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Purpose of Review: Low-level evidence and opinion-based clinical practice guidelines highlight the substantial uncertainty in the practice patterns of hyperphosphatemia management in patients with chronic kidney disease (CKD). This manuscript reviews the evidence for the choice of phosphate binders and its impact on clinical outcomes., Recent Findings: Phosphate binders are among the most common medications prescribed for patients on dialysis. Clinical practice guidelines recommend lowering phosphate levels toward normal range and restricting calcium-based binders in all CKD patients. There is substantial gap in the evidence underlying these recommendations with lack of any placebo-controlled, randomized trials showing survival benefits for any class of phosphate-binders. Despite the lack of evidence for specific phosphate target or if lowering phosphate improves survival, use of phosphate binders has remained central strategy in approach to hyperphosphatemia. Use of binders has added to the cost and contributed significant pill burden. Restriction of calcium-based binders to avoid positive calcium balance and consequent vascular calcification risk has a physiological rationale and weight of observational studies., Summary: There is currently no conclusive evidence that definitively guides the choice of any specific binders for management of hyperphosphatemia in patients with CKD. Use of noncalcium-based binders has a theoretical advantage in restricting total calcium intake to decrease the risk of vascular calcification but no proven benefits for mortality., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

This study aimed to explore the therapeutic efficacy and safety of alfacalcidol among Chinese postmenopausal women (age >65 years) with osteoporosis or osteopenia.A total of 62 postmenopausal women with osteoporosis or osteopenia (>65 years) were recruited from urban residential community of Beijing. The patients daily took oral calcium and alfacalcidol (Alpha D3, 1 μg) for 9 months. Safety and efficacy assessments were performed at baseline and regular intervals. Alfacalcidol was adjusted to a daily dose of 0.5 μg in case of hypercalcemia or hypercalciuria.A significant improvement in "timed up and go test" and "chair rising test" was achieved 3 months after treatment. Significant decreases in bone turnover markers were observed 3 months after the treatment and lasted throughout the study. Nineteen patients discontinued due to adverse events (17 hypercalciuria, 1 hydronephrosis, and 1 stomach ache), while alfacalcidol was adjusted to a daily dose of 0.5 μg in 18 patients (29.0%). Increased serum creatinine was observed when compared to baseline (P <.001), but all the values were in normal range.The treatment with 1 μg alfacalcidol can significantly improve muscle function and bone metabolism. Regular monitoring of urine calcium and timely dosage-adjustments are very important to guarantee the safety of alfacalcidol treatment in Chinese menopausal women.

Objectives: To determine the incidence of hypovitaminosis D and to evaluate a supplementation intervention. We hypothesized that patients would exhibit high adherence with a free sample, and levels would become sufficient., Design: Prospective observational study., Setting: Level 1 trauma center., Patients: One hundred forty-four consecutive, skeletally mature patients treated for acute fractures., Intervention: All were provided 600 mg calcium and 800 IU vitamin D3 capsules twice daily., Main Outcome Measurements: Serum 25(OH) D levels were obtained on presentation and after supplementation. Patient surveys determined adherence, vitamin D intake, and sun exposure., Results: Ninety-one men and 53 women, mean age 45 years, mean body mass index 28.1, were studied. Mean baseline 25(OH) D level was 20.2 ng/mL, including 9 patients taking vitamin D supplements before injury. All others (mean baseline 16.9 ng/mL) were prescribed calcium and vitamin D and were offered free supplements when discharged. Seventy-seven patients completed surveys, and mean 25(OH) D level was 36.7 ng/mL after a mean of 7.0 weeks of supplementation (P < 0.0001). Seventy-nine percent reported adherence to supplement recommendations. All adherent patients achieved normal levels. Sixteen patients were nonadherent, with 10 who forgot to take the supplement, 4 choosing not to use it, 1 choosing to sell the sample, and 1 losing the sample., Conclusion: Hypovitaminosis D was present in 97% of orthopaedic trauma patients who were not already taking supplements. The intervention was effective in reducing hypovitaminosis D within several weeks, with all supplemented patients achieving normal levels. Seventy-nine percent of patients adhered to recommendations. Further study to determine the long-term cost-effectiveness of this strategy seems warranted., Level of Evidence: Therapeutic, Level II. See Instructions for Authors for a complete description of levels of evidence.

