Calcium Malabsorption Research Articles

CROHN'S DISEASE AND OSTEOPOROSIS: RISK FACTORS, DIAGNOSIS AND CLINICAL TREATMENT

Crohn's disease (CD) is a chronic inflammatory bowel disease that affects any part of the gastrointestinal tract. Osteoporosis, in turn, is a skeletal disease characterized by decreased bone mass and deterioration of bone microarchitecture, increasing the risk of fractures. The association between these two diseases has been increasingly investigated, with evidence suggesting that patients with CD are at increased risk of developing osteoporosis. This comorbidity can be attributed to several factors, including corticosteroid use, nutrient malabsorption, chronic inflammation, and hormonal dysfunction. Objective: The objective of this systematic review was to identify and synthesize the available scientific evidence on the relationship between Crohn's disease and osteoporosis, focusing on risk factors, diagnosis, and clinical treatment. Methodology: A systematic review of the literature was performed, following the recommendations of the PRISMA statement. The PubMed, Scielo and Web of Science databases were searched using the following descriptors: “Crohn’s disease”, “Osteoporosis”, “Risk factors”, “Diagnosis” and “Treatment”. Original articles published in the last 10 years, in Portuguese or English, that investigated the association between CD and osteoporosis in adults were included. Case studies, narrative reviews and articles that did not address the relationship between the two diseases were excluded. Results: The results of the review demonstrated that osteoporosis is a frequent complication in patients with CD. Several risk factors were identified, including the use of corticosteroids, malabsorption of calcium and vitamin D, chronic inflammation and hormonal dysfunction. The diagnosis of osteoporosis in patients with CD can be challenging due to the presence of other factors that can affect bone mineral density, such as malnutrition and immobilization. Treatment of osteoporosis in patients with CD should be individualized and may include pharmacological and non-pharmacological measures, such as calcium and vitamin D supplementation, regular physical activity, and reduced tobacco and alcohol consumption. Conclusion: Crohn's disease represents a significant risk factor for the development of osteoporosis. The association between these two diseases is complex and multifactorial, involving several pathogenic mechanisms. Early diagnosis and appropriate treatment of osteoporosis in patients with CD are essential to prevent fractures and improve the quality of life of these patients. It is essential that health professionals are aware of this comorbidity and offer integrated clinical management for these patients.

Effects of vitamin D supplementation (oily form) in patients with thalassemia

Background. Thalassemia is congenital disease case by mutation effect to synthesis of beta globin chain of hemoglobin result in combination of metabolic and endocrine disorder. Bone disease is a not rare complication in thalassemia due to malabsorption of calcium, the secondary chronic renal disorder with low vitamin D (VD), as well as many endocrine risk factors. Aim. Evaluation of vitamin D treatment (oily form) in patients with thalassemia. Method. Post Marketing Surveillance (PMS) in 26 patients with Thalassemia in Ibn Al-Atheer Hospital. All patient take vitamin D oral vial oily form with dose 50000 IU, this PMS continued in 4 weeks, every week the patient take one vial. The Parameter for the level of VD. Result. The total number of patients was 26; mean age was 13.5 years, between 3-41 years, with 53.8% were males and 46.2% were females. mean serum level of vitamin D was statically significantly very lower in thalassemia patients than in than normal level; (89%) of cases had deficient VD (≤ 20 ng/ml), (7%) of cases had insufficient vitamin D (21–29 ng/ml), and (4%) of cases had deficient VD optimal vitamin D (more than 30 ng/ml), our study showed that 4 weeks of VD supplementation significantly increased the serum level of VD. Conclusion. VD (Oily based oral vial) “High D” significantly raise the VD level in serum in majority of thalassemia patients, the result was sustained regardless of age, gender and existence of other comorbidities.

