Impaired Calcium Absorption Research Articles

Prevention and Treatment of Glucocorticoid-Induced Osteoporosis in Adults: Consensus Recommendations From the Belgian Bone Club.

Glucocorticoids are effective immunomodulatory drugs used for many inflammatory disorders as well as in transplant recipients. However, both iatrogenic and endogenous glucocorticoid excess are also associated with several side effects including an increased risk of osteoporosis and fractures. Glucocorticoid-induced osteoporosis (GIOP) is a common secondary cause of osteoporosis in adults. Despite availability of clear evidence and international guidelines for the prevention of GIOP, a large treatment gap remains. In this narrative review, the Belgian Bone Club (BBC) updates its 2006 consensus recommendations for the prevention and treatment of GIOP in adults. The pathophysiology of GIOP is multifactorial. The BBC strongly advises non-pharmacological measures including physical exercise, smoking cessation and avoidance of alcohol abuse in all adults at risk for osteoporosis. Glucocorticoids are associated with impaired intestinal calcium absorption; the BBC therefore strongly recommend sufficient calcium intake and avoidance of vitamin D deficiency. We recommend assessment of fracture risk, taking age, sex, menopausal status, prior fractures, glucocorticoid dose, other clinical risk factors and bone mineral density into account. Placebo-controlled randomized controlled trials have demonstrated the efficacy of alendronate, risedronate, zoledronate, denosumab and teriparatide in GIOP. We suggest monitoring by dual-energy X-ray absorptiometry (DXA) and vertebral fracture identification one year after glucocorticoid initiation. The trabecular bone score might be considered during DXA monitoring. Extended femur scans might be considered at the time of DXA imaging in glucocorticoid users on long-term (≥ 3 years) antiresorptive therapy. Bone turnover markers may be considered for monitoring treatment with anti-resorptive or osteoanabolic drugs in GIOP. Although the pathophysiology of solid organ and hematopoietic stem cell transplantation-induced osteoporosis extends beyond GIOP alone, the BBC recommends similar evaluation, prevention, treatment and follow-up principles in these patients. Efforts to close the treatment gap in GIOP and implement available effective fracture prevention strategies into clinical practice in primary, secondary and tertiary care are urgently needed.

Malabsorption syndrome aggravates calcium homeostasis impairment in chronic kidney disease patients

Abstract. Recent data on the role of digestive pathology in the progression of chronic kidney disease (CKD) remain scarce. Calcium homeostasis plays an important role in the progression of renal pathology, especially in patients with malabsorption syndrome (MAS).
 The research aimed to evaluate calcium homeostasis in CKD patients with MAS.
 Methods. In this cross-sectional observational study, 99 CKD patients with MAS were enrolled. The patients were divided into 4 groups according to the CKD stage and the presence of MAS. Group I included 25 patients with CKD stages 1 and 2 without MAS; Group II consisted of 26 patients with CKD stages 1 and 2, and MAS; Group ІІІ (n = 23) and Group ІV (n = 25) included patients with CKD stage 3 without and with MAS, respectively. According to the morphological study of in vivo biopsies of the small intestinal mucosa, mild and moderate morphological changes were observed among all patients. The levels of calcium, phosphorus, parathyroid hormone, osteocalcin, and calcitonin in the blood, as well as urinary calcium levels, were detected.
 Results. Pathological changes in calcium metabolism were observed among CKD patients with MAS. The severity of calcium homeostasis disorders was more evident among patients with CKD stage 3 compared with stages 1 and 2. Urinary calcium levels were reduced in the patients of Groups III and IV. No changes were detected in phosphorus levels. Changes in parathyroid hormone and osteocalcin are caused primarily by combined renal pathology with impaired renal calcium absorption.
 Conclusion. MAS in CKD patients leads to deep violations of calcium homeostasis resulting in rapid CKD progression and bone tissue violation.