Background: Evidence supports the role of lifestyle interventions as a primary intervention strategy among individuals with dyslipidemia. The role of micronutrients, and calcium in particular, on cholesterol metabolism is not clear and warrants further investigation., Objective: The aim of this study is to conduct a meta-analysis of controlled clinical trials that have examined the effects of calcium supplements on blood lipids among adults., Methods: MEDLINE, EMBASE, Web of Science, and Cochrane Central Register of Controlled Trials databases were searched up to March 2016 for calcium supplements clinical trials. Other trials were selected from searching bibliography of reviews, meta-analysis, and included trials. Clinical trials with random allocation to calcium supplementation or calcium plus vitamin D supplementation, or control were selected. Data collected included study design, participant characteristics, information of the intervention, and outcomes. Data synthesis was conducted using random effect models., Results: A total of 22 trials, representing 4071 participants, met the eligibility criteria. Compared with control group, calcium supplements significantly reduced low-density lipoprotein cholesterol level by -0.12 mmol/L (95% confidence interval, -0.22 to -0.02) and increased high-density lipoprotein cholesterol level by 0.05 mmol/L (95% confidence interval, 0.00 to 0.10). Subgroup analyses revealed that the associations were consistent across study duration and vitamin D cosupplementation status., Conclusions: Calcium supplementation has beneficial effect on blood lipids. Such supplements may be useful as a nonpharmaceutical strategy in cholesterol control.

Purpose of Review: This review summarizes recent findings on musculoskeletal health in three chronic renal conditions of childhood: chronic kidney disease stages 2-5D, nephrotic syndrome, and urolithiasis. Findings with important clinical implications warranting further investigation are highlighted., Recent Findings: Recent cohort studies have demonstrated a high burden of fracture and progressive deficits of cortical bone in children with chronic kidney disease. Lower cortical density is associated with incident fracture and may be an important therapeutic target. Parathyroid hormone and calcium are independent correlates of cortical density, and modifiable factors for fracture include parathyroid hormone and phosphate binder use. Children with nephrotic syndrome, even with normal renal function, have evidence of abnormal bone metabolism and structure, and vitamin D deficiency may be an important modifiable risk factor in this population. Urolithiasis has been associated with reduced bone mineral density and is increasingly common in children and adolescents. Population-based data found a significantly increased risk of fracture in adolescent males and young women., Summary: Recent findings substantiate concern regarding the particular vulnerability of the growing skeleton to chronic renal disease. Studies are needed to determine how to optimize assessment and management of bone health in children with these conditions, particularly in terms of calcium and vitamin D requirements, with the goal of improving childhood bone accrual for lifelong fracture prevention.

In 2012 there were 135,943 infants of multiple pregnancies born in the United States, nearly a 2-fold increase since 1980, with twins accounting for 96% of all multiple births. To date, most perinatal morbidities associated with multiple births have proven resistant to technological or pharmaceutical interventions. Maternal nutrition can have a profound effect on the course and outcome of multiple pregnancy, with the goal of achieving optimal intrauterine growth and birthweights, and minimizing prenatal and perinatal complications for the mother and her children.

This chapter provides a summary of the literature including results from large trials, meta-analyses, and recent major recommendations. Two well-accepted and recent recommendations include those from the Agency for Health Research and Quality on calcium and vitamin D supplementation and from the Institute of Medicine's dietary reference intakes for calcium and vitamin D. This review suggests that there is strong evidence for synergistic roles of calcium and vitamin D in maintaining bone health in postmenopausal women, but the correlation between vitamin D alone and bone health is overall inconclusive.

Women who have significant bone loss or a new fracture on monotherapy are considered for combination therapy. Combination therapies increase bone density more than monotherapy by targeting different parts of the osteoclast pathway.In early postmenopausal women who are symptomatic, the use of combination antiresorptives should include hormone therapy with a bisphosphonate or with bazodoxifene. In women who initially receive a weaker antiresorptive such as the SERM raloxifene, a combination with bisphosphonates and calcium supplementation is necessary to prevent bone loss. In older women over 65 years of age who often have impaired calcium absorption, the combination of calcitriol with bisphosphonates has been shown to increase bone density more than monotherapy.

The purpose of this review is to evaluate current evidence regarding the use of dietary and exercise interventions to prevent fractures in postmenopausal women with osteoporosis. The key lifestyle modifications that can decrease risk of fracture in postmenopausal women include regular weight-bearing exercise and a balanced diet with adequate calcium and vitamin D intake. Other modifiable lifestyle factors critical to bone health and to decrease fracture risk include the avoidance of smoking, an excessively low body weight, excessive alcohol intake, and fall risks at home. Emerging modifiable factors may include B-vitamin, omega-3 fatty acid, soy isoflavone, and dehydroepiandrosterone supplementation.

