Association between undercarboxylated osteocalcin, bone mineral density, and metabolic parameters in postmenopausal women

ABSTRACT Objective: Osteocalcin has been associated with several effects on energy and glucose metabolism. However, the physiological role of undercarboxylated osteocalcin (U-osc; the hormonally active isoform of osteocalcin) is still controversial. To correlate the serum levels of U-osc with bone mineral density (BMD) values and metabolic parameters in postmenopausal women. Subjects and methods: Cross-sectional study including 105 postmenopausal women (age 56.5 ± 6.1 years, body mass index [BMI] 28.2 ± 4.9 kg/m2) grouped based on the presence of three or less, four, or five criteria of metabolic syndrome according to the International Diabetes Federation (IDF). The subjects underwent dualenergy x-ray absorptiometry (DXA) for the assessment of body composition and BMD and blood tests for the measurement of U-osc and bone-specific alkaline phosphatase (BSAP) levels. Results: The mean U-osc level was 3.1 ± 3.4 ng/mL (median 2.3 ng/mL, range 0.0-18.4 ng/mL) and the mean BSAP level was 12.9 ± 4.0 ng/mL (median 12.1 ng/mL, range 73-24.4 ng/mL). There were no associations between U-osc and BSAP levels with serum metabolic parameters. Lower fasting glucose levels were observed in participants with increased values of U-osc/femoral BMD ratio (3.61 ± 4 ng/mL versus 10.2 ± 1.6 ng/mL, p = 0.036). When the participants were stratified into tertiles according to the U-osc/ femoral BMD and U-osc/lumbar BMD ratios, lower fasting glucose levels correlated with increased ratios (p = 0.029 and p = 0.042, respectively). Conclusion: Based on the ratio of U-osc to BMD, our study demonstrated an association between U-osc and glucose metabolism. However, no association was observed between U-osc and metabolic parameters.The U-osc/BMD ratio is an innovative way to correct the U-osc value for bone mass.

Changes in the Expressions of Iba1 and Calcitonin Gene-Related Peptide in Adjacent Lumbar Spinal Segments after Lumbar Disc Herniation in a Rat Model

Lumbar disc herniation is commonly encountered in clinical practice and can induce sciatica due to mechanical and/or chemical irritation and the release of proinflammatory cytokines. However, symptoms are not confined to the affected spinal cord segment. The purpose of this study was to determine whether multisegmental molecular changes exist between adjacent lumbar spinal segments using a rat model of lumbar disc herniation. Twenty-nine male Sprague-Dawley rats were randomly assigned to either a sham-operated group (n=10) or a nucleus pulposus (NP)-exposed group (n=19). Rats in the NP-exposed group were further subdivided into a significant pain subgroup (n=12) and a no significant pain subgroup (n=7) using mechanical pain thresholds determined von Frey filaments. Immunohistochemical stainings of microglia (ionized calcium-binding adapter molecule 1; Iba1), astrocytes (glial fibrillary acidic protein; GFAP), calcitonin gene-related peptide (CGRP), and transient receptor potential vanilloid 1 (TRPV1) was performed in spinal dorsal horns and dorsal root ganglions (DRGs) at 10 days after surgery. It was found immunoreactivity for Iba1-positive microglia was higher in the L5 (P=0.004) dorsal horn and in the ipsilateral L4 (P=0.009), L6 (P=0.002), and S1 (P=0.002) dorsal horns in the NP-exposed group than in the sham-operated group. The expression of CGRP was also significantly higher in ipsilateral L3, L4, L6, and S1 segments and in L5 DRGs at 10 days after surgery in the NP-exposed group than in the sham-operated group (P<0.001). Our results indicate that lumbar disc herniation upregulates microglial activity and CGRP expression in many adjacent and ipsilateral lumbar spinal segments.

Fetuin-A is related to syndesmophytes in patients with ankylosing spondylitis: a case control study

