this longitudinal retrospective study was to investigate short-term and long-term effects of Covid-19 pandemic on physical activity and eating habits of the Italian population investigating three time periods: pre-, during- and post-lockdown. METHODS: A sample of 2773 adults recruited through social media provided data by an online survey administered from July to October 2023. Participants completed the International Physical Activity Questionnaire-Short Form (IPAQ-SF), the Mediterranean Diet Adherence Screener (MEDAS) and provided information about eating habits, socio-demographic and anthropometric characteristics. RESULTS: There was a significant increase (p < 0.001) in mean BMI from pre-pandemic period (24.53 ± 5.34 Kg/m2) to post-pandemic period (25.22 ± 6.0 Kg/m2). Physical Activity significantly decreased during the pandemic period compared to the pre-pandemic period (χ² = 271.97; p < 0.001; φ = 0.31) with an increase in inactive subjects from 25.7% to 52.8%. In the post pandemic period, there was an increase in the level of Physical Activity compared to the pandemic period (χ² = 413.61; p < 0.001; φ = 0.39) with a reduction of inactive subjects from 52.8% to 25.6%. Adherence to Mediterranean Diet score significantly (p < 0.001) increase from pre-pandemic (7.18 ± 1.58) to during-pandemic (7.29 ± 1.69) and post-pandemic (7.75 ± 1.63) periods with significant differences emerged in the consumption of single MEDAS items during the pandemic period by different BMI classes. Consumption of seasonal fruit and vegetables, water intake, the preparation/consumption of traditional or local dishes and the time dedicated for dinner and lunch significant increase (p < 0.001) during pandemic. CONCLUSIONS: The Covid-19 pandemic changed people's lifestyles, but in different ways for Physical Activity and diet. During the pandemic there was a negative effect for PA that decreased while the time spent sitting increased. This seems to be a temporary effect as, after the end of the phase of mandatory restrictions, it returns to the original level. The lockdown period improved the quality of the Italian population's eating habits, with an increase in adherence to the Mediterranean diet even after the end of the pandemic showing a rediscovery of traditional dishes, increase in consumption of seasonal products, greater preference for local products and more time spent preparing meals.

Bone-active drugs in premenopausal women with breast cancer under hormone-deprivation therapies.

BACKGROUND: Bone health management in premenopausal women with breast cancer (BC) under hormone-deprivation therapies (HDTs) is often challenging, and the effectiveness of bone-active drugs is still unknown. METHODS: This retrospective multicenter study included 306 premenopausal women with early BC undergoing HDTs. Bone mineral density (BMD) and morphometric vertebral fractures (VFs) were assessed 12 months after HDT initiation and then after at least 24 months. RESULTS: After initial assessment, bone-active drugs were prescribed in 77.5% of women (151 denosumab 60 mg/6 months, 86 bisphosphonates). After 47.0 ± 20.1 months, new VFs were found in 16 women (5.2%). Vertebral fracture risk was significantly associated with obesity (odds ratio [OR] 3.87, P = .028), family history of hip fractures or VFs (OR 3.21, P = .040], chemotherapy-induced menopause (OR 6.48, P < .001), preexisting VFs (OR 25.36, P < .001), baseline T-score less than or equal to -2.5 standard deviation (SD) at any skeletal site (OR 4.14, P = .036), and changes at lumbar and total hip BMD (OR 0.94, P = .038 and OR 0.88, P < .001, respectively). New VFs occurred more frequently in women untreated compared to those treated with bone-active drugs (14/69, 20.8% vs 2/237, 0.8%; P < .001) and the anti-fracture effectiveness remained significant after correction for BMI (OR 0.03; P < .001), family history of fractures (OR 0.03; P < .001), chemotherapy-induced menopause (OR 0.04; P < .001), and preexisting VFs (OR 0.01; P < .001). CONCLUSIONS: Premenopausal women under HDTs are at high risk of VFs in relationship with high BMI, densitometric diagnosis of osteoporosis, preexisting VFs, and family history of osteoporotic fractures. Vertebral fractures in this setting might be effectively prevented by bisphosphonates or denosumab.

