MO055STABLE CALCIUM ISOTOPES: A NOVEL BIOMARKER OF BONE MINERAL CONTENT IN PATIENTS WITH CHRONIC KIDNEY DISEASE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Rukshana Shroff ◽  
Alex Heuser ◽  
Alex Lalayiannis ◽  
Aysun Karabay Bayazit ◽  
Augustina Jankauskiene ◽  
...  

Abstract Background and Aims In CKD dysregulated calcium (Ca) homeostasis is common and causally associated with reduced bone mineral density (BMD) and vascular calcification. Currently available radiological measures and biomarkers do not allow accurate evaluation of BMD. The aim of our study was to determine the sensitivity and specificity of stable Ca isotopes in determining bone mineral content. Method We measured stable Ca isotopes 44Ca and 42Ca by plasma-ionization mass-spectrometry in blood and urine. The relationship between bone Ca gain and loss is calculated using a compartment model based on Ca kinetics, and expressed as δ44/42Ca. Ca absorption from bones increases δ44/42CaBlood and δ44/42CaUrine, and resorption decreases these fractions. 104 children in CKD4-5 and on dialysis (CKD4-5D), 40 matched controls and 100 adults underwent Ca isotope measurement, bone biomarkers, dual energy x-ray absorptiometry (DXA) and tibial peripheral quantitative CT scan (pQCT), an accurate measure of cortical BMD. Results In healthy children the δ44/42CaBlood and δ44/42CaUrine were higher than in adults (p<0.0001), reflecting avid Ca uptake during bone formation. Since urinary Ca excretion is impaired in CKD, δ44/42CaBlood was higher and δ44/42CaUrine lower in children with CKD4-5D compared to controls (p<0.001 for both); Figure 1. In CKD2-5D δ44/42CaBlood positively correlated with cholecalciferol (p=0.01) and alfacalcidol (p=0.002) doses, implying increased bone Ca uptake when Ca bioavailability is increased. δ44/42CaBlood positively correlated with biomarkers of bone formation (alkaline phosphatase, p=0.05) and negatively with bone resorption markers (PTH, p=0.013; TRAP5b, p<0.001 and CTX, p=0.006). δ44/42CaBlood positively correlated with tibial cortical BMD-Z-score (p=0.006, R2=0.39), and DXA hip BMD-Z-score (p=0.02). On multivariable linear regression analysis significant and independent predictors of tibial cortical BMD-Z-score were δ44/42CaBlood (β=0.68, p=0.006) and PTH (β-0.39, p=0.04), together predicting 67% of the variability in BMD. Conclusion Ca isotope ratios provide a novel, non-invasive method of assessing bone mineralization. Further studies are in progress to define optimal levels of δ44/42CaBlood that can guide safe and effective treatment to prevent Ca deficiency or overload.

2002 ◽  
Vol 93 (3) ◽  
pp. 1152-1158 ◽  
Author(s):  
Takuya Notomi ◽  
Yuichi Okazaki ◽  
Nobukazu Okimoto ◽  
Yuri Tanaka ◽  
Toshitaka Nakamura ◽  
...  

To determine the effects of a tower climbing exercise on mass, strength, and local turnover of bone, 70 9-wk-old Sprague-Dawley rats were assigned to seven groups: a baseline control and three groups of sham-operated sedentary, orchidectomized (ORX)-sedentary and ORX-exercise rats. Rats voluntarily climbed a 200-cm tower to drink water from a bottle set at the top. At 4 wk, the periosteal bone formation rate (BFR), moment of inertia, bone mineral content, bone mineral density, and bending load at the midfemur were maintained in ORX-exercise rats, whereas these parameters were reduced in ORX-sedentary rats. At 8 wk, the periosteal mineral apposition rate and BFR in ORX-exercise rats were significantly higher, whereas the parameters in ORX-sedentary rats did not differ compared with sham-sedentary rats. In ORX-exercise rats, the trabecular mineralizing surface, BFR, and bone volume of the lumbar vertebrae were maintained at the same levels as those in the sham-sedentary group, whereas the osteoclast surface decreased compared with the ORX-sedentary group. However, the climbing exercise did not affect bone mineral content, bone mineral density, or the compression load of the lumbar vertebrae. These results show that, in the midfemur, the voluntary climbing exercise maintained cortical bone mass and strength by stimulating periosteal bone formation and partially prevented ORX-induced trabecular bone loss, depressing the elevation of turnover. Interestingly, in ORX rats, the climbing exercise had the opposite effect on bone formation at the periosteal femoral cortical bone, where the exercise increased the bone formation compared with vertebral trabecular bone, where the exercise decreased it.


2019 ◽  
Vol 109 (1) ◽  
pp. 186-196 ◽  
Author(s):  
Anna T Nakayama ◽  
Laura J Lutz ◽  
Adela Hruby ◽  
James P Karl ◽  
James P McClung ◽  
...  

