Prevalence and risk factors for hypercalcemia among non-dialysis patients with chronic kidney disease-mineral and bone disorder.

PURPOSE: To examine the prevalence and risk factors for hypercalcemia among non-dialysis chronic kidney disease (CKD) patients with mineral and bone disorder (MBD). METHODS: A retrospective cohort study was conducted in Singapore General Hospital, involving all CKD stage 4 and 5 pre-dialysis patients who were on treatment for MBD in June 2016. Each patient was followed up for 1 year and screened for hypercalcemia episodes. Mild, moderate and severe hypercalcemia were defined as corrected calcium of 2.47-3.00, 3.01-3.50 and ≥ 3.51 mmol/l respectively. Patients who were on dialysis, post-renal transplant, post-parathyroidectomy or had no calcium levels taken during the study period were excluded. Details related to patients' clinical information and hypercalcemia episodes were collected. Multivariate logistic regression analysis was performed to evaluate risk factors for hypercalcemia. RESULTS: Of 557 patients, 75 (13.4%) patients developed hypercalcemia. There were 120 (97.6%) mild and 3 (2.4%) moderate hypercalcemia episodes. The daily elemental calcium intake from phosphate binders and usage of vitamin D analogues did not differ between patients with and without hypercalcemia (p > 0.05). After adjusting for covariates, lower baseline iPTH level [odds ratio (OR) 0.96, 95% CI 0.93-0.99], history of hypercalcemia in past 1 year (OR 11.11, 95% CI 3.36-36.75) and immobility (OR 3.34, 95% CI 1.34-8.40) were associated with increased hypercalcemia risk. CONCLUSION: Hypercalcemia affects a significant proportion of pre-dialysis patients with MBD. More studies should be undertaken to evaluate other risk factors associated with hypercalcemia.

The relationship between intact PTH and biointact PTH (1-84) with bone and mineral metabolism in pre-dialysis chronic kidney disease (CKD).

OBJECTIVES: Abnormalities in PTH are implicated in the pathogenesis of bone abnormalities in chronic kidney disease (CKD)-mineral bone disorder (CKD-MBD). PTH concentrations are important in clinical decision and management. This emphasises the importance of providing an assay which measures biologically active PTH. We compared concentrations of intact PTH with biointact PTH (1-84) in CKD and end stage renal disease (ESRD) and investigated the relationship between the 2 PTH assays with bone and mineral laboratory parameters and bone mineral density (BMD) in CKD. DESIGN AND METHODS: We assessed 140 patients (61 in ESRD and 79 with CKD stages 1-4) in this cross-sectional study. We measured biointact PTH (1-84) as well as routine biochemical parameters on all subjects. In the CKD cohort, bone turnover markers; bone alkaline phosphatase (BAP) and tartrate resistant acid phosphatase (TRACP)-5b and bone mineral density (BMD) were also determined. RESULTS: In ESRD, intact PTH concentration was significantly higher compared to biointact PTH (1-84) (422 [443] v/s 266 [251] pg/mL, (p<0.001) with an average bias of 60%. In CKD, intact PTH concentration was also higher compared to biointact PTH (1-84) (79[55] v/s 68[49] pg/mL p<0.001) with an average bias of 18%. Only the biointact PTH (1-84) assay showed any significant correlation with serum calcium concentrations (r=-0.26, p<0.05) and phosphate (r=0.25, p<0.05) in CKD. Following multilinear regression analysis and adjustment for all significant co-variables, only eGFR, BAP and 25 (OH)vitamin remained significantly associated with intact PTH and biointact PTH (1-84). The strength of association was stronger between BAP and biointact PTH (1-84) (biointact PTH (1-84): p=0.007, intact PTH: p=0.01). In adjusted analyses, only biointact PTH (1-84) was significantly associated with BMD at the fore-arm (FARM) (p=0.049). CONCLUSIONS: The study confirms the differences between intact PTH and biointact PTH (1-84) in ESRD. Whilst there may be similarities in the diagnostic ability of both intact and biointact PTH (1-84), our data suggest that biointact PTH (1-84) assay may better reflect bone metabolism and BMD in CKD. Further longitudinal studies are needed.