Nutrition, Vitamin D, and Calcium in Elderly Patients before and after a Hip Fracture and Their Impact on the Musculoskeletal System: A Narrative Review.

Hip fractures are a major health issue considerably impacting patients' quality of life and well-being. This is particularly evident in elderly subjects, in which the decline in bone and muscle mass coexists and predisposes individuals to fall and fracture. Among interventions to be implemented in hip fractured patients, the assessment and management of nutritional status is pivotal, particularly in subjects older than 65. Nutrition plays a central role in both primary and secondary preventions of fracture. An adequate protein intake improves muscle mass and strength and the intestinal absorption of calcium. Other nutrients with recognized beneficial effects on bone health are calcium, vitamins D, K, and C, potassium, magnesium, folate, and carotenoids. With reference to calcium, results from longitudinal studies showed that the consumption of dairy foods has a protective role against fractures. Moreover, the most recent systematic reviews and meta-analyses and one umbrella review demonstrated that the combination of calcium and vitamin D supplementation significantly reduces hip fracture risk, with presumed higher efficacy in older and institutionalized subjects. Owing to these reasons, the adequate intake of calcium, vitamin D, protein, and other macro and micronutrients has been successfully implemented in the Fracture Liaison Services (FLSs) that represent the most reliable model of management for hip fracture patients. In this narrative review, papers (randomized controlled trials, prospective and intervention studies, and systematic reviews) retrieved by records from three different databases (PubMed, Embase, and Medline) have been analyzed, and the available information on the screening, assessment, and management of nutritional and vitamin D status and calcium intake in patients with hip fractures is presented along with specific prevention and treatment measures.

Organ Neuroprosthetics: Connecting Transplanted and Artificial Organs with the Nervous System.

Implantable neural interfaces with the central and peripheral nervous systems are currently used to restore sensory, motor, and cognitive functions in disabled people with very promising results. They have also been used to modulate autonomic activities to treat diseases such as diabetes or hypertension. Here, this study proposes to extend the use of these technologies to (re-)establish the connection between new (transplanted or artificial) organs and the nervous system in order to increase the long-term efficacy and the effective biointegration of these solutions. In this perspective paper, some clinically relevant applications of this approach are briefly described. Then, the choices that neural engineers must implement about the type, implantation location, and closed-loop control algorithms to successfully realize this approach are highlighted. It is believed that these new "organ neuroprostheses" are going to become more and more valuable and very effective solutions in the years to come.

Italian Guidelines for the Management of Sporadic Primary Hyperparathyroidism.

AIM: This guideline (GL) is aimed at providing a clinical practice reference for the management of sporadic primary hyperparathyroidism (PHPT) in adults. PHPT management in pregnancy was not considered. METHODS: This GL has been developed following the methods described in the Manual of the Italian National Guideline System. For each question, the panel appointed by Associazione Medici Endocrinology (AME) and Società Italiana dell'Osteoporosi, del Metabolismo Minerale e delle Malattie dello Scheletro (SIOMMMS) identified potentially relevant outcomes, which were then rated for their impact on therapeutic choices. Only outcomes classified as "critical" and "important" were considered in the systematic review of evidence. Those classified as "critical" were considered for the clinical practice recommendations. RESULTS: The present GL provides recommendations about the roles of pharmacological and surgical treatment for the clinical management of sporadic PHPT. Parathyroidectomy is recommended in comparison to surveillance or pharmacologic treatment in any adult (outside of pregnancy) or elderly subject diagnosed with sporadic PHPT who is symptomatic or meets any of the following criteria: • Serum calcium levels >1 mg/dL above the upper limit of normal range. • Urinary calcium levels >4 mg/kg/day. • Osteoporosis disclosed by DXA examination and/or any fragility fracture. • Renal function impairment (eGFR <60 mL/min). • Clinic or silent nephrolithiasis. • Age ≤50 years. Monitoring and treatment of any comorbidity or complication of PHPT at bone, kidney, or cardiovascular level are suggested for patients who do not meet the criteria for surgery or are not operated on for any reason. Sixteen indications for good clinical practice are provided in addition to the recommendations. CONCLUSION: The present GL is directed to endocrinologists and surgeons - working in hospitals, territorial services or private practice - and to general practitioners and patients. The recommendations should also consider the patient's preferences and the available resources and expertise.