Osteoporosis, a "silent disease," is often unrecognized until fracture. Lifestyle modification with nutritional counseling is recommended during menopausal transition. Bone density testing is recommended for women aged 65 years and older, younger postmenopausal women with risk factors, or to follow therapy. Bisphosphonates treat osteoporosis (prevent bone resorption). Raloxifene and hormone therapy prevent bone loss and fracture, with extraskeletal benefits. Denosumab treats osteoporosis, although bone effects reverse rapidly. Teriparatide (anabolic therapy) is considered for women at high risk of fracture. Bazedoxifene with conjugated estrogens, novel delivery of teriparatide, new parathyroid hormone proteins, anti-sclerostin antibodies, cathepsin K inhibitors, and stem cell therapies are in testing.

Treatment of infectious diarrheas remains a challenge, particularly in immunocompromised patients in whom infections usually persist and resultant diarrhea is often severe and protracted. Children with infectious diarrhea who become dehydrated are normally treated with oral or intravenous rehydration therapy. Although rehydration therapy can replace the loss of fluid, it does not ameliorate diarrhea. Thus, during the last decades, there has been continuous effort to search for ways to safely stop diarrhea. Herein, we report 3 immunocompromised children who developed severe and/or protracted infectious diarrhea. Their diarrheas were successfully "halted" within 1 to 2 days following the administration of calcium.

Osteoporosis is frequently called the silent disease because it lacks symptoms or signs until a fracture has occurred. Osteoporosis is common in aging women because of progressive postmenopausal bone loss. Fractures related to bone loss can result in reduced quality of life, lengthy hospital stays, long-term institutionalization, and death. Early diagnosis and treatment of low bone mass to reduce fracture risk is a cost-effective element of routine health care for women. With appropriate patient screening, ObGyn care providers can implement effective interventions before fractures occur, thereby improving patients' quality of life and reducing society's osteoporosis-related costs.

Purpose of Review: Postoperative hypocalcemia is one of the most common complications following thyroidectomy. This review examines recent literature on predictive factors for hypocalcemia, measurement of serum calcium and parathyroid hormone (PTH) levels, and algorithms for supplementation with calcium and/or vitamin D., Recent Findings: Risk factors for developing postthyroidectomy hypocalcemia include hyperthyroidism, vitamin D deficiency, female sex, substernal thyroid disease, and thyroid cancer, necessitating central neck lymphadenectomy. Several studies have shown that routine postoperative oral calcium and calcitriol supplementation results in lower rates of tetany. Recent studies have focused on the predictive value of intraoperative and postoperative serum PTH levels for the development of symptomatic hypocalcemia. Although the exact timing and serum levels of PTH have been variable, studies have confirmed that patients with very low postoperative PTH levels require oral calcitriol and calcium supplementation. A societal-level cost-utility analysis examining the use of routine vs. selective oral calcium and calcitriol supplementation found that routine supplementation is more cost-effective, and is associated with improved quality of life, irrespective of the surgeons' specific rates of hypocalcemia., Summary: Although some clinicians favor routine supplementation postoperatively, others advocate selective supplementation, guided by postoperative PTH levels. The optimal algorithm is unknown, although a recent cost-analysis study suggests that routine supplementation may be favored at the societal level.