Bariatric surgery and secondary hyperparathyroidism; a mini-review

Bariatric surgery is a type of weight loss surgery that is commonly used to treat obesity. However, this surgery can also affect the body’s calcium and PTH metabolism, leading to the development of secondary hyperparathyroidism (SHPT). Several factors contribute to the development of SHPT after bariatric surgery. Malabsorption of calcium due to reduced intestinal surface area, decreased intake of calcium-rich foods, and altered vitamin D metabolism play a significant role. The loss of weight-bearing adipose tissue can also disrupt the balance between bone formation and resorption, leading to increased bone turnover and calcium release from the skeleton. The management of SHPT after bariatric surgery involves a multidisciplinary approach. Calcium and vitamin D supplementation is essential to correct deficiency and maintain bone health. However, achieving optimal calcium and vitamin D levels can be challenging due to malabsorption issues and the need for higher supplementation doses. In some cases, pharmacological interventions such as calcimimetics or PTH analogs may be required to control PTH levels. However, these medications should be used cautiously due to limited data on their safety and efficacy in the bariatric surgery population. Prevention of SHPT is an important aspect of managing patients undergoing bariatric surgery. Nutritional counseling and regular monitoring of calcium, vitamin D, and PTH levels can help identify and address deficiencies early on. Additionally, using procedures that preserve the duodenum and proximal jejunum, such as duodenal switch or biliopancreatic diversion with duodenal switch, may reduce the risk of developing SHPT.

The Effect of a Gluten-Free Diet on Vitamin D Metabolism in Celiac Disease: The State of the Art.

Celiac disease is a chronic autoimmune disorder involving the small intestine, characterized by villous atrophy, crypt hyperplasia and an increase in intraepithelial lymphocytes. Due to both calcium malabsorption and immune activation, a high prevalence of bone mass derangement is evident in this condition, regardless of the presence of overt malabsorption. Alterations of mineral metabolism are also frequently described, and in this review, the modifications of serum levels of vitamin D are analyzed, according to the available literature on this topic. In untreated patients, secondary hyperparathyroidism is responsible for the hyperconversion of 25-vitamin D into 1,25-vitamin D making mandatory the determination of serum levels of both vitamin metabolites to avoid a wrong diagnosis of vitamin D deficit. A gluten-free diet allows for a normalization of bone and mineral metabolism, reverting these abnormalities and raising some doubts on the need for vitamin supplementation in all the patients. Data available do not support this wide indication, and a complete evaluation of bone and mineral metabolism should be performed to select patients who need this therapeutic approach.

Celiac disease and bone.

Celiac disease (CD) is an autoimmune disorder characterized by small intestinal inflammation triggered by gluten ingestion in genetically-predisposed individuals. A frequent extra-intestinal manifestation of CD is metabolic bone disease which contributes to an increased risk of fracture. The mechanisms underlying bone disease in CD remain incompletely understood, but multiple processes have been proposed including (1) malabsorption of calcium and vitamin D leading to secondary hyperparathyroidism and increased skeletal resorption, (2) pro-inflammatory cytokines altering the osteoprotegerin and receptor activator of nuclear kappa-B ligand ratio favoring osteoclastogenesis, (3) hypogonadism, and (4) low weight and malnutrition. Most studies show reduced bone mineral density in patients with CD. Bone microarchitecture is also deteriorated leading to reduced whole bone stiffness. Many, but not all investigations, have shown an increased risk of fracture associated with CD. The main stay of therapy for CD is maintaining a gluten-free diet. Improvement in bone mineral density with adherence to a gluten-free diet has been well-established. Bone mineral density remains lower, however, compared to controls and increased fracture risk can persist. There is no consensus on the timing of dual-energy x-ray absorptiometry for bone mineral density assessment in patients with CD. Routine screening for CD in patients with osteoporosis is not recommended. Little data are available on the use or efficacy of prescription osteoporosis therapeutics in patients with CD. Studies are needed to develop standardized guidelines for screening and treatment of metabolic bone disease in patients with CD to identify those who may need early intervention with prescription osteoporosis therapy.