Drug-induced hypocalcemia

Hypocalcemia (HCa) is one of the main water-electrolyte disturbances in clinical practice. An acute decrease in serum calcium levels can lead to seizures, ventricular arrhythmias, bronchospasm and laryngospasm. Chronic HCa can result in disorientation and confusion. To prevent these complications, the risk factors for low calcium levels must be carefully evaluated. One of these factors is drugs, in which case we are talking about drug-induced (DI) HCa. The list of drugs-inducers of DI HCa is quite extensive, but the leading role in this disorder is played by drugs for the treatment of osteoporosis, antineoplastic and antiepileptic drugs, as well as drugs for anti-tuberculosis therapy. When taking zoledronic acid, DI HCa is observed with a frequency of up to 39%. When taking imatinib, a targeted anticancer drug, a decrease in calcium levels was observed in 40% of cases. The pathophysiological mechanisms of DI HCa can be a decrease in bone resorption, a decrease in the concentration of vitamin D, inhibition of the action of parathyroid hormone and impaired calcium absorption. Risk factors in most cases of DI HCa are vitamin D deficiency and hypomagnesemia. An acute decrease in calcium levels leads to symptoms of neuromuscular excitability, abnormalities on the electrocardiogram (ECG) and electroencephalogram (EEG). The basis for the treatment of DI HCa is the drug withdrawal and the appointment of calcium. It is also necessary to prescribe vitamin D. The main methods of prevention of DI HCa are to determine the level of calcium and vitamin D before starting therapy with culprit medication, and to correct its level. It is also important to prescribe additional amounts of calcium and vitamin D during therapy with such drugs. Awareness of the attending physicians about the problem of DI HCa, a thorough assessment of its risk factors and the prophylactic administration of calcium and vitamin D preparations will help to effectively prevent those serious complications resulting from a decrease in calcium levels in clinical practice.

Benign Paroxysmal Positional Vertigo Risk Factors Unique to Perimenopausal Women.

Many investigations have found common occurrences of benign paroxysmal positional vertigo (BPPV) in women, and clinical experience has shown that BPPV can develop due to increased hormonal fluctuations, especially during menopause. Therefore, knowledge about neurochemicals and their involvement with BPPV is imperative for the management of neurological issues in women. This review will discuss appropriate gender-based considerations of BPPV based on experimental and clinical evidence. The studies describe 2 lines of evidence regarding the association of perimenopause in women and the development of BPPV: (1) experimental evidence: the existence of estrogen receptors in the inner ear, otoconial malformations in osteopenic/osteoporotic rats, changes in otoconin 90 caused by hormone replacement therapy, and impaired calcium absorption following estrogen deprivation corrected by estrogen replacement therapy and (2) clinical evidence: epidemiological aspects, osteoporosis and estrogen deficiency. Future studies are necessary to validate the effects of hormonal replacement therapy and phytoestrogen in women with recurrent BPPV.

Parathyroid Hormone Profile In Sickle Cell Disease In School Aged Children

Background: Sickle cell disease (SCD) is group of hemoglobinopathies associated with hemolytic anemia and vasoocclusive complications. All forms of SCD are inherited in an autosomal recessive fashion. Parathyroid hormone plays an essential role in calcium and phosphorus homeostasis, which is achieved by its action on target organs (intestine, bone and kidney), leading to normal bone formation and mineralization and normal physiological concentration of calcium and phosphorus. Objectives: This study aimed to detect the effect of sickle cell disease on parathyroid hormone and consequently on serum calcium (S.Ca), phosphorus (ph), alkaline phosphatase (alk.Ph) and magnesium (Mg) on patients with sickle cell anemia. Subjects and Methods: Forty children known as sickle cell disease patients, twenty of them were SCD (HbSS) (11 males and 9 females). The other twenty were known SC trait (10 males and 10 females). The ages of the children ranged from 5 to 15 years old. All were in non-crises state in routine Outpatient Clinic visits, compared to twenty apparently healthy, age matched and with normal hemoglobin from Atfal Masr Hospital as control. Neither patients nor control received calcium supplementation before the study. Results: The results indicated that sickle cell patients and sickle cell trait patients had hypocalcaemic tendency associated with supernormal parathyroid hormone level and implied impaired calcium absorption from intestine leading to disturbed calcium metabolism, which might contribute in skeletal changes seen in sickle cell patients. Conclusion: We found that there was statistically significant decrease in serum Ca levels accompanied with increase in serum PTH, ph, alk Ph and Mg levels in SCD and Sickle cell trait patients compared to control group.