This 8-week study investigated the effects of increasing dietary Ca2+ content from 1.0% to 3.0% and hypercalcemia induced by oral 1alpha-OH vitamin D3 (1OH-D3, 1.2 microg/kg), on arterial tone in NaCl-hypertensive rats. The high-Ca2+ diet completely prevented the increase in blood pressure induced by the 6.0% NaCl chow, while plasma total Ca2+ and body weight were not different from controls. The 1OH-D3 treatment moderately elevated plasma total Ca2+ and attenuated the NaCl-induced rise in blood pressure, but also impaired weight gain. The tone of isolated mesenteric arterial rings was examined at the end of study. The endothelium-independent relaxations to nitroprusside, isoproterenol, and cromakalim were impaired in NaCl-hypertension. Experiments with NG-nitro-l-arginine methyl ester and tetraethylammonium in vitro suggested that both the nitric oxide- and hyperpolarization-mediated components of endothelium-dependent relaxation to acetylcholine were reduced in NaCl-hypertensive rats. All of the impaired relaxations in NaCl hypertension were normalized by concomitant Ca2+ supplementation. The 1OH-D3 treatment did not affect vascular relaxation, but it attenuated maximal contractile responses induced by norepinephrine and KCl by more than 50%. The reduced vasoconstrictor responses could not be explained by increased apoptosis in the vessel wall, but calcification may have played a role, since moderate signs of medial or adventitial calcification were observed in the aortic preparations after the 1OH-D3 treatment. In conclusion, a high-Ca2+ diet, which did not cause hypercalcemia, normalized blood pressure and endothelium-dependent and endothelium-independent vasorelaxation in NaCl-hypertensive rats. In contrast, chronic hypercalcemia induced by 1OH-D3 was associated with moderately lowered blood pressure, possibly because of reduced vasoconstrictor responses in arterial smooth muscle.

Osteoporosis is a major health problem facing women and men, and the number of people affected is likely to increase substantially as the population ages. The gold standard for treatment has always been prevention. This article reviews therapeutic options, with an emphasis on nutrition; outlines current recommendations for calcium and vitamin D throughout the life span; and discusses food and supplemental sources of calcium. Guidelines are given for identifying high- and low-risk patients, and appropriate interventions are highlighted.

A European multicentric intervention study, led by the colon group of the European Cancer Prevention Organization, is under way. The main aim of the study is to test the efficacy of oral calcium supplementation with 2 g calcium per day and oral dietary supplementation with mucilaginous substances (as 3.8 g of ispaghula husk) on adenoma recurrence. Secondary aims are the study of treatment efficacy on colonic cell proliferation and on stool bile acid and sterol concentration. Serum and plasma samples are also collected. To better interpret the effect of the intervention, a diet history questionnaire and an aspirin and anti-inflammatory drug questionnaire are administered. The aim will be achieved through a randomized placebo-controlled clinical trial using a parallel design in patients aged 35 to 75 at entry with a complete colonoscopy and a clean colon. Overall, 655 subjects have been included. All randomized patients are followed up every six months for 3 years. If one of the evaluated interventions proves efficient, the benefits of a simple, safe and inexpensive prophylaxy for a very common cancer will be clear.

Background: Dietary calcium intake has been suggested to correlate inversely with blood pressure in humans and experimental animals. However, the effects of calcium supplementation on hypertensive disturbances of the endothelium have not been well characterized., Methods and Results: Wistar-Kyoto rats made hypertensive by deoxycorticosterone (DOC)-NaCl treatment, but a concurrent increase in chow calcium content from 1.1% to 2.5% markedly attenuated the rise in blood pressure. The function of isolated mesenteric arterial rings in vitro was investigated at the close of the 10-week study. In norepinephrine-precontracted rings, the relaxations to acetylcholine (ACh) and ADP, as well as to nitroprusside, 3-morpholinosydnonimine, and isoproterenol were attenuated in hypertensive rats on 1.1% calcium supplementation. In the presence of NG-nitro-L-arginine methyl ester (L-NAME), the relaxations to ACh in hypertensive animals on normal calcium were practically absent, whereas in normotensive rats and calcium-supplemented hypertensive rats, distinct relaxations to higher concentrations of ACh were still present. These responses were reduced by 30% to 50% with apamin, a blocker of Ca2+-activated K+ channels, and were further inhibited by blockade of ATP-dependent K+ channels with glyburide. Interestingly, relaxations elicited by ACh and ADP during precontraction with 60 mmol/L KCl (preventing endothelium-dependent hyperpolarization) were not impaired in hypertensive animals. The contractile sensitivity of endothelium-intact arterial rings to 5-hydroxytryptamine and norepinephrine was higher in hypertensive rats on either normal or high-calcium diet, whereas the increase in contractile sensitivity caused by L-NAME corresponded in all groups., Conclusion: High-calcium diet markedly opposed experimental DOC-NaCl hypertension, an effect associated with improved arterial relaxation, while abnormalities of vascular contractile properties remained unaffected. In particular, the hyperpolarization-related component of endothelium-dependent arterial relaxation, mediated via opening of arterial K+ channels, could be augmented by calcium supplementation in DOC-NaCl hypertension.

