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1.
Primary hyperparathyroidism.
Silva, BC, Cusano, NE, Bilezikian, JP
Best practice & research. Clinical endocrinology & metabolism. 2024;(1):101247
Abstract
Primary hyperparathyroidism (PHPT), the most common cause of hypercalcemia, is most often identified in postmenopausal women with hypercalcemia and parathyroid hormone (PTH) levels that are either frankly elevated or inappropriately normal. The clinical presentation of PHPT includes three phenotypes: target organ involvement of the renal and skeletal systems; mild asymptomatic hypercalcemia; and more recently, high PTH levels in the context of persistently normal albumin-corrected and ionized serum calcium values. The factors that determine which of these three clinical presentations is more likely to predominate in a given country include the extent to which biochemical screening is employed, the prevalence of vitamin D deficiency, and whether a medical center or practitioner tends to routinely measure PTH levels in the evaluation of low bone density or frank osteoporosis. When biochemical screening is common, asymptomatic primary hyperparathyroidism is the most likely form of the disease. In countries where vitamin D deficiency is prevalent and biochemical screening is not a feature of the health care system, symptomatic disease with skeletal abnormalities is likely to predominate. Finally, when PTH levels are part of the evaluation for low bone mass, the normocalcemic variant is seen. Guidelines for surgical removal of hyperfunctioning parathyroid tissue apply to all three clinical forms of the disease. If guidelines for surgery are not met, parathyroidectomy can also be an appropriate option if there are no medical contraindications to surgery. In settings where either the serum calcium or bone mineral density is of concern, and surgery is not an option, pharmacological approaches are available and effective. Referencing in this article the most current published articles, we review the different presentations of PHPT, with particular emphasis on recent advances in our understanding of target organ involvement and management.
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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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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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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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Abstract
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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Proceedings of the 2023 Santa Fe Bone Symposium: Progress and Controversies in the Management of Patients with Skeletal Diseases.
Lewiecki, EM, Bellido, T, Bilezikian, JP, Brown, JP, Farooki, A, Kovacs, CS, Lee, B, Leslie, WD, McClung, MR, Prasarn, ML, et al
Journal of clinical densitometry : the official journal of the International Society for Clinical Densitometry. 2023;(4):101432
Abstract
The Santa Fe Bone Symposium (SFBS) held its 23rd annual event on August 5-6, 2023, in Santa Fe, New Mexico, USA. Attendees participated in-person and remotely, representing many states and countries. The program included plenary presentations, panel discussions, satellite symposia, a Project ECHO workshop, and a session on healthcare policy and reimbursement for fracture liaison programs. A broad range of topics were addressed, including transitions of osteoporosis treatments over a lifetime; controversies in vitamin D; update on Official Positions of the International Society for Clinical Densitometry; spine surgery and bone health; clinical applications of bone turnover markers; basic bone biology for clinicians; premenopausal-, pregnancy-, and lactation-associated osteoporosis; cancer treatment induced bone loss in patients with breast cancer and prostate cancer; genetic testing for skeletal diseases; and an update on nutrition and bone health. There were also sessions on rare bone diseases, including managing patients with hypophosphatasia; treatment of X-linked hypophosphatemia; and assessment and treatment of patients with hypoparathyroidism. There were oral presentations of abstracts by endocrinology fellows selected from those who participated in the Santa Fe Fellows Workshop on Metabolic Bone Diseases, held the 2 days prior to the SFBS. These proceedings of the 2023 SFBS present the clinical highlights and insights generated from many formal and informal discussions in Santa Fe.
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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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Abstract
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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Abstract
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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Management of Primary Hyperparathyroidism.
Bilezikian, JP, Silverberg, SJ, Bandeira, F, Cetani, F, Chandran, M, Cusano, NE, Ebeling, PR, Formenti, AM, Frost, M, Gosnell, J, et al
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2022;(11):2391-2403
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Abstract
Since the last international guidelines were published in 2014 on the evaluation and management of primary hyperparathyroidism (PHPT), new information has become available with regard to evaluation, diagnosis, epidemiology, genetics, classical and nonclassical manifestations, surgical and nonsurgical approaches, and natural history. To provide the most current summary of these developments, an international group, consisting of over 50 experts in these various aspects of PHPT, was convened. This paper provides the results of the task force that was assigned to review the information on the management of PHPT. For this task force on the management of PHPT, two questions were the subject of systematic reviews using the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) methodology. The full report addressing surgical and nonsurgical management of PHPT, utilizing the GRADE methodology, is published separately in this series. In this report, we summarize the results of that methodological review and expand them to encompass a much larger body of new knowledge that did not specifically fit the criteria of the GRADE methodology. Together, both the systematic and narrative reviews of the literature, summarized in this paper, give the most complete information available to date. A panel of experts then considered the last set of international guidelines in light of the newer data and assessed the need for their revision. This report provides the evidentiary background to the guidelines report. In that report, evidence from all task forces is synthesized into a summary statement and revised guidelines for the evaluation and management of PHPT. © 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).
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Complications, Symptoms, Presurgical Predictors in Patients With Chronic Hypoparathyroidism: A Systematic Review.
Yao, L, Hui, X, Li, M, Li, J, Ahmed, MM, Lin, C, Kandi, M, Sreekanta, A, Makhdami, N, Tamilselvan, D, et al
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 2022;(12):2642-2653
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The complications and symptoms of hypoparathyroidism remain incompletely defined. Measuring serum parathyroid hormone (PTH) and calcium levels early after total thyroidectomy may predict the development of chronic hypoparathyroidism. The study aimed (i) to identify symptoms and complications associated with chronic hypoparathyroidism and determine the prevalence of those symptoms and complications (Part I), and (ii) to examine the utility of early postoperative measurements of PTH and calcium in predicting chronic hypoparathyroidism (Part II). We searched Medline, Medline In-Process, EMBASE, and Cochrane CENTRAL to identify complications and symptoms associated with chronic hypoparathyroidism. We used two predefined criteria (at least three studies reported the complication and symptom and had statistically significantly greater pooled relative estimates). To estimate prevalence, we used the median and interquartile range (IQR) of the studies reporting complications and symptoms. For testing the predictive values of early postoperative measurements of PTH and calcium, we used a bivariate model to perform diagnostic test meta-analysis. In Part I, the 93 eligible studies enrolled a total of 18,973 patients and reported on 170 complications and symptoms. We identified nine most common complications or symptoms probably associated with chronic hypoparathyroidism. The complications or symptoms and the prevalence are as follows: nephrocalcinosis/nephrolithiasis (median prevalence among all studies 15%), renal insufficiency (12%), cataract (17%), seizures (11%), arrhythmia (7%), ischemic heart disease (7%), depression (9%), infection (11%), and all-cause mortality (6%). In Part II, 18 studies with 4325 patients proved eligible. For PTH measurement, regarding the posttest probability, PTH values above 10 pg/mL 12-24 hours postsurgery virtually exclude chronic hypoparathyroidism irrespective of pretest probability (100%). When PTH values are below 10 pg/mL, posttest probabilities range from 3% to 64%. Nine complications and symptoms are probably associated with chronic hypoparathyroidism. A PTH value above a threshold of 10 pg/mL 12-24 hours after total thyroidectomy is a strong predictor that the patients will not develop chronic hypoparathyroidism. Patients with PTH values below the threshold need careful monitoring as some will develop chronic hypoparathyroidism. © 2022 American Society for Bone and Mineral Research (ASBMR).