Responses of primary osteoblasts and osteoclasts from hemizygous \u03b2-globin knockout thalassemic mice with elevated plasma glucose to 1,25-dihydroxyvitamin D3

β-thalassemia is often associated with hyperglycemia, osteoporosis and increased fracture risk. However, the underlying mechanisms of the thalassemia-associated bone loss remain unclear. It might result from abnormal activities of osteoblasts and osteoclasts, and perhaps prolonged exposure to high extracellular glucose. Herein, we determined the rate of duodenal calcium transport in hemizygous β-globin knockout thalassemic (BKO) mice. Their bones were collected for primary osteoblast and osteoclast culture. We found that BKO mice had lower calcium absorption than their wild-type (WT) littermates. Osteoblasts from BKO mice showed aberrant expression of osteoblast-specific genes, e.g., Runx2, alkaline phosphatase and osteocalcin, which could be partially restored by 1,25(OH)2D3 treatment. However, the mRNA expression levels of RANK, calcitonin receptor (Calcr), c-Fos, NFATc1, cathepsin K and DMT1 were similar in both BKO and WT groups. Exposure to high extracellular glucose modestly but significantly affected the expression of osteoclast-specific markers in WT osteoclasts with no significant effect on osteoblast-specific genes in WT osteoblasts. Thus, high glucose alone was unable to convert WT bone cells to BKO-like bone cells. In conclusion, the impaired calcium absorption and mutation-related aberrant bone cell function rather than exposure to high blood glucose were likely to be the principal causes of thalassemic bone loss.

Prevalence and predictors of vitamin D insufficiency in adult population of yazd – The sun province in center of Iran

BackgroundVitamin D insufficiency (VDI) is one of impaired calcium absorption causes. It is associated with increased risk of several diseases. The aim of this study was to survey the prevalence and predictors of VDI in Yazd. Method and materialThis cross sectional study was conducted on 700 participant aged between 20 and 70 years old on second phase of the Iranian Multi-Center Osteoporosis Study (IMOS) in Yazd province. All analyzes were performed with the SPSS 20 and Stata 14.1 software. Chi-squared test, Pearson correlation and binary logistic regression were used. A significance level was considered for all tests P ≤ 0.05. ResultsThe prevalence of VDI was 55.1% (51.37–58.87%) in total participant of this study. Predictors of VDI including: age 31–45 years old (OR = 1.68, CI = 1.04–2.70), female (OR = 3.49, CI = 1.80–6.78), live in the apartment houses (OR = 2.15, CI = 1.06–4.35), inability of climbing of steps (OR = 2.59, CI = 1.17–5.69), serum Calcium (OR = 0.53, CI = 0.34–0.81) and serum PTH (OR = 1.04, CI = 1.02–1.06). ConclusionsThe prevalence of VDI in Yazd is high. It is recommended to people that to be exposed to sunlight per day. And people should consumption vitamin D supplements under their physician.

