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Volume 8 · Number 4 · December 2016
101 Editorial  ( PDF )
Chronic renal failure, vascular calcification and the RNK/RANKL/OPG system
Rev Osteoporos Metab Mineral 2016 8;4:101-104
Cardiovascular complications are among the most important clinical challenges in patients with chronic kidney failure (CKF). These are frequent processes that present high morbidity and mortality. As an example, around 50% of patients with terminal CRF die from this disease [1]....
AUTHORS
Olmos JM*, Hernández JL
Departamento de Medicina Interna - Hospital Universitario Marqués de Valdecilla -IDIVAL- Universidad de Cantabria - Santander (España)
KEYWORDS
105 Original Articles  ( PDF )
Effect of RANK/RANKL/OPG pathway on bone demineralization and vascular calcification in chronic kidney disease
Rev Osteoporos Metab Mineral 2016 8;4:105-114

Introduction: In cases of chronic kidney disease (CKD), bone and mineral metabolism changes occur which favor soft tissue calcification. Alterations in the RANK/RANKL/OPG system could also favor vascular calcification, a major cause of morbidity and mortality in CKD.

Objective: In an in vivo experimental model of chronic renal failure progression, we assess the effect of CKD on vascular calcification and bone loss correlating these changes in the RANK/RANKL/OPG pathway. An in vitro system was used to confirm findings.

Material and Methods: Two models of vascular calcification were used: an in vivo rat model with chronic renal failure fed on a diet with different phosphorus content, and an in vitro model in vascular smooth muscle cells (VSMC) subjected to different calcifying stimuli.

Results: At 20 weeks, 50% of animals with a diet high in phosphorus presented aortic calcification accompanied by increased aortic expression of RANKL. In contrast, OPG decreased probably as a consequence of an inflammatory component.

At 20 weeks, expression of RANKL and OPG in the tibia increased, while the increase in OPG occurred at earlier stages.

In VSMC, the addition of uremic serum and calcification medium increased calcium content and expression of RANKL and OPG. The addition of OPG and silencing of RANK inhibited this increase.

...

AUTHORS
Martínez Arias L1, Solache Berrocal G1, Panizo García S1, Carrillo López N1, Avello Llano N2, Quirós Caso C2, Naves Díaz M1, Cannata Andía JB1
1 Servicio de Metabolismo Óseo y Mineral - Instituto Reina Sofía de Investigación Nefrológica - Red de Investigación Renal (REDinREN) del Instituto de Salud Carlos III - Universidad de Oviedo - Oviedo (España)
2 Laboratorio de Medicina - Hospital Universitario Central de Asturias - Oviedo (España)
KEYWORDS
RANK, RANKL, OPG, chronic kidney disease, vascular calcification.
115 Original Articles  ( PDF )
The association of MMP1 1G>2G polymorphism with aortic valve
Rev Osteoporos Metab Mineral 2016 8;4:115-120

Introduction: The most common cause of aortic stenosis is active calcium accumulation in the valve cusps, which implies serious clinical consequences. Various extracellular matrix metalloproteases (MMPs) have been implicated in the development of this disease. Therefore, the possible association between a functional MMP1 polymorphism and the amount of calcium deposited on the aortic valve is studied.

Patients and methods: 45 patients undergoing valve replacement were included in the study. The calcium content in valve cusps removed during surgery was determined by computed micro-tomography. DNA was extracted from peripheral blood samples for genotyping the -1607 1G>2G polymorphism of MMP1 by PCR and subsequent digestion.

Results: Significant differences were observed in the calcium content in aortic valves in individuals with different -1607 1G>2G genotypes (p=0.042). Thus, 2G allele carriers (homozygous or heterozygous) present higher calcium levels measured as BMD (p=0.004) as well as BV/TV (p=0.002). The association with BV/TV was independent of sex, age, degree of renal function and anatomy of the valve (p=0.02). BMD tendency (p=0.07) was also observed.

Conclusion: The association between 1G>2G MMP1 polymorphism and calcium content of the aortic valve suggests that the 1G allele would have a protective effect against calcium depos...

AUTHORS

Solache-Berrocal G1, Barral A2,4, Martín M3, Román-García P1, Llosa JC2, Naves-Díaz M1, Cannata-Andía JB1, Rodríguez I1

1 Servicio de Metabolismo Óseo y Mineral - Instituto Reina Sofía de Investigación - Hospital Universitario Central de Asturias - Universidad de Oviedo - REDinREN del Instituto de Salud Carlos III - Oviedo (España)
2 Servicio de Cirugía Cardiaca - Área del Corazón - Hospital Universitario Central de Asturias - Oviedo (España)
3 Servicio de Cardiología - Área del Corazón - Hospital Universitario Central de Asturias - Oviedo (España)
4 Servicio de Cirugía Cardiovascular - Hospital Universitario Miguel Servet - Zaragoza (España)

KEYWORDS
aortic valve disease, matrix metalloproteinase polymorphisms, microCT, calcium content.
121 Original Articles  ( PDF )
Functional study of promoter gene polymorphisms of sclerostin
Rev Osteoporos Metab Mineral 2016 8;4:121-126

Sclerostin, encoded by the SOST gene, inhibits the Wnt pathway and, consequently, tends to decrease bone mass. Some polymorphisms of the SOST promoter have been associated with bone mineral density (BMD), but the molecular mechanisms involved are unknown. The aim of this study was to study the functional role of one polymorphism in vitro. We cloned the proximal promoter region of SOST gene, containing different alleles at the rs851054 SNP, in luciferase reporter vectors and transfected them into the cell lines HEK-293T, SAOS-2 and HOS-TE85. We did not find significant differences in the transcriptional activity of vectors with either the A or the G allele of the SNP. The co-transfection of vectors expressing RUNX2 and OSX markedly increased the transcriptional activity of the SOST promoter constructs (A allele, 2.5±0.9 fold, p<0.05; G allele, 1.9±0.8 fold, p<0.05), without significant differences between the rs851054 alleles. Moreover, no allele differences were detected in EMSAs.

