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.

The effects of vegetarian diets on bone health: A literature review.

In these recent years many people are adopting a vegetarian type diet due to the numerous positive health effects of this regimen such as the reduction of the incidence of many chronic disorders like diabetes, hypertension, obesity and cancer. However this diet is quite restrictive and so it could be possible to have a deficiency in some specific nutrients, increasing the risk of osteoporosis and fractures. Although there are conflicting results on the effects of the vegetarian diet on bone health and fracture incidence, it is always recommendable in vegetarian people to have an adequate intake of calcium and vitamin D, through an increased intake of supplements, natural and fortified foods, an adequate intake of protein, fruit, vegetables, as well as vitamin B12. The aim of this literature review is to revise the actual knowledge of the effect of some nutrients and vegetarian diets on bone health.

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).

Selenium: A Trace Element for a Healthy Skeleton - A Narrative Review.

Inadequate serum selenium levels may delay the growth and physiological changes in bone metabolism. In humans, reduced serum selenium concentrations are associated with both increased bone turnover and reduced bone mineral density. Moreover, a reduced nutritional intake of selenium may lead to an increased risk of bone disease. Therefore, selenium is an essential nutrient playing a role in bone health, probably due to specific selenium-proteins. Some selenium-proteins have an antioxidation enzymatic activity and participate in maintaining the redox cellular balance, regulating inflammation and proliferation/differentiation of bone cells too. At least nine selenium-proteins are known to be expressed by fetal osteoblasts and appear to protect bone cells from oxidative stress at bone microenvironment. Mutations of selenium-proteins and reduced circulating levels of selenium are known to be associated with skeletal diseases such as the Kashin-Beck osteoarthropathy and postmenopausal osteoporosis. In addition, the intake of selenium appears to be inversely related to the risk of hip fragility fractures. Recent data suggest that an altered selenium state may affect bone mass even in males and selenium-proteins and selenium concentrations were positively associated with the bone mass at femoral, total and trochanteric sites. However, selenium, but not selenium-proteins, seems to be associated with femoral neck bone mass after adjustment for many bone fracture risk factors. The present review summarizes the findings of observational and interventional studies, which have been designed for investigating the relationship between selenium and bone metabolism.

Updates in epidemiology, pathophysiology and management strategies of glucocorticoid-induced osteoporosis.

INTRODUCTION: Endogenous or exogenous (corticosteroid-induced) glucocorticoids (GCs) excess represents, together with diabetes, the most common cause of secondary osteoporosis. AREAS COVERED: We present a comprehensive overview about the pathophysiology, clinical management and treatment of GCs induced osteoporosis (GIOP). According to PRISMA guidelines, a literature search identifying articles about bone and GCs was done. EXPERT OPINION: Despite the progress over the years and the increase in therapeutic options, there still are controversial issues about the management of GIOP. These mainly include the failure of BMD or FRAX to completely account for the rapid increase in fracture risk of most GC-treated patients, the understanding about the independent contribution on bone fragility of the underlying disease requiring GCs therapy, and the necessity of clearer information about the anti-fracture efficacy and long term-safety of most therapeutic options. Moreover, there are no specific indications for the management of bone fragility in endogenous hypercortisolism. Notwithstanding the above limitations there is a general consensus to recommend an assessment of fracture risk in all individuals >40 years committed to receive (or continuing) high dose (>7.5 mg of prednisone equivalent) GCs for ≥3 months and in all patients with fragility fracture history.

Bone metabolism, bone mass and structural integrity profile in professional male football players.