EXPERIENCE OF LONG-TERM TERIPARATIDE USE FOR THE TREATMENT OF POSTOPERATIVE HYPOPARATHYROIDISM ASSOCIATED WITH OSTEOPOROSIS IN ELDERLY PATIENT

The aim of studyis to reflect the possibilities and effectiveness of teriparatide for the treatment of postoperative hypoparathyroidism associated with severe systemic osteoporosis, based on the data of the clinical case.Materials and methods.Patient N., aged 69, having a history of resection of 2/3 of the stomach according by Bilrot-2, urolithiasis, hypertension; since 2011 has been repeatedly hospitalized in National Medical Research Centre of Endocrinology, Ministry of Health of Russia, for secondary hyperparathyroidism and severe systemic osteoporosis. In 2016 thyroidectomy was performed in connection with papillary thyroid cancer and removal of left parathyroid gland adenoma, after which the patient developed postoperative hypoparathyroidism with severe uncontrolled hypocalcemia. As a replacement therapy, a synthetic analogue of parathyroid hormone, teriparatide, was used. For this work we used epicrisis of 2011–2016, as well as the results of the patient’s examination performed during the inpatient treatment in the Endocrinology Department of City Clinical Hospital № 4 (Ivanovo) from 2016 to 2018.Results.As a result of treatment with teriparatide in this patient, according to the results of a three-year follow-up, there is a positive clinical effect in the form of absence of convulsive syndrome, normalization of total and ionized calcium levels, absence of new compression fractures of vertebral bodies. Since the recovery of parathyroid gland function after surgery has not occurred, the use of this drug to the patient is recommended for the life term.Conclusion.The study describes a clinical case involving teriparatide as a therapy for postoperative hypoparathyroidism in combination with severe systemic osteoporosis and impaired calcium absorption in an elderly patient. The clinical effect of this type of treatment over a period of 3 years was proved in the form of normalization of phosphorus-calcium metabolism and the processes of bone remodeling in the absence of any side effects.

Proton Pump Inhibitors, Histamine-2 Receptor Antagonists, and Hip Fracture Risk among Patients on Hemodialysis.

An association between proton pump inhibitor (PPI) use and hip fracture risk has been described in the general population, where the primary causative hypothesis focuses on impaired gastrointestinal calcium absorption. The impact of acid suppressor use on hip fracture risk in a high-risk subset, patients with ESKD requiring hemodialysis, is unknown and could help further distinguish the reason for higher susceptibility among PPI users. Using the US Renal Data System, we identified all hip fracture events recorded between 2009 and 2014 among patients dependent on hemodialysis. Eligible cases were matched on index date with ten controls. We identified PPI and histamine-2 receptor antagonist use from Medicare Part D claims covering 3 years before the index date and stratified according to proportion of days covered by filled prescriptions. Using logistic regression with multiple imputation for missing data, we estimated unadjusted and multivariable-adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs). We studied 4551 cases and 45,510 controls. Patients were older, more likely to be female and white, and had shorter dialysis vintage; fewer were obese. A larger proportion of patients had any prior PPI (70% versus 63%) or histamine-2 receptor antagonist (25% versus 23%) use. Use of PPI was associated with higher risk of hip fracture (adjusted OR, 1.19; 95% CI, 1.11 to 1.28). This association remained within subgroups of low, moderate, and high PPI use, yielding adjusted ORs of 1.16 (95% CI, 1.06 to 1.27), 1.21 (95% CI, 1.11 to 1.31), and 1.19 (95% CI, 1.08 to 1.31), respectively. Among patients with ESKD on hemodialysis, PPIs and not histamine-2 receptor antagonists were associated with hip fracture events.

Phosphate-dependent luminal ATP metabolism regulates transcellular calcium transport in intestinal epithelial cells.

