Prevalence of vertebral fracture and densitometric osteoporosis in Spanish adult men: The Camargo Cohort Study.

The aim of this study was to assess the prevalence of densitometric osteoporosis and vertebral fractures in Spanish men aged ≥50 years, and to study how the relationship between them may change depending on how osteoporosis is diagnosed. A community-based population of 1003 men aged ≥50 years was studied. Bone mineral density (BMD) was measured by DXA at the lumbar spine, femoral neck and total hip. Vertebral fractures were assessed by lateral thoracic and lumbar spine radiographs. The prevalence of osteoporosis was estimated with both the World Health Organization (WHO) (T-score of <-2.5 at the femoral neck, calculated using the young white female normal reference database) and the National Osteoporosis Foundation (NOF) criteria (T-score of <-2.5 at the femoral neck, total hip or lumbar spine, calculated using the young white male normal reference database). The prevalence of osteoporosis using the WHO criterion was 1.1% and using the NOF criterion was 13%, while that of vertebral fractures was 21.3%. The area under the curve (AUC) for the relationship between BMD and vertebral fracture prevalence was 0.64. The odds ratio for osteoporosis using the WHO definition was 2.57 (p = 0.13), and 1.78 (p = 0.007) using the NOF definition. Vertebral fracture prevalence rose with age. The prevalence of osteoporosis increased only moderately in men aged >70 years with the WHO criterion, and showed no change using the NOF definition. The prevalence of osteoporosis in Spanish men using the WHO definition is too small to have any meaningful clinical use. Although the figure is higher using the NOF definition, it would seem that population-based studies of BMD in men are of questionable value.

Relationship between spinal osteoarthritis and vertebral fractures in men older than 50 years: data from the Camargo Cohort Study.

Spinal osteoarthritis has been suggested as a risk factor for vertebral fractures. However, results are conflicting: most of the data are focused on the lumbar region, and referred to postmenopausal women, whereas data for men are scarce. The aim of this study is to assess the relationship between spinal osteoarthritis and vertebral fractures in men over 50 years of age. We conducted a cross-sectional study, nested in a prospective population-based cohort, including 507 community-dwelling men, 93 of them with at least one vertebral fracture. Vertebral fractures, osteophytosis, and disc space narrowing (DSN) were assessed by lateral thoracic and lumbar radiographs. Anthropometric, clinical, and densitometric variables were also analyzed. A multiple logistic regression model was performed. Eighty-five percent of vertebral fractures were located at the thoracic spine. Osteophytosis and DSN showed a bimodal distribution, with major frequency peaks at mid- and distal lumbar spine. The three distributions overlapped around the T9 vertebra. We did not find any relationship between lumbar osteoarthritis and vertebral fractures. Nevertheless, thoracic osteophytosis (OR, 1.84; 95 % CI, 1.05-3.17; p = 0.03) and DSN (OR, 2.52; 95 % CI, 1.43-4.46; p = 0.001) were found to be independently associated with prevalent vertebral fractures, after adjusting for confounders. Our results suggest a positive relationship between radiologic osteoarthritic changes at the thoracic spine and prevalent vertebral fractures in men more than 50 years of age. Osteoarthritis may act as a local risk factor, in addition to other mechanical factors, resulting in a greater propensity to fracture, especially at the mid-thoracic region.

A genome-wide copy number association study of osteoporotic fractures points to the 6p25.1 locus.

BACKGROUND: Osteoporosis is a systemic skeletal disease characterised by reduced bone mineral density and increased susceptibility to fracture; these traits are highly heritable. Both common and rare copy number variants (CNVs) potentially affect the function of genes and may influence disease risk. AIM: To identify CNVs associated with osteoporotic bone fracture risk. METHOD: We performed a genome-wide CNV association study in 5178 individuals from a prospective cohort in the Netherlands, including 809 osteoporotic fracture cases, and performed in silico lookups and de novo genotyping to replicate in several independent studies. RESULTS: A rare (population prevalence 0.14%, 95% CI 0.03% to 0.24%) 210 kb deletion located on chromosome 6p25.1 was associated with the risk of fracture (OR 32.58, 95% CI 3.95 to 1488.89; p = 8.69 × 10(-5)). We performed an in silico meta-analysis in four studies with CNV microarray data and the association with fracture risk was replicated (OR 3.11, 95% CI 1.01 to 8.22; p = 0.02). The prevalence of this deletion showed geographic diversity, being absent in additional samples from Australia, Canada, Poland, Iceland, Denmark, and Sweden, but present in the Netherlands (0.34%), Spain (0.33%), USA (0.23%), England (0.15%), Scotland (0.10%), and Ireland (0.06%), with insufficient evidence for association with fracture risk. CONCLUSIONS: These results suggest that deletions in the 6p25.1 locus may predispose to higher risk of fracture in a subset of populations of European origin; larger and geographically restricted studies will be needed to confirm this regional association. This is a first step towards the evaluation of the role of rare CNVs in osteoporosis.

