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New insights into the vitamin D/PTH axis in endocrine-driven metabolic bone diseases.
di Filippo, L, Bilezikian, JP, Canalis, E, Terenzi, U, Giustina, A
Endocrine. 2024
Abstract
BACKGROUND Endocrine regulation of bone metabolisms is the focus of the "Skeletal Endocrinology" series of meetings. AIMS To report on the outcome of the discussion on the role of vitamin D/PTH axis in endocrine osteopathies held during the 10th Skeletal Endocrinology Meeting which took place in Stresa (Italy) in March 2023. OUTCOMES Vitamin D/PTH axis has relevant influence on several outcomes in the general population and in patients affected by endocrinopathies such as hypoparathyroidism and secreting pituitary adenomas. CONCLUSIONS Assessing the status of the vitamin D/PTH axis and using vitamin D and PTH as therapeutic agents is mandatory in several endocrine-related bone metabolic conditions.
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Use of vitamin D with anti-osteoporotic drugs: are available clinical trials telling us the whole story?
di Filippo, L, Ulivieri, FM, Nuti, R, Giustina, A
Endocrine. 2024;(2):342-348
Abstract
There is a strong rationale for using vitamin D in combination with anti-osteoporotic drugs. Still, available trials do not give clear indications in this setting, presenting a suboptimal and heavily inhomogeneous experimental design. Health authorities should revise requirements for using vitamin D in anti-osteoporotic drug trials to maximise their effect and produce reliable indications for clinical practice in this setting.
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Correction: Vitamin D status and supplementation before and after Bariatric Surgery: Recommendations based on a systematic review and meta‑analysis.
Giustina, A, di Filippo, L, Facciorusso, A, Adler, RA, Binkley, N, Bollerslev, J, Bouillon, R, Casanueva, FF, Cavestro, GM, Chakhtoura, M, et al
Reviews in endocrine & metabolic disorders. 2024;(2):447-448
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Mechanisms and risk factors of metabolic syndrome in children and adolescents.
Codazzi, V, Frontino, G, Galimberti, L, Giustina, A, Petrelli, A
Endocrine. 2024;(1):16-28
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Metabolic syndrome (MetS) is a complex disorder characterized by abdominal obesity, elevated blood pressure, hyperlipidemia, and elevated fasting blood glucose levels. The diagnostic criteria for MetS in adults are well-established, but there is currently no consensus on the definition in children and adolescents. The etiology of MetS is believed to involve a complex interplay between genetic predisposition and environmental factors. While genetic predisposition explains only a small part of MetS pathogenesis, modifiable environmental risk factors play a significant role. Factors such as maternal weight during pregnancy, children's lifestyle, sedentariness, high-fat diet, fructose and branched-chain amino acid consumption, vitamin D deficiency, and sleep disturbances contribute to the development of MetS. Early identification and treatment of MetS in children and adolescents is crucial to prevent the development of chronic diseases later in life. In this review we discuss the latest research on factors contributing to the pathogenesis of MetS in children, focusing on non-modifiable and modifiable risk factors, including genetics, dysbiosis and chronic low-grade inflammation.
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Vitamin D in the older population: a consensus statement.