The sequential antifracturative treatment: a meta-analysis of randomized clinical trials.

Background: Subjects with a fragility fracture have an increased risk of a new fracture and should receive effective strategies to prevent new events. The medium-term to long-term strategy should be scheduled by considering the mechanisms of action in therapy and the estimated fracture risk. Objective: A systematic review was conducted to evaluate the sequential strategy in patients with or at risk of a fragility fracture in the context of the development of the Italian Guidelines. Design: Systematic review and meta-analysis. Data sources and methods: PubMed, Embase, and the Cochrane Library were investigated up to February 2021 to update the search of a recent systematic review. Randomized clinical trials (RCTs) that analyzed the sequential therapy of antiresorptive, anabolic treatment, or placebo in patients with or at risk of a fragility fracture were eligible. Three authors independently extracted data and appraised the risk of bias in the included studies. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation methodology. Effect sizes were pooled in a meta-analysis using fixed-effects models. The primary outcome was the risk of refracture, while the secondary outcome was the bone mineral density (BMD) change. Results: In all, 17 RCTs, ranging from low to high quality, met our inclusion criteria. A significantly reduced risk of fracture was detected at (i) 12 or 24 months after the switch from romosozumab to denosumab versus placebo to denosumab; (ii) 30 months from teriparatide to bisphosphonates versus placebo to bisphosphonates; and (iii) 12 months from romosozumab to alendronate versus the only alendronate therapy (specifically for vertebral fractures). In general, at 2 years after the switch from anabolic to antiresorptive drugs, a weighted BMD was increased at the lumbar spine, total hip, and femoral neck site. Conclusion: The Task Force formulated recommendations on sequential therapy, which is the first treatment with anabolic drugs or 'bone builders' in patients with very high or imminent risk of fracture.

A systematic review to evaluate the sequential therapy of antiresorptive (denosumab and bisphosphonate, such as alendronate, minodronate, risedronate, and etidronate), anabolic treatment (such as romosozumab, teriparatide), or placebo in patients with or at risk of a fragility fracture in the context of the development of the Italian Guidelines Subjects with previous fragility fractures should promptly receive effective strategies to prevent the risk of subsequent events. Indeed, patients with a fragility fracture have a doubled risk of a new fracture. For this reason, it is essential to provide adequate sequential therapy based on the mechanisms and the rapidity of action. A systematic review was performed to identify the sequential strategy in patients at high- or imminent-risk of (re)fracture and to support the Panel of the Italian Fragility Fracture Guideline in formulating recommendations. Our systematic review included seventeen studies mostly focused on women and enabled us to strongly recommend the anabolic drugs as first-line treatment. Specifically, for the sequential therapy from anabolic to antiresorptive treatment, there was a significant reduction in the risk of different types of fractures after the switch from romosozumab to denosumab versus placebo to denosumab. These findings were confirmed at 24 months after the switch. Considering the sequential treatment from antiresorptive to anabolic medications, there was a decreased risk of fracture 12 months after the switch from placebo to teriparatide versus bisphosphonate or antiresorptive to teriparatide. Moreover, a greater bone mineral density increase after the switch from anabolic to antiresorptive medications was shown in the lumbar spine, total hip, and femoral neck. The results of this systematic review and meta-analysis confirm that initial treatment with anabolic drugs produces substantial bone mineral density improvements, and the transition to antiresorptive drugs can preserve or even amplify the acquired benefit. These findings support the choice to treat very high-risk individuals with anabolic drugs first, followed by antiresorptive drugs.

Targeting the Hallmarks of Aging with Vitamin D: Starting to Decode the Myth.

