Vitamin D status and supplementation before and after Bariatric Surgery: Recommendations based on a systematic review and meta-analysis.

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.

Long-Term Safety and Efficacy of Recombinant Human Parathyroid Hormone (1-84) in Adults With Chronic Hypoparathyroidism.

Context: Chronic hypoparathyroidism is conventionally treated with oral calcium and active vitamin D to reach and maintain targeted serum calcium and phosphorus levels, but some patients remain inadequately controlled. Objective: To assess long-term safety and efficacy of recombinant human parathyroid hormone (1-84) (rhPTH(1-84)) treatment. Methods: This was an open-label extension study at 12 US centers. Adults (n = 49) with chronic hypoparathyroidism were included. The intervention was rhPTH(1-84) for 6 years. The main outcome measures were safety, biochemical measures, oral supplement doses, bone indices. Results: Thirty-eight patients (77.6%) completed the study. Throughout 72 months, mean albumin-adjusted serum calcium was within 2.00 to 2.25 mmol/L (8.0-9.0 mg/dL). At baseline, 65% of patients with measurements (n = 24/37) were hypercalciuric; of these, 54% (n = 13/24) were normocalciuric at month 72. Mean serum phosphorus declined from 1.6 ± 0.19 mmol/L at baseline (n = 49) to 1.3 ± 0.20 mmol/L at month 72 (n = 36). Mean estimated glomerular filtration rate was stable. rhPTH(1-84)-related adverse events were reported in 51.0% of patients (n = 25/49); all but 1 event were mild/moderate in severity. Mean oral calcium supplementation reduced by 45% ± 113.6% and calcitriol by 74% ± 39.3%. Bone turnover markers declined by month 32 to a plateau above pretreatment values; only aminoterminal propeptide of type 1 collagen remained outside the reference range. Mean bone mineral density z score fell at one-third radius and was stable at other sites. Conclusion: 6 years of rhPTH(1-84) treatment was associated with sustained improvements in biochemical parameters, a reduction in the percentage of patients with hypercalciuria, stable renal function, and decreased supplement requirements. rhPTH(1-84) was well tolerated; no new safety signals were identified.

Vitamin D and malabsorptive gastrointestinal conditions: A bidirectional relationship?

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.

The Clinical and Skeletal Effects of Long-Term Therapy of Hypoparathyroidism With rhPTH(1-84).

Hypoparathyroidism (HypoPT) is a disorder characterized by hypocalcemia, low or absent parathyroid hormone (PTH) levels, reduced bone remodeling, and high areal bone mineral density (aBMD). PTH is a therapeutic option, yet data on the prolonged clinical and skeletal effects of PTH treatment are limited. We tracked annual daily doses of calcium and active vitamin D supplements, calciotropic biochemistries, estimated glomerular filtration rate (eGFR), and aBMD measurements in 27 HypoPT patients (16 postsurgical, 11 nonsurgical) who were treated with recombinant human PTH(1-84) [rhPTH(1-84)] for at least 8 (n = 27) and up to 12 (n = 14) years. We also performed high-resolution-peripheral quantitative computed tomography (HRpQCT) imaging and report results at baseline, 5, 8, and 12 years of rhPTH(1-84) treatment. With prolonged use of rhPTH, reductions in the need for supplemental calcium and active vitamin D were maintained. The eGFR did not decline. Serum calcium was maintained within the lower limit of the normal range. aBMD by dual-energy X-ray absorptiometry (DXA) showed an increase at the lumbar spine and a decrease at the distal 1/3 radius. By HRpQCT, cortical volumetric BMD (vBMD) at the tibia decreased at year 5: -20.0% ± 1.5%. The magnitude of this reduction was mitigated in year 8: -8.5% ± 1.6% and in year 12: -10.3% ± 2.2% but all were significantly below the mean baseline value (p < 0.001). A similar pattern of decline was observed at the radius. Cortical porosity progressively increased at the tibia in year 5: 17.4% ± 10% (p < 0.05), year 8: 55.2% ± 11% (p < 0.001), and year 12: 83.5% ± 14% (p < 0.001). A similar pattern of increase was observed at the radius. Failure load, which was higher than normal at baseline, decreased but remained above normal at year 12. This is the longest experience, to date, with PTH therapy in HypoPT. These results demonstrate sustained biochemical stability but overall decreases in bone mass. © 2023 American Society for Bone and Mineral Research (ASBMR).

