CASE REPORT: A 29-year-old wheelchair-bound woman was presented to us by the gastroenterologist with suspected osteomalacia. She had lived in the Netherlands all her life and was born of Moroccan parents. Her medical history revealed iron deficiency, growth retardation, and celiac disease, for which she was put on a gluten-free diet. She had progressive bone pain since 2 years, difficulty with walking, and about 15 kg weight loss. She had a short stature, scoliosis, and pronounced kyphosis of the spine and poor condition of her teeth. Laboratory results showed hypocalcemia, an immeasurable serum 25-hydroxyvitamin D level, and elevated parathyroid hormone and alkaline phosphatase levels. Spinal radiographs showed unsharp, low contrast vertebrae. Bone mineral density measurement at the lumbar spine and hip showed a T-score of -6.0 and -6.5, respectively. A bone scintigraphy showed multiple hotspots in ribs, sternum, mandible, and long bones. A duodenal biopsy revealed villous atrophy (Marsh 3C) and positive antibodies against endomysium, transglutaminase, and gliadin, compatible with active celiac disease. A bone biopsy showed severe osteomalacia but normal bone volume. She was treated with calcium intravenously and later orally. Furthermore, she was treated with high oral doses of vitamin D and a gluten-free diet. After a few weeks of treatment, her bone pain decreased, and her muscle strength improved.

DISCUSSION: In this article, the pathophysiology and occurrence of osteomalacia as a complication of celiac disease are discussed. Low bone mineral density can point to osteomalacia as well as osteoporosis.

Full Citation: "SUMMARY: The impact of calcium and vitamin D intake on bone density and one-year fracture risk was assessed in 76,507 postmenopausal Caucasian women. Adequate calcium with or without vitamin D significantly reduced the odds of osteoporosis but not the risk of fracture in these Caucasian women. INTRODUCTION: Calcium and vitamin D intake may be important for bone health; however, studies have produced mixed results. METHODS: The impact of calcium and vitamin D intake on bone mineral density (BMD) and one-year fracture incidence was assessed in 76,507 postmenopausal Caucasian women who completed a dietary questionnaire that included childhood, adult, and current consumption of dairy products. Current vitamin D intake was calculated from milk, fish, supplements and sunlight exposure. BMD was measured at the forearm, finger or heel. Approximately 3 years later, 36,209 participants returned a questionnaire about new fractures. The impact of calcium and vitamin D on risk of osteoporosis and fracture was evaluated by logistic regression adjusted for multiple covariates. RESULTS: Higher lifetime calcium intake was associated with reduced odds of osteoporosis (peripheral BMD T-score < or =-2.5; OR = 0.80; 95% CI 0.72, 0.88), as was a higher current calcium (OR = 0.75; (0.68, 0.82)) or vitamin D intake (OR = 0.73; 95% CI 0.0.66, 0.81). Women reported 2,205 new osteoporosis-related fractures. The 3-year risk of any fracture combined or separately was not associated with intake of calcium or vitamin D. CONCLUSIONS: Thus, higher calcium and vitamin D intakes significantly reduced the odds of osteoporosis but not the 3-year risk of fracture in these Caucasian women."