Aging is the result of several complex and multifactorial processes, where several agents contribute to an increased intrinsic vulnerability and susceptibility to age-related diseases. The hallmarks of aging are a set of biological mechanisms that are finely regulated and strictly interconnected, initiating or contributing to biological changes and anticipating several age-related diseases. The complex network of cellular and intercellular connections between the hallmarks might represent a possible target for the research of agents with pleiotropic effects. Vitamin D (VitD) is known to have a positive impact not only on muscle and bone health but also on several extra-skeletal districts, due to the widespread presence of Vitamin D Receptors (VDRs). VitD and VDR could be molecules potentially targeting the hallmarks of the aging network. To date, evidence about the potential effects of VitD on the hallmarks of aging is scarce in humans and mainly based on preclinical models. Although underpowered and heterogeneous, in-human studies seem to confirm the modulatory effect of VitD on some hallmarks of aging and diseases. However, more investigations are needed to clarify the pleiotropic effects of VitD and its impact on the hallmark of aging, hopefully highlighting the courses for translational applications and potential clinical conclusions.

Medication holidays in osteoporosis: evidence-based recommendations from the Italian guidelines on 'Diagnosis, risk stratification, and continuity of care of fragility fractures' based on a systematic literature review.

Background: Noncommunicable, chronic diseases need pharmacological interventions for long periods or even throughout life. The temporary or permanent cessation of medication for a specific period, known as a 'medication holiday,' should be planned by healthcare professionals. Objectives: We evaluated the association between continuity (adherence or persistence) of treatment and several outcomes in patients with fragility fractures in the context of the development of the Italian Guidelines. Design: Systematic review. Data Sources and Methods: We systematically searched PubMed, Embase, and the Cochrane Library up to November 2020 for randomized clinical trials (RCTs) and observational studies that analyzed medication holidays in patients with fragility fracture. Three authors independently extracted data and appraised the risk of bias of the included studies. The quality of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation methodology. Effect sizes were pooled in a meta-analysis using random effects models. Primary outcomes were refracture and quality of life; secondary outcomes were mortality and treatment-related adverse events. Results: Six RCTs and nine observational studies met our inclusion criteria, ranging from very low to moderate quality. The adherence to antiosteoporotic drugs was associated with a lower risk of nonvertebral fracture [relative risk (RR) 0.42, 95% confidence interval (CI) 0.20-0.87; three studies] than nonadherence, whereas no difference was detected in the health-related quality of life. A reduction in refracture risk was observed when continuous treatment was compared to discontinuous therapy (RR 0.49, 95% CI 0.25-0.98; three studies). A lower mortality rate was detected for the adherence and persistence measures, while no significant differences were noted in gastrointestinal side effects in individuals undergoing continuous versus discontinuous treatment. Conclusion: Our findings suggest that clinicians should promote adherence and persistence to antiosteoporotic treatment in patients with fragility fractures unless serious adverse effects occur.

Executive summary: Italian guidelines for diagnosis, risk stratification, and care continuity of fragility fractures 2021.

Background: Fragility fractures are a major public health concern owing to their worrying and growing burden and their onerous burden upon health systems. There is now a substantial body of evidence that individuals who have already suffered a fragility fracture are at a greater risk for further fractures, thus suggesting the potential for secondary prevention in this field. Purpose: This guideline aims to provide evidence-based recommendations for recognizing, stratifying the risk, treating, and managing patients with fragility fracture. This is a summary version of the full Italian guideline. Methods: The Italian Fragility Fracture Team appointed by the Italian National Health Institute was employed from January 2020 to February 2021 to (i) identify previously published systematic reviews and guidelines on the field, (ii) formulate relevant clinical questions, (iii) systematically review literature and summarize evidence, (iv) draft the Evidence to Decision Framework, and (v) formulate recommendations. Results: Overall, 351 original papers were included in our systematic review to answer six clinical questions. Recommendations were categorized into issues concerning (i) frailty recognition as the cause of bone fracture, (ii) (re)fracture risk assessment, for prioritizing interventions, and (iii) treatment and management of patients experiencing fragility fractures. Six recommendations were overall developed, of which one, four, and one were of high, moderate, and low quality, respectively. Conclusions: The current guidelines provide guidance to support individualized management of patients experiencing non-traumatic bone fracture to benefit from secondary prevention of (re)fracture. Although our recommendations are based on the best available evidence, questionable quality evidence is still available for some relevant clinical questions, so future research has the potential to reduce uncertainty about the effects of intervention and the reasons for doing so at a reasonable cost.

