Cynthia Brandão

Vitamin D Receptor Gene Polymorphism: Correlation with Bone Mineral Density in a Brazilian Population with Insulin-Dependent Diabetes Mellitus

Abstract: Patients with insulin-dependent diabetes mellitus (IDDM) are at higher risk of developing osteoporosis. Among the genetic factors related to the development of osteoporosis, a possible association between vitamin D receptor (VDR) gene polymorphism and bone mineral density (BMD) has been described in some populations. We characterized the VDR gene polymorphism in a healthy adult Brazilian population and in a group of patients with IDDM and correlated these findings with densitometric values in both groups. The Brazilian population is characterized by an important racial heterogeneity and therefore is considered an ethnically heterogeneous population. We recruited 94 healthy adult Brazilian volunteers (63 women and 31 men), mean (+ SD) age 32.4 + 6.5 years (range 18–49 years), and 78 patients with IDDM (33 women and 45 men) diagnosed before 18 years of age, mean (+ SD) age 23.3 + 5.5 years (range 18–39 years). VDR genotype was assessed by polymerase chain reaction amplification followed by BsmI digestion on DNA isolated from peripheral blood leukocytes. Statistical analysis included Bonferroni t-test to compare densitometric values within different genotypes in both groups and multiple regression analysis of bone density adjusted for potential confounding factors. The IDDM group had a lower BMD compared with the control group. The VDR genotype distribution in the control group was 43 Bb (45.7%), 39 bb (41.5%) and 12 BB (12.8%). This distribution did not differ from that observed in the IDDM group: 39 Bb (50%), 26 bb (33.3%) and 13 BB (16.7%). In the IDDM group, patients with the Bb genotype had a higher body weight when compared with the BB genotype (p= 0.02). However, when diabetic patients were controlled for age, sex and body mass index, BB genotype was associated with a lower mean BMD at lumbar spine and femoral neck than in Bb and bb patients. BB patients had a shorter duration of IDDM than bb and Bb patients. These findings suggest a small influence of VDR gene polymorphism on BMD of a racially heterogeneous population with IDDM.

Posições oficiais 2008 da Sociedade Brasileira de Densitometria Clínica (SBDens)

With the evolution of bone densitometry, differences in technologies, acquisition techniques, reference databases, reporting methods, diagnostic criteria and terminology have developed and the International Society for Clinical Densitometry (ISCD) periodically holds Position Development Conferences, the latest in 2007. The Brazilian Society for Clinical Densitometry (SBDens), with support from many Brazilian societies interested in bone health, gathered numerous specialists to discuss the ISCD proposals and to evaluate the validity of the extension of those norms to Brazilian population. The SBDens reunion of consensus made a very utile document to help the understanding and interpretation of bone densitometry and other methods of bone assessment.

Serum leptin concentration during puberty in healthy nonobese adolescents

Data obtained during the past five years have indicated that there are important age- and gender-based differences in the regulation and action of leptin in humans. To study the physiological changes of leptin during puberty in both sexes, and its relationship with body composition and sexual maturation, we measured leptin concentrations in 175 healthy adolescents (80 girls, 95 boys, 10-18 years of age), representing all pubertal stages. We excluded individuals with a body mass index (BMI) below the 5th or above the 95th percentile relative to age. Serum concentrations of leptin were determined by a monoclonal antibody-based immunofluorimetric assay, developed in our laboratory. Body composition was determined by dual-energy X-ray absorptiometry. Pubertal stage was assigned by physical examination, according to Tanner criteria for breast development in females and genital development in males. Leptin concentration in girls (N = 80) presented a positive linear correlation with age (r = 0.35, P = 0.0012), BMI (r = 0.65, P < 0.0001) and %fat mass (r = 0.76, P < 0.0001). In boys (N = 95) there was a positive correlation with BMI (r = 0.49, P < 0.0001) and %fat mass (r = 0.85, P < 0.0001), but a significant negative linear correlation with Tanner stage (r = -0.45, P < 0.0001) and age (r = -0.40, P < 0.0001). The regression equation revealed that %fat mass and BMI are the best parameters to be used to estimate leptin levels in both sexes. Thus, the normal reference ranges for circulating leptin during adolescence should be constructed according to BMI or %fat mass to assure a correct evaluation.