OBJECTIVES: New bone formation is one of the hallmark characteristics of ankylosing spondylitis, which is thereby associated with syndesmophytes. Fetuin-A is a molecule that is abundantly found in calcified tissues and it shows high affinity for calcium phosphate minerals and related compounds. Considering the role of fetuin-A in the regulation of calcified matrix metabolism, we compared the fetuin-A levels in ankylosing spondylitis patients with syndesmophytes with those in patients without syndesmophytes and in healthy controls. We also studied other biomarkers that are thought to be related to syndesmophytes. METHODS: Ninety-four patients (49 patients without syndesmophytes, 67.3% male, 40.7±8.7 years; 45 patients with syndesmophytes, 71.1% M, 43.9±9.9 years) and 68 healthy controls (44.2±10.6 years and 70.6% male) were included in this study. Syndesmophytes were assessed on the lateral radiographs of the cervical and lumbar spine. The serum levels of fetuin-A, dickkopf-1, sclerostin, IL-6, high-sensitivity C-reactive protein and bone morphogenetic protein-7 were measured with an enzyme-linked immunosorbent assay. RESULTS: Patients with syndesmophytes had significantly higher levels of fetuin-A compared with patients without syndesmophytes and controls (1.16±0.13, 1.05±0.09 and 1.08±0.13 mg/ml, respectively). However, fetuin-A was not different between the patients without syndesmophytes and controls. Bone morphogenetic protein-7 was significantly lower; dickkopf-1 was significantly higher in patients with ankylosing spondylitis compared with controls. The sclerostin concentrations were not different between the groups. In regression analysis, fetuin-A was an independent, significant predictor of syndesmophytes. CONCLUSION: Our results suggest that fetuin-A may a role in the pathogenesis of bony proliferation in ankylosing spondylitis. .

Influence of Ovariectomy on Bone Turnover and Trabecular Bone Mass in Mature Cynomolgus Monkeys

PURPOSE: To examine the influence of ovariectomy (OVX) on bone turnover and trabecular bone mass at the 3 clinically important skeletal sites in mature cynomolgus monkeys. MATERIALS AND METHODS: Six female cynomolgus monkeys, aged 17-21 years, were randomized into 2 groups by the stratified weight: the OVX and sham-operation groups (n = 3 in each group). The experimental period was 16 months. Lumbar bone mineral density (BMD) in vivo and serum and urinary bone turnover markers were longitudinally measured, and peripheral quantitative computed tomographic and bone histomorphometric analyses were performed on trabecular bone of the lumbar vertebra, femoral neck, and distal radius at the end of the experiment. RESULTS: OVX induced in a reduction in lumbar BMD compared with the sham controls and the baseline, as a result of increased serum levels of bone-specific alkaline phosphatase and urinary levels of cross-lined N- and C-terminal telopeptides of type I collagen. Furthermore, OVX induced reductions in trabecular volumetric BMD and trabecular bone mass compared with the sham controls, with increased bone formation rate at the lumbar vertebra, femoral neck, and distal radius. CONCLUSION: The results indicated that OVX in mature cynomolgus monkeys (17-21 years of age) increased bone turnover and induced trabecular bone loss at the three skeletal sites compared with the sham controls. Thus, mature cynomolgus monkeys could be utilized for preclinical studies to examine the effects of interventions on bone turnover and trabecular bone mass at the 3 clinically important skeletal sites.

Genotypes of vitamin D and estrogen receptors in pre and perimenopausal women from Córdoba, Argentina

El propósito del estudio fue determinar la frecuencia de los genotipos de los receptores de vitamina D y de estrógeno y su relación con la densidad mineral ósea en mujeres sanas pre y perimenopáusicas de la ciudad de Córdoba y alrededores. Los genotipos se determinaron con la técnica de reacción en cadena de la polimerasa y análisis de los polimorfismos de longitud de fragmentos de restricción. Se usaron como restrictasas Bsm I y Fok I para el gen del receptor de vitamina D y Pvu II y Xba I para el gen del receptor de estrógeno. Se reclutaron y agruparon por edad doscientos diez mujeres pre y peri-menopáusicas. Sus niveles séricos de Ca y de hormona paratiroidea fueron similares, pero los de fósforo y b-Cross Laps disminuyeron con la edad. La densidad mineral ósea de cuello femoral disminuyó después de los 30 años. Las frecuencias genotípicas de ambos receptores fueron similares a aquéllas de otras mujeres caucásicas. No hubo asociación entre los genotipos de los receptores y la densidad mineral ósea. Los análisis de interacción entre ambos genes no evidenciaron influencia sobre la densidad mineral ósea, utilizándose edad, talla e índice de masa corporal como covariables. Los estilos de vida y hábitos de fumar y beber alcohol tampoco afectaron la densidad mineral ósea. En conclusión, estos datos no sostienen la hipótesis de que los genotipos de los receptores de vitamina D y de estrógeno influencian la densidad mineral ósea de columna lumbar y cuello femoral en mujeres sanas pre y perimenopáusicas de esta región de Argentina.