PSAT227 Clinically Suspected Calcium Malabsorption and Secondary Hyperparathyroidism Due to Chronic Proton Pump Inhibitor Use in a Child

Abstract Background Proton Pump Inhibitors (PPI) are commonly in clinical practice as agents to treat multiple acid-related gastrointestinal disorders. Studies have shown that long-term PPI-based therapy may be associated with decreased bone mineral density that could be related to hypochlorhydria-associated malabsorption of calcium and gastrin-induced parathyroid hyperplasia. Clinical Case We report the case of a 6-year-old female born premature at 25 weeks, with global developmental delay, chronic lung disease, G-tube and tracheostomy dependent that was admitted for tracheal reconstruction surgery. She was on a PPI (lansoprazole) since the age of 4 years. She was found to have mild hypocalcemia 8.5 mg/dL (Ref 8.8-10.4 mg/dL), mild hypomagnesemia 1.5 mg/dL (Ref 1.6-2.6 mg/dL), and hyperparathyroidism 117 pg/dL (Ref 14-72 pg/dL). Her vitamin D 25 hydroxy level was 28 ng/dL (Ref<19 ng/dL) and vitamin D 1,25 dihydroxy 44.8 pg/dL (Ref 19.9-79.3 pg/dL). In addition, her bone x-ray showed evidence of demineralization, with nofracture. PTH (308.6, 429.4, 253.1pg/mL) continue to rise over the next 2 months despite normal Ca/vitamin D level. We suspected the etiology of hypocalcemia and hyperPTH was related to chronic PPI use. This was also associated with markedly elevated, hypergastrinemia of 574 pg/dL (Ref <100 pg/dL), PTHrp was not detectable. Due to high risk of aspiration, her pulmonologist noted that her PPI needed to be continued at the time. She was fed via G-tube and took Pediasure 1.4 L daily which contained elemental calcium of 32 mg/kg/day. Her vitamin D intake was 1000 units daily. However, we suspected that she had calcium malabosoprtion in light of hypochlorhydria and hypergastrinemia, both leading to hyperPTH. Subsequently, she was started on oral calcium citrate 1200mg daily as the absorption of calcium citrate is non PH dependent. One month later, her PPI was discontinued as well. She responded well to therapy and calcium normalized to 9.7 mg/dl (Ref 8.8-10.4 mg/dl) after 3 months, Gastrin 85 pg/dL (Ref<100 pg/dL) and PTH 90.1 pg/dL (Ref 14-72 pg/dL). Conclusion Bone health status of patients on long-term PPI treatment should be addressed with particular attention to calcium/vitamin D intake. The possible mechanisms of hyperPTH and bone demineralization induced by PPIs include calcium malabsorption. In addition, hypochlohydria induced hypergastrinemia can also exacerbate hyperPTH by causing parathyroid hyperplasia. Bone health and mineral status of patients on long-term PPIs should be regularly monitored. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.

New Entity-Thalassemic Endocrine Disease: Major Beta-Thalassemia and Endocrine Involvement.

New Entity-Thalassemic Endocrine Disease: Major Beta-Thalassemia and Endocrine Involvement.

Investigating the Effects of Diet-Induced Pre-Diabetes on the Functioning of Calcium-Regulating Organs in Male Sprague Dawley Rats: Effects on Selected Markers.

Derangements to the functioning of calcium-regulating organs have been associated with type 2 diabetes mellitus (T2DM), a condition preceded by pre-diabetes. Type 2 diabetes has shown to promote renal calcium wastage, intestinal calcium malabsorption and increased bone resorption. However, the changes to the functioning of calcium-regulating organs in pre-diabetes are not known. Subsequently, the effects of diet-induced pre-diabetes on the functioning of calcium-regulating organs in a rat model for pre-diabetes was investigated in this study. Male Sprague Dawley rats were separated into two groups (n=6, each group): non-pre-diabetic (NPD) group and a diet-induced pre-diabetic (DIPD) group for 20 weeks. After the experimental period, postprandial glucose and HOMA-IR were analysed in addition to plasma and urinary calcium concentrations. Gene expressions of intestinal vitamin D (VDR), intestinal calbindin-D9k, renal 1-alpha hydroxylase and renal transient receptor potential vanilloid 5 (TRPV5) expressions in addition to plasma osteocalcin and urinary deoxypyridinoline concentrations were analysed at week 20. The results demonstrated significantly increased concentrations of postprandial glucose, HOMA-IR and urinary calcium in addition to unchanged plasma calcium levels in the DIPD group by comparison to NPD. Renal TRPV5, renal 1-alpha hydroxylase, intestinal VDR and intestinal calbindin-D9k expressions were increased in the DIPD group by comparison to NPD. Furthermore, plasma osteocalcin levels were increased and urine deoxypyridinoline levels were decreased in the DIPD group by comparison to NPD. These observations may suggest that calcium-regulating organs compensate for the changes to calcium homeostasis by inducing increased renal calcium reabsorption, increased intestinal calcium absorption and decreased bone resorption followed by increased bone formation.