Fractures of the proximal femur: correlation with vitamin D receptor gene polymorphism

Fractures are the feared consequences of osteoporosis and fractures of the proximal femur (FPF) are those that involve the highest morbidity and mortality. Thus far, evaluation of bone mineral density (BMD) is the best way to determine the risk of fracture. Genetic inheritance, in turn, is one of the major determinants of BMD. A correlation between different genotypes of the vitamin D receptor (VDR) and BMD has been recently reported. On this basis, we decided to determine the importance of the determination of VDR genotype in the presence of an osteoporotic FPF in a Brazilian population. We studied three groups: group I consisted of 73 elderly subjects older than 65 years (78.5 +/- 7.2 years) hospitalized for nonpathological FPF; group II consisted of 50 individuals older than 65 years (72.9 +/- 5.2 years) without FPF and group III consisted of 98 young normal Brazilian individuals aged 32.6 +/- 6.6 years (mean +/- SD). Analysis of VDR gene polymorphism by restriction fragment length polymorphism (RFLP) was performed by PCR amplification followed by BsmI digestion of DNA isolated from peripheral leukocytes. The genotype distribution in group I was 20.5% BB, 42.5% Bb and 37% bb and did not differ significantly from the values obtained for group II (16% BB, 36% Bb and 48% bb) or for group III (10.2% BB, 47.6% Bb and 41.8% bb). No differences in genotype distribution were observed between sexes or between the young and elderly groups. We conclude that determination of VDR polymorphism is of no practical use for the prediction of FPF. Other nongenetic factors probably start to affect bone mass, the risk to fall and consequently the occurrence of osteoporotic fractures with advancing age.

Bone mineral density and bone histomorphometry in children on long-term dialysis.

Bone mineral density (BMD) at the lumbar vertebrae (L1–L4) was assessed by dual-energy X-ray absorptiometry (DXA) in 20 children with chronic kidney disease (CKD) on dialysis, and its results were compared with bone biopsy and biochemical parameters. Biopsy specimens provided evidence of hyperparathyroid bone disease in eight cases (40%), and low bone turnover in 12 (60%). For BMD, expressed as Z-scores relative to normal, median Z-scores were −1.05 (range −2.36 to 1.06) for hyperparathyroid patients and −1.05 (range −4.40 to −0.03) for low bone turnover patients, with no statistical differences between groups (P = 0.512). In relation to BMD, of the whole sample, five (25%) had a Z-score under −2.0. When it was corrected for height, BMD was in the normal range. Additionally, there were no significant differences in single samples of serum calcium, alkaline phosphatase, phosphorus and intact parathyroid hormone (PTH) between groups with high or low bone turnover. Assessment of nutritional status, through height/age, showed that ten patients had Z-scores below −2.0 (median −2.12, range −7.13 to 0.73). In conclusion, renal osteodystrophy (ROD) seems to have a high prevalence among CKD pediatric patients, although only approximately a quarter of them developed changes in BMD. In children with CKD, measurements of bone mineral density may not be used for classification of various forms of ROD.

Increased Hip Bone Mineral Density in a Woman with Gluteal Silicon Implant

Conditions and artifacts such as aortic calcification, osteophytes, hip prostheses, and metallic objects can mislead the results of dual energy X-ray absorptiometry (DXA) scanning of the spine and hip. Gluteal silicon implants increasingly are being used for aesthetic purposes by women in Brazil, some of whom are at an age of high risk for the development of postmenopausal osteoporosis. We herein report a case of a woman whose hip bone mineral density by DXA clearly increased after the placement of bilateral gluteal implants of silicon. This case demonstrates the importance of inquiring about the presence of this artifact to avoid unnecessary evaluation of hip bone densitometry in these situations.