Bone mineral density in statin users: a population-based analysis from a Spanish cohort.

We studied 2,315 subjects (1,422 women and 893 men) from the Camargo Cohort and analyzed the differences in BMD between statin or non-statin users. We also studied effects of the type of statin, dose, pharmacokinetic properties, and length of treatment on bone mineral density (BMD). Of the subjects, 478 (21 %) were taking statins (256 women and 222 men). Overall, they had higher BMD than non-users (p < 0.0001). In adjusted multivariate models, women taking statins had higher BMD at femoral neck (p = 0.002) and total hip (p = 0.04) than non- users. No differences were found in men. Women taking simvastatin had higher increases in BMD than non-statin users at femoral neck (p = 0.02) and total hip (p = 0.009), those taking fluvastatin had lower BMD values at lumbar spine (p = 0.028), and those receiving lovastatin had higher increases at femoral neck (p = 0.006). In men, only atorvastatin was associated with higher femoral neck BMD than non-statin use (p = 0.029). Comparing with non-statin users, only women receiving lipophilic statins had greater BMD at femoral neck (p = 0.003). According to drug potency, women on high- or lower-potency agents showed higher BMD values at femoral neck than non-users (p = 0.028 and 0.022, respectively). In men, only high-potency statins were associated with higher femoral neck BMD than non-use (p = 0.021). No differences between dose or length of statin therapy were noted regarding BMD in either sex. In summary, in a large population-based cohort, women on statins had higher BMD at the hip than non-users. Overall, this increase in BMD was more evident in subjects on lipophilic or high-potency statins.

[Frailty, Sarcopenia and Osteoporosis]. / Fragilidad, sarcopenia y osteoporosis.

Frailty, sarcopenia and osteoporosis are entities specific to the elderly, who share some risk factors. For this reason, their relationship has been studied in different works, which have provided disparate results, probably because these studies have not always focused on the same aspects. This article reviews the relationship of frailty and sarcopenia with osteoporosis.

Long-Term Treatment and Effect of Discontinuation of Calcifediol in Postmenopausal Women with Vitamin D Deficiency: A Randomized Trial.

Vitamin D plays a major role in bone health and probably also in multiple extraskeletal acute and chronic diseases. Although supplementation with calcifediol, a vitamin D metabolite, has demonstrated efficacy and safety in short-term clinical trials, its effects after long-term monthly administration have been studied less extensively. This report describes the results of a 1-year, phase III-IV, double-blind, randomized, controlled, parallel, multicenter superiority clinical trial to assess the efficacy and safety of monthly calcifediol 0.266 mg versus cholecalciferol 25,000 IU (0.625 mg) in postmenopausal women with vitamin D deficiency (25(OH)D < 20 ng/mL). A total of 303 women were randomized and 298 evaluated. Patients were randomized 1:1:1 to calcifediol 0.266 mg/month for 12 months (Group A1), calcifediol 0.266 mg/month for 4 months followed by placebo for 8 months (Group A2), and cholecalciferol 25,000 IU/month (0.625 mg/month) for 12 months (Group B). By month 4, stable 25(OH)D levels were documented with both calcifediol and cholecalciferol (intention-to-treat population): 26.8 ± 8.5 ng/mL (Group A1) and 23.1 ± 5.4 ng/mL (Group B). By month 12, 25(OH)D levels were 23.9 ± 8.0 ng/mL (Group A1) and 22.4 ± 5.5 ng/mL (Group B). When calcifediol treatment was withdrawn in Group A2, 25(OH)D levels decreased to baseline levels (28.5 ± 8.7 ng/mL at month 4 versus 14.4 ± 6.0 ng/mL at month 12). No relevant treatment-related safety issues were reported in any of the groups. The results confirm that long-term treatment with monthly calcifediol in vitamin D-deficient patients is effective and safe. The withdrawal of treatment leads to a pronounced decrease of 25(OH)D levels. Calcifediol presented a faster onset of action compared to monthly cholecalciferol. Long-term treatment produces stable and sustained 25(OH)D concentrations with no associated safety concerns. © 2023 Faes Farma SA. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Sarcopenic osteoporosis, sarcopenic obesity, and sarcopenic osteoporotic obesity in the Camargo cohort (Cantabria, Spain).