Effect of Aerobic Exercises in Prevention of Bone Mass Loss Post Bariatric Surgeries

Background: Patients who have been submitted to bariatric surgery are prone to bone mass abnormalities caused by restriction of calcium intake associated with malabsorption of both calcium and vitamin D. Reduced calcium absorption is secondary to the exclusion of duodenum and proximal jejunum where calcium is maximally absorbed. Aerobic weight bearing exercise is more adapted to improve bone mass over whatever viable physical activity, they assume a double part over stressing the bones as they set both gravitational and muscular stress on bones. Objective: To determine the effect of aerobic exercises in prevention of bone mass loss post bariatric surgeries. Patients and Methods: Thirty female patients with post bariatric surgeries participated in this, their ages were between 25 to 45 years selected from Shebin El-Kom Hospital, Menoufia and randomly distributed into two equal groups: Group A (Study group): included 15 patients who received 30 minutes of aerobic exercise through walking on treadmill, in addition to conventional medical care 3 days per week and group B (Control group): included 15 patients who were on their conventional medical care. Results: There was no significant difference in T score of spine (L2-L4), femoral neck and total femur between both groups pre-treatment (p > 0.05). Comparison between both groups post treatment revealed a significant increase in T score of spine (L2-L4), femoral neck and total femur of the study group compared with that of the control group (p > 0.001). Conclusion: It can be concluded that aerobic exercises had fruitful effects in cases of osteoporosis patients after bariatric surgery as evidenced by the significant increase in BMD and T-score mean, so decrease risk of fractures and enhance physical performance.

Effect of Aerobic Exercises in Prevention of Bone Mass Loss Post Bariatric Surgeries

Background: Patients who have been submitted to bariatric surgery are prone to bone mass abnormalities caused by restriction of calcium intake associated with malabsorption of both calcium and vitamin D. Reduced calcium absorption is secondary to the exclusion of duodenum and proximal jejunum where calcium is maximally absorbed. Aerobic weight bearing exercise is more adapted to improve bone mass over whatever viable physical activity, they assume a double part over stressing the bones as they set both gravitational and muscular stress on bones. Objective: To determine the effect of aerobic exercises in prevention of bone mass loss post bariatric surgeries. Patients and Methods: Thirty female patients with post bariatric surgeries participated in this, their ages were between 25 to 45 years selected from Shebin El-Kom Hospital, Menoufia and randomly distributed into two equal groups: Group A (Study group): included 15 patients who received 30 minutes of aerobic exercise through walking on treadmill, in addition to conventional medical care 3 days per week and group B (Control group): included 15 patients who were on their conventional medical care. Results: There was no significant difference in T score of spine (L2-L4), femoral neck and total femur between both groups pre-treatment (p > 0.05). Comparison between both groups post treatment revealed a significant increase in T score of spine (L2-L4), femoral neck and total femur of the study group compared with that of the control group (p > 0.001). Conclusion: It can be concluded that aerobic exercises had fruitful effects in cases of osteoporosis patients after bariatric surgery as evidenced by the significant increase in BMD and T-score mean, so decrease risk of fractures and enhance physical performance.

