Impaired Calcium Absorption Research Articles

Impaired Intestinal Calcium Absorption in Protein 4.1R-deficient Mice Due to Altered Expression of Plasma Membrane Calcium ATPase 1b (PMCA1b)

Protein 4.1R was first identified in the erythrocyte membrane skeleton. It is now known that the protein is expressed in a variety of epithelial cell lines and in the epithelia of many tissues, including the small intestine. However, the physiological function of 4.1R in the epithelial cells of the small intestine has not so far been explored. Here, we show that 4.1R knock-out mice exhibited a significantly impaired small intestinal calcium absorption that resulted in secondary hyperparathyroidism as evidenced by increased serum 1,25-(OH)2-vitamin D3 and parathyroid hormone levels, decreased serum calcium levels, hyperplasia of the parathyroid, and demineralization of the bones. 4.1R is located on the basolateral membrane of enterocytes, where it co-localizes with PMCA1b (plasma membrane calcium ATPase 1b). Expression of PMCA1b in enterocytes was decreased in 4.1(-/-) mice. 4.1R directly associated with PMCA1b, and the association involved the membrane-binding domain of 4.1R and the second intracellular loop and C terminus of PMCA1b. Our findings have enabled us to define a functional role for 4.1R in small intestinal calcium absorption through regulation of membrane expression of PMCA1b.

Vitamin D and atypical femoral fractures

Dear Editors, There have been recent reports of atypical femoral fractures occurring in patients treated with bisphosphonates [1]. While the primary hypothesis has centered on the oversuppression of bone turnover, there have been suggestions that vitamin D deficiency might also be an important risk factor [1, 2]. Thus far, only one series has examined the association between vitamin D levels and atypical femoral fractures [2]. In the study by Girgis et al., serum 25-hydroxyvitamin D (25OHD) of less than 16 ng/mL was associated with an increased the risk of atypical subtrochanteric fractures (OR03.2). While it is plausible that vitamin D deficiency may play a role in the pathogenesis of these fractures since it is associated with impaired calcium absorption, compensatory hyperparathyroidism, and increased bone resorption, it was not an evident risk factor in our clinical experience. In our case series, which was one of the first published series describing this phenomenon [3], there were 16 women, age 52 to 91 years and of Asian ethnicity, who had a serum 25OHD level ascertained at the time of presentation between May 2004 and March 2010. They were compared to age-, ethnicity-, and sex-matched controls with low-energy osteoporotic femoral neck or pertrochanteric fractures admitted during the same period of time. Vitamin D deficiency was defined as 25OHD <20 ng/mL. Baseline characteristics were similar between cases and controls. The median 25OHD was 26.2 ng/mL in cases vs 19.0 ng/mL in controls (p00.0127), consistent with a greater use of calcium (81.3 vs 37.5 %, p00.004) and vitamin D (68.8 vs 34.4 %, p0 0.024) supplementation in cases vs. controls. Only 3 out of 16 cases (18.75 %) were vitamin D deficient, while 17 out of 32 controls (53.13 %) were vitamin D deficient (p0 0.031). The odds ratio for vitamin D deficiency in cases vs controls was 0.20 (95 % CI 0.03, 0.97). The main limitation of this analysis was the measurement of 25OHD at the time of presentation rather than at the initiation of and during bisphosphonate therapy. Nevertheless, our study indicated that vitamin D status was significantly better in cases vs controls at the time of fracture, suggesting that vitamin D status might be a less important factor than previously thought in the development of bisphosphonate-associated atypical femoral fractures.

MENOPAUSE DAN PENGARUHNYA DALAM KEHIDUPAN PERKAWINAN

Menopause occurs exactly at the end of the last menstrual cycle, but the new certainty is obtained if a woman has not experienced the cycle for at least 12 months. When the levels of estrogen and progesterone decline, the hypothalamus and the pituitary gland trying to correct it and this leads to disruption of the normal operation of other body systems, including metabolism, brain chemistry, and bone conditions. The resulting changes include changes in the physical and psychological conditions are very individual (there are experienced and some not). Common physical changes experienced by menopausal women include: skin wrinkles or loosened, urinary incontinence (urinary control disorders), heart palpitations during activity, body temperature increases abruptly, headache, and easy to forget. While the changes in psychological conditions often lead to feelings of depression, and quick to anger. In addition it is the threat of osteoporosis (bone loss), which makes easy fractures impaired calcium absorption and poses a risk of cardiovascular disorders that contribute to raise the risk of heart disease and stroke.