Vitamin D in hypoparathyroidism: insight into pathophysiology and perspectives in clinical practice.

Hypoparathyroidism (HypoPT) is a rare endocrine disorder characterized by the absence or insufficient parathyroid hormone production resulting in chronic hypocalcemia. Complications of HypoPT include perturbation of several target organs. The conventional treatment consists of the administration of active vitamin D, namely calcitriol. Regarding vitamin D status, few data are available, mostly in HypoPT subjects supplemented with parent vitamin D. In addition, perturbation of vitamin D metabolism has been poorly investigated, as well as the contribution of altered vitamin D status on the clinical expression of the disease. The most recent consensus on the management of chronic HypoPT suggests the baseline evaluation of serum 25-hydroxy-vitamin D [25(OH)D] and supplementation with parent vitamin D with the aim to achieve and maintain serum 25(OH)D levels in the range of 30-50 ng/mL. The rationale for using supplementation with parent vitamin D (either ergocalciferol or cholecalciferol) in HypoPT would be to provide sufficient 25(OH)D substrate to the residual 1-α-hydroxylase activity, thus ensuring its conversion to active vitamin D in renal and extra-renal tissues. More data from experimental and clinical studies are needed for better assessing how these mechanisms may significantly influence metabolic control in HypoPT and eventually skeletal and extra-skeletal manifestation of the disease. Finally, future data will clarify how the currently available parent vitamin D compounds (ergocalciferol, cholecalciferol, calcifediol) would perform in addressing these specific issues.

Evaluation of food and nutrient intake in a population of subjects affected by periodontal disease with different levels of bone mineral density.

Introduction: Both osteoporosis and periodontitis are pathologies characterized by an imbalance in the bone tissue. Vitamin C is an important factor involved in maintaining the health of the periodontium; its deficiency causes characteristic lesions to periodontal tissues such as bleeding and redness of the gums. Among the essential minerals for the health of the periodontium we find instead calcium.Objectives of the study: The objectives of the proposed study are to study the association between the presence of osteoporosis and periodontal disease. We tried to identify the possible connections between particular dietary patterns and therefore the etiopathogenesis of periodontal disease and secondarily of osteoporosis.Materials and methods: 110 subjects were recruited in a single-center observational cross-sectional study carried through the collaboration between the University of Florence and the private institute of dentistry Excellence Dental Network based in Florence, suffering of periodontitis, 71 osteoporotic/osteopenic and 39 non-osteoporotic/osteopenic. Anamnestic data and information on eating habits were collected. Results: The population showed eating habits that do not meet the intake levels recommended by the L.A.R.N. Regarding the relationship between nutrient intake and plaque index, it appears that in the population, the higher the intake of vitamin C through food, the lower the plaque index value is. This result could reinforce the scientific evidence that there is a protective factor in the onset of periodontal disease by the consumption of vitamin C which to date is still the subject of investigation. In addition, the same type of trend would also have been observed for calcium intake, but a larger sample size would be required to make this effect significant. Conclusions: The relationship between osteoporosis and periodontitis and the role of nutrition in influencing the evolution of these pathologies still seems to be deeply explored. However, the results obtained seem to consolidate the idea that there is a relationship between these two diseases and that eating habits play an important role in their prevention.

Reply to Wimalawansa, S.J. Comment on "Bertoldo et al. Definition, Assessment, and Management of Vitamin D Inadequacy: Suggestions, Recommendations, and Warnings from the Italian Society for Osteoporosis, Mineral Metabolism and Bone Diseases (SIOMMMS). Nutrients 2022, 14, 4148".