S2888 Tetany and Carpopedal Spasm as the Initial Presentation of Celiac Disease

INTRODUCTION: Celiac disease (CD) presents with a wide variety of symptoms, with gastrointestinal manifestations being the most common. We discuss a rare case of celiac disease diagnosed by severe hypocalcemia and carpopedal spasm. CASE DESCRIPTION/METHODS: A 25 year old male with no significant medical history presented with complaints of paresthesias in his hands and arms and a few weeks of diarrhea. Physical exam revealed carpopedal spasm. Initial lab work was significant for severe hypocalcemia (ionized calcium level of 0.66), hypomagnesemia and undetectable vitamin D 25-hydroxy level, along with elevated PTH (583.2). His electrolytes were aggressively replaced intravenously, and after stabilization, transitioned to oral supplementation. Vitamin D supplementation was also initiated. Patient was found to have elevated tissue transglutaminase IgA antibodies and gliadin peptide levels. EGD demonstrated scalloped mucosa with complete flattening of villi in the duodenum consistent with celiac disease, which was also confirmed on biopsy. Patient was initiated on calcium and vitamin D replacement and a gluten-free diet on discharge. DISCUSSION: CD usually presents with diarrhea and weight loss. However, >40% of patients present with atypical manifestations, many of which are secondary to malabsorption from a loss of absorptive area and the presence of immature surface epithelial cells whose have impaired absorptive and secretory functions. Hypocalcemia in CD occurs due to intestinal malabsorption of calcium, both from loss of villous surface area and depletion of calbindin from enterocytes leading to decreased active intestinal calcium transport mechanisms. Concurrent malabsorption of vitamin D may also play a role, although there have been reported cases with hypocalcemia despite a normal vitamin D. Hypocalcemia in CD is common, with studies demonstrating that average serum calcium is 0.02 mmol/l lower in asymptomatic CD patients that the general population. However, there are few reports, especially in the developed world, of severe hypocalcemia and neurological symptoms being the initial presentation of CD. Management includes intravenous or oral calcium replacement, with replacement of other electrolytes (magnesium, phosphorous and potassium) and vitamin D as well. These levels should be monitored at follow up visits, but it is expected that they will normalize after management of CD. It is important for a clinician to recognize atypical presentations of CD, especially in countries with high prevalence.Figure 1.: Endoscopic view of duodenal bulb showing scalloped mucosa and complete flattening of villi.Figure 2.: Microscopic view showing villous blunting and increased intraepithelial lymphocytes, H&E staining.

Effect of milk fat-based infant formulae on stool fatty acid soaps and calcium excretion in healthy term infants: two double-blind randomised cross-over trials

BackgroundPalmitic acid (PA) is predominantly esterified at the SN-2 position of triacylglycerols in human milk. PA at the SN-2 position is more efficiently absorbed and results in reduced formation of PA soaps, as well as reduced fatty acid (FA) and calcium malabsorption. Bovine milk fat (MF), a natural source of SN-2-palmitate, was used in the fat blend of infant formulae (IF) in the current study to investigate its effect on stool fatty acid soaps, calcium excretion and stool characteristics.MethodsTwo double-blind, randomised cross-over trials (CS1, CS2) were conducted in parallel with healthy term, formula-fed infants aged 9–14 weeks. After a two-week run-in period, infants in CS1 (n = 17) were randomly allocated to receive either a 50% MF-based formula (50MF) or a 100% vegetable fat (VF) formula; in CS2 (n = 18), infants received either a 20% MF-based formula (20MF) or the VF formula, in a 2 × 2-week cross-over design. At the end of each two-week intervention period, stool samples were collected for FA, FA soaps and calcium excretion analysis and stool consistency was assessed according to the Amsterdam Infant Stool Scale (AISS).ResultsMF-based groups showed no significant difference in PA in stools compared to VF group, although reduced stool PA soaps (CS1: 111.28 ± 18.33 vs. 220.25 ± 29.35 mg/g dry weight, p < 0.0001; CS2: 216.24 ± 25.16 vs. 233.94 ± 35.12 mg/g dry weight, p = 0.0023), total FA soaps and calcium excretion (CS1: 46.40 ± 5.27 vs. 49.88 ± 4.77 mg/g dry weight, p = 0.0041; CS2: 46.20 ± 4.26 vs. 50.47 ± 6.71 mg/g dry weight, p = 0.0067) were observed. Furthermore, the 50MF group showed a favourable lower mean stool consistency score compared to the VF group (1.64 ± 0.49 vs. 2.03 ± 0.19, p = 0.0008).ConclusionsWhile the use of bovine MF in IF did not affect PA concentrations in stool, lower excretion of palmitate soaps, total FA soaps and calcium was seen in healthy term infants. 50MF formula also showed improved stool consistency. The use of MF in IF could be an interesting approach to improve gut comfort and stool characteristics in infants, warranting further research.Trial registrationNetherlands Trial Registry Identifier: NTR6702. Date registered: December 01, 2017.