Giustina, A, Bouillon, R, Dawson-Hughes, B, Ebeling, PR, Lazaretti-Castro, M, Lips, P, Marcocci, C, Bilezikian, JP
Endocrine. 2023;(1):31-44
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BACKGROUND This paper reports results from the 5th International Conference "Controversies in Vitamin D" that was held in Stresa, Italy, 15-18 September 2021. The conference is part of this series that started in 2017 and has been conducted annually since. The objective of these conferences is to identify timely and controversial topics related to Vitamin D. Dissemination of the results of the conference through publications in peer-reviewed journals is an important means by which the most up to date information can be shared with physicians, investigators, and other health care professionals. Vitamin D and aging, the subject of this paper was featured at the conference. METHODS Participants were selected to review available literature on assigned topics related to vitamin D and aging and to present their findings with illustrative material, the intent of which was to stimulate discussion and to arrive at a consensus. The presentations were directed towards the following areas: impact of aging on vitamin D production and levels; skeletal effects of vitamin D deficiency in the older population; falls and vitamin D in the aging; potential extra skeletal effects of vitamin D; and strategies to prevent vitamin D deficiency. A final topic was related to how vitamin D might influence the efficacy of vaccines for Covid-19. RESULTS Hypovitaminosis D can lead to several skeletal and extra-skeletal outcomes. Older adults are at risk for vitamin D deficiency as both production and metabolism of vitamin D change with aging due to factors, such as reduced sun exposure and reduced production capacity of the skin. Skeletal consequences of these age-related changes can include reduced bone mineral density, osteomalacia and fractures. Potential extra-skeletal effects can include added risks for falls, reduced muscle strength, diabetes, cancer, and cardiovascular disease. Strategies to avoid these vitamin D deficiency-related negative outcomes include sun exposure, food fortification, and supplementation. While aging does not diminish sufficient reserve capacity for cutaneous vitamin D production, concerns about skin cancers and practical matters for the institutionalized elderly limit this option. Supplementation with vitamin D is the best option either pharmacologically or through food fortification. Regardless of treatment strategies, interventions to restore sufficient vitamin D status will show positive results only in those who are truly deficient. Thus, treatment goals should focus on avoiding 25(OH)D serum levels <30 nmol/l, with a goal to reach levels >50 nmol/l. CONCLUSIONS The results of this conference has led to consensus on several issues. Vitamin D supplementation should be combined with calcium to reduce fractures in the older population. The goal for adequate Vitamin D status should be to reach a serum level of 25(OH)D >50 nmol/l. It appears that daily low-dose vitamin D regimens reduce the risk of falling, especially in the elderly, compared with infrequent, large bolus doses that may increase it. The role of Vitamin D supplementation on muscle strength remains to be clarified. On the other hand, supplementation decreases the risk of progression to T2D from prediabetes among those who are Vitamin Ddeficient. Of three possible strategies to establish vitamin D sufficiency - sunshine exposure, food fortification, and supplementation - the latter seems to be the most effective and practical in the aging population.
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Consensus and Controversial Aspects of Vitamin D and COVID-19.
Bilezikian, JP, Binkley, N, De Luca, HF, Fassio, A, Formenti, AM, El-Hajj Fuleihan, G, Heijboer, AC, Giustina, A
The Journal of clinical endocrinology and metabolism. 2023;(5):1034-1042
Abstract
OBJECTIVE This work aims to review and discuss controversial topics in the field of vitamin D, SARS-CoV-2 infection, and COVID-19. METHODS The International Conferences "Controversies in Vitamin D" are a series of workshops that started in 2017 featuring international experts and leaders in vitamin D research and clinical practice. The fifth annual conference was held in Stresa, Italy, September 15 to 18, 2021. EVIDENCE Before the event, participants reviewed available studies on their assigned topic, drafted a related abstract, and presented their findings at the time of the conference. Relevant literature that became available since was also discussed within the panel and updated accordingly. CONSENSUS Before the event, the drafted abstracts had been merged to prepare a preliminary document. After the conference presentations, in-depth discussions in open sessions led to consensus. The document was subsequently modified according to discussions and up-to-date literature inclusion. CONCLUSIONS There is quite consistent evidence for an association between low 25 OH vitamin D (25(OH)D) levels and poor COVID-19 outcomes, despite heterogeneous publications of variable quality. However, the low vitamin D status in COVID-19 patients might also reflect reverse causality. Vitamin D supplementation might have a positive role in COVID-19 prevention. The evidence supporting a beneficial effect of vitamin D treatment in decreasing the risk of COVID-19 complications is conflicting. Conclusive statements regarding the beneficial effect of vitamin D in this context await high-quality, randomized controlled trials.
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Vitamin D and malabsorptive gastrointestinal conditions: A bidirectional relationship?