Vitamin D in the older population: a consensus statement.

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.

Consensus and Controversial Aspects of Vitamin D and COVID-19.

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.

Calcium Citrate Versus Calcium Carbonate in the Management of Chronic Hypoparathyroidism: A Randomized, Double-Blind, Crossover Clinical Trial.

In hypoparathyroidism (HypoPT), calcium supplementation is virtually always required, although the disease is likely to be associated with an increased risk of nephrolithiasis. The use of calcium citrate (Ca-Cit) theoretically could have a positive impact on the nephrolithiasis risk because citrate salts are used to reduce this risk. Our objective was to evaluate the potential therapeutic advantage of Ca-Cit in comparison with calcium carbonate (CaCO3 ) in HypoPT, on nephrolithiasis risk factors, as well as to their ability to maintain desirable serum calcium levels. We also evaluated these preparations on quality of life (QOL). This randomized, double-blind, crossover trial recruited 24 adults with postsurgical chronic hypoparathyroidism at Campus Bio-Medico University of Rome. Participants were randomized 1:1 to Ca-Cit or CaCO3 for 1 month and then crossed over to the other treatment for another month. The primary outcomes were changes in albumin-adjusted serum calcium and in ion activity product of calcium oxalate levels (AP[CaOx] index). Secondary efficacy outcomes included changes in SF-36 survey score, fatigue score, constipation, and adverse events. No difference in terms of AP(CaOx) index was observed between the two groups. However, Ca-Cit was associated with a significant reduction in the oxalate/creatinine ratio compared with CaCO3 (-2.46 mmol/mol [SD 11.93] versus 7.42 mmol/mol [SD 17.63], p = 0.029). Serum calcium and phosphorus concentration was not different between the two calcium preparations. Ca-Cit was associated with less constipation (p = 0.047). No difference was found in QOL scores. Although Ca-Cit did not modify the AP(CaOx) index when compared with CaCO3, it was associated with a reduction in urinary oxalate excretion that could have a potential beneficial effect on nephrolithiasis risk. These results are likely to have clinical implications in HypoPT, particularly those who do not tolerate CaCO3 and those affected by nephrolithiasis. A longer-term experience is needed to confirm these findings. © 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).

Vitamin D status in Armenian women: a stratified cross-sectional cluster analysis.

BACKGROUND: Vitamin D plays a critical role in skeletal development and maintenance, thus sufficiency is an important goal for public health programs. Given the absence of foods fortified in vitamin D in Armenia, we hypothesized that vitamin D insufficiency would be widespread. METHODS: We conducted a random modified cluster model survey of vitamin D status of women in the country. We measured 25-hydroxyvitamin D [25(OH)D] by liquid chromatography mass spectrometry in dried blood spot samples and utilized a questionnaire to assess lifestyle factors. RESULTS: In summer, we sampled 1206 participants from 40 communities in Armenia. Mean 25-OH D level among women aged 18-24 was 20 ± 8 ng/mL; aged 25-64 was 21 ± 7 ng/mL; and >65 was 18 ± 8 ng/mL. The country-wide mean of the entire female population was 20 ± 8 ng/mL. A majority (>54%) had 25-OH D levels <20 ng/mL with nearly 13% having 25-OH D levels <12 ng/mL. Participants who reported calcium, vitamin D, or multivitamin supplementation had higher levels of 25-OH D (p values 0.004, 0.0002, and 0.03 respectively) as did pre- vs. postmenopausal women (p = 0.01), pregnant vs. nonpregnant women (p = <0.0001), and women who had experienced a sunburn in the past year (p = 0.004). CONCLUSION: In Armenia, there is a high prevalence of vitamin D insufficiency. This information provides data that can be used to inform public health directives to address this pervasive threat to optimal health.

Vitamin D: Dosing, levels, form, and route of administration: Does one approach fit all?