BACKGROUND: The role of total calcium intake in the prevention of hip fracture risk has not been well established. OBJECTIVE: The objective of the study was to assess the relation of calcium intake to the risk of hip fracture on the basis of meta-analyses of cohort studies and clinical trials. RESULTS: In women (7 prospective cohort studies, 170,991 women, 2,954 hip fractures), there was no association between total calcium intake and hip fracture risk [pooled risk ratio (RR) per 300 mg total Ca/d = 1.01; 95% CI: 0.97, 1.05]. In men (5 prospective cohort studies, 68,606 men, 214 hip fractures), the pooled RR per 300 mg total Ca/d was 0.92 (95% CI: 0.82, 1.03). On the basis of 5 clinical trials (n = 5666 women, primarily postmenopausal, plus 1074 men) with 814 nonvertebral fractures, the pooled RR for nonvertebral fractures between calcium supplementation (800-1600 mg/d) and placebo was 0.92 (95% CI: 0.81, 1.05). On the basis of 4 clinical trials with separate results for hip fracture (6,504 subjects with 139 hip fractures), the pooled RR between calcium and placebo was 1.64 (95% CI:1.02, 2.64). Sensitivity analyses including 2 additional small trials with <100 participants or per-protocol results did not substantially alter results. CONCLUSIONS: Pooled results from prospective cohort studies suggest that calcium intake is not significantly associated with hip fracture risk in women or men. Pooled results from randomized controlled trials show no reduction in hip fracture risk with calcium supplementation, and an increased risk is possible. For any nonvertebral fractures, there was a neutral effect in the randomized trials.

Full Citation: "BACKGROUND: Short trials of calcium supplementation show that it reduces loss of bone density in postmenopausal women; longer observational studies do not generally find a lower risk of hip fracture with higher-calcium diets. Fewer studies have focused on vitamin D in preventing postmenopausal osteoporosis or fractures. OBJECTIVE: We assessed relations between postmenopausal hip fracture risk and calcium, vitamin D, and milk consumption. DESIGN: In an 18-y prospective analysis in 72 337 postmenopausal women, dietary intake and nutritional supplement use were assessed at baseline in 1980 and updated several times during follow-up. We identified 603 incident hip fractures resulting from low or moderate trauma. Relative risks (RRs) from proportional hazards models were controlled for other dietary and nondietary factors. RESULTS: Women consuming > or = 12.5 microg vitamin D/d from food plus supplements had a 37% lower risk of hip fracture (RR = 0.63; 95% CI: 0.42, 0.94) than did women consuming < 3.5 microg/d. Total calcium intake was not associated with hip fracture risk (RR = 0.96; 95% CI: 0.68, 1.34 for > or = 1200 compared with < 600 mg/d). Milk consumption was also not associated with a lower risk of hip fracture (P for trend = 0.21). CONCLUSIONS: An adequate vitamin D intake is associated with a lower risk of osteoporotic hip fractures in postmenopausal women. Neither milk nor a high-calcium diet appears to reduce risk. Because women commonly consume less than the recommended intake of vitamin D, supplement use or dark fish consumption may be prudent."

Full Citation: "The purpose of this study was to clarify the effects of dietary calcium (Ca) supplementation on bone metabolism of magnesium (Mg)-deficient rats. Male Wistar rats were randomized by weight into three groups, and fed a control diet (control group), a Mg-deficient diet (Mg- group) or a Mg-deficient diet having twice the control Ca concentrations (Mg-2Ca group) for 14 days. Trabecular bone volume was significantly lower in the Mg- and Mg-2Ca groups than in the control group. Trabecular number was also significantly lower in the Mg- and Mg-2Ca groups than in the control group. Mineralizing bone surface, mineral apposition rate (MAR), and surface referent bone formation rate (BFR/BS) were significantly lower in the Mg- and Mg-2Ca groups than in the control group. Furthermore, MAR and BFR/BS were significantly lower in the Mg-2Ca group than in the Mg- group. These results suggest that dietary Ca supplementation suppresses bone formation in Mg-deficient rats."

To explore the relation between esophageal cancer and dietary trace elements in humans, we estimated the average daily intake of zinc, copper, iron, selenium, molybdenum, silicon, cadmium, and nickel in 21 Chinese communes, where the annual mortality rate from esophageal cancer among the population 30 years of age and over ranged from 0 to 495/100,000 person-years. We also estimated the relative level of calcium consumption. Zinc and copper intake were inversely related to esophageal cancer mortality, and calcium intake levels was positively related to esophageal cancer mortality. The predicted esophageal cancer mortality among a vegetarian population with a high level of dietary calcium and a low level of dietary zinc was 5.3 times as high as that in a vegetarian population with a low level of dietary calcium and a high level of dietary zinc. The influence of a high level of dietary calcium in a vegetarian population may be explained by a reduction in the absorption of dietary zinc.