With regard to Dr. Wimalawansa's comment [...].

Osteomalacia Is Not a Single Disease.

Among bone-material qualities, mineralization is pivotal in conferring stiffness and toughness to the bone. Osteomalacia, a disease ensuing from inadequate mineralization of the skeleton, is caused by different processes leading to decreased available mineral (calcium and/or phosphate) or enzymatic alterations. Vitamin D deficiency, which remains the major cause of altered mineralization leading to inadequate intestinal calcium and phosphate absorption, may be also associated with other conditions primarily responsible for abnormal mineralization. Given the reality of widespread vitamin D inadequacy, a full biochemical assessment of mineral metabolism is always necessary to rule out or confirm other conditions. Both too-high or too-low serum alkaline phosphatase (ALP) levels are important for diagnosis. Osteomalacic syndrome is reversible, at least in part, by specific treatment. Osteomalacia and bone mineralization themselves constitute largely unexplored fields of research. The true prevalence of the different forms of osteomalacia and the recovery after proper therapy have yet to be determined in the real world. Although non-invasive techniques to assess bone mineralization are not available in clinical practice, the systematic assessment of bone quality could help in refining the diagnosis and guiding the treatment. This review summarizes what is known of osteomalacia recent therapeutic developments and highlights the future issues of research in this field.

Hypoparathyroidism: Genetics and Diagnosis.

This narrative report summarizes diagnostic criteria for hypoparathyroidism and describes the clinical presentation and underlying genetic causes of the nonsurgical forms. We conducted a comprehensive literature search from January 2000 to January 2021 and included landmark articles before 2000, presenting a comprehensive update of these topics and suggesting a research agenda to improve diagnosis and, eventually, the prognosis of the disease. Hypoparathyroidism, which is characterized by insufficient secretion of parathyroid hormone (PTH) leading to hypocalcemia, is diagnosed on biochemical grounds. Low albumin-adjusted calcium or ionized calcium with concurrent inappropriately low serum PTH concentration are the hallmarks of the disease. In this review, we discuss the characteristics and pitfalls in measuring calcium and PTH. We also undertook a systematic review addressing the utility of measuring calcium and PTH within 24 hours after total thyroidectomy to predict long-term hypoparathyroidism. A summary of the findings is presented here; results of the detailed systematic review are published separately in this issue of JBMR. Several genetic disorders can present with hypoparathyroidism, either as an isolated disease or as part of a syndrome. A positive family history and, in the case of complex diseases, characteristic comorbidities raise the clinical suspicion of a genetic disorder. In addition to these disorders' phenotypic characteristics, which include autoimmune diseases, we discuss approaches for the genetic diagnosis. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Definition, Assessment, and Management of Vitamin D Inadequacy: Suggestions, Recommendations, and Warnings from the Italian Society for Osteoporosis, Mineral Metabolism and Bone Diseases (SIOMMMS).

In the recent years, both the prescriptions of serum 25(OH)D levels assay, and vitamin D supplementation are constantly increasing, as well as the costs to be incurred relating to these specific aspects. As in many other countries, the risk of vitamin D deficiency is particularly high in Italy, as recently confirmed by cohort studies in the general population as well as in patients with metabolic bone disorder. Results confirmed the North-South gradient of vitamin D levels described among European countries, despite the wide use of supplements. Although vitamin D supplementation is also recommended by the Italian Medicine Agency for patients at risk for fragility fracture or for initiating osteoporotic medication, the therapeutic gap for osteoporosis in Italy is very high. There is a consistent proportion of osteoporotic patients not receiving specific therapy for osteoporosis following a fragility fracture, with a poor adherence to the recommendations provided by national guidelines and position paper documents. The failure or inadequate supplementation with vitamin D in patients on antiresorptive or anabolic treatment for osteoporosis is thought to further amplify the problem and exposes patients to a high risk of re-fracture and mortality. Therefore, it is important that attention to its possible clinical consequences must be given. Thus, in light of new evidence from the literature, the SIOMMMS board felt the need to revise and update, by a GRADE/PICO system approach, its previous original recommendations about the definition, prevention, and treatment of vitamin D deficiency in adults, released in 2011. Several key points have been here addressed, such as the definition of the vitamin D status: normality values and optimal values; who are the subjects considered at risk of hypovitaminosis D; opportunity or not of performing the biochemical assessment of serum 25(OH)D levels in general population and in subjects at risk of hypovitaminosis D; the need or not to evaluate baseline serum 25(OH)D in candidate subjects for pharmacological treatment for osteoporosis; how and whether to supplement vitamin D subjects with hypovitaminosis D or candidates for pharmacological treatment with bone active agents, and the general population; how and whether to supplement vitamin D in chronic kidney disease and/or chronic liver diseases or under treatment with drugs interfering with hepatic metabolism; and finally, if vitamin D may have toxic effects in the subject in need of supplementation.

