Jesús González-Macías

Seasonal deficiency of vitamin D in children : A potential target for osteoporosis-preventing strategies?

Peak bone mass attained after skeletal growth is a major determinant of the risk of developing osteoporosis later in life, hence the importance of nutritional factors that contribute to bone mass gain during infancy and adolescence. An adequate supply of vitamin D is essential for normal bone homeostasis. This study was undertaken to determine what the levels are of 25‐hydroxyvitamin D (25(OH)D) that may be considered desirable in children and to assess if normal children maintain these levels throughout the year. Vitamin D metabolites and parathyroid hormone (PTH) serum levels were measured in 21 children in March and October, prior to and after the administration of a daily supplement of 25(OH)D (40 μg for 7 consecutive days). There were inverse correlations between basal 25(OH)D levels and supplementation‐induced changes in serum 1,25(OH)2D (r = 0.57, p < 0.05) and PTH (r = 0.41, p < 0.05). When basal levels of 25(OH)D were below 20 ng/ml, the supplement induced an increase in serum 1,25(OH)2D; with basal 25(OH)D under 10–12 ng/ml, the supplement also decreased serum PTH. The lowest serum level of 25(OH)D in 43 normal children studied in summer was 13 ng/ml. Those results suggested that the lowest limit for desirable levels of 25(OH)D in children was somewhere between 12 and 20 ng/ml. However, 31% of 51 normal children studied in winter had levels below 12 ng/ml, and 80% had levels lower than 20 ng/ml. Those children are likely to have suboptimal bioavailability of vitamin D, which might hamper their achievement of an adequate peak bone mass. Since cutaneous synthesis of vitamin D is rather limited in winter, oral vitamin D supplementation should be considered.

FASCIOLIASIS IN DEVELOPED COUNTRIES : A REVIEW OF CLASSIC AND ABERRANT FORMS OF THE DISEASE

Cases of human infestation by Fasciola hepatica are not uncommon in Spain and other European countries. We report our experience with 20 patients diagnosed from 1982 to 1991 and present a critical review of published cases from western countries. Because F. hepatica has a special tropism for the liver, abdominal pain, hepatomegaly, and constitutional symptoms are among the most common manifestations of acute-stage fascioliasis. However, in the chronic stage, biliary colic and cholangitis are the predominant manifestations. The clinical spectrum of fascioliasis is variable, and patients may present with extrahepatic abnormalities, such as pulmonary infiltrates, pleuropericarditis, meningitis, or lymphadenopathy. Therefore, a high index of suspicion is required to establish a correct diagnosis. Eosinophilia is the most frequent laboratory abnormality. The CT scan has become a useful technique in the diagnostic work-up. A definitive diagnosis may be established by the observation of parasite ova in the feces, but most cases may be diagnosed by serologic methods. Triclabendazole and bithionol are the most effective drugs against F. hepatica. The efficacy of praziquantel is controversial.

Trend in hip fracture epidemiology over a 14-year period in a Spanish population

Spain lacks detailed data on hip fracture trends despite being the country with the greatest increase in the pensioner-to-provider ratio in Europe. We reproduced a study on hip fracture incidence in a region of northern Spain (Cantabria) carried out 14 years ago to determine whether a secular trend to change is taking place. If such a trend could be found, our objective was to determine whether the effect is solely due to ageing or whether additional variables are involved. We assessed the incidence of hip fracture in patients aged ≥50 years through clinical records from Emergency Units and Orthopedic Surgical Units of all hospitals in the region of Cantabria in 1988 and 2002. A total of 318 new cases of hip fracture were recorded in 1988 and 490 in 2002 (54% increase; p<0.001). No significant changes were noticed following an adjustment for age. Women accounted for the increase in crude hip fracture incidence [246 women and 72 men suffered a hip fracture in 1988 compared to 404 women and 86 men in 2002 (64% increase in women and 19% increase in men; p<0.005 and not significant, respectively)]. The female:male ratio was 3.4 in 1988 versus 4.7 in 2002; following age-adjustment, no significant changes were found (1.8 in 1988 and 1.9 in 2002). The increase in crude hip fracture incidence was greater at cervical (versus trochanteric) sites. Patient residence, time of the year, site of fracture, kind of injury, previous contralateral hip fracture, length of stay, and peri-operative mortality did not differ significantly. In conclusion, a crude hip fracture incidence increase of about 50% in the northern Spanish region of Cantabria has taken place over the last 14 years. This effect does not persist after adjustments have been made for age. The crude rate increase occurred mainly at the expense of women, with a more noticeable rise in cervical fractures as opposed to trochanteric lesions.

Relationship between bone quantitative ultrasound and fractures : A meta-analysis

The relationship between bone QUS and fracture risk was estimated in a systematic review of data from 14 prospective studies of 47,300 individuals and 2350 incident fractures. In older women, low QUS values were associated with overall fracture risk, low‐trauma fractures, and with hip, forearm, and humerus fractures separately.