[Adolescents do not lose bone mineral density postpartum: comparative study with adult women]. / Las adolescentes no pierden densidad mineral ósea en el posparto: estudio comparativo con adultas.

OBJECTIVE: To analyze the pattern of bone mineral density (BMD), serum concentrations of estradiol and calcium levels, dietary calcium, body mass index (BMI), and lactation in adolescents and adult women at 15, 90, and 365 postpartum days (ppd). MATERIAL AND METHODS: A prospective cohort study was conducted of 33 adolescents and 39 adult women. Anthropometric and dietetic evaluations were performed, as well as evaluations of bone mineral density in L2-L4 and femur neck. Estradiol concentrations and calcium serum levels were determined. RESULTS: L2-L4 BMD increased by 16% in adolescents, and 3% in adult women from day 15 to 365 ppd. While age was associated with this change (ß=13.779, EE=3.5, p=0.001), lactation was not (ß=-0.705, EE=0.647, p=0.283). The adult women had a higher L2-L4 BMD at 15, 90, and 635 ppd (1.151 vs 0.978 g/cm², 1.195 vs 1.070 g/cm², 1.195 vs 1.123 g/cm², respectively) (p<0.003). CONCLUSIONS: Adolescents' BMD increased three times more than that of adult women. For all women, BMD was dependent of age and independent of lactation.

Las adolescentes no pierden densidad mineral ósea en el posparto: estudio comparativo con adultas / Adolescents do not lose bone mineral density postpartum: comparative study with adult women

OBJETIVO: Analizar el patrón de la densidad mineral ósea (DMO), calcio y estradiol séricos, consumo de calcio, índice de masa corporal (IMC) y lactancia en adolescentes y adultas a 15, 90 y 365 días posparto (dpp). MATERIAL Y MÉTODOS: Cohorte prospectivo en 33 adolescentes y 39 adultas con evaluación antropométrica, dietética y ósea en L2-L4 y cuello de fémur; bioquímica con estradiol y calcio séricos. RESULTADOS: Las adolescentes aumentaron de los 15 a los 365 dpp 16 por ciento su DMO de L2-L4, las adultas 3 por ciento. La edad se asoció a este cambio (β=13.779, EE=3.5, p=0.001); la lactancia no se asoció (β=-0.705, EE=0.647, p=0.283). Las adultas presentaron mayor DMO de L2-L4 a 15, 90 y 365 dpp respectivamente (1.151vs 0.978g/cm², 1.195vs1.070g/cm², 1.195vs1.123g/cm², p<0.003). CONCLUSIONES: Las adolescentes incrementaron su DMO tres veces más que las adultas. El cambio en la DMO fue dependiente de la edad e independiente de la práctica de lactancia.

OBJECTIVE: To analyze the pattern of bone mineral density (BMD), serum concentrations of estradiol and calcium levels, dietary calcium, body mass index (BMI), and lactation in adolescents and adult women at 15, 90, and 365 postpartum days (ppd). MATERIAL AND METHODS: A prospective cohort study was conducted of 33 adolescents and 39 adult women. Anthropometric and dietetic evaluations were performed, as well as evaluations of bone mineral density in L2-L4 and femur neck. Estradiol concentrations and calcium serum levels were determined. RESULTS: L2-L4 BMD increased by 16 percent in adolescents, and 3 percent in adult women from day 15 to 365 ppd. While age was associated with this change (β=13.779, EE=3.5, p=0.001), lactation was not (β=-0.705, EE=0.647, p=0.283). The adult women had a higher L2-L4 BMD at 15, 90, and 635 ppd (1.151 vs 0.978g/cm², 1.195 vs 1.070g/cm², 1.195 vs 1.123g/cm², respectively) (p<0.003). CONCLUSIONS: Adolescents' BMD increased three times more than that of adult women. For all women, BMD was dependent of age and independent of lactation.

Low bone density is not always bisphosphonate deficiency.

Low bone density is not a one-size-fits-all disorder. We need to carefully consider the diagnostic and therapeutic options before assuming that low bone density is osteoporosis.