The associations of sarcopenia with osteoporosis or obesity have a very low prevalence. No trend towards an association between osteoporosis and sarcopenia is observed. Sarcopenia and obesity tend not to coincide, as if they were antagonistic disorders. PURPOSE: To know (a) the prevalence in our region of sarcopenic osteoporosis (association of sarcopenia and osteoporosis (T-score < - 2.5)), sarcopenic obesity, and the association of osteoporosis, sarcopenia, and obesity; (b) the tendency of osteoporosis, sarcopenia, and obesity to associate with each other; and (c) the bone mineral density (BMD), the components of sarcopenia, and the prevalence of fragility fractures in these associations. METHODS: The study was performed in the Camargo cohort. Osteoporosis was diagnosed by DXA, sarcopenia by the EWGSOP-1 criteria, and obesity by body mass index (BMI) and fat percentage. Fractures were verified radiographically or by consulting the medical records. RESULTS: The prevalence of sarcopenic osteoporosis was 2.8% and the OR for this association 1.03 (p = 0.89). The prevalence of sarcopenic obesity by BMI was 1.4% and by fat percentage 5.9% (corresponding ORs: 0.18 (p < 0.0001) and 0.58 (p < 0.003) respectively). The prevalence of the association of osteoporosis, sarcopenia, and obesity was 0.0% when assessed by BMI and 0.8% when assessed by fat percentage. Patients with sarcopenic osteoporosis have less muscle mass and more fragility fractures than sarcopenic patients overall. In patients with sarcopenic obesity by fat percentage, muscle mass and strength, as well as physical performance, were similar to those of sarcopenic patients overall. Neither BMD nor fracture prevalence showed differences between patients with sarcopenic obesity and patients with sarcopenia or obesity in general. CONCLUSION: Our study supports the idea that the prevalence of the mixed disorders studied is low. No significant association between osteoporosis and sarcopenia was found. Sarcopenia and obesity seem to tend to occur in different people, as if suffering from one of them hinders suffering from the other.

Aminobisphosphonates: Reconsideration 25 years after their approval for the treatment of osteoporosis. / Aminobisfosfonatos: reconsideración a los 25 años de su aprobación para el tratamiento de la osteoporosis.

Aminobisphosphonates are widely used in the treatment of osteoporosis. They have a high affinity for hydroxyapatite, binding primarily to resorbing surfaces, but also to forming surfaces and to some extent to resting surfaces. They inhibit osteoclasts, thereby decreasing remodelling units. Consequently, they increase bone mass and reduce stress risers. This decreases the risk of fractures. If this decrease is sufficient, they can be temporarily withdrawn (drug holidays), which prevents serious complications (atypical femoral fracture). They probably reduce mortality. Virtually all patients with osteoporosis can benefit from them at some point in the course of their disease (at the beginning of treatment or after the administration of anabolics, selective estrogen receptor modulators or denosumab). If well tolerated orally, alendronate and risedronate are preferable. Otherwise, zoledronate is preferred. Their efficacy vs. cost-safety-convenience ratio makes aminobisphosphonates reference drugs in the field of osteoporosis.

Osteocyte deficiency in hip fractures.

Osteocytes play a central role in the regulation of bone remodeling. The aim of this study was to explore osteocyte function, and particularly the expression of SOST, a Wnt inhibitor, in patients with hip fractures. Serum sclerostin levels were measured by ELISA. The expression of several osteocytic genes was studied by quantitative PCR in trabecular samples of the femoral head of patients with hip fractures, hip osteoarthritis and control subjects. The presence of sclerostin protein and activated caspase 3 was revealed by immunostaining. There were no significant differences in serum sclerostin between the three groups. Patients with fractures have fewer lacunae occupied by osteocytes (60 ± 5% vs. 64 ± 6% in control subjects, P = 0.014) and higher numbers of osteocytes expressing activated caspase 3, a marker of apoptosis. The proportion of sclerostin-positive lacunae was lower in patients with fractures than in control subjects (34 ± 11% vs. 69 ± 10%, P = 2 × 10(-8)). The proportion of sclerostin-positive osteocytes was also lower in patients. RNA transcripts of SOST, FGF23 and PHEX were also less abundant in fractures than in control bones (P = 0.002, 5 × 10(-6), and 0.04, respectively). On the contrary, in patients with osteoarthritis, there was a decreased expression of SOST and FGF23, without differences in PHEX transcripts or osteocyte numbers. Osteocyte activity is altered in patients with hip fractures, with increased osteocyte apoptosis and reduced osteocyte numbers, as well as decreased transcription of osteocytic genes. Therefore, these results suggest that an osteocyte deficiency may play a role in the propensity to hip fractures.