Extracellular low phosphate strongly enhances intestinal calcium absorption independently of active vitamin D [1,25(OH)2D3] signaling, but the underlying mechanisms remain poorly characterized. To elucidate the phosphate-dependent regulation of calcium transport, we investigated part of the enteral environment that is involved in 1,25(OH)2D3-independent calcium absorption, which responds to dietary phosphate levels in mice that lack intestinal vitamin D receptor ( Vdr) activity. Impaired calcium absorption in intestinal Vdr-null mice was improved by dietary phosphate restriction. Accordingly, calcium transport in cultured intestinal epithelial cells was increased when the apical side was exposed to low phosphate levels (0.5 mM) compared with normal or high phosphate levels (1.0 or 5.0 mM, respectively). Mechanistically, low phosphate increased ATP in the apical side medium and allowed calcium entry into epithelial cells via the P2X7 purinoreceptor, which results in increased calcium transport. We found that luminal ATP was regulated by the release and degradation of ATP at the epithelium, and phosphate restriction increased ATP release from epithelial cells via connexin-43 hemichannels. Furthermore, ATP degradation by ectonucleotide pyrophosphatase-1 was reduced, which was caused by the reduction of the MAPK cascade. These findings indicate that luminal ATP metabolism regulates transcellular calcium transport in the intestine by an 1,25(OH)2D3-independent mechanism in response to dietary phosphate levels.-Uekawa, A., Yamanaka, H., Lieben, L., Kimira, Y., Uehara, M., Yamamoto, Y., Kato, S., Ito, K., Carmeliet, G., Masuyama, R. Phosphate-dependent luminal ATP metabolism regulates transcellular calcium transport in intestinal epithelial cells.

Hypocalciuria as a Predictor of Reduced Intestinal Calcium Absorption.

Impaired intestinal calcium absorption contributes to osteoporosis, but its measurement is limited to research settings. We hypothesized that 24-hour urine calcium (24HUC) values could diagnose low fractional calcium absorption (FCA). We performed a post hoc analysis of clinical trial data to determine whether 24HUC predicted low FCA compared with the gold standard dual calcium isotope method. Two hundred thirty postmenopausal women <75 years old without osteoporosis underwent 445 FCA measurements using calcium isotopes (8 mg of oral 44Ca, 3 mg of intravenous 42Ca) and a 24-hour inpatient urine collection at 0 and 12 months. We determined subjects’ total calcium intake via review of food diaries and supplements. Net calcium absorption (NCA) was total calcium intake × FCA. NCA and 24HUC values demonstrated a positive correlation (r = 0.34; 95% confidence interval, 0.25 to 0.42; P < 0.001). We calculated sensitivity, specificity, positive (PPV) and negative predictive value (NPV) for the ability of 24HUC thresholds to predict calcium malabsorption. When low calcium absorption was defined as <120 mg/d, a 24HUC value <150 mg demonstrated 65% sensitivity, 67% specificity, 31% PPV, and 89% NPV. When calcium malabsorption was defined as <100 mg/d, a 24HUC value <150 mg demonstrated 72% sensitivity, 65% specificity, 22% PPV, and 94% NPV. A 24HUC value <150 mg demonstrated a high NPV for calcium malabsorption. We suggest that 24HUC levels can exclude calcium malabsorption in postmenopausal women.

Dietary and commercialized fructose: Sweet or sour?

Metabolic syndrome and diabetes are main health problems of modern life in the twenty-first century. Alarming ratios of global prevalence lead to conduct more and more researches about etiological factors and pathogenesis. Disease mechanism is elementary for advancing more efficient and practicable treatment methods. Concurrent increase in both fructose consumption with Western diet and metabolic syndrome has revealed fructose hypothesis that suggests fructose as one of etiological factor of metabolic syndrome (insulin resistance, central obesity, hypertension, etc.). Recent studies have increasingly lightened the unknowns about role of fructose on pathogenesis. This review discusses fructose hypothesis by exploring current studies and their results in wide perspective. Potential mechanisms covering low-grade inflammation or de novo lipogenesis, etc., in the development of insulin resistance and obesity are explained. Clinical trials have revealed connection of fructose-induced hyperuricemia with insulin resistance and chronic inflammatory state leading to hepatosteatosis or obesity. Further, novel hypothesizes suggesting role of fructose-induced modifications in epigenetics, gut microbiota and oxidative stress on disease pathogenesis are reviewed based on recent clinical trials. More innovative theories including fructose-induced malignancy; decreased satiety feeling, and unfavorable bone health are argued covering fructose-induced neurotransmitter changes in central nervous system, more aggressive malignancy phenotype and impaired calcium absorption.