Low bone mass in children and adolescents

Osteoporosis is a disease characterized by low bone mass and micro architectural alterations of bone tissue leading to enhanced bone fragility and increased fracture risk. Although research in osteoporosis has focused mainly on the role of bone loss in the elderly population, it is becoming increasingly clear that the amount of bone that is gained during growth is also an important determinant of future resistance to fractures. Thus, considerable interest is being placed on defining preventive strategies that optimize the gain of bone mass during childhood and adolescence. Knowledge of the determinants accounting for the physiologic and genetic variations in bone accumulation in children will provide the best means toward the early diagnosis and treatment of osteoporosis. This article reviews the techniques available for bone mass measurements in children and the major determinants and diseases influencing bone accretion during childhood and adolescence.Osteoporosis is a disease characterized by low bone mass and micro architectural alterations of bone tissue leading to enhanced bone fragility and increased fracture risk. Although research in osteoporosis has focused mainly on the role of bone loss in the elderly population, it is becoming increasingly clear that the amount of bone that is gained during growth is also an important determinant of future resistance to fractures. Thus, considerable interest is being placed on defining preventive strategies that optimize the gain of bone mass during childhood and adolescence. Knowledge of the determinants accounting for the physiologic and genetic variations in bone accumulation in children will provide the best means toward the early diagnosis and treatment of osteoporosis. This article reviews the techniques available for bone mass measurements in children and the major determinants and diseases influencing bone accretion during childhood and adolescence

Bone Mass and Hormone Analysis in Patients With Spinal Cord Injury: Evidence for a Gonadal Axis Disruption

CONTEXT Bone loss is a constant finding in patients with spinal cord injury (SCI). OBJECTIVE We sought to evaluate potential modifiable factors that could lead to bone loss in complete motor paraplegia by examining gonadal axis hormones, vitamin D status, and bone markers. DESIGN This is a cross sectional. SETTING It includes SCI Outpatient. PATIENTS AND OTHER PARTICIPANTS Twenty-nine chronic male patients with SCI were compared with 17 age-matched, able-bodied men. MAIN OUTCOME MEASURE The bone mineral density (BMD) of lower limbs and lumbar spine were measured using dual x-ray absorptiometry. Parathormone, 25-hydroxyvitamin D [25(OH)D], collagen type I C-terminal telopeptide (CTX), and sexual hormone were measured. RESULTS Patients with SCI had lower BMD at the inferior limbs sites. CTX showed an inverse relationship with the time since injury. Patients had lower free T levels (SCI, 12.00 ± 2.91 vs controls, 19.51 ± 5.72; P ≤ .001), and the majority (72%) had normal/low levels of gonadotropins. Low T, however, was not related to low bone mass in patients with SCI. In the controls, the 25(OH)D level was positively correlated with the T and with the lumbar spine BMD, but these correlations were not observed in the SCI. CONCLUSIONS Impairment of testicular function after SCI was indicated by the low levels of T and the loss of correlation between T and 25(OH)D levels; this correlation was present in the able-bodied controls. Inappropriate levels of gonadotropins were identified in most patients, featuring a hypogonadotropic hypogonadism and suggesting a disruption of the pituitary-gonadal axis. T concentrations might not be an effective target for bone loss therapy.

Fatores envolvidos no pico de massa óssea

Bone mass in the adult life, which is closely related to osteoporotic fracture risk, depends on the differences between the peak bone mass attained at the end of the sexual and skeletal maturation and the rate of involutional bone mass. The great variability in peak bone mass observed at adolescence is related not only to genetic factors, but also to diet, hormonal status, anthropometric variables, as weight and height, physical activity, drugs and intercurrent diseases. The identification of the factors involved with the acquisition of the peak bone mass and the comprehension of this long period of skeletal maturation will indicate strategies for prevention of osteoporosis.

Bone Mineral Density in Spinal Cord Injury: An Evaluation of the Distal Femur

Osteoporosis (OP) in spinal cord injury (SCI) patients is a secondary process in which numerous factors are involved. Diagnosing OP and the threshold for fractures in this population, based on bone mineral density (BMD) measured by double energy X-ray absorptiometry (DXA), is still a challenge. The aim of this study was to evaluate bone mineral loss by DXA, its relationship with body composition and fracture incidence, in complete paraplegics patients, compared with aged-matched controls; we include a nonstandard bone site, the distal femur, and describe the technical and practical aspects of this procedure. Twenty-five SCI patients were included in the study and 17 subjects as control group. No prior or recent fractures were observed in X-ray analysis. The BMD of all femoral sites was significantly lower in patients than in controls (femoral neck, total femur, and distal femur); no difference was observed between BMD of the lumbar spine of patients and controls. We found inverse relationship between time of SCI and bone mineral mass only for distal femur BMD. We conclude that the distal femur is a more sensitive bone site for assessing bone loss by DXA, in SCI patients, than the proximal femoral sites.