Vascular cognitive impairment in small vessel disease: clinical and neuropsychological features of lacunar state and Binswanger's disease.

BACKGROUND: ischaemic cerebrovascular small vessel disease (SVD) is a prevalent and under-diagnosed condition that triggers vascular cognitive impairment (VCI). OBJECTIVE: to describe the neuropsychological and clinical profiles in SVD (Binswanger's disease, BD; lacunar state, LS) from the clinician's perspective at the VCI stage. METHODS: a total of 1257 patients admitted to a tertiary center with a diagnosis of stroke, neuroradiological vascular disease, cognitive impairment/dementia, during a 13-year period were investigated. We prospectively assessed cognition in a subset of 141 patients with VCI (LS n = 28, BD n = 69, large vessel disease-LVD-n = 44) with MMSE, CAMDEX-H, WAIS-R, EXIT-25 and Trail making test. RESULTS: executive dysfunction (ECD) (n = 89, 91.7% versus n = 10, 22.7%; P < 0.001) and gait disturbances (n = 74, 76.3% versus n = 15, 34.1%; P < 0.001) characterized SVD. Prior strokes (n = 9, 9.3% versus n = 23, 52.3%; P < 0.001) and embologenous cardiopathy (n = 39, 40.2% versus n = 28, 63.6%; P < 0.04) featured LVD cases. BD was defined by hypertension (n = 52, 75.4% versus n = 30, 44.1%; P < 0.001), ECD (n = 65, 94.2% versus n = 34, 47.2%; P < 0.001) and VCI onset with cognitive impairment but not strokes (n = 44, 63.8% versus n = 34, 50%; P < 0.01). CONCLUSIONS: ECD and a frontal gait are SVD's clinical landmarks in our sample. LS and BD cases share a similar cognitive profile.

Calcifediol is superior to cholecalciferol in improving vitamin D status in postmenopausal women: a randomized trial.

Vitamin D has shown to play a role in multiple diseases due to its skeletal and extraskeletal actions. Furthermore, vitamin D deficiency has become a worldwide health issue. Few supplementation guidelines mention calcifediol treatment, despite being the direct precursor of calcitriol and the biomarker of vitamin D status. This 1-year, phase III-IV, double-blind, randomized, controlled, multicenter clinical trial assessed the efficacy and safety of calcifediol 0.266 mg soft capsules in vitamin D-deficient postmenopausal women, compared to cholecalciferol. Results reported here are from a prespecified interim analysis, for the evaluation of the study's primary endpoint: the percentage of patients with serum 25-hydroxyvitamin D (25(OH)D) levels above 30 ng/ml after 4 months. A total of 303 patients were enrolled, of whom 298 were included in the intention-to-treat (ITT) population. Patients with baseline levels of serum 25(OH)D <20 ng/ml were randomized 1:1:1 to calcifediol 0.266 mg/month for 12 months, calcifediol 0.266 mg/month for 4 months followed by placebo for 8 months, and cholecalciferol 25,000 IU/month for 12 months. At month 4, 35.0% of postmenopausal women treated with calcifediol and 8.2% of those treated with cholecalciferol reached serum 25(OH)D levels above 30 ng/ml (p < 0.0001). The most remarkable difference between both drugs in terms of mean change in serum 25(OH)D levels was observed after the first month of treatment (mean ± standard deviation change = 9.7 ± 6.7 and 5.1 ± 3.5 ng/ml in patients treated with calcifediol and cholecalciferol, respectively). No relevant treatment-related safety issues were reported in any of the groups studied. These results thus confirm that calcifediol is effective, faster, and more potent than cholecalciferol in raising serum 25(OH)D levels and is a valuable option for the treatment of vitamin D deficiency. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Haplotypes of intron 4 of the estrogen receptor alpha gene and hip fractures: a replication study in Caucasians.