Secondary Hyperparathyroidism, Vitamin D Sufficiency, and Serum Calcium 5 Years After Gastric Bypass and Duodenal Switch

The prevalence of secondary hyperparathyroidism (SHPT) is high after bariatric surgery. Vitamin D is supplied to counteract SHPT and bone disease, and we studied vitamin D associations with SHPT. We measured serum levels of 25-OH vitamin D and parathyroid hormone (PTH) 5 years after gastric bypass and duodenal switch. One hundred twenty-five patients were included, of whom 114 (91 %) had undergone gastric bypass and 11 (9 %) had undergone duodenal switch. SHPT was defined as PTH > 7.0 pmol/l in the absence of hypercalcemia. 25-OH vitamin D levels were divided into three categories: <50, 50-74, and ≥75 nmol/l. Serum ionized calcium, magnesium, phosphate, and creatinine were divided into tertiles. Mean age ± SD was 44 ± 9 years at 5 years follow-up. Ninety out of 125 (72 %) patients were women. SHPT was present in 45 out of 114 (40 %) gastric bypass patients and in 11 out of 11 (100 %) duodenal switch patients. The prevalence was high in all vitamin D categories studied. An inverse association between ionized calcium and PTH was found. For the gastric bypass patients, the odds ratio for SHPT in the upper two tertiles of ionized calcium was 0.35; 95 % CI, 0.15-0.79; p = 0.011, compared with the lowest tertile. Supplements of vitamin D and calcium were not associated with a lower prevalence of SHPT at 5 years follow-up. The prevalence of SHPT was high 5 years after gastric bypass and duodenal switch. SHPT was inversely associated with serum ionized calcium, but not with vitamin D. The supplementation used was insufficient to compensate for the impaired calcium absorption after surgery.

May Long Term Oxcarbazepine Treatment Be Lead to Secondary Hyperparathyroidism?

Background and PurposeThe adverse effects of newer antiepileptic drugs are not well-known. This study assessed the impact of oxcarbazepine (OXC) treatment on bone turnover.MethodsForty-four children with idiopathic focal (and/or secondarily generalized) epilepsy who had been treated with OXC for more than 1 year were compared with 33 healthy, age- and sex-matched children. Serum calcium, phosphorus, alkaline phosphatase, parathyroid hormone, osteocalcin, calcitonin, and 25-hydroxyvitamin D, and bone mineral density were measured to evaluate and compare bone mineralization between the two groups.ResultsThe serum levels of calcium, osteocalcin, 25-hydroxyvitamin D, and bone mineral density did not differ significantly between the study and control groups. However, serum levels of parathyroid hormone, alkaline phosphatase, phosphorus, and calcitonin differed significantly between the two groups.ConclusionsThese findings suggest that OXC treatment leads to secondary hyperparathyroidism with high-turnover bone disease and/or impaired intestinal calcium absorption.

Should Spine Surgeons Screen Vitamin D3 Levels Prior to Spinal Fusion and Total Disc Arthroplasty Surgery

Spinal fusion and total disc arthroplasty require bone healing and bone ingrowth. Vitamin D3 plays a vital role in the absorption of calcium, bone healing, and bone remodeling. Vitamin D3 levels below 10 ng/ml are associated with osteomalacia. Vitamin D3 levels between 10 and 30 ng/ml impair calcium absorption and may be associated with hyperparathyroidism. To optimize the non skeletal effects (such as cancer prevention) from vitamin D3, the literature suggests that levels of at least 50 ng/ml be maintained.