Giustina, A, di Filippo, L, Allora, A, Bikle, DD, Cavestro, GM, Feldman, D, Latella, G, Minisola, S, Napoli, N, Trasciatti, S, et al
Reviews in endocrine & metabolic disorders. 2023;(2):121-138
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This paper is one of the outcomes of the 5th International Conference "Controversies in Vitamin D" held in Stresa, Italy from 15 to 18 September 2021 as part of a series of annual meetings which was started in 2017. The scope of these meetings is to discuss controversial issues about vitamin D. Publication of the outcomes of the meeting in international journals allows a wide sharing of the most recent data with the medical and academic community. Vitamin D and malabsorptive gastrointestinal conditions was one of the topics discussed at the meeting and focus of this paper. Participants to the meeting were invited to review available literature on selected issues related to vitamin D and gastrointestinal system and to present their topic to all participants with the aim to initiate a discussion on the main outcomes of which are reported in this document. The presentations were focused on the possible bidirectional relationship between vitamin D and gastrointestinal malabsorptive conditions such as celiac disease, inflammatory bowel diseases (IBDs) and bariatric surgery. In fact, on one hand the impact of these conditions on vitamin D status was examined and on the other hand the possible role of hypovitaminosis D on pathophysiology and clinical course of these conditions was also evaluated. All examined malabsorptive conditions severely impair vitamin D status. Since vitamin D has known positive effects on bone this in turn may contribute to negative skeletal outcomes including reduced bone mineral density, and increased risk of fracture which may be mitigated by vitamin D supplementation. Due to the immune and metabolic extra-skeletal effects there is the possibility that low levels of vitamin D may negatively impact on the underlying gastrointestinal conditions worsening its clinical course or counteracting the effect of treatment. Therefore, vitamin D status assessment and supplementation should be routinely considered in all patients affected by these conditions. This concept is strengthened by the existence of a possible bidirectional relationship through which poor vitamin D status may negatively impact on clinical course of underlying disease. Sufficient elements are available to estimate the desired threshold vitamin D level above which a favourable impact on the skeleton in these conditions may be obtained. On the other hand, ad hoc controlled clinical trials are needed to better define this threshold for obtaining a positive effect of vitamin D supplementation on occurrence and clinical course of malabsorptive gastrointestinal diseases.
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Vitamin D status and supplementation before and after Bariatric Surgery: Recommendations based on a systematic review and meta-analysis.
Giustina, A, di Filippo, L, Facciorusso, A, Adler, RA, Binkley, N, Bollerslev, J, Bouillon, R, Casanueva, FF, Cavestro, GM, Chakhtoura, M, et al
Reviews in endocrine & metabolic disorders. 2023;(6):1011-1029
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Bariatric surgery is associated with a postoperative reduction of 25(OH) vitamin D levels (25(OH)D) and with skeletal complications. Currently, guidelines for 25(OH)D assessment and vitamin D supplementation in bariatric patients, pre- and post-surgery, are still lacking. The aim of this work is to analyse systematically the published experience on 25(OH)D status and vitamin D supplementation, pre- and post-surgery, and to propose, on this basis, recommendations for management. Preoperatively, 18 studies including 2,869 patients were evaluated. Prevalence of vitamin D insufficiency as defined by 25(OH)D < 30 ng/mL (75 nmol/L) was 85%, whereas when defined by 25(OH)D < 20 ng/mL (50 nmol/L) was 57%. The median preoperative 25(OH)D level was 19.75 ng/mL. After surgery, 39 studies including 5,296 patients were analysed and among those undergoing either malabsorptive or restrictive procedures, a lower rate of vitamin D insufficiency and higher 25(OH)D levels postoperatively were observed in patients treated with high-dose oral vitamin D supplementation, defined as ≥ 2,000 IU/daily (mostly D3-formulation), compared with low-doses (< 2,000 IU/daily). Our recommendations based on this systematic review and meta-analysis should help clinical practice in the assessment and management of vitamin D status before and after bariatric surgery. Assessment of vitamin D should be performed pre- and postoperatively in all patients undergoing bariatric surgery. Regardless of the type of procedure, high-dose supplementation is recommended in patients after bariatric surgery.