Quality of Life in Primary Hyperparathyroidism.

Quality of life is impaired in primary hyperparathyroidism (PHPT), regardless of the severity of the disease. Clinical studies have employed different instruments, including standardized and disease-specific questionnaires, and including patients with different phenotypes of PHPT. Neuropsychiatric symptoms and decline in cognitive status are common in PHPT. Patients may complain of these issues or they can be ascertained by questionnaires; they include depression, anxiety, impaired vitality, social and emotional functions, sleep disturbances, and altered mental function. Randomized controlled trials on the effects of surgical versus non-surgical treatments have collectively shown improvement in quality of life after parathyroidectomy, but results have been heterogeneous.

Cardiovascular Safety and Effectiveness of Bisphosphonates: From Intervention Trials to Real-Life Data.

Both osteoporosis with related fragility fractures and cardiovascular diseases are rapidly outspreading worldwide. Since they are often coexistent in elderly patients and may be related to possible common pathogenetic mechanisms, the possible reciprocal effects of drugs employed to treat these diseases have to be considered in clinical practice. Bisphosphonates, the agents most largely employed to decrease bone fragility, have been shown to be overall safe with respect to cardiovascular diseases and even capable of reducing cardiovascular morbidity in some settings, as mainly shown by real life studies. No randomized controlled trials with cardiovascular outcomes as primary endpoints are available. While contradictory results have emerged about a possible BSP-mediated reduction of overall mortality, it is undeniable that these drugs can be employed safely in patients with high fracture risk, since no increased mortality has ever been demonstrated. Although partial reassurance has emerged from meta-analysis assessing the risk of cardiac arrhythmias during bisphosphonates treatment, caution is warranted in administering this class of drugs to patients at risk for atrial fibrillation, possibly preferring other antiresorptives or anabolics, according to osteoporosis guidelines. This paper focuses on the complex relationship between bisphosphonates use and cardiovascular disease and possible co-management issues.

Persistence and recurrence in tumor-induced osteomalacia: A systematic review of the literature and results from a national survey/case series.

PURPOSE: Tumor induced osteomalacia (TIO) is a rare disease of mineral metabolism, whose clinical picture is dominated by hypophosphatemia usually due to an excess of circulating FGF23 produced by small mesenchymal tumors. Data on the real prevalence of the disease are lacking, with the knowledge of the disease mainly relying on case reports and small case series. No estimate is available on the prevalence of uncured TIO. METHODS: National multi-center, cross-sectional and retrospective study on persistent or recurrent cases of TIO followed in referral centers for bone diseases; systematic review of the published persistent and recurrent cases of TIO. Data from patients consecutively evaluated in referral Italian centers for bone diseases were collected; a PubMed search on persistent, recurrent and unoperable cases of TIO was carried out. RESULTS: Sixteen patients (mean age at diagnosis 52.5 ± 10.6 years) with persistent (n = 6, 37,5%), recurrent (n = 7, 43.7%) or not operable (n = 3, 18.8%) TIO were described. Delay in diagnosis (2.5 ± 1.3 years) was demonstrated. All patients experienced fragility fractures or pseudofractures and disabling bone and muscle pain. BMD was significantly reduced (mean T-score -2.7 ± 1.7 and -2.7 ± 0.9 at lumbar spine and femoral neck, respectively). Fourteen patients were maintained under therapy with phosphate salts and calcitriol, while in 2 patients therapy with burosumab, an anti-FGF23 antibody, was commenced. CONCLUSION: A significant number of patients with TIO remain either undiagnosed for tumor localization or tumor recur or persist after surgery. These patients with active disease represent possible candidates for burosumab treatment.