BACKGROUND: Physical exercise plays an important role in bone mineralization as well as factors involved in bone metabolism influence the athletic performance. In European countries, soccer is the most popular sport. The aim of the study was to investigate bone metabolism, bone mass and structural integrity profile in professional male adult football players. METHODS: Sixteen professional male football players from a single team of the Second division Italian League (mean age 22.4±0.7 years) were enrolled. Bone biochemical parameters, including serum calcium, phosphorus, albumin, creatinine, alkaline phosphatase, intact plasma PTH, 25-hydroxy-vitamin D (25-OHD), 24-h urinary calcium and phosphorus, and calcaneal quantitative ultrasound (QUS), were evaluated at the beginning (October 2012) and at the end of the League (May 2013). RESULTS: 25-OHD levels were significantly lower at the end of the League compared to the beginning (27.1±5.9 vs. 36.6±9.5 ng/mL, fold change [FC]=0.25, P=0.008), and the prevalence of 25-OHD deficiency increased from 25% to 73%. Moreover, higher rate of previous bone, cartilage or ligament injuries correlated with 25-OHD deficiencies (P=0.014). T-score and Z-score were at the upper limits of the normality ranges, without significant difference between the beginning and end of the League. Phosphaturia was slightly decreased at the end of the League (691.0±364.5 vs. 934.0±274.3 mg/24h, FC=0.26, P=0.06). A significant correlation was found between phosphaturia and BQI (R2=0.28, P=0.03), and both T-s and Z-s (R2=0.28, P=0.03) at the beginning of the League. CONCLUSIONS: With this pilot study, we demonstrated that vitamin D status significantly worsened at the end of the League. Therefore, vitamin D supplementation might be suggested in adult football players in order to prevent vitamin D deficiency and improve the athletic performance.

Calcium citrate: from biochemistry and physiology to clinical applications.

Adequate daily calcium intake should normally be achieved by dietary sources. Since low calcium diets are quite common in subjects that do not reach the recommended intake and particularly those at risk of fractures, calcium supplements may become necessary. Different forms of calcium salts are available, but products containing calcium citrate and calcium carbonate complexes are the most frequently used. Although only limited evidence on the efficacy and long-term safety of calcium citrate is available, these supplements may represent a valuable product for the management of different chronic pathological conditions. The aim of this review was to evaluate the current and potential clinical applications of calcium citrate. In particular, we focused on the use of calcium citrate supplementation in subjects with osteoporosis or in bariatric patients. Other pathological conditions that could benefit calcium citrate supplementation may include achloridria, chronic hypoparathyroidism and hypocitraturic subjects with moderate/high risk of nephrolithiasis. Indeed, citrate salts are widely used in the treatment of nephrolithiasis, since they have shown an inhibitory effect on kidney stone formation and recurrence.

Hypovitaminosis D: Is It Time to Consider the Use of Calcifediol?

Hypovitaminosis D is becoming a notable health problem worldwide. A consensus exists among several different medical societies as to the need for adequate levels of vitamin D for bone and general health. The correct method by which to restore normal vitamin D levels is still a matter of debate. Although cholecalciferol remains the most commonly distributed form of vitamin D supplementation worldwide, several drugs with vitamin D activity are available for clinical use, and making the correct selection for the individual patient may be challenging. In this narrative review, we aim to contribute to the current knowledge base on the possible and appropriate use of calcifediol-the 25-alpha-hydroxylated metabolite-in relation to its chemical characteristics, its biological properties, and its pathophysiological aspects. Furthermore, we examine the trials that have aimed to evaluate the effect of calcifediol on the restoration of normal vitamin D levels. Calcifediol is more soluble than cholecalciferol in organic solvents, due to its high polarity. Good intestinal absorption and high affinity for the vitamin-D-binding protein positively affect the bioavailability of calcifediol compared with cholecalciferol. In particular, orally administered calcifediol shows a much shorter half-life than oral cholecalciferol. Most findings suggest that oral calcifediol is about three- to five-fold more powerful than oral cholecalciferol, and that it has a higher rate of intestinal absorption. Accordingly, calcifediol can be particularly useful in treating diseases associated with decreased intestinal absorption, as well as obesity (given its lower trapping in the adipose tissue) and potentially neurological diseases treated with drugs that interfere with the hepatic cytochrome P-450 enzyme system, resulting in decreased synthesis of calcifediol. Up to now, there has not been enough clinical evidence for its use in the context of osteoporosis treatment.