Vitamin D‐mediated calcium absorption in patients with clinically stable Crohn's disease: A pilot study

Vitamin D is the critical hormone for intestinal absorption of calcium. Optimal calcium absorption is important for proper mineralization of bone in the prevention of osteoporosis and osteoporotic fractures, among other important functions. Diseases associated with gut inflammation, such as Crohn's disease (CD), may impair calcium absorption. This pilot study evaluated vitamin D- dependent calcium absorption in subjects with CD. Male subjects with CD (n=4) and healthy age-matched controls (n=5) were studied. All subjects had fractional calcium absorption (FCA; by the dual calcium isotope method), serum 25-hydroxyvitamin D, serum calcium and 24 h urinary calcium excretion measurements at baseline. The FCA in response to vitamin D therapy was re-assessed following administration of oral calcitriol 0.25 mcg twice daily for 1 wk, followed by oral calcitriol 0.50 mcg twice daily for 1 wk. Serum calcium and 24 h urinary calcium determinations were re-assessed after each increasing dose of calcitriol as safety measures. There was no significant difference in calcium FCA at baseline or after increasing doses of calcitriol between the CD and controls. FCA in the control and CD group was approximately 35% at baseline, which increased to 60% after calcitriol therapy. No subject developed hypercalcemia or hypercalciuria. Our results suggest that CD patients have a normal response to vitamin D in enhancing the efficacy of calcium absorption. This suggests that stable CD patients can follow calcium and vitamin D guidelines of non-CD adults. Other factors independent of vitamin D status may impair intestinal calcium absorption in CD, including the degree and location of inflammation, presence of surgical resection and/or use of glucocorticoids.

Presence of impaired intestinal calcium absorption in chronic hypovitaminosis D and its change after cholecalciferol supplementation: assessment by the calcium load test

Hypovitaminosis D is common in Asian Indians and its functional significance is currently under investigation. Previous studies have reported on the effect of low serum 25(OH)D levels (<50 nmol L(-1)) on bone mineral density and serum parathyroid hormone values. The present study assessed the effect of chronic hypovitaminosis D in Asian Indians on intestinal calcium absorption and its change after cholecalciferol supplementation. Subjects included 29 healthy volunteers [mean (SD) age, 28.4 +/- 6.4 years] with low serum 25(OH)D levels on screening. Intestinal calcium absorption was assessed by the 'calcium load test' with 1 g of oral elemental calcium. Subjects were put on a calcium restricted diet 1 week prior to the test. The calcium load test was repeated in 26 of them after 8 weeks of supplementation with oral cholecalciferol (60 000 IU week(-1)). The mean urinary calcium/creatinine ratio of the study subjects was 0.027 +/- 0.023 mg mg(-1) under fasting conditions and increased to 0.035 +/- 0.032 mg mg(-1) after calcium loading (delta change = 29.6%, P = 0.33). After 8 weeks of cholecalciferol supplementation, the mean serum 25(OH)D increased from 18.9 +/- 11.9 to 84.4 +/- 34.9 nmol L(-1) (P < 0.0001). Concomitantly, the mean urinary calcium/creatinine ratio of the study subjects increased from 0.030 +/- 0.024 mg mg(-1) under fasting conditions to 0.059 +/- 0.045 mg mg(-1) after calcium loading (delta change = 96.6%, P = 0.008). The results obtained in the present study show that chronic hypovitaminosis D in Asian Indians has functional relevance in terms of its effect on intestinal calcium absorption, which improves with cholecalciferol supplementation. These findings support the need for improving the vitamin D status of Asian Indians through dietary supplementation and exposure to sunshine.

Evidence of association of Vitamin D receptor Apa I gene polymorphism with bone mineral density in postmenopausal women with osteoporosis

The vitamin D receptor (VDR) was the first candidate gene to be studied in relation to osteoporosis, and most attention has focused on polymorphisms situated near the 3' flank of VDR. The aim of this study was to investigate the association about VDR gene Apa I polymorphism with bone mineral density (BMD) in postmenopausal women with osteoporosis. We studied a total of 136 postmenopausal women with a mean age of 56.36 +/- 10.29 years. Among them, a total of 75 had osteoporosis, 37 had osteopenia, and 24 had normal BMD. Venous blood samples were obtained for evaluation of bone metabolism and genotyping. The VDR Apa I genotype was determined by polymerase chain reaction-restriction fragment length polymorphism. BMDs at the lumbar spine and hip were measured by dual-energy X-ray absorptiometry. Postmenopausal women with aa genotype had significantly lower BMD values (grams per centimeter square) at lumbar spines compared to persons with AA genotype. Also, postmenopausal women with AA genotype had significantly higher serum Ca level than the subjects with aa genotype. In conclusion, our result may indicate that VDR Apa I gene polymorphism may be responsible for a important part of the heritable component of lumbar spine BMD in postmenopausal women, possibly related to impaired calcium absorption from the bowel.