Intestinal Regulation of Calcium: Vitamin D and Bone Physiology.

The principal function of vitamin D in the maintenance of calcium homeostasis is to increase intestinalcalcium absorption. This conclusion was made from studies in vitamin D receptor (VDR) null mice which showed that rickets and osteomalacia were prevented when VDR null mice were fed a rescue diet that included high calcium, indicating that the skeletal abnormalities of the VDR null mice are primarily the result of impaired intestinal calcium absorption. Although vitamin D is critical for controlling intestinal calcium absorption, the mechanisms involved have remained incomplete. This chapter reviews studies, including studies in genetically modified mice, that have provided new insight and have challenged the traditional model of VDR-mediated calcium absorption.

Derangement of calcium metabolism in diabetes mellitus: negative outcome from the synergy between impaired bone turnover and intestinal calcium absorption.

Both types 1 and 2 diabetes mellitus (T1DM and T2DM) are associated with profound deterioration of calcium and bone metabolism, partly from impaired intestinal calcium absorption, leading to a reduction in calcium uptake into the body. T1DM is associated with low bone mineral density (BMD) and osteoporosis, whereas the skeletal changes in T2DM are variable, ranging from normal to increased and to decreased BMD. However, both types of DM eventually compromise bone quality through production of advanced glycation end products and misalignment of collagen fibrils (so-called matrix failure), thereby culminating in a reduction of bone strength. The underlying cellular mechanisms (cellular failure) are related to suppression of osteoblast-induced bone formation and bone calcium accretion, as well as to enhancement of osteoclast-induced bone resorption. Several other T2DM-related pathophysiological changes, e.g., osteoblast insulin resistance, impaired productions of osteogenic growth factors (particularly insulin-like growth factor 1 and bone morphogenetic proteins), overproduction of pro-inflammatory cytokines, hyperglycemia, and dyslipidemia, also aggravate diabetic osteopathy. In the kidney, DM and the resultant hyperglycemia lead to calciuresis and hypercalciuria in both humans and rodents. Furthermore, DM causes deranged functions of endocrine factors related to mineral metabolism, e.g., parathyroid hormone, 1,25-dihydroxyvitamin D3, and fibroblast growth factor-23. Despite the wealth of information regarding impaired bone remodeling in DM, the long-lasting effects of DM on calcium metabolism in young growing individuals, pregnant women, and neonates born to women with gestational DM have received scant attention, and their underlying mechanisms are almost unknown and worth exploring.

Hepcidin and 1,25(OH)2D3effectively restore Ca2+transport in β-thalassemic mice: reciprocal phenomenon of Fe2+and Ca2+absorption

Previously, β-thalassemia, an inherited anemic disorder with iron overload caused by loss-of-function mutation of β-globin gene, has been reported to induce osteopenia and impaired whole body calcium metabolism, but the pathogenesis of aberrant calcium homeostasis remains elusive. Herein, we investigated how β-thalassemia impaired intestinal calcium absorption and whether it could be restored by administration of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] or hepcidin, the latter of which was the liver-derived antagonist of intestinal iron absorption. The results showed that, in hemizygous β-globin knockout (BKO) mice, the duodenal calcium transport was lower than that in wild-type littermates, and severity was especially pronounced in female mice. Both active and passive duodenal calcium fluxes in BKO mice were found to be less than those in normal mice. This impaired calcium transport could be restored by 7-day 1,25(OH)2D3 treatment. The 1,25(OH)2D3-induced calcium transport was diminished by inhibitors of calcium transporters, e.g., L-type calcium channel, NCX1, and PMCA1b, as well as vesicular transport inhibitors. Interestingly, the duodenal calcium transport exhibited an inverse correlation with transepithelial iron transport, which was markedly enhanced in thalassemic mice. Thus, 3-day subcutaneous hepcidin injection and acute direct hepcidin exposure in the Ussing chamber were capable of restoring the thalassemia-associated impairment of calcium transport; however, the positive effect of hepcidin on calcium transport was completely blocked by proteasome inhibitors MG132 and bortezomib. In conclusion, both 1,25(OH)2D3 and hepcidin could be used to alleviate the β-thalassemia-associated impairment of calcium absorption. Therefore, our study has shed light on the development of a treatment strategy to rescue calcium dysregulation in β-thalassemia.