ALPL Genotypes in Patients With Atypical Femur Fractures or Other Biochemical and Clinical Signs of Hypophosphatasia.

CONTEXT: Hypophosphatasia (HPP) is a rare metabolic disorder caused by deficiency of alkaline phosphatase (ALP) enzyme activity, leading to defective mineralization, due to pathogenic variants of the ALPL gene, encoding the tissue nonspecific alkaline phosphatase (TNSALP) enzyme. Inheritance can be autosomal recessive or autosomal dominant. An abnormal ALPL genetic test enables accurate diagnosis, avoiding the administration of contraindicated antiresorptive drugs that, in patients with HPP, substantially increase the risk of atypical femur fractures (AFFs) and worsen the fracture healing process that is usually already compromised in these patients. OBJECTIVE: Performing ALPL genetic testing to identify rare variants in suspected adult patients with HPP. Comparing frequencies of ALPL common variants in individuals with biochemical and/or clinical signs suggestive of adult HPP and non-HPP controls, and among different clinical subgroups of patients with a clinical suspicion of adult HPP. METHODS: Patients with suspected adult HPP were retrospectively selected for the genetic testing of the ALPL gene. Patients included were from 3 main European Bone Units (Florence, Naples, and Geneva); 106 patients with biochemical and/or clinical signs suggestive of a mild form of HPP were included. RESULTS: Genetic testing led to the identification of a heterozygote rare variant in 2.8% of cases who were initially referred as suspected osteoporosis. The analysis of frequencies of ALPL common variants showed a high prevalence (30.8%) of homozygosity in subjects who developed an AFF, in association with normal serum total ALP activity. CONCLUSION: The results suggest homozygosity of common ALPL variants as a possible genetic mark of risk for these fractures.

The Vessels-Bone Axis: Iliac Artery Calcifications, Vertebral Fractures and Vitamin K from VIKI Study.

Vascular calcification and fragility fractures are associated with high morbidity and mortality, especially in end-stage renal disease. We evaluated the relationship of iliac arteries calcifications (IACs) and abdominal aortic calcifications (AACs) with the risk for vertebral fractures (VFs) in hemodialysis patients. The VIKI study was a multicenter cross-sectional study involving 387 hemodialysis patients. The biochemical data included bone health markers, such as vitamin K levels, vitamin K-dependent proteins, vitamin 25(OH)D, alkaline phosphatase, parathormone, calcium, and phosphate. VF, IACs and AACs was determined through standardized spine radiograms. VF was defined as >20% reduction of vertebral body height, and VC were quantified by measuring the length of calcium deposits along the arteries. The prevalence of IACs and AACs were 56.1% and 80.6%, respectively. After adjusting for confounding variables, the presence of IACs was associated with 73% higher odds of VF (p = 0.028), whereas we found no association (p = 0.294) for AACs. IACs were associated with VF irrespective of calcification severity. Patients with IACs had lower levels of vitamin K2 and menaquinone 7 (0.99 vs. 1.15 ng/mL; p = 0.003), and this deficiency became greater with adjustment for triglycerides (0.57 vs. 0.87 ng/mL; p < 0.001). IACs, regardless of their extent, are a clinically relevant risk factor for VFs. The association is enhanced by adjusting for vitamin K, a main player in bone and vascular health. To our knowledge these results are the first in the literature. Prospective studies are needed to confirm these findings both in chronic kidney disease and in the general population.