Meals and Dephytinization Affect Calcium and Zinc Absorption in Nigerian Children with Rickets

Nutritional rickets resulting from calcium insufficiency is common in Nigeria and high dietary phytate is thought to inhibit calcium and zinc absorption. We compared the effects of a high-phytate meal and enzymatic dephytinization on calcium and zinc absorption in Nigerian children with and without rickets. Nineteen children with rickets and 15 age-matched control children, aged 2–10 y, were given calcium (600 mg/d) and ergocalciferol (1250 μg/wk). After 6 wk, calcium and zinc absorption were measured in both groups with and without maize porridge using stable isotopes. One week later, absorption measurements were repeated to assess the effects of enzymatic dephytinization and fermentation of the maize porridge. The phytate concentration of maize porridge (3.87 ± 0.38 g/kg wet weight) was reduced by enzymatic dephytinization (2.83 ± 0.41 g/kg; P < 0.001) but not by fermentation (3.35 ± 0.27 g/kg; P = 0.08). Calcium and zinc absorption were unaffected by the presence of rickets or by fermentation of maize porridge. Calcium absorption was greater with a meal (61.3 ± 25.1%) than without (27.8 ± 14.6%; P < 0.001). Zinc absorption was lower with a meal (16.2 ± 8.0%) than without (63.4 ± 23.9%; P < 0.001). Enzymatic dephytinization increased relative zinc absorption from a meal by 101 ± 81% (P < 0.001) but did not affect calcium absorption. Rickets was not associated with impaired calcium or zinc absorption. Calcium absorption was enhanced by maize porridge, but zinc absorption was reduced. Enzymatic dephytinization increased zinc absorption. Multiple strategies may be required to optimize calcium and zinc absorption in deficient populations.

Abstract 5686: Predictors of Hypocalcemia after Wide Area Circumferential Ablation of Atrial Fibrillation

Introduction: Hypocalcemia occurs frequently after wide area circumferential ablation (WACA) of atrial fibrillation and is more common with the use of open-irrigated tip ablation catheters (ITAC) than 8-mm tip ablation catheters. The mechanism of this phenomenon is unknown, but may be related to binding of calcium to myocardial proteins, volume infusion, or other factors. The present study aims to identify variables associated with acute hypocalcemia after WACA with ITAC. Methods: We analyzed 106 patients undergoing WACA with ITAC. Pre- and post-procedural values of calcium, creatinine, glomerular filtration rate (GFR), hemoglobin, cardiac enzymes (CK, CK-MB and troponin-I), albumin, left atrial size, presence of post-procedure pericardial effusion, infused volume of normal saline, urine output, heparin, furosemide dosage, and procedure time were recorded. Univariate and multivariate analysis were performed to determine variables associated with post-ablation hypocalcemia. Results: The population had mean age of 59±9 years, mean weight of 95±22 kilograms, and 76% were male. Mean pre-procedure GFR was 101±39 mL/min, and mean volume of normal saline infused was 5.5±1.3 liters. The means for pre-procedure calcium, post-procedure calcium, and decrease in calcium were 9.2±0.4, 7.3±0.6, and 1.9±0.7 mg/dL respectively. Of the variables measured, multivariate analysis identified pre-procedure GFR (parameter estimate −0.005) and infused volume of normal saline (parameter estimate 0.11) as factors independently associated with post-ablation hypocalcemia (p value = 0.03). Factors associated with myocardial injury were not apparently related. Conclusions: Lower GFR and higher infused volume of normal saline correlated with acute hypocalcemia after WACA with ITAC. Rather than binding to injured myocardium, these results suggest impaired renal calcium absorption and/or dilutional effects as the principal mechanism(s).