Treatment failure in osteoporosis.

SummaryGuidelines concerning the definition of failure of therapies used to reduce the risk of fracture are provided.IntroductionThis study aims to provide guidelines concerning the definition of failure of therapies used to reduce the risk of fracture.MethodsA working group of the Committee of Scientific Advisors of the International Osteoporosis Foundation was convened to define outcome variables that may assist clinicians in decision making.ResultsIn the face of limited evidence, failure of treatment may be inferred when two or more incident fractures have occurred during treatment, when serial measurements of bone remodelling markers are not suppressed by anti-resorptive therapy and where bone mineral density continues to decrease.ConclusionThe provision of pragmatic criteria to define failure to respond to treatment provides an unmet clinical need and may stimulate research into an important issue.

BONE DENSITOMETRY AND BIOCHEMICAL BONE REMODELING MARKERS IN TYPE 1 DIABETES MELLITUS

Bone mineral density (BMD) at the lumbar spine, quantified by dual energy X-ray absorptiometry, and biochemical bone remodeling markers (serum alkaline phosphatase, osteocalcin, tartrate-resistant acid phosphatase and urinary hydroxyproline) have been studied in 94 patients with diabetes mellitus aged 18-62 years. BMD was normal (1.13 +/- 0.02 g/cm2 in patients vs. 1.16 +/- 0.12 g/cm2 in controls), although it was found to be negatively correlated with HbA1, microalbuminuria, age and the duration of the disease. Serum alkaline phosphatase (188 +/- 75 I.U./l vs. 168 +/- 42 I.U./1; P < 0.03), serum tartrate-resistant acid phosphatase (14.3 +/- 4.3 I.U./l vs. 11.7 +/- 3.7 I.U./l; P < 0.0001) and urinary hydroxyproline (0.018 +/- 0.016 mmol/mmol creatinine vs. 0.011 +/- 0.008 mmol/mmol creatinine; P < 0.001) were higher in diabetics than in controls. Serum osteocalcin was lower (2.5 +/- 1.3 ng/ml vs. 3.4 +/- 1.2 ng/ml; P < 0.0001). No relationship was found between bone remodeling markers and BMD. It is concluded that lumbar BMD is normal in type 1 diabetic patients, although the degree of metabolic control, age and duration of the disease may affect it. In the light of the biochemical markers, bone remodeling may be disturbed in diabetes, but such disturbance seems to be unimportant regarding BMD.

Wnt pathway genes in osteoporosis and osteoarthritis: differential expression and genetic association study

SummaryIn comparison with hip fractures, increased expression of genes in the Wnt pathway and increased Wnt activity were found in bone samples and osteoblast cultures from patients with osteoarthritis, suggesting the involvement of this pathway in subchondral bone changes. No consistent differences were found in the genetic association study.IntroductionThis study aims to explore the allelic variations and expression of Wnt pathway genes in patients with osteoporosis and osteoarthritis.MethodsThe expression of 86 genes was studied in bone samples and osteoblast primary cultures from patients with hip fractures and hip or knee osteoarthritis. The Wnt-related activity was assessed by measuring AXIN2 and in transfection experiments. Fifty-five SNPs of the LRP5, LRP6, FRZB, and SOST genes were analyzed in 1,128 patients.ResultsSeveral genes were differentially expressed in bone tissue, with the lowest values usually found in hip fracture and the highest in knee osteoarthritis. Overall, seven genes were consistently upregulated both in tissue samples and in cell cultures from patients with knee osteoarthritis (BCL9, FZD5, DVL2, EP300, FRZB, LRP5, and TCF7L1). The increased expression of AXIN2 and experiments of transient transfection of osteoblasts with the TOP-Flash construct confirmed the activation of Wnt signaling. Three SNPs of the LRP5 gene and one in the LRP6 gene showed marginally significant differences in allelic frequencies across the patient groups, but they did not resist multiple-test adjustment.ConclusionsGenes in the Wnt pathway are upregulated in the osteoarthritic bone, suggesting their involvement not only in cartilage distortion but also in subchondral bone changes.