Commentary: Myths and facts on vitamin D amidst the COVID-19 pandemic

Commentary: Myths and facts on vitamin D amidst the COVID-19 pandemic

SUN-392 Bone Mineral Density and Body Mass Index in Men with Cystic Fibrosis

Osteoporosis is an important endocrine complication of cystic fibrosis (CF). Low bone mass in CF patients has multiple contributing causes including vitamin D deficiency, calcium malabsorption, pulmonary infection and cytokine production, malnutrition, a sedentary life style, cumulative steroid dose, delayed puberty, and hypogonadism. The objective of this study was to examine the relationship between BMI and bone density of the hip and spine in adult men with CF. We conducted a retrospective chart review of adult men with CF receiving care at an academic medical center. Medical records of 43 men ages 19-60 (32.1±9.8) years were reviewed. 8 men with lung transplant, or receiving chronic glucocorticoid or androgen treatment were excluded. One subject was excluded as his BMI was >3SD above the mean. BMD was measured by dual-energy x-ray absorptiometry at the lumbar spine (LS) and hip. The mean ± SD BMI of the study population was 24.10 ± 5.24 kg/m2, mean LS BMD was 0.96 ± 0.204 g/cm2 and mean hip BMD was 0.701 ± 0.382 g/cm2. Men were divided into three groups: normal BMD, osteopenia, or osteoporosis, based on current guidelines. 8 (24%) men were found to have normal bone density (Z=0.40±0.60), 19 (56%) had osteopenia (Z= -1.57±0.67) and 7 (20%) had osteoporosis (Z= -3.27±0.83). Of these 7, 6 had osteoporosis of the LS only, and one patient had osteoporosis of the hip; 5 were being treated with a bisphosphonate. The three groups of men were similar in age (P=0.93). 25OH-vitamin D levels were 22.6±4.4, 35.6±12.7 and 27.0±13.4 ng/mL, respectively (p=0.03). There was a significant (p=0.023) difference in BMI among these three groups (26.33±4.80 vs 23.25 ± 3.01 vs 20.96±3.64 kg/m2). BMI was strongly positively correlated with LS BMD (r = 0.54, P<0.001) but not with BMD of the hip (r = 0.11, p=0.55). Moreover, LS BMD was highly predicted by body weight (r = 0.90, P<0.0001) but not significantly by height (r = 0.26, p=0.16). These findings indicate that CF-related bone disease (CF-RBD) affecting the LS is common in adult men, and that body weight is a major determinant of LS BMD in men with CF. Possible mechanisms for this association include signaling pathways related to nutritional status and sex steroids.

Abstract #802642: Deceptive 24-Hour Urine Calcium Excretion in a Patient with Secondary Hyperparathyroidism from Calcium Malabsorption and Primary Hypercalciuria

Abstract #802642: Deceptive 24-Hour Urine Calcium Excretion in a Patient with Secondary Hyperparathyroidism from Calcium Malabsorption and Primary Hypercalciuria

Celiakie dospělých

Celiac disease is a lifelong autoimmune disorder that occurs in genetically predisposed people when consuming gluten. Its prevalence is around 1% of the population with about twice higher proportion of women. Celiac disease is one of the most common causes of malabsorption, however, its manifestations can be quite diverse - from completely asymptomatic to fully developed malabsorption syndrome. Extraintestinal manifestations are a common finding in adults. The gold standard of diagnosis is the serological detection of specific antibodies (the serum tissue transglutaminase IgA antibodies) in combination with a typical histological finding from a duodenal biopsy. Causal treatment is a lifelong gluten-free diet. Strict adherence to gluten-free diet will reduce the risk of serious complications (intestinal T-cell lymphoma). In the following case report we present a case of a 58-year-old patient, who have been diagnosed with celiac disease at this age based on non-classical symptoms. Specifically, these were multiple pathological fractures from metabolic bone disease due to malabsorption of calcium and vitamin D and subsequent secondary hyperparathyroidism.