Gastrointestinale Erkrankungen und Osteomalazie

Osteomalacia is a metabolic bone disease associated with impaired mineralization of the bone due to Vitamin D and Calcium deficiency that can develop in gastrointestinal disorders. Gastrointestinal malabsorption after surgery, in disorders of the small bowl, in diseases of the hepatobiliary tree and in pancreatic insufficiency can lead to decreased enteral resorption of the fat-soluble Vitamin D and/or depletion of endogenous Vitamin D stores due to abnormal enterohepatic circulation. As a consequence of the Vitamin D deficiency in combination with the underlying condition patients develop an impaired calcium absorption resulting in hypocalcaemia, which leads to defective bone mineralization. Additionally chronic gastrointestinal inflammation and corticosteroid therapy - which is often needed in these patients - have a negative effect on bone metabolism as well. The therapy consists of oral substitution of Vitamin D and Calcium as well as sufficient sun light exposure or in severe cases the use of artificial UVB-radiation.

Intestinal hyperabsorption of calcium and low bone turnover in hypercalciuric postmenopausal osteoporosis

Hypercalciuria of intestinal origin has been linked with bone loss in calcium nephrolithiasis and idiopathic osteoporosis. This retrospective data analysis was performed to explore potential pathogenetic link between intestinal hyperabsorption of calcium and postmenopausal osteoporosis. Data were retrieved from postmenopausal women who were evaluated for osteoporosis or osteopenia at the Mineral Metabolism Clinic of UT Southwestern Medical Center. A total of 319 patients underwent the test of calciuric response to oral calcium load to obtain an indirect measure of intestinal calcium absorption. Serum and urinary biochemistry and L2-L4 bone mineral density (BMD) were compared between five quintiles of calciuric response. There was a statistically significant trend toward a rise in 24-h urinary calcium and a decrease in urinary deoxypyridinoline (DPD) and BMD, with increasing order of quintiles. The presentation of those in the 1st quintile was consistent with vitamin D insufficiency or deficiency, with impaired calcium absorption, secondary hyperparathyroidism, and stimulated bone turnover (high normal urinary DPD). In contrast, patients in the 5th quintile displayed a picture of absorptive hypercalciuria of stone disease, with intestinal hyperabsorption of calcium, high or high normal urinary calcium and suppressed bone turnover (low or low normal urinary DPD). Thus, the assessment of intestinal calcium absorption in a seemingly homogeneous group of postmenopausal women with osteoporosis or osteopenia revealed a spectrum of calciuric response whose extremes may represent two physiologically distinct subtypes that have important diagnostic and therapeutic implications.

Inulin and Oligofructose and Mineral Metabolism: The Evidence from Animal Trials

Nondigestible oligosaccharides have been shown to increase the absorption of several minerals (calcium, magnesium, in some cases phosphorus) and trace elements (mainly copper, iron, zinc). Inulin-type fructans including oligofructose and fructooligosaccharides derived from sucrose by enzymatic transfructosylation are the best investigated food ingredients in this respect. The stimulation of absorption was more pronounced when the demand for calcium was high, i.e., in animals in the rapid growing stage and in animals with impaired calcium absorption because of either ovariectomy or gastrectomy. Even a small stimulation of calcium absorption increased the mineral accumulation in the skeleton because of its persisting effect over months. Inulin-type fructans stimulated mineral absorption and bone mineral accretion when combined with probiotic lactobacilli and in the presence of antibiotics. Direct comparison of different inulin-type fructans revealed a more pronounced effect by inulin or a mixture of long-chain inulin and oligofructose than by oligofructose alone. Mechanisms on how inulin-type fructans mediate this effect include acidification of the intestinal lumen by short-chain fatty acids increasing solubility of minerals in the gut, enlargement of the absorption surface, increased expression of calcium-binding proteins mainly in the large intestine, modulated expression of bone-relevant cytokines, suppression of bone resorption, increased bioavailability of phytoestrogens, and, via stimulation of beneficial commensal microorganisms, increase of calcium uptake by enterocytes. Under certain conditions, inulin-type fructans may improve mineral absorption by their impact on the amelioration of gut health including stabilization of the intestinal flora and reduction of inflammation. The abundance of reports indicate that inulin-type fructans are promising substances that could help to improve the supply with available calcium in human nutrition and by this contribute to bone health.