Osteoporosis and low bone mineral density affect millions of Americans. The majority of adults in North America have insufficient intake of vitamin D and calcium along with inadequate exercise. Physicians are aware that vitamin D, calcium and exercise are essential for maintenance of bone health. Physicians are less likely to be aware that dietary insufficiencies of magnesium, silicon, Vitamin K, and boron are also widely prevalent, and each of these essential nutrients is an important contributor to bone health. In addition, specific nutritional factors may improve calcium metabolism and bone formation. It is the authors' opinion that nutritional supplements should attempt to provide ample, but not excessive, amounts of factors that are frequently insufficient in the typical American diet.In contrast to dietary insufficiencies, several nutrients that support bone health are readily available in the average American diet. These include zinc, manganese, and copper which may have adverse effects at higher levels of intake. Some multivitamins and bone support products provide additional quantities of nutrients that may be unnecessary or potentially harmful.The purpose of this paper is to identify specific nutritional components of bone health, the effects on bone, the level of availability in the average American diet, and the implications of supplementation for each nutritional component. A summary of recommended dietary supplementation is included.

Full Citation: "This study examined the feasibility of increasing food-derived calcium to 1500 mg/d and the impact of this change on plasma lipids and nutrient consumption in hypertensive (n = 130) and normotensive (n = 196) participants. Three interventions were applied in a randomized, parallel, placebo-controlled fashion: 1) counseling to increase dietary calcium through food consumption to 1500 mg/d (n = 106), 2) a 1000-mg/d calcium supplement (n = 109), or 3) placebo (n = 111). Plasma lipids were measured before and after 12 wk of intervention whereas nutrient intake was monitored throughout the study. At baseline, hypertensive patients reported lower intakes of carbohydrates, calcium, magnesium, phosphorus, potassium, iron, vitamin D, thiamin, and riboflavin (all P < 0.05). They also had lower HDL (P = 0.014) and higher LDL (P < 0.05) compared with normotensive subjects. During intervention, calcium, magnesium, phosphorus, potassium, thiamin, riboflavin, and vitamins C and D increased (P < 0.01) in the group receiving food calcium but not in the placebo or supplement groups.No changes occurred in plasma lipids or lipoproteins after 12 wk of intervention."

Caloric restriction prolongs life span. Calcium restriction may preserve bone health. In osteoporosis, bone mineral density (BMD) has significantly decreased, due to a lack of osteoblast bone formation. Traditional osteoporosis prevention is aimed at maximizing BMD, but the lifetime effects of continuously maintaining a high BMD on eventual bone health in old age, have not been studied. Strikingly, in countries with a high mean BMD, fracture rates in the elderly are significantly higher than in countries with a low mean BMD. Studies show that this is not based on genetic differences. Also, in primary hyperparathyroidism, on the brink of osteoporosis, BMD levels may be significantly higher than normal. Maybe, BMD does not represent long term bone health, but merely momentary bone strength. And maybe, maintaining a high BMD might actually wear out bone health. Since osteoporosis particularly occurs in the elderly, and because in osteoporotic bone less osteoblasts are available, the underlying process may have to do with ageing of osteoblastic cells. In healthy subjects, osteoblastic bone cells respond to the influx of calcium by composing a matrix upon which calcium precipitates. In the process of creating this matrix, 50-70% of the involved osteoblasts die. The greater the influx of calcium, the greater osteoblast activity, and the greater osteoblast apoptosis rate. An increased osteoblast apoptosis rate leads to a decrease in the age-related osteoblast replicative capacity (ARORC). In comparison to healthy bone, in osteoporotic bone the decrease in the replicative capacity of osteoblastic cells is greater. Due to the eventual resulting lack of osteoblast activity, micro-fractures cannot be repaired. Continuously maintaining a high BMD comes with continuously high bone remodeling rates, which regionally exhaust the ARORC, eventually leading to irreparable microfractures. Regarding long time influences on bone health, adequate estrogen levels are known to be protective against osteoporosis. This is generally attributed to its inhibiting influence on osteoclast activity. Instead, its net effects on osteoblast metabolism may be the key to osteoporosis prevention. Adequate estrogen levels inhibit osteoblast activity, calcium apposition and osteoblast apoptosis rate, preserving the ARORC. CONCLUSION: Regarding osteoporosis prevention, ARORC better than BMD represents bone health. Regarding ARORC, adequate estrogen levels are protective, opposing the similar effects of hyperparathyroidism and a high calcium diet. Tests need to be performed in mice to assess the lifetime effects of a high versus a low calcium diet, on eventual bone fracture toughness.