The 4th International Conference on Controversies in Vitamin D was held as a virtual meeting in September, 2020, gathering together leading international scientific and medical experts in vitamin D. Since vitamin D has a crucial role in skeletal and extra-skeletal systems, the aim of the Conference was to discuss improved management of vitamin D dosing, therapeutic levels and form or route of administration in the general population and in different clinical conditions. A tailored approach, based on the specific mechanisms underlying vitamin D deficiency in different diseases that were discussed, was recommended. Specifically, in comparison to healthy populations, higher levels of vitamin D and greater amounts of vitamin D were deemed necessary in osteoporosis, diabetes mellitus, obesity (particularly after bariatric surgery), and in those treated with glucocorticoids. Emerging and still open issues were related to target vitamin D levels and the role of vitamin D supplementation in COVID-19 since low vitamin D may predispose to SARS-CoV-2 infection and to worse COVID-19 outcomes. Finally, whereas oral daily cholecalciferol appears to be the preferred choice for vitamin D supplementation in the general population, and in most clinical conditions, active vitamin D analogs may be indicated in patients with hypoparathyroidism and severe kidney and liver insufficiency. Parenteral vitamin D administration could be helpful in malabsorption syndromes or in states of vitamin D resistance.Specific guidelines for desired levels of vitamin D should be tailored to the different conditions affecting vitamin D metabolism with the goal to define disease-specific normative values.

Skeletal abnormalities in Hypoparathyroidism and in Primary Hyperparathyroidism.

Both hypoparathyroidism (HypoPT), as well as its pathological counterpart, primary hyperparathyroidism (PHPT), can lead to skeletal abnormalities. Chronic deficiency of PTH in patients with HypoPT is associated with a profound reduction in bone remodeling, with consequent increases in bone density, and abnormalities in microarchitecture and bone strength. It is still not clear whether there is an increase in fracture risk in HypoPT. While standard therapy with calcium supplements and active vitamin D does not restore bone homeostasis, treatment of HypoPT with PTH appears to correct some of those abnormalities. In PHPT, the continuous exposure to high levels of PTH causes an increase in bone remodeling, in which bone resorption prevails. In the symptomatic form of PHPT, patients can present with fragility fractures, and/or the classical radiological features of osteitis fibrosa cystica. However, even in mild PHPT, catabolic skeletal actions of PTH are evident through reduced BMD, deterioration of bone microarchitecture and increased risk of fragility fractures. Successful parathyroidectomy improves skeletal abnormalities. Medical treatment, such as bisphosphonates and denosumab, can also increase bone density in patients with PHPT who do not undergo surgery. This article reviews skeletal involvement in HypoPT and in PHPT, as assessed by bone remodeling, DXA, trabecular bone score, and quantitative computed tomography, as well as data on bone strength and fracture risk. The effects of PTH replacement on the skeleton in subjects with HypoPT, and the outcome of parathyroidectomy in patients with PHPT, are also reviewed here.

Controversies in Vitamin D: A Statement From the Third International Conference.

The Third International Conference on Controversies in Vitamin D was held in Gubbio, Italy, September 10-13, 2019. The conference was held as a follow-up to previous meetings held in 2017 and 2018 to address topics of controversy in vitamin D research. The specific topics were selected by the steering committee of the conference and based upon areas that remain controversial from the preceding conferences. Other topics were selected anew that reflect specific topics that have surfaced since the last international conference. Consensus was achieved after formal presentations and open discussions among experts. As will be detailed in this article, consensus was achieved with regard to the following: the importance and prevalence of nutritional rickets, amounts of vitamin D that are typically generated by sun exposure, worldwide prevalence of vitamin D deficiency, the importance of circulating concentrations of 25OHD as the best index of vitamin D stores, definitions and thresholds of vitamin D deficiency, and efficacy of vitamin D analogues in the treatment of psoriasis. Areas of uncertainly and controversy include the following: daily doses of vitamin D needed to maintain a normal level of 25OHD in the general population, recommendations for supplementation in patients with metabolic bone diseases, cutaneous production of vitamin D by UVB exposure, hepatic regulation of 25OHD metabolites, definition of vitamin D excess, vitamin D deficiency in acute illness, vitamin D requirements during reproduction, potential for a broad spectrum of cellular and organ activities under the influence of the vitamin D receptor, and potential links between vitamin D and major human diseases. With specific regard to the latter area, the proceedings of the conference led to recommendations for areas in need of further investigation through appropriately designed intervention trials. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research.