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Adult-type hypolactasia and calcium availability: decreased calcium intake or impaired calcium absorption?

Adult-type hypolactasia, as mediated by a widespread genetic predisposition, not only reduces calcium intake but also calcium absorption in the presence of high amounts of lactose and may, therefore, promote osteoporosis. A lactose-reduced diet and lactose-free calcium supplements may reverse this imbalance. Adult-type hypolactasia (HL) defined by the LCT(-13910) polymorphism may reduce calcium intake by reducing dairy consumption and, therefore, promote osteoporosis. This study aimed to evaluate whether lactose also decreases intestinal calcium absorption in subjects with HL and whether lactose-reduced diet and lactose-free calcium supplementation as recommended could maintain bone mineral density (BMD). Based on LCT genotyping, 73 postmenopausal women with and without HL underwent a conventional H(2) breath test with a concomitant oral strontium absorption test lasting 150 minutes, which closely reflects intestinal calcium absorption. In addition, we compared bone-specific laboratory parameters, lumbar and femoral BMD, and spinal radiographs to a similar bone assessment 5 years earlier. LCT genotyping and functional lactose malabsorption tests were highly correlated. Dairy product consumption was reduced by 80% in HL individuals. During concomitant lactose application, mean strontium absorption was blunted by 54% in HL subjects after 150 minutes (1272 +/- 629 microg/L vs. 2020 +/- 1130 microg/L in lactose tolerant subjects, p=0.001). Nevertheless, BMD in HL subjects remained stable with lactose-free calcium supplements during the observation period. Both decreased calcium intake as well as lactose-associated impaired calcium absorption may predispose subjects with HL to osteoporosis. Lactose-free calcium supplementation may help to maintain BMD in HL subjects.

Contrasting mammalian PTH promoters: identification of transcription factors controlling PTH gene expression

Parathyroid hormone (PTH) is a key component in the maintenance of calcium and phosphate homeostasis. The steady-state expression of the PTH gene can be modeled as a balance between transcriptional activators and repressors. During renal failure, the gradual loss of kidney function is often accompanied by increased circulating concentrations of PTH and decreased synthesis of 1,25-di-hydroxyvitamin D3 (1,25(OH)2D3). The latter finding results in impaired calcium absorption and the removal of a known repressor of PTH gene transcription. Current regimens for treating secondary hyperparathyroidism associated with renal insufficiency are focused on boosting activities that repress PTH gene transcription or secretion of the hormone, and involve the use of vitamin D and its analogues or calcimimetic agents. However, in recent years, concerns have arisen over the use of the steroid hormone and alternative treatments are being sought. Here, we present new information regarding transcription factors controlling PTH gene expression, which include the specificity proteins (Sp) and the nuclear factor Y (NF-Y) complex. A highly conserved DNA response element for the Sp proteins has been identified in mammalian promoters, while an NF-Y binding site is uniquely positioned in the human promoter. Both of these factors are expressed in the parathyroid gland and their DNA elements appear to be functioning as activators of PTH gene expression. Further elucidation of such pathways may offer novel approaches for treating hyperparathyroidism associated with renal failure via suppression of transcriptional activators. That work is currently in progress.