We studied the effects of a high Ca (4.07%) diet on mean arterial pressure (MAP) and renal hemodynamics in young (6 weeks) spontaneously hypertensive rats (SHR) fed a normal (0.66%) or a high-salt (8.00%) diet for 4 weeks. The high-salt diet accelerated development of hypertension (213 +/- 5 vs. 159 +/- 2 mm Hg, p < 0.01) and increased renal vascular resistance (RVR) (26.4 +/- 2.3 vs. 18.2 +/- 1.2 U, p < 0.01) in young SHR. Simultaneous Ca supplementation prevented the salt-induced increase in MAP (158 +/- 3 mm Hg, p < 0.01) and in RVR (17.3 +/- 1.1 U, p < 0.01). The high-Ca diet did not affect MAP (151 +/- 3 mm Hg, NS) and RVR (17.4 +/- 1.3 U, NS) in young SHR fed a normal salt diet. RVR and MAP were positively correlated in all rats (r = 0.634, n = 38, p < 0.001). The high-Ca diet also prevented salt-induced left ventricular (LV) hypertrophy. Dietary Ca supplementation attenuated the increased salt sensitivity of arterial pressure, possibly by normalizing renal hemodynamics, in salt-loaded young SHR.

To determine the clinical significance of parathyroid hypertensive factor (PHF), physiological studies previously performed in animal models of hypertension were parallelled by human studies. These studies revealed that PHF-like activity is present in human hypertension, where it correlates with the salt-sensitive, low-renin state. As in spontaneously hypertensive rats, both supplemental calcium and calcium-channel blockers appear to be useful in the treatment of PHF-related hypertension. In primary hyperparathyroid patients, PHF presence is linked with the presence of hypertension. Postparathyroidectomy blood pressure falls in parallel with PHF levels. These preliminary human studies suggest that PHF may be a useful marker in the treatment of hypertension.

High levels of dietary calcium attenuate the elevation of arterial pressure induced by deoxycorticosterone (DOC)-salt in trained, conscious dogs. This response resulted primarily from the failure of the expected rise in peripheral vascular resistance to develop. In addition, the enhanced pressor sensitivity to norepinephrine and angiotensin II associated with DOC-salt hypertension was normalized by high levels of dietary calcium. These changes could not be explained by changes in serum potassium concentration, plasma catecholamines concentration, or plasma volume. A possible explanation is that high levels of dietary calcium inhibit a parathyroid hypertensive factor that has been observed to be elevated in mineralocorticoid-induced hypertension. This hypothesis requires further studies.

In an effort to reduce the risk of colorectal cancer development, oral calcium carbonate supplementation has been used in previous studies for the precipitation of cytotoxic bile acids and fatty acids. In human intervention trials its effect on mucosal hyperproliferation in the colorectum has not always been satisfactory. Because the complexation of calcium and bile acids requires the formation of calcium phosphate, we performed an intervention study in 14 healthy volunteers, giving them 1,500 mg calcium as Ca3(PO4)2 for 1 week. The effects of tricalcium phosphate on luminal and faecal parameters of cytolytic activity were evaluated before, during, and after calcium phosphate supplementation. The cytolytic activity of faecal water and intestinal alkaline phosphatase activity in faecal water were not affected by supplemental calcium phosphate. In duodenal bile, the proportion of cholic acid tended to increase, whereas that of chenodeoxycholic acid tended to decrease during calcium phosphate supplementation. Neither concentrations of total and individual faecal bile acids, nor that of faecal fat were affected during calcium phosphate supplementation. It is suggested that, although phosphate is involved in bile acid precipitation, phosphate competes for calcium in the binding of fatty acids. This might possibly explain the unchanged cytolytic potency of faecal water, and therefore does not make tricalcium phosphate a suitable calcium compound for dietary intervention.

The issue of nondrug treatment, either as a sole or an adjunct therapy in combination with a drug treatment for high blood pressure (BP), is controversial. In an attempt to resolve controversies and to arrive at a consensus, the Canadian Consensus Conference on Nonpharmacological Approaches to the Management of High Blood Pressure was convened in March 1989 in Halifax, Nova Scotia. State-of-the-art information on seven key nonpharmacological issues about body weight, alcohol, salt, potassium and calcium intake, physical exercise, and relaxation were reviewed, and a multidisciplinary consensus panel arrived at recommendations aimed at those members of the general public who are normotensive, those with high BP, health professionals, and, in some cases, the government and the food industry. This panel also suggested further studies in each of the topic areas.