Vitamin D: Giveth to Those Who Needeth.

Severe vitamin D deficiency may cause rickets. While this point is not disputed, the use of vitamin D in the elderly to prevent fractures has been challenged recently by a meta-analysis of 81 RCTs, suggesting that the effects of vitamin D were trivial. As is true for any review of the literature, the interpretation of a meta-analysis can be confounded by the choice of publications to include or exclude. Indeed, the authors excluded RCTs with combined vitamin D and calcium supplementation, included futile studies of very short duration, or studies with high bolus doses known to transiently increase fracture risk. The best available data show that calcium and vitamin D supplementation of elderly subjects can decrease the risk of hip and other non-vertebral fractures, especially in institutionalized subjects or elderly subjects with poor calcium and vitamin D status. Vitamin D deficiency is associated with many chronic diseases. The VIDA and VITAL trials did not show a protective effect on cardiovascular diseases and cancer. The D2d study also did not influence the progress of prediabetes to diabetes. However, the baseline 25OHD concentrations of the majority of the participants of all these trials were essentially normal. Post-hoc analysis of these studies suggest some possibly beneficial health outcomes in vitamin D deficient subjects. A meta-analysis suggested that vitamin D could partly prevent upper respiratory infections. Mendelian randomization studies suggest a causal link between lifelong low vitamin D status and multiple sclerosis. A vitamin D supplement in pregnant women may decrease maternal morbidity and improve the health of their offspring. Better-designed studies are needed to answer all outstanding questions. However, based on all available data, it seems that correction of vitamin D and/or calcium deficiency of infants, pregnant women and elderly subjects can improve their health. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Therapy of Hypoparathyroidism With rhPTH(1-84): A Prospective, 8-Year Investigation of Efficacy and Safety.

CONTEXT: Conventional treatment of hypoparathyroidism is associated with decreased renal function and increased bone mineral density (BMD). OBJECTIVE: To evaluate the effects of 8 years of recombinant human parathyroid hormone (1-84) [rhPTH(1-84)] therapy on key biochemical and densitometric indices. DESIGN: Prospective open-label trial. SETTING: Tertiary medical center. PARTICIPANTS: Twenty-four subjects with hypoparathyroidism. INTERVENTION: Treatment with rhPTH(1-84) for 8 years. MAIN OUTCOME MEASURES: Supplemental calcium and vitamin D requirements, serum calcium and phosphorus levels, calcium-phosphate product, urinary calcium excretion, estimated glomerular filtration rate (eGFR) and BMD. RESULTS: PTH therapy was associated with progressive reduction in supplemental calcium (57%; P < 0.01) and active vitamin D (76%; P < 0.001) requirements over 8 years. Serum calcium concentration was stable; urinary calcium excretion declined 38% (P < 0.01). eGFR remained stable and was related to baseline eGFR and serum calcium levels. Calcium-phosphate product was below the recommended limit; serum phosphorus remained within normal range. Lumbar spine and total hip BMD increased, peaking at 4 (mean ± SE, 4.6% ± 1.5%; P = 0.01) and 8 years (2.6% ± 1.1%; P = 0.02), whereas femoral neck BMD did not change and one-third radius BMD decreased (mean ± SE, -3.5% ± 1.1%; P = 0.001). BMD at all sites was higher throughout the 8 years than in the age- and sex-matched reference population. Hypercalcemia and hypocalcemia were uncommon. CONCLUSION: rhPTH(1-84) is a safe and effective treatment for hypoparathyroidism for 8 years. Long-term reductions in supplemental requirements and biochemical improvements with stable renal function are maintained.

Quality of Life in Hypoparathyroidism Improves With rhPTH(1-84) Throughout 8 Years of Therapy.