Reduced bone mineral density (BMD) is frequently found in individuals with untreated celiac disease (CD), possibly due to calcium and vitamin D malabsorption, release of pro-inflammatory cytokines, and misbalanced bone remodeling. A gluten-free diet (GFD) promotes a rapid increase in BMD that leads to complete recovery of bone mineralization in children. Children may attain normal peak bone mass if the diagnosis is made and treatment is given before puberty, thereby preventing osteoporosis in later life. A GFD improves, but rarely normalizes, BMD in patients diagnosed with CD in adulthood. In some cases, nutritional supplementation may be necessary. More information on therapeutic alternatives is needed.

The effect of Medetopect, a food additive, on the metabolic kinetics of transuranics (239Pu and 241Am) has been studied experimentally in white mongrel rats following chronic intake by ingestion. The Medetopect application has been shown to be advantageous for reduction of the 239Pu and 241Am absorption from and content of the gastrointestinal tract of the animals. Note: Medetopect is produced by Sanofi Pharma and contains low-esterified apple pectins, redoxin (vitamin C) and calcium phosphate.

Based on the findings presented in this study, we propose the hypothesis that calcium could be a mediator for the development of atherosclerosis. Figure 8 shows a schematic illustration of the hypothesis. The presence of risk factors such as hypertension, hyperlipidemia, and smoking may increase the influx of calcium into vascular ECs. We have shown that reactive oxygen species, which are considered to be a risk factor for the development of atherosclerosis, actually increase [Ca++]i in vascular ECs. Increased intracellular calcium may damage the function of ECs, resulting in platelet aggregation at the damaged site. Increased intracellular calcium may also increase uptake of macromolecules in plasma such as fibrinogen and LDL, eventually forming atherosclerotic plaque. We have also shown that the influx of calcium into vascular ECs is associated with LDL transport across vascular ECs. The pretreatment by nifedipine inhibited both the increase in [Ca++]i and the increase in LDL transport, suggesting that intracellular calcium modulates LDL transport across ECs. Growth factors released from platelets may provoke migration and proliferation of medial SMCs in the aterial intima. It has been reported that migration of SMCs from arterial media to intima is enhanced by the presence of calcium, and can be inhibited by the pretreatment of calcium antagonist. As demonstrated in this study, calcium also plays an important role in the proliferation of SMCs provoked by some kinds of growth factors such as EGF. On the other hand, we found that an increased amount of dietary Mg suppressed the development of atherosclerotic lesions in the aorta of cholesterol-fed rabbits without affecting plasma total cholesterol and HDL-cholesterol concentrations. The mechanism of action might also be related to the calcium entry blocking action. The clinical and nutritional implications of these phenomena should be investigated further. The evidences presented in this study, however, would not be sufficient to fully explain the etiological role of calcium in atherogenesis. Further studies are required to elucidate the mechanism of the contribution of calcium to atherogenesis. The efficacy of calcium antagonist for the prevention of atherosclerosis in humans should also be investigated further.