Index of Suspicion In the Nursery

A 9-day-old Hispanic boy presents to the emergency department with seizures and apnea. The seizure lasts for about 3 minutes and is characterized by stiffening of the body and laryngospasm. Laboratory evaluation reveals a serum calcium concentration of 6 mg/dL (1.5 mmol/L). Hypocalcemic tetany resolves after administration of intravenous calcium. The infant also has fever of 100.4°F (37.7°C). The infant was born at term, and his birthweight was 3.2 kg. He is the fifth child born of nonconsanguineous parentage. The antenatal period was uneventful. Because the family does not have insurance, the mother had not taken prenatal vitamins and supplements. The baby has been fed with human milk and formula. On physical examination upon admission to the hospital, his temperature is 99°F (36.9°C), pulse is 186 beats/min, respiratory rate is 54 breaths/min, blood pressure is 97/64 mm Hg, and weight is 3.83 kg. He has no dysmorphic features and is normocephalic, with an open and flat anterior fontanelle without craniotabes. No cataracts or Chvostek sign are present. Cardiovascular examination reveals a regular heart rate and rhythm, with no murmurs. The lungs are clear to auscultation bilaterally, and there is no hepatosplenomegaly. Neurologic findings are normal. Laboratory evaluation reveals: sodium, 136 mEq/L (136 mmol/L); potassium, 5.2 mEq/L (5.2 mmol/L); chloride, 101 mEq/L (101 mmol/L); bicarbonate, 26 mEq/L (26 mmol/L); blood urea nitrogen, 10 mg/dL (3.57 mmol/L); creatinine, 0.3 mg/dL (26.5 mcmol/L); glucose, 109 mg/dL (6.1 mmol/L); calcium, 6.6 mg/dL (1.65 mmol/L); phosphorous, 10.5 mg/dL (3.4 mmol/L); albumin, 3.0 g/dL (30 g/L); and magnesium, 2 mg/dL (0.82 mmol/L). The white blood cell count and differential count are normal. Findings on cerebrospinal fluid evaluation are normal. However, the 25-hydroxyvitamin D concentration is less than 7 ng/mL (17.5 nmol/L) (normal, 10 to 68 ng/mL [25 to 169.7 nmol/L]), the 1,25-dihydroxyvitamin D concentration is 45 …

Pathophysiology of bone loss in patients receiving anticonvulsant therapy

Many studies have shown that patients taking antiepileptic drugs (AEDs) are at increased risk for metabolic bone disease and low bone mineral density. Although early reports of bone disease in patients with epilepsy often involved institutionalized patients, who may be at risk because of lack of physical activity, reduced sunlight exposure, and poor nutrition, low bone density has also been reported in well-nourished, ambulatory outpatients with epilepsy. Traditionally, attention to the problem of AED-induced bone loss has been focused on those drugs that induce the hepatic cytochrome P450 enzyme system, thereby increasing the metabolism of vitamin D. However, the mechanisms of AED-induced bone loss appear to be multiple, and all types of AEDs are potentially implicated. Besides hepatic enzyme induction, mechanisms may include direct effects of AEDs on bone cells, resistance to parathyroid hormone, inhibition of calcitonin secretion, and impaired calcium absorption. An understanding of bone biology and the pathophysiology of bone loss can aid in the identification and monitoring of patients at risk and in the planning of appropriate prophylactic and therapeutic measures, by which most of the morbidity associated with AED-induced bone loss can be prevented.

Radiocalcium absorption is reduced in postmenopausal women with vertebral and most types of peripheral fractures.

Intestinal calcium absorption accounts for 60% of the variance in calcium balance and is therefore a potentially very important determinant of bone status. Whether measured by the balance technique or with radiocalcium, it is known to be significantly reduced in postmenopausal women with vertebral and hip fractures. By contrast, there is very little information about calcium absorption in other types of postmenopausal fracture. We now report a series of 549 untreated, Caucasian postmenopausal women in whom we recorded prevalent fractures, measured radiocalcium absorption, and obtained radiographs of the lateral thoracic and lumbar spine. Of these women, 172 had no prevalent fractures, showed normal spine radiographs, and served as controls; 72 had one or more peripheral fractures but normal spine radiographs; 147 had one or more wedged or crushed vertebrae but no peripheral fractures; and 158 had a history of peripheral fracture and one or more fractured vertebrae. Age-adjusted radiocalcium absorption was significantly lower in the two groups with spinal fractures than in the controls ( P<0.001) but not in the group with peripheral fractures only. It was also lower in the cases with more than two spinal fractures than in those with two or less (P<0.001). In respect of peripheral fractures, the greatest age-adjusted absorption deficit was found in fractures of the humerus (35%) followed by hip (32%), spine (21%), wrist (19%), and rib 17% (all significant but not significantly different from each other). Lesser deficits in tibia, ankle and foot fractures were not significant but type 2 errors could not be excluded. We conclude that impaired calcium absorption is particularly associated with those fractures for which osteoporosis is a significant risk factor.