CONTEXT: Calcium and vitamin D treatment does not improve reduced quality of life (QOL) in hypoparathyroidism. Recombinant human (rh) PTH(1-84) therapy improves QOL metrics for up to 5 years. Data on QOL beyond this time point are not available. OBJECTIVES: To evaluate the effects of 8 years of rhPTH(1-84) therapy on QOL and factors associated with long-term benefit. DESIGN: Prospective, open-label trial. SETTING: Referral center. PATIENTS: Twenty patients with hypoparathyoidism. MAIN OUTCOME MEASURES: RAND 36-Item Short Form Health Survey (SF-36). RESULTS: rhPTH therapy led to substantial improvement in five of the eight SF-36 domains [vitality, social functioning (SF), mental health (MH), bodily pain (BP) and general health] and three of these domains (SF, MH, BP) were no longer lower than the reference population. The improvement in the mental component summary (MCS) score was sustained through 8 years, while the physical component summary (PCS) score improved through 6 years. A lower baseline QOL score was associated with greater improvement. A threshold value <238 (MCS) and <245 (PCS) predicted long-term improvement in 90% and 100% of the cohort, respectively. In patients whose calcium supplementation was reduced, MCS and PCS scores improved more than those whose supplementation did not decline to the same extent. Improvement in PCS was greater in patients whose calcitriol dosage was reduced and duration of disease was shorter. CONCLUSIONS: rhPTH(1-84) improves long-term well-being in hypoparathyroidism. The improvements are most prominent in those with impaired SF-36 at baseline and those whose requirements for conventional therapy decreased substantially.

Controversies in Vitamin D: Summary Statement From an International Conference.

Context: Vitamin D is classically recognized as a regulator of calcium and phosphorus metabolism. Recent advances in the measurement of vitamin D metabolites, diagnosis of vitamin D deficiency, and clinical observations have led to an appreciation that along with its role in skeletal metabolism, vitamin D may well have an important role in nonclassical settings. Measurement of the circulating form of vitamin D that best describes total body stores, namely 25-hydroxyvitamin D, can be unreliable despite many sophisticated methodologies that have been proposed and implemented. Likewise, evidence from clinical studies showing a beneficial role of vitamin D in different disease states has been controversial and at times speculative. Moreover, the target concentrations of 25-hydroxyvitamin D to address a number of putative links between vitamin D inadequacy and nonskeletal diseases are further areas of uncertainty. Setting: To address these issues, an international conference on "Controversies in Vitamin D" was held in Pisa, Italy, in June 2017. Three main topics were addressed: (i) vitamin D assays and the definition of hypovitaminosis D; (ii) skeletal and extraskeletal effects of vitamin D; (iii) therapeutics of vitamin D. Results: This report provides a summary of the deliberations of the expert panels of the conference. Conclusions: Despite great advances in our appreciation of vitamin D metabolism, measurements, biological actions on classical and nonclassical tissues, and therapeutics, all of which this report summarizes, much more work remains to be done so that our knowledge base can become even more secure.

ACTIVExtend: 24 Months of Alendronate After 18 Months of Abaloparatide or Placebo for Postmenopausal Osteoporosis.

Purpose: In women with postmenopausal osteoporosis, we investigated the effects of 24 months of treatment with alendronate (ALN) following 18 months of treatment with abaloparatide (ABL) or placebo (PBO). Methods: Women who completed ABL or PBO treatment in ACTIVE were eligible to receive up to 24 months of ALN. We evaluated the incidence of vertebral and nonvertebral fractures and changes in bone mineral density (BMD) during the entire 43-month period from ACTIVE baseline to the end of ACTIVExtend and for the 24-month extension only. Results: Five hundred fifty-eight women from ACTIVE's ABL group and 581 from its PBO group (92% of ABL and PBO completers) were enrolled. During the full 43-month treatment period, 0.9% of evaluable women in the ABL/ALN group experienced a new radiographic vertebral fracture vs 5.6% of women in the PBO/ALN group, an 84% relative risk reduction (RRR, P < 0.001). Kaplan-Meier incidence rates for other reported fracture types were significantly lower for ABL/ALN vs PBO/ALN (all P < 0.05). Gains in BMD achieved during ACTIVE were further increased during ACTIVExtend. For ACTIVExtend only, RRR for vertebral fractures was 87% with ABL/ALN vs PBO/ALN (P = 0.001). Adverse events were similar between groups. A supplemental analysis for regulatory authorities found no hip fractures in the ABL/ALN group vs five in the PBO/ALN group. Conclusions: Eighteen months of ABL followed by 24 months of ALN reduced the risk of vertebral, nonvertebral, clinical, and major osteoporotic fractures and increased BMD. Sequential ABL followed by ALN appears to be an effective treatment option for postmenopausal women at risk for osteoporosis-related fractures.