[The comparative analysis of the parameters used for diagnostics of lowering mineralization of osteous tissue].

With the purpose of a choice of optimal biochemical parameters for individual diagnostics of bone tissue mineralization disturbances bone mineral density (T-criterion), a blood serum level of the transport form of vitamin D (25-OH D), osteocalcin and calcitonin, and also calcium daily urine excretion and calcium excretion in morning urinary portion per creatinin has been determined. The most informative parameters have appeared T-criterion, blood serum level of 25-OH D3) or osteocalcin due their interchangeability, and also calcium urine excretion per creatinin.

Polar bears (Ursus maritimus), the most evolutionary advanced hibernators, avoid significant bone loss during hibernation.

Some hibernating animals are known to reduce muscle and bone loss associated with mechanical unloading during prolonged immobilisation,compared to humans. However, here we show that wild pregnant polar bears (Ursus maritimus) are the first known animals to avoid significant bone loss altogether, despite six months of continuous hibernation. Using serum biochemical markers of bone turnover, we showed that concentrations for bone resorption are not significantly increased as a consequence of hibernation in wild polar bears. This is in sharp contrast to previous studies on other hibernating species, where for example, black bears (Ursus americanus), show a 3-4 fold increase in serum bone resorption concentrations posthibernation,and must compensate for this loss through rapid bone recovery on remobilisation, to avoid the risk of fracture. In further contrast to black bears, serum concentrations of bone formation markers were highly significantly increased in pregnant female polar bears compared to non-pregnant,thus non-hibernating females both prior to and after hibernation. However, bone formation concentrations in new mothers were significantly reduced compared to pre-hibernation concentrations. The de-coupling of bone turnover in favour of bone formation prior to hibernation, suggests that wild polar bears may posses a unique physiological mechanism for building bone in protective preparation against expected osteopenia associated with disuse,starvation, and hormonal drives to mobilise calcium for reproduction, during hibernation. Understanding this physiological mechanism could have profound implications for a natural solution for the prevention of osteoporosis in animals subjected to captivity with inadequate space for exercise,humans subjected to prolonged bed rest while recovering from illness, or astronauts exposed to antigravity during spaceflight.© 2008 Elsevier Inc. All rights reserved.

Bone demineralization in adult thalassaemic patients: contribution of GH and IGF-I at different skeletal sites.

BACKGROUND AND OBJECTIVE: GH and IGF-I exert an important role in the control of bone formation, as shown by decreased bone mineral density and increased fracture risk in adult hypopituitary patients untreated for GH deficiency (GHD). Different degrees of bone demineralization are frequently reported in patients affected by beta-thalassaemia. Considering the high prevalence of GHD recently observed by our group among adult thalassaemic patients, we elected to study the possible role of GH-IGF-I abnormalities in the pathogenesis of the osteopenia/osteoporosis of this disease. DESIGN: Sixty-four adult thalassaemic patients (49 with thalassaemia major and 15 with thalassaemia intermedia, 23 men and 41 women, aged 31.4 +/- 6.8 years) were studied. METHODS: Bone mineral density was assessed by dual energy X-ray absorptiometry at lumbar spine in 62 patients and at proximal femur in 58. All patients underwent GHRH (1 microg/kg as an i.v. bolus) plus arginine (0.5 g/kg as a 30-min i.v. infusion) testing. Severe GHD was defined by GH peaks < 9 microg/l, whereas partial GHD was defined by GH peaks ranging from 9 to 16.5 microg/l. Blood samples for IGF-I measurement were collected. RESULTS: Lumbar osteoporosis and osteopenia were demonstrated in 46/62 (74.1%) and 14/62 (22.5%) patients, respectively. Femoral osteoporosis and osteopenia were documented in 22/58 (37.9%) and 32/58 (55.1%) patients, respectively. Severe GHD was demonstrated in 16/64 patients (25%), while 11 additional patients (17.1%) displayed partial GHD. IGF-I standard deviation score (SDS) was low, that is, below -1.88, in the majority (54.6%) of patients. Lumbar T-score values were not correlated with either GH peaks or IGF-I SDS values. Femoral T-score values were positively correlated with GH peaks (r = 0.38, P < 0.005) and IGF-I SDS values (r = 0.39, P < 0.005). Multiple regression analysis pointed to both GH peak and IGF-I SDS as predictors of femoral T-score. Furthermore, mean femoral T-score was significantly lower in patients with severe GHD than in those with normal GH secretion (-2.94 +/- 0.25 vs.-2.15 +/- 0.12, P < 0.01). CONCLUSION: This study, while confirming the high prevalence of both osteopenia/osteoporosis and somatotropin-somatomedin deficiency in adult thalassaemic patients, indicates that defective GH secretion and diminished serum IGF-I levels may contribute to femoral demineralization in these patients. Further studies are worth carrying out to evaluate the efficacy of biosynthetic GH administration on bone abnormalities of GH-deficient thalassaemic adults.