ABSTRACT Background Stress fracture risk is elevated during initial military training (IMT), particularly in lower-extremity bones such as the tibia. Although the etiology of stress fractures is multifactorial, lower bone strength increases risk. Objective The objective of this study was to assess, through the use of peripheral quantitative computed tomography, whether adherence to a dietary pattern rich in calcium, potassium, and protein before IMT is positively associated with bone indexes in young adults entering IMT. Design A cross-sectional analysis was performed with the use of baseline data from 3 randomized controlled trials in Army, Air Force, and Marine recruits (n = 401; 179 men, 222 women). Dietary intake was estimated from a food-frequency questionnaire. A dietary pattern characterized by calcium, potassium, and protein was derived via reduced rank regression and a pattern z score was computed for each volunteer, where higher scores indicated greater adherence to the pattern. At the 4% (metaphysis) and 14% (diaphysis) sites of the tibia, bone mineral content (BMC), volumetric bone mineral density, robustness, and strength indexes were evaluated. Associations between dietary pattern z score as the predictor variable and bone indexes as the response variables were evaluated by multiple linear regression. Results Pattern z score was positively associated with BMC (P = 0.004) and strength (P = 0.01) at the metaphysis and with BMC (P = 0.0002), strength (P = 0.0006), and robustness (P = 0.02) at the diaphysis when controlling for age, sex, race, energy, smoking, education, and exercise. Further adjustment for BMI attenuated the associations, except with diaphyseal BMC (P = 0.005) and strength (P = 0.01). When height and weight were used in place of body mass index, the association with BMC remained (P = 0.046). Conclusions A dietary pattern rich in calcium, potassium, and protein is positively associated with measures of tibia BMC and strength in recruits entering IMT. Whether adherence to this dietary pattern before IMT affects injury susceptibility during training remains to be determined. These trials were registered at clinicaltrials.gov as NCT01617109 and NCT02636348.


2013 ◽  
Author(s):  
N Hangartner Thomas ◽  
F Short David ◽  
Gilsanz Vicente ◽  
J Kalkwarf Heidi ◽  
M Lappe Joan ◽  
...  

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Hideki Agata ◽  
Yoshinori Sumita ◽  
Tatsuro Hidaka ◽  
Mayumi Iwatake ◽  
Hideaki Kagami ◽  
...  

Mesenchymal stem/stromal cells (MSCs) are known to be useful for treating local bone diseases. However, it is not known if MSCs are effective for treating systemic bone diseases, as the risk for mortality following intravenous MSC administration has hindered research progress. In this study, we compared the safety and efficacy of intra-bone marrow and intravenous administration of MSCs for the treatment of ovariectomy- (OVX-) induced osteoporosis. Cells capable of forming bone were isolated from the murine compact bones and expanded in culture. Relatively pure MSCs possessing increased potential for cell proliferation, osteogenic differentiation, and inhibition of osteoclastogenesis were obtained by magnetic-activated cell sorting with the anti-Sca-1 antibody. Sca-1-sorted MSCs were administered to OVX mice, which were sacrificed 1 month later. We observed that 22% of the mice died after intravenous administration, whereas none of the mice died after intra-bone marrow administration. With respect to efficacy, intravenous administration improved bone mineral density (BMD) by increasing bone mineral content without affecting bone thickness, whereas intra-bone marrow administration improved BMD by increasing both bone mineral content and bone thickness. These results indicate that intra-bone marrow administration of pure MSCs is a safer and more effective approach for treating osteoporosis.


1996 ◽  
Vol 82 (1) ◽  
pp. 65-67 ◽  
Author(s):  
Sandro Barni ◽  
Paolo Lissoni ◽  
Gabriele Tancini ◽  
Antonio Ardizzoia ◽  
Marina Cazzaniga

In this study, the authors have analyzed the possible effects of one-year adjuvant treatment with tamoxifen on bone mineral density in postmenopausal breast cancer women. Bone mineral content was studied by photon absorptiometry (I-125), whereas bone balance was analyzed indirectly by serum PTH, osteocalcin, calcitonin, calcium and alkaline phosphatase levels. Bone mineral content and serum bone-related substances were measured before starting treatment and after one year. Results were analyzed using Student's t test for paired data. No difference was found between the two measurements for bone mineral content, PTH, calcitonin, calcium and alkaline phosphatase levels. Measurements at entry and after one year of treatment showed a statistically significant difference ( P < 0.001) only for osteocalcin. In accordance with other authors, we can conclude that treatment with tamoxifen does not cause an increase in menopausal bone resorption. The finding that osteocalcin levels decreased after one year of therapy with tamoxifen is interesting, but further studies are necessary to clarify the role of such levels in predicting a turnover of bone balance towards osteoblastic activity.


2011 ◽  
Vol 78 (6) ◽  
pp. 616-618 ◽  
Author(s):  
Katarzyna Wesolowska ◽  
Bozena Czarkowska-Paczek ◽  
Jerzy Przedlacki ◽  
Jacek Przybylski

Bone ◽  
2006 ◽  
Vol 38 (3) ◽  
pp. 13 ◽  
Author(s):  
Arjun L. Khandare ◽  
G. Shanker Rao ◽  
N. Balakrishna

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