IODINE NUTRITION IN THE REPUBLIC OF ARTSAKH (NAGORNO KARABAKH).

OBJECTIVE: Iodine is a required nutrient for thyroid function. The mountainous terrain in the Republic of Artsakh (Nagorno Karabakh) in the south Caucasus suggests that it is likely to be endogenously deficient in iodine. The region is heavily dependent on neighboring Armenia for food imports including iodized salt. Since 2005, iodine is a government-sanctioned compulsory supplemental ingredient in salt in Armenia. However, there has never been a study of iodine nutrition in Artsakh. We sought to determine the level of iodine nutrition in Artsakh and the iodine content of table salt in the region. METHODS: Using a cross-sectional modified cluster model, we measured urine and salt iodine concentrations from a representative sample of children living in Artsakh. From 30 schools throughout the territory, we obtained 772 urine samples from children aged 8 to 10, and 323 samples of table salt. Repeat urine samples from 18.6% of participants were obtained. RESULTS: The median adjusted urinary iodine content was 203 µg/L (mean 206 µg/L, 95% confidence interval 202-210), within the range indicating sufficient iodine nutrition. There were small but statistically significant differences between the 8 administrative regions; however, there were no differences between individual sites. We found that 97.2% of table salt samples tested had iodine concentrations within the standard of 25 to 55 mg/kg. CONCLUSION: Among school-age children in Artsakh, iodine nutrition is adequate, and the salt is appropriately iodized. These results illustrate the remarkable success of the Armenian salt iodization program in providing sufficient but not excessive iodine to the mountainous territory of Artsakh. Abbreviation: UIC = urinary iodine concentration.

Recombinant Human Parathyroid Hormone Effect on Health-Related Quality of Life in Adults With Chronic Hypoparathyroidism.

Context: Reduced health-related quality of life (HRQoL) is common in patients with hypoparathyroidism treated conventionally with calcium and active vitamin D supplements. Objective: To examine the effects of recombinant human parathyroid hormone [rhPTH(1-84)] on HRQoL as measured by the 36-Item Short-Form Health Survey (SF-36) during a multinational, randomized, placebo-controlled study. Patients: Adults (N = 122) with chronic hypoparathyroidism. Intervention(s): After an optimization period when calcium and/or active vitamin D supplements were adjusted to reach target serum calcium levels (8.0 to 9.0 mg/dL; 2.0 to 2.2 mmol/L), patients were randomly assigned to receive placebo (n = 39) or rhPTH(1-84) (n = 83) (starting dose, 50 µg/d, could be titrated up to 100 µg/d); supplement doses were adjusted to maintain target serum calcium levels. Main Outcome Measure(s): Change from baseline (postoptimization, at randomization) to week 24 in HRQoL as assessed by the SF-36. Results: Overall, the between-group differences were not statistically significant. However, in the rhPTH(1-84) group, there were significant improvements in the physical component summary score (P = 0.004), and in body pain (P < 0.05), general health (P < 0.05), and vitality (P < 0.001) domains as compared with baseline values. In the placebo group, there were no significant changes for any domains. The magnitude of change between 0 and 24 weeks in SF-36 scores was negatively correlated with baseline scores, such that patients with lower HRQoL at baseline were more likely to experience improvement in response to treatment. Conclusion: Treatment with rhPTH(1-84) may improve HRQoL in adults with hypoparathyroidism.