In conclusion, the DNA region upstream of the TSS of the SOST gene has a strong promoter activity that is enhanced by RUNX2 and OSX. Frequent allelic variants in this region have been associated with BMD, but the mechanisms involved remain to be elucidated because no functional differences between alleles were detected in vitro.

...
AUTHORS

Pérez-Campo FM2, Sañudo C1, Krebesova R1, Delgado-Calle J3, Riancho JA1

1 Departamento de Medicina Interna - Hospital U.M. Valdecilla - Universidad de Cantabria - IDIVAL - Santander (España)
2 Departamento de Biología Molecular - Universidad de Cantabria - Santander (España)
3 Departamento de Anatomía y Biología Celular - Facultad de Medicina de la Universidad de Indiana - Centro Médico de Administración de Veteranos Roudebush - Indianápolis - Indiana (EE.UU.)

KEYWORDS
sclerostin, gene regulation, polymorphisms, transfection.
127 Original Articles  ( PDF )
Prevalence of low levels of vitamin D in patients with breast cancer who live in Northern latitudes 21-22º
Rev Osteoporos Metab Mineral 2016 8;4:127-133

Objective: Vitamin D has been involved in various diseases, including cancer. Several studies have linked vitamin D levels with breast cancer. The aim of our study was to establish the importance of adequate vitamin D concentrations to prevent breast cancer.

Materials and methods: The study included 76 patients. Dietary habits, sun exposure, body mass index (BMI), and skin type were evaluated. Vitamin D determination in serum was measured by liquid chromatography. Vitamin D receptor pleomorphism was analyzed by immunohistochemistry.

Results: Vitamin D ingestion was deficient in 18 patients and 22 controls; and sufficient in 6 patients and 30 controls, odds ratio of 4.09, confidence interval 95% 1.04-11.0, (p=0.016). Sun exposure was present in 9 patients and 15 controls; 15 patients and 37 controls had less sun exposure or used protection. Two patients and 13 controls had normal levels of vitamin D (30-60), two patients and 26 controls had low levels (20-30), and 18 patients and 12 controls had very low levels (<20). Odds ratio for patients with vitamin D serum levels of 20 ng/mL or less, or higher was 9, CI 95% 2.95-27.5, (p<0.001). These levels were independent from BMI.

Conclusion: Low concentrations of vitamin D are strongly related to breast cancer in a region with high solar exposure. More studies are needed to confirm this rela...

AUTHORS

González-Fisher RF1, Pérez-Jaime S2, Buz K3, Sotelo-Félix E1, Álvarez Ordorica O1, González Riestra HJ1, Rolon Padilla A4

1 Grupo Oncológico - Hospital Médica Avanzada Contigo - Central Médico-Quirúrgica de Aguascalientes (México)
2 Servicio de Nutrición Clínica - Hospital Miguel Hidalgo - Instituto de Salud del Estado de Aguascalientes (México)
3 Servicio de Nutrición Clínica - Hospital Médica Avanzada Contigo – Central Médico-Quirúrgica de Aguascalientes (México)
4 Biopath - Aguascalientes (México)

KEYWORDS
breast cancer, vitamin D, risk factor, sun exposure, diet, skin type.
134 Clinical Notes  ( PDF )
Hemochromatosis and osteoporosis, in reference to 4 cases
Rev Osteoporos Metab Mineral 2016 8;4:134-137

Although most people's osteoporotic conditions treated in clinical practice may be categorized in the postmenopausal osteoporosis group or related to aging, there are some osteoporosis cases linked to the development of some other disease or identifiable factor.

Most of these causes are associated with the taking of steroids, hypogonadism, malignant processes such as multiple myeloma, gastric surgery, alcoholism and treatment with anticonvulsant drugs. Hereditary hemochromatosis is another disorder related to the onset of osteoporosis. In this paper, we present 4 cases of patients with osteoporosis who also suffer hereditary hemochromatosis. The latter’s characteristics are described and also its possible relationship with bone disease.

...
AUTHORS
Montaño Jaramillo D, Díaz Curiel M
Unidad de Enfermedades Metabólicas Óseas - Servicio de Medicina Interna - Fundación Jiménez Díaz/Quirón Salud Madrid - Madrid (España)
KEYWORDS
hemochromatosis, osteoporosis, iron.
138 Reviews  ( PDF )
Oxidative stress as a possible therapeutic target for osteoporosis associated with aging
Rev Osteoporos Metab Mineral 2016 8;4:138-146

Senile or involutional osteoporosis is a major problem in the developed world. Recent studies point to increased oxidative stress associated with aging, whether biological or chronological, as an important factor in its development. In this review paper, we focus on bone tissue disorders related to aging, the source of oxidative stress and negative influence on bone tissue. Finally, we consider the potential oxidative stress therapies currently being developed for this disease.

...
AUTHORS
Portal-Núñez S1,4, de la Fuente M2,4, Díez A3,4, Esbrit P1,4
1 Área de Reumatología y Metabolismo Óseo - Instituto de Investigación Sanitaria-Fundación Jiménez Díaz - UAM - Madrid (España)
2 Departamento de Fisiología Animal II - Universidad Complutense - Madrid (España)
3 Hospital del Mar-IMIM-Universidad Autónoma de Barcelona - Barcelona (España)
4 Red Temática de Investigación Cooperativa en Envejecimiento y Fragilidad (RETICEF) - Instituto de Salud Carlos III - Madrid (España)

KEYWORDS
oxidative stress, osteoporosis, aging, fragility.
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