[Bone metabolism in adolescent girls with short course of anorexia nervosa]. / Metabolizm tkanki kostnej u mlodych dziewczat z krótkim przebiegiem jadlowstretu psychicznego.

OBJECTIVE: The objective of this study was to determine the prevalence of bone mass reduction and determine its causes in young girls with short course of anorexia nervosa (AN). METHOD: Bone mineral density (BMD)of lumber spine by dual energy x-ray absorptiometry, total alkaline phosphatase (TAP), bone-Gla protein (BGP), urine deoxypyridinoline (DPYR), DPYR, urine calcium, sex hormones were measured in 24 in-patient girls with diagnosed AN and 20 healthy volunteers. RESULTS: Girls with AN had a significantly lower BMD than their age-matched controls. Osteopenia and osteoporosis were present even in the group with AN diagnosed within the previous 12 months. BMD correlated negatively with minimal BMI and positively with the duration of regular menses before AN onset. BGP and DPYR were significantly lower in AN patient than in the control group. Values of urine calcium of AN patients were comparable with control group, but showed a positive correlation with disease duration. DISCUSSION: Reduction of bone mineral density is present in girls with short course of AN. Nutritional status is the most important predictor of BMD. Bone metabolism is decreased in the early stages of the disease.

Cortical tibial bone volume in two strains of mice: effects of sciatic neurectomy and genetic regulation of bone response to mechanical loading.

Although C3H/HeJ (C3H) and C57BL/6J (B6) mice are similar in body size (and adult weight), and have bones of similar external size, C3H mice have higher peak bone densities than B6 mice (e.g., 53% higher peak bone density in the femora). The current studies were intended to assess the role of mechanical loading/unloading as a possible determinant of the bone density difference between these inbred strains of mice and, specifically, to assess the effect of sciatic neurectomy on histomorphometric indices of bone formation and resorption in the tibiae of female C3H and B6 mice. Groups of 10 mice of each strain were subjected to left-side sciatic neurectomy (left hindlimb immobilization) or a sham procedure. The contralateral (right) legs of each mouse were used as controls. Four weeks of immobilization produced no systemic changes in bone formation indices in either strain of mice (i.e., no change in serum alkaline phosphatase or serum osteocalcin). However, histomorphometric assessments at the tibiofibular junction showed that 4 weeks of immobilization caused a time-dependent decrease in the length of the endosteal bone forming perimeter (e.g., 14% of control single-labeled, noneroded surface at 4 weeks, p < 0.005) with a concomitant increase in the length of the endosteal bone resorbing perimeter (i.e., 424% of control eroded surface at 4 weeks, p < 0.005), in the B6 mice. These effects were associated with an increase in medullary area (132% of control, p < 0.05) at this site, in the B6 mice. The pattern of response was different in the tibiae of the C3 mice-a much smaller decrease in bone forming perimeter (88% of control at 4 weeks, p < 0.05), with no associated increase in bone resorbing perimeter, and no change in medullary area. Similar effects were seen at a second cross-sectional sampling site, in the proximal tibia. Together, these findings indicate that B6 mice are more sensitive to endosteal bone loss from hindlimb immobilization than C3H mice.