The aim of this study was to determine the frequency of vitamin D receptor and estrogen receptor genotypes and their relationship with the lumbar spine or femoral neck bone mineral density in healthy pre and perimenopausal women from Córdoba (Argentina) and adjacent areas. Genotypes were assessed by restriction fragment length polymorphism-polymerase chain reaction technique. Bsm I and Fok I for vitamin D receptor gene and XbaI and PvuII for estrogen receptor gene were used as restrictases. Two hundred and ten healthy pre and perimenopausal women were recruited and analyzed by age. Calcemia and serum parathyroid hormone did not change, but serum P and b-CrossLaps decreased with age. Femoral neck bone mineral density decreased significantly after 30 years old. Vitamin D receptor and estrogen receptor genotype frequencies were similar to those from other Caucasian women. No association between vitamin D receptor and estrogen receptor genotypes with the lumbar spine or femoral neck bone mineral density has been detected. Analysis of interaction between vitamin D receptor and estrogen receptor genes using covariates such as age, height and body mass index did not show any influence of the combination of those genotypes on bone mineral density. Lifestyle, smoking and alcohol intake had no effect on lumbar spine and femoral neck bone mineral density. To conclude, these data do not support the hypothesis that vitamin D receptor and estrogen receptor genotypes influence on lumbar spine and femoral neck bone mineral density in healthy pre and perimenopausal women from this area of Argentina.

Evaluation of bone mineral density in children with diabetes mellitus.

Multiple studies have documented reduction in peripheral bone mass in children with insulin dependent diabetes mellitus (IDDM). In this study, the bone mineral density (BMD) of the lumbar vertebrae (L2-L4) was measured by dual photon absorptiometry in 14 female and 16 male diabetic patients of age 11 to 16 years with varying clinical duration. Twenty three children between 11 to 16 years with normal anthropometric measurements between 10th and 97th percentile and no known history of metabolic bone disease served as a control group. BMD values, weight, height, body mass index, metabolic, biochemical and growth parameters of the study group were compared with those of the control group. BMD (L2 AP 0.732 +/- 0.15 gm/cm2, L2 lateral 0.534 +/- 0.09 gm/cm2 in the study group and 0.812 +/- 0.63 gm/cm2 and 0.619 +/- 0.20 gm/cm2 in the control group) and osteocalcin (10.10 +/- 3.40 ng/ml and 23.12 +/- 2.74 ng/ml in diabetes and control respectively) levels were significantly lower in diabetic patients (p < 0.05, p < 0.01 respectively). Within the study group BMD correlated positively with age but not with the duration of the disease nor with the level of metabolic control.

El olpadronato previene la perdida de hueso cortical y trabecular inducida por dosis suprafisiologicas de tiroxina en ratas ovariectomizadas / Olpadronate prevents cortical and trabecular bone loss induced by supraphysiological dosis of thyroxine in ovariectomized rats

En el presente estudio experimental en ratas se evaluaron los efectos de la ovariectomia (OVX) y la administración de tiroxina (T4) sobre la densidad mineral ósea (DMO) del hueso cortical y trabecular. Además se estudió la eficacia del olpadronato (Olpa) para prevenir la pérdida ósea axial y periférica inducida por el exceso e hormonas tiroideas. Ratas hembras Sprague-Dawley (220 + 2 gr)se dividieron en los siguientes grupos: SHAM, OVX+Vh (Vh: vehículo); OVX+T4 (T4 250 mug/Kg peso/día); OVX+Olpa (0.3 mg de Olpa/Kg de peso/semana) y OVX+T4+Olpa (ambos: T4+Olpa). La DMO de las OVX+Vh fue significativamente menor que la de las SHAM en tibia total (p<0.01) pero no en el fémur ni en la columna lumbar. En el segmento medio de la tibia los resultados fueron similares en ambos grupos; un valor menor se observó en la parte distal (pns) y en la proximal (p <0.003) en el grupo OVX+Vh. La DMO de las OVX+T4 fue significativamente menor que la de las OVX+Vh en la tibia total (p<0.02), el fémur (p<0.006), la columna lumbar (p<0.006); además, la DMO de las OVX+T4 fue menor en todos los sectores analizados de la tibia, pero alcanzó un nivel estadísticamente significativo sólo en la parte media (p<0.004). La DMO de las OVX+Olpa fue mayor que la de las OVX+Vh en fémur (p<0.002), columna lumbar (p<0.03), tibia total (p<0.001) y tibia proximal (p<0.001). Sorprendentemente, la DMO de las OVX+Olpa fue mayor que la de las SHAM, en tibia total y proximal (p<0.05 y p<0.001, respectivamente). La DMO del grupo OVX+T4+Olpa fue significativamente mayor que el de OVX+T4 en fémur (p<0.001), columna lumbar (p<0.001), tibia total (p<0.001), tibia proximal (p<0.0001); asimismo, alcanzó niveles significativamente mayores que la de las SHAM en columna lumbar, tibia total y proximal (p<0.01 para todas ellas). El presente estudio sugiere que el hueso cortical, en condiciones de deficiencia estrogénica, sería más sensible que el trabecular al efecto de la T4. El Olpa prevendría la pérdida ósea axial y periférica del hueso inducida por un exceso de hormonas tiroideas.