Status of Serum Calcium, Vitamin D and Parathyroid Hormone and Hematological Indices Among Lead Exposed Jewelry Workers in Dhaka, Bangladesh.

Jewelry utilizes lead either directly or as a base metal. Costume jewelry requires lead before molding and plating the product with valuable metals. Therefore, such ornaments have a great potential to release heavy metals having health hazards. Also, jewelry makers engaged in preparing German silver, an alloy, apply lead in smelting, alloying, rolling and milling silver wires and pieces. The metal is taken up by blood, soft tissues and bone. The biological effects of lead are dependent upon the level and duration of exposure. Lead inhibits three enzymes of heme biosynthesis- δ-amino-levulinic-acid dehydratase (ALAD), coproporphyrin oxidase, and ferrochelatase, impairing heme synthesis and depressing serum level of erythropoietin resulting in decreased hemoglobin synthesis. Lead exposure also affects calcium metabolism and impair the synthesis of Calcitriol. In the present study, jewelry makers from Dhaka, Bangladesh, were shown to have significantly high levels of lead, protein, albumin, and parathormone in their blood, and significantly high amount of zinc-protoporphyrin and δ-amino-levulinic-acid in their urine. The control group, on the other hand showed significantly higher amounts of calcium (both total and ionized form) Vitamin D3 and non-activated erythrocyte ALAD in their blood, along with hemoglobin. It might be due to inhibition of 1-α-hydroxylase enzyme in renal tubules. Lead causes nephro-toxicity and inhibits 1-α- hydroxylase enzyme leading to decreased calcitriol synthesis resulting in impaired calcium absorption across gastro-intestinal tract and renal tubules. Low Vitamin D3 and significantly increased Parathyroid hormone (PTH) in study group has been found.

Prevalence of Vitamin D Insufficiency in Adult Hematopoietic Cell Transplant (HCT) Patients with Documented Osteopenia or Osteoporosis after Steroid Exposure: A Quality Assurance Study

Background: Steroid exposure is a known risk factor for osteopenia and osteoporosis. Vitamin D insufficiency is a known factor that contributes to bone loss. Low concentrations of vitamin D are associated with impaired calcium absorption, negative calcium balance and a compensatory rise in parathyroid hormone, which results in excessive bone resorption. Historically at Seattle Cancer Care Alliance, adult allogeneic HCT patients treated with steroids routinely have a Dual Energy X-ray Absorptiometry (DEXA) scan at departure. While many patients were found to have osteopenia or osteoporosis, it was unknown how many of these patients were additionally vitamin D deficient. Objective: The aims of this quality assurance study were: 1) to identify the prevalence of vitamin D insufficiency in adult HCT patients with osteopenia or osteoporosis post-HCT and 2) to evaluate the need to change standard practice guidelines at our center to assess for vitamin D insufficiency more regularly in at-risk groups. Design: We identified all allogeneic HCT patients with postHCT steroid exposure and documented osteopenia or osteoporosis on departure DEXA scan over a six month period. A serum 25-OH vitamin D level was drawn on patients meeting these criteria. Results: 40 adults met inclusion criteria: 22 males and 18 females. All patients were receiving 1500 mg calcium and 800 international units vitamin D3 daily with combination of diet, multivitamin and/or supplements per standard practice guidelines at Seattle Cancer Care Alliance. All patients were counseled by a registered dietitian to ensure adequate calcium and vitamin D intake. 4 patients had deficient 25-OH vitamin D levels (25-OH vitamin D 30 ng/mL). The prevalence of insufficiency or deficiency was 73% (29/ 40). Stratified by age, the prevalence of insufficiency or deficiency was:

Calcium gluconate supplementation is effective to balance calcium homeostasis in patients with gastrectomy.