Metabolic syndrome and bone metabolism: the Camargo Cohort Study

Objectives: The aims of this study were to compare in participants with and without metabolic syndrome (1) bone mineral density (BMD), (2) prevalent vertebral and nonvertebral fractures, and (3) calciotropic hormones and bone turnover markers and to examine the association of each component of metabolic syndrome with bone parameters. Methods: A cross-sectional study (495 men and 1,013 women) from the Camargo Cohort Study was conducted. A multivariable regression approach was used to analyze the relationship between the components of metabolic syndrome and bone parameters. Results: Women with metabolic syndrome had higher age-adjusted BMD at all localizations (P < 0.0001) than did women without metabolic syndrome. Adjusting for body mass index canceled out this difference at the spine and femoral neck, although borderline significance persisted at the total hip. Moreover, in regression analyses, waist circumference (P < 0.0001) and hypertension (P between 0.002 and <0.0001) highly correlated with BMD at the three sites. However, no significant differences in BMD were found in men between those with and without metabolic syndrome. No differences in the prevalence of vertebral or nonvertebral fractures between participants with metabolic syndrome and controls were found for either sex. 25-Hydroxyvitamin D was significantly lower (P < 0.0001) and parathyroid hormone was significantly higher (P < 0.0001) in women with metabolic syndrome than in women without metabolic syndrome, whereas no differences were seen in men. Propeptide of type I collagen and C-terminal telopeptide of type I collagen were significantly lower in participants with metabolic syndrome than in controls in either sex. Conclusions: Women with metabolic syndrome show higher BMD than controls do, mainly driven by their higher body weight. Bone remodeling in these women is lower. Despite the greater bone mass and lower bone turnover, fracture prevalence is not reduced, suggesting worse bone quality and/or higher tendency to fall. No differences in BMD or fractures were seen in men, suggesting that the impact of metabolic syndrome on bone is sex dependent.

Expression of Opioid Receptors in Osteoblast-Like MG-63 Cells, and Effects of Different Opioid Agonists on Alkaline Phosphatase and Osteocalcin Secretion by These Cells

We have previously shown that several stressful situations associated with tissue injury determine a decrease in serum osteocalcin concentration. Since reduced osteocalcin production is a marker of decreased osteoblastic activity, this finding could be related to the pathogenesis of osteoporosis secondary to some diseases. Endogenous opioids are involved in stress response. Proenkephalin-derived peptides have been shown to inhibit alkaline phosphatase activity, another marker of bone formation, in the murine cell line ROS-17/2.8. On the other hand, serum osteocalcin has been reported as being low in heroin abusers. We have therefore thought it of interest to study the presence of opioid receptors in the human osteoblast-like cell line MG-63, and to evaluate the effects of different opioid agonists on the secretion of alkaline phosphatase and osteocalcin by these cells. The presence of opioid receptors was studied by means of RT-PCR and immunohistochemistry. RT-PCR studies suggested the presence of specific mRNA for the three types of receptors, and immunohistochemistry clearly showed their occurrence. Osteocalcin synthesis was significantly inhibited by high concentrations of the mu agonists morphine and (D-Ala2,N-MePhe4,Gly5-ol)-enkephalin although no changes were seen with the delta agonist (D-Ala2,D-leu5)-enkephalin. Morphine-induced osteocalcin inhibition was abolished when osteoblastic cells were incubated simultaneously with naloxone, whereas it was potentiated when cells were preincubated with naloxone. None of the opioid agonists modified the secretion of alkaline phosphatase. In conclusion, human osteoblast-like cells MG-63 express the three types of opioid receptors. Endogenous opioids may be involved in the reduction of osteocalcin observed in stressful situations associated with tissue injury.

Probability of fractures predicted by FRAX® and observed incidence in the Spanish ECOSAP Study cohort

PURPOSE To assess the ability of the Spanish version of the WHO fracture risk assessment tool (FRAX®) to predict the observed incident fractures in the ECOSAP Study cohort. METHODS 5201 women, aged 65 or older, were enrolled in a three-year, prospective study by a non-randomized sampling of consecutive cases in 58 primary care centers in Spain. Participants completed an osteoporosis and fracture risk questionnaire and attended follow-up visits every 6 months. All radiologically or surgically confirmed low-trauma, non-spinal fractures were collected. The individual 10-year absolute risks of hip and major osteoporotic fractures were calculated with the FRAX® algorithms for Spain without the inclusion of the bone mineral density (BMD) measurements. Calibration was evaluated by comparing the three-year estimated (E) fractures predicted with FRAX® with the number of observed (O) fractures, and their discriminative ability for the probability of new fractures with the area under the receiving operating characteristic (ROC) curves. RESULTS Fifty (0.96%) women sustained an incident hip fracture, and 201 (3.81%) women presented with major osteoporotic fractures (hip, forearm or humerus). The E/O ratios for hip and major osteoporotic fractures were 1.10 and 0.66 respectively. Clinical vertebral fractures were not collected; therefore, the E/O ratio for major fractures should be expected to be lower. The difference between E and O cases reached statistical significance (χ(2), p<0.001). Areas under the ROC curves were 0.640 and 0.615 for hip and major osteoporotic fractures respectively. CONCLUSIONS The Spanish FRAX® underestimates the risk for major osteoporotic fractures. The estimated risk for hip fractures was similar to the observed fractures; however the algorithm had only modest discriminative ability. These results should be interpreted in the context of the relatively low number of observed fractures, especially at the hip.