The Science of History: Why the Egyptians Never Smiled for Pictures [NYU School of Medicine, New York Institute of Technology, Stony Brook School of Medicine

The Ancient Nubians have historically been renowned for their significant contributions to medicine. In spite of this, extremely poor oral health plagued this population. Paleopathological studies depict pronounced dental deterioration patterns far exceeding normal physiological progression. The advanced wear is popularly attributed to sand particle contamination of their daily diets. However, considering that individual wear mechanisms rarely act in isolation, we propose that adverse biochemical factors arising from regular consumption of tetracycline- fortified beer induced calcium malabsorption, and thus provided a synergistic diathesis in potentiating these effects. We examine these implications within the context of prevalent therapeutic remedies, bone fluorescence labeling data, and sociocultural attitudes when making the link between tetracycline and the compromised integrity of teeth, while citing the emergence of antibiotics actually predating formally-accepted convention.

SAT-221 False-Positive Urinary Free Cortisol with Oral Contraceptive Use

Introduction It is well-established that estrogen-containing oral contraceptives can raise serum cortisol levels and yield false-positive results on dexamethasone suppression testing, however it is less known that they can raise urinary free cortisol levels by an unknown mechanism. Case presentation A 47-year old woman taking microgestin 1/20 oral contraceptive (OC) was found incidentally to have osteopenia on chest X-ray. Subsequent DEXA scan demonstrated osteoporosis. During the work-up to determine the underlying etiology of her osteoporosis, she underwent a 24-hour urinary free cortisol, which was 207 ug/24 hours (0-50 ug/24 hours). Serum cortisol was 40.1 (6.2-19.4 ug/dL) and overnight 1mg dexamethasone suppression test yielded a cortisol of 2.7. After one week off her OC, serum cortisol was 24.6. After five weeks off her OC, urinary free cortisol was 19 and 1mg dexamethasone suppression test yielded a cortisol of 0.8. On exam, the patient did not have any cushingoid features. MRI of the brain showed a small hypoenhancing lesion, which was determined by neurosurgery to be insignificant. Ultimately, the cause of her osteoporosis was thought to be likely secondary to vitamin D deficiency and calcium malabsorption due to celiac disease. Discussion The biochemical diagnosis of hypercortisolism during treatment with estrogen-containing OCs remains a challenge. Prior studies have demonstrated that serum cortisol levels are typically elevated during OC use and that 1mg dexamethasone suppression testing may yield false-positive results in more than 50% of cases. This is thought to be due to an increase in the major binding protein for cortisol, corticosteroid-binding globulin. Although it is commonly thought that OCs do not affect urinary free cortisol measurements, a recent study showed that more than one-third of women taking OCs had a mild elevation of urinary free cortisol. There are a few hypotheses for the mechanism by which OC use leads to elevated urinary free cortisol, including direct effect on steroidogenesis in the adrenal glands. Our patient had a significantly elevated 24-hour urinary free cortisol and an equivocal 1mg dexamethasone suppression test while on OCs that normalized with OC discontinuation. Further, serum cortisol decreased with OC discontinuation. Conclusion The 24-hour urinary free cortisol level may be altered by oral contraceptive use and is therefore not a valid tool to evaluate for hypercortisolism in women on OCs. References Nickelsen T, et al. (1989). The dexamethasone suppression test and long-term contraceptive treatment. Experimental and Clinical Endocrinology, 94, 275–280. Paschali M, et al. (2013). False positives on both dexamethasone testing and urinary free cortisol in women on oral contraception. Clin Endocrinol, 79, 443-445. Trainer PJ. (2002). Corticosteroids and pregnancy. Seminars in Reproductive Medicine, 20, 375–280.