We demonstrate histological evidence for hyperparathyroidism in patients with gastrectomy. This is, at least in part, explained by impaired calcium absorption, resulting in mineralization defects and secondary hyperparathyroidism. Additionally, we demonstrate improved bone mineralization in patients with gastrectomy after gluconate therapy and showed the effectiveness of calcium gluconate over carbonate to balance impaired calcium hemostasis in mice. Gastrectomy and hypochlorhydria due to long-term proton pump inhibitor therapy are associated with increased fracture risk because of intestinal calcium malabsorption. Hence, our objectives were to histologically investigate bone metabolism in patients with gastrectomy and to analyze the impact of calcium gluconate supplementation on skeletal integrity in the setting of impaired gastric acidification. Undecalcified bone biopsies of 26 gastrectomized individuals were histologically analyzed. In the clinical setting, we retrospectively identified 5 gastrectomized patients with sufficient vitamin D level, who were additionally supplemented with calcium gluconate and had a real bone mineral density (aBMD) follow-up assessments. A mouse model of achlorhydria (ATP4b-/-) was used to compare the effect of calcium gluconate and calcium carbonate supplementation on bone metabolism. Biopsies from gastrectomized individuals showed significantly increased osteoid, osteoclast, and osteoblast indices and fibroosteoclasia (p < 0.05) as well as impaired calcium distribution in mineralized bone matrix compared to healthy controls. Five gastrectomized patients with sufficient vitamin D level demonstrated a significant increase in aBMD after a treatment with calcium gluconate alone for at least 6 months (p < 0.05). Calcium gluconate was superior to calcium carbonate in maintaining calcium metabolism in a mouse model of achlorhydria. Gastrectomy is associated with severe osteomalacia, marrow fibrosis, and impaired calcium distribution within the mineralized matrix. We show that calcium gluconate supplementation can increase bone mineral density in gastrectomized individuals and performs superior to calcium carbonate in restoring calcium/skeletal homoeostasis in a mouse model of achlorhydria.

Bone mineral density and expression of vitamin D receptor-dependent calcium uptake mechanisms in the proximal small intestine after bariatric surgery.

Roux-en-Y gastric bypass may lead to impaired calcium uptake. Therefore, operation-specific effects of gastric bypass and vertical banded gastroplasty on bone mineral density (BMD) were examined in a randomized clinical trial. Bone resorption markers and mechanisms of decreased calcium uptake after gastric bypass were investigated using blood and endoscopic samples from two additional patient cohorts. Total BMD and non-weight-bearing skull BMD were measured by dual-energy X-ray absorptiometry at baseline, and 1 and 6 years after gastric bypass or vertical banded gastroplasty in patients who were not receiving calcium supplements. Bone resorption markers in serum and calcium uptake mechanisms in jejunal mucosa biopsies were analysed after gastric bypass by proteomics including radioimmunoassay, gel electrophoresis and mass spectrometry. One year after surgery, weight loss was similar after gastric bypass and vertical banded gastroplasty. There was a moderate decrease in skull BMD after gastric bypass, but not after vertical banded gastroplasty (P < 0·001). Between 1 and 6 years after gastric bypass, skull BMD and total BMD continued to decrease (P = 0·001). C-terminal telopeptide levels in serum had increased twofold by 18 months after gastric bypass. Proteomic analysis of the jejunal mucosa revealed decreased levels of heat-shock protein 90β, a co-activator of the vitamin D receptor, after gastric bypass. Despite increased vitamin D receptor levels, expression of the vitamin D receptor-regulated calcium transporter protein TRPV6 decreased. BMD decreases independently of weight after gastric bypass. Bone loss might be attributed to impaired calcium absorption caused by decreased activation of vitamin D-dependent calcium absorption mechanisms mediated by heat-shock protein 90β and TRPV6.

Controversies in Osteoporosis Management

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.