Bone metabolism in orthotopic liver transplantation: a prospective study.

Bone mineral density (BMD) and mineral metabolism were assessed in 54 patients with end-stage liver disease who were evaluated for orthotopic liver transplantation (OLT) and assessed 3, 6, and 12 months after surgery in 26 patients who underwent OLT. Serum and urinary electrolyte and mineral levels, serum liver function test results, and parathyroid hormone (PTH), osteocalcin (BGP), 25-hydroxyvitamin D, and urinary hydroxyproline levels were assessed. BMD of the lumbar spine was measured at baseline and 3, 6, and 12 months after OLT. At baseline, 40.7% of patients had BMD below the fracture threshold (0.800 g/cm2). Using multiple stepwise regression analysis, we found that BMD was significantly (P < .0001) affected by age, serum creatinine level, and PTH level but not by indices of cholestasis or liver function. In the patients who underwent OLT, a 1.4% reduction (P < .006) was observed in BMD 3 months after OLT. Thereafter, BMD returned to pretransplant values. A significant increase in serum BGP was observed after 6 (P < .02) and 12 (P < . 005) months. PTH levels increased progressively 3 (P < .02), 6 (P < . 001), and 12 (P < .0001) months after OLT. This increase did not seem to be caused by cyclosporine-induced nephropathy. It was concluded that osteopenia is a major complication in hepatic cirrhosis, regardless of its causes. The increase in serum BGP levels 6 and 12 months after OLT indicates metabolic activation of osteoblasts. The increase in PTH levels after OLT warrants further investigation.

Factors affecting bone demineralization and blood lead levels of postmenopausal women--a population-based study from Germany.

We investigated the influence of various lifestyle factors on blood lead levels in postmenopausal women from the general population of Germany. Particular consideration was given to those factors which are suspected to be related to bone demineralization. The study population consisted of 424 women, aged 45 to 80 years, who were examined in a substudy of the National Health and Nutrition Survey called VERA (Verbundstudie Ernährungserhebung, und Risikofaktorenanalyse) from 1987 to 1988. Mean blood lead level was 61.4 micrograms/liter (SD, 27.3). In multiple linear regression analysis alcohol consumption, former use of oral contraception, hematocrit, and age were positively associated with blood lead levels, whereas calcium intake and high physical activity showed a negative association with blood lead levels. Some of the identified risk factors which are suspected to exert their influence on blood lead levels by affecting bone demineralization can be influenced by change of individual behavior. Thus, we conclude that reduction of alcohol consumption, adequate calcium intake, and physical activity may reduce blood lead levels as well as negative health effects of osteoporosis in postmenopausal women.

A comparative bear model for immobility-induced osteopenia.

The National Institutes of Health (NIH) and the National Aeronautics and Space Administration (NASA) are seeking solutions to the human problem of osteopenia, or immobility-induced bone loss. Bears, during winter dormancy, appear uniquely exempted from the debilitating effects of immobility osteopenia. NIH and ESA, Inc. are creating a large database of metabolic information on human ambulatory and bedrest plasma samples for comparison with metabolic data obtained from bear plasma samples collected in different seasons. The database generated from NASA's HR113 human bedrest study showed a clear difference between plasma samples of ambulatory and immobile subjects through cluster analysis using compounds determined by high performance liquid chromatography with coulometric electrochemical array detection (HPLC-EC). We collected plasma samples from black bears (Ursus americanus) across 4 seasons and from 3 areas and subjected them to similar analysis, with particular attention to compounds that changed significantly in the NASA human study. We found seasonal differences in 28 known compounds and 33 unknown compounds. A final database contained 40 known and 120 unknown peaks that were reliably assayed in all bear and human samples; these were the primary data set for interspecies comparison. Six unidentified compounds changed significantly but differentially in wintering bears and immobile humans. The data are discussed in light of current theories regarding dormancy, starvation, and anabolic metabolism. Work is in progress by ESA Laboratories on a larger database to confirm these findings prior to a chemical isolation and identification effort. This research could lead to new pharmaceuticals or dietary interventions for the treatment of immobility osteopenia.