Th17 cell frequency is associated with low bone mass in primary sclerosing cholangitis

Osteoporotic fractures are a major cause of morbidity and reduced quality of life in patients with primary sclerosing cholangitis (PSC), a progressive bile duct disease of unknown origin. Although it is generally assumed that this pathology is a consequence of impaired calcium homeostasis and malabsorption, the cellular and molecular causes of PSC-associated osteoporosis are unknown. We determined bone mineral density by dual-X-ray absorptiometry and assessed bone microstructure by high-resolution peripheral quantitative computed tomography in patients with PSC. Laboratory markers of liver and bone metabolism were measured, and liver stiffness was assessed by FibroScan. We determined the frequency of Th17 cells by the ex vivo stimulation of peripheral blood mononuclear cells in a subgroup of 40 patients with PSC. To investigate the potential involvement of IL-17 in PSC-associated bone loss, we analyzed the skeletal phenotype of mice lacking Abcb4 and/or Il-17. Unlike in patients with primary biliary cholangitis, bone loss in patients with PSC was not associated with disease duration or liver fibrosis. However, we observed a significant negative correlation between the bone resorption biomarker deoxypyridinoline and bone mineral density in the PSC cohort, indicating increased bone resorption. Importantly, the frequency of Th17 cells in peripheral blood was positively correlated with the urinary deoxypyridinoline level and negatively correlated with bone mass. We observed that Abcb4-deficient mice displayed a low-bone-mass phenotype, which was corrected by an additional Il-17 deficiency or anti-IL-17 treatment, whereas the liver pathology was unaffected. Our findings demonstrate that an increased frequency of Th17 cells is associated with bone resorption in PSC. Whether antibody-based IL-17 blockade is beneficial against bone loss in patients with PSC should be addressed in future studies. Primary sclerosing cholangitis (PSC) is a cholestatic liver disease characterized by progressive bile duct destruction. One serious complication of PSC is reduced bone mass resulting in increased fracture risk. Herein, we demonstrate that Th17 cells mediate bone loss in PSC by inducing bone resorption, which suggests that antibody-based IL-17 blockade might be beneficial for the treatment of bone loss in affected patients.

Evaluation of vitamin D status bone mineral density and dental health in children with cholestasis

Hepatic osteodystrophy caused by vitamin D and calcium malabsorption is thought to develop in children with cholestatic liver disease leading to secondary hyperparathyroidism and rickets or osteomalacia. The aim of this study was to evaluate the dental and bone mineral densities and the serum level of vitamin D in cholestatic infants and children and to correlate this process with clinical and laboratory parameters. This is a cross-sectional study that include 50 patients presenting with cholestasis. Thirty age and sex matched controls recruited not complaining of liver disease. All cases were subjected to full history taking, clinical and dental examination, 25(OH)D level, ALT, AST, bilirubin, albumin, GGT, alkaline phosphatase, PT, INR, calcium, corrected calcium, phosphorus and DXA scan to those above 5 years old. Controls were subjected to measuring the serum levels of 25(OH)D, total bilirubin, direct bilirubin, ALT, GGT, AST, PT, INR, alkaline phosphatase, albumin, calcium and phosphorus. Out of the 50 cases; 23 were females (46%), with a mean age of 6.17±3.9 years ranging from 1.1 to 17 years. Twenty-eight of the cases had signs of rickets (56%), 6 of them had bone fracture (12%) and 42.8% had milky teeth caries. The level of 25(OH) vitamin D was below normal range in around half of the patients. There was significant difference between cases and controls in calcium and phosphorus levels, ALT and alkaline phosphatase. Low bone mineral density (BMD) was present in 50% and 5 cases (17.9%) were diagnosed as having osteoporosis. There was a negative correlation between the Z-score, BMD of total body, BMD and bone mineral content (BMC) of spine and total and direct bilirubin. There was a positive correlation between (BMD of total body, spine and BMC of spine) and serum phosphorus, alkaline phosphatase and albumin. There was a positive correlation between the Z-score of total body and serum calcium. Decreased level of 25-OH vitamin D is present in more than half of cholestatic patients, and is correlated positively to serum calcium. Decreased BMD was present in more than half of studied cholestatic patients correlated to the low serum calcium rather than the vitamin D level. The decreased BMD and the dental affection in cholestatic children is related to the level of hyperbilirubinemia.