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Low Vitamin D Levels Are Associated With Long COVID Syndrome in COVID-19 Survivors.
di Filippo, L, Frara, S, Nannipieri, F, Cotellessa, A, Locatelli, M, Rovere Querini, P, Giustina, A
The Journal of clinical endocrinology and metabolism. 2023;(10):e1106-e1116
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CONTEXT Long COVID is an emerging syndrome affecting 50% to 70% of COVID-19 survivors that still lacks predicting factors. OBJECTIVE Due to the extraskeletal effects of vitamin D, we retrospectively assessed the association between 25(OH) vitamin D levels and long COVID in COVID-19 survivors 6 months after hospitalization. METHODS Long COVID was defined according to NICE guidelines. Fifty long COVID and 50 non-long-COVID subjects matched on a 1:1 basis were enrolled from an outpatient clinic post-COVID cohort seen from August to November 2020. Therapies/comorbidities affecting calcium/vitamin D/bone metabolism, and/or admission to the intensive care unit during hospitalization were exclusion criteria. 25(OH) Vitamin D was measured at hospital admission and 6 months after discharge. RESULTS We observed lower 25(OH) vitamin D levels, evaluated at follow-up, in subjects with long COVID than those without (20.1 vs 23.2 ng/mL, P = .03). Regarding the affected health areas evaluated in the entire cohort, we observed lower 25(OH) vitamin D levels in those with neurocognitive symptoms at follow-up (n = 7) than those without (n = 93) (14.6 vs 20.6 ng/mL, P = .042). In patients presenting vitamin D deficiency (<20 ng/mL), both at admission and at follow-up (n = 42), those affected by long COVID (n = 22) presented lower 25(OH) vitamin D levels at follow-up than those not affected (n = 20) (12.7 vs 15.2 ng/mL, P = .041). In multiple regression analyses, lower 25(OH) vitamin D levels at follow-up were the only variable significantly associated with long COVID in our cohort (P = .008, OR 1.09, CI 1.01-1.16). CONCLUSION COVID-19 survivors with long COVID have lower 25(OH) vitamin D levels than matched patients without long COVID. Our data suggest that vitamin D levels should be evaluated in COVID-19 patients after hospital discharge. The role of vitamin D supplementation as a preventive strategy of COVID-19 sequelae should be tested in randomized controlled trials.
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Evaluation of Muscle Mass and Stiffness with Limb Ultrasound in COVID-19 Survivors.
Damanti, S, Cilla, M, Tuscano, B, De Lorenzo, R, Manganaro, G, Merolla, A, Pacioni, G, Pomaranzi, C, Tiraferri, V, Martinenghi, S, et al
Frontiers in endocrinology. 2022;:801133
Abstract
BACKGROUND acute illnesses, like COVID-19, can act as a catabolic stimulus on muscles. So far, no study has evaluated muscle mass and quality through limb ultrasound in post-COVID-19 patients. METHODS cross sectional observational study, including patients seen one month after hospital discharge for SARS-CoV-2 pneumonia. The patients underwent a multidimensional evaluation. Moreover, we performed dominant medial gastrocnemius ultrasound (US) to characterize their muscle mass and quality. RESULTS two hundred fifty-nine individuals (median age 67, 59.8% males) were included in the study. COVID-19 survivors with reduced muscle strength had a lower muscle US thickness (1.6 versus 1.73 cm, p =0.02) and a higher muscle stiffness (87 versus 76.3, p = 0.004) compared to patients with normal muscle strength. Also, patients with reduced Short Physical Performance Battery (SPPB) scores had a lower muscle US thickness (1.3 versus 1.71 cm, p = 0.01) and a higher muscle stiffness (104.9 versus 81.07, p = 0.04) compared to individuals with normal SPPB scores. The finding of increased muscle stiffness was also confirmed in patients with a pathological value (≥ 4) at the sarcopenia screening tool SARC-F (103.0 versus 79.55, p < 0.001). Muscle stiffness emerged as a significant predictor of probable sarcopenia (adjusted OR 1.02, 95% C.I. 1.002 - 1.04, p = 0.03). The optimal ultrasound cut-offs for probable sarcopenia were 1.51 cm for muscle thickness (p= 0.017) and 73.95 for muscle stiffness (p = 0.004). DISCUSSION we described muscle ultrasound characteristics in post COVID-19 patients. Muscle ultrasound could be an innovative tool to assess muscle mass and quality in this population. Our preliminary findings need to be confirmed by future studies comparing muscle ultrasound with already validated techniques for measuring muscle mass and quality.