Italian Association of Clinical Endocrinologists (AME) and Italian Chapter of the American Association of Clinical Endocrinologists (AACE) Position Statement: Clinical Management of Vitamin D Deficiency in Adults.

Vitamin D deficiency is very common and prescriptions of both assay and supplementation are increasing more and more. Health expenditure is exponentially increasing, thus it is timely and appropriate to establish rules. The Italian Association of Clinical Endocrinologists appointed a task force to review literature about vitamin D deficiency in adults. Four topics were identified as worthy for the practicing clinicians. For each topic recommendations based on scientific evidence and clinical practice were issued according to the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) System. (1) What cut-off defines vitamin D deficiency: even though 20 ng/mL (50 nmol/L) can be considered appropriate in the general population, we recommend to maintain levels above 30 ng/mL (75 nmol/L) in categories at risk. (2) Whom, when, and how to perform screening for vitamin D deficiency: categories at risk (patients with bone, liver, kidney diseases, obesity, malabsorption, during pregnancy and lactation, some elderly) but not healthy people should be screened by the 25-hydroxy-vitamin D assay. (3) Whom and how to treat vitamin D deficiency: beyond healthy lifestyle (mostly sun exposure), we recommend oral vitamin D (vitamin D2 or vitamin D3) supplementation in patients treated with bone active drugs and in those with demonstrated deficiency. Dosages, molecules and modalities of administration can be profitably individually tailored. (4) How to monitor the efficacy of treatment with vitamin D: no routine monitoring is suggested during vitamin D treatment due to its large therapeutic index. In particular conditions, 25-hydroxy-vitamin D can be assayed after at least a 6-month treatment. We are confident that this document will help practicing clinicians in their daily clinical practice.

Biological effects of various regimes of 25-hydroxyvitamin D3 (calcidiol) administration on bone mineral metabolism in postmenopausal women.

Introduction. It is evident from several studies that vitamin D inadequacy is widespread among women with osteoporosis across all continents regardless of season or latitude, with similar prevalence in patients treated for osteoporosis and in untreated women. These results underscore a need to improve physician and patient awareness of the importance of adequate vitamin D supplementation in postmenopausal women with osteoporosis.Materials and Methods. As the daily administration of vitamin D combined with 1 gr calcium is hampered by an insufficient patient adherence, we performed a longitudinal study in 90 randomly recruited postmenopausal women aged 65-75 years with inadequate calcium intake and circulating levels of 25-hydroxyvitamin D3 (lower than 30 ng/mL). The prevalence of secondary hyperparathyroidism (parathyroid hormone > 65 pg/mL) was 36% in the all population. The possible repercussion of oral single weekly or monthly calcidiol administration on phospho-calcium metabolism was observed after three months treatment (from April through July) with 500 mg calcium daily and with three different therapeutic regimens of calcidiol (Group I: 25 drops weekly; Group II: 50 drops monthly; and Group III: 100 drops monthly). The general baseline characteristics of the three groups were superimposable. We measured fasting morning serum 25-hydroxyvitamin D3, parathyroid hormone, calcium, phosphate, bone alkaline phosphatase, urinary deoxypyridinoline, and 24hr-calcium, - phosphate, and - creatinine.Results. The adherence to the weekly calcidiol treatment was over 80% in 90% of the patients. All three therapeutic regimens of calcidiol led to normalization of 25-hydroxyvitamin D3 after 3 months, yet with a significantly higher potency (P >0.01) of regimens I and III, when compared to Group II. Also the decrease of circulating levels of parathyroid hormone was significantly higher (P < 0.001) in Groups I and III versus Group II. No biochemically and clinically relevant adverse effects were observed at the end of the 90-day follow-up.ConclusionsIn postmenopausal women with inadequate circulating levels of 25-hydroxyvitamin D3, calcium and pulsed calcidiol supplementation normalized 25-hydroxyvitamin D3 levels and reduced circulating parathyroid hormone levels.