BACKGROUND: Despite their great impact, few genetic association studies have used hip fractures as an endpoint. However, the association of two polymorphisms on intron 4 of estrogen receptor alpha (ESR1) with hip fractures was recently reported in a Chinese population. The aim of this study was to investigate whether such association is also present in Caucasians. METHODS: We analyzed those two SNPs and another neighbour SNP located on the exon 4 of ESR1 in 787 patients with hip fractures and 953 controls from Spain. RESULTS: The allelic frequencies differed markedly from those reported in Asian populations. Nevertheless, haplotypes including the rs3020314 and rs1884051 loci in intron 4 showed a significant association with hip fractures (omnibus test p = 0.006 in the whole group and 0.00005 in women). In the sex-stratified analysis, the association was significant in females, but not in males. In women, the CA haplotype appeared to have a protective influence, being present in 6.5% of the controls, but only in 3% of patients with fractures (odds ratio 0.39; 95% confidence interval 0.26-0.59; estimated population preventive fraction 3.5%). The inclusion of the rs1801132 SNP of exon 4 further increased the statistical significance of the association (odds ratio 0.17; 95% CI 0.08-0.37; p = 0.00001). Each SNP appeared to contribute independently to the association. No genotype-related differences in gene expression were found in 42 femoral bone samples. CONCLUSIONS: This study confirms the association of some polymorphisms in the region of exon 4/intron 4 of ESR1 and hip fractures in women. However, there are marked differences in allele frequencies between Asian and Caucasian populations.

Time course of bone loss in patients with anorexia nervosa.

OBJECTIVE: To evaluate the time course of bone mineral density (BMD) in women with anorexia nervosa (AN) during 2-year follow-up. METHOD: We prospectively studied 51 female with AN aged 18-38 years, and 40 age-matched healthy women (19-34 years). BMD was measured in lumbar spine (LS), femoral neck (FN), and total hip (TH) by DXA. RESULTS: At baseline, weight, body mass index, and lumbar and hip BMD were significantly (p < .001) lower in AN patients than in controls. Patients who gain weight showed a significant increase in BMD at FN (+1.6%; p < .05), and TH (+4.4%; p < .05) and lower nonsignificant changes in LS (+1.3%). Weight at entry, and percent change of weight were significant determinants (p < .05) of the variability in percent change of BMD at FN and TH, whereas weight at entry was the main determinant of bone modifications at lumbar spine. DISCUSSION: Our data emphasize the influence of weight gain in recovery of bone mass in AN patients, especially at the hip.

Serum lipids and bone metabolism in Spanish men: the Camargo cohort study.

There is growing evidence of a link between lipid and bone metabolism, although data on this association in European men are scarce. This cross-sectional study from a community-based prospective cohort aims to explore the association of serum lipids with different aspects of bone metabolism in Spanish men. Demographic and anthropometric measurements, biochemical parameters including serum lipids, bone remodelling markers and calciotropic hormones, bone mineral density (BMD) assessed by dual X-ray absorptiometry and heel quantitative ultrasound, and prevalent vertebral and non-vertebral fractures, were evaluated in 289 men. Calciotropic hormones or bone markers were not associated with serum lipids. Serum total (TC) and LDL cholesterol, as well as LDL/HDL ratio were positively correlated to BMD at lumbar spine and hip. No significant correlation was noted for triglycerides or HDL. We observed a positive association between triglycerides, LDL/HDL ratio and BUA, and between TC/HDL ratio and both, QUI and BUA. BMD at the femoral neck and total hip was significantly higher in men with hypercholesterolemia after controlling for all the covariates (p=0.007). We did not observe any association between serum lipids and prevalent vertebral fractures. However, we found that TC (p=0.03) and LDL (p=0.04) were lower in subjects with non-vertebral fractures. In conclusion, we have found that a more unfavorable lipid profile (mainly higher LDL-C levels) is associated with higher BMD at lumbar spine and hip in Spanish men. Moreover, we did not observe any association between hypercholesterolemia and prevalent vertebral fractures, but we found lower serum TC and LDL-C levels in men with prevalent non-vertebral fractures.

Trabecular bone score and bone quantitative ultrasound in Spanish postmenopausal women. The Camargo Cohort Study.

OBJECTIVE: To evaluate trabecular bone score (TBS) in Spanish postmenopausal women from our area. To analyze its relationship with bone mineral density (BMD), bone quantitative ultrasound (QUS) and serum concentrations of 25-hydroxyvitamin D (25(OH)D), intact parathyroid hormone (PTH) and bone turnover markers. STUDY DESIGN: A total of 1450 postmenopausal women aged 44-94 (62 ± 10) participated in this cross-sectional study nested in a population-based cohort. BMD and TBS were assessed by DXA. QUS measurements were performed using a Sahara Clinical Sonometer. Serum 25(OH)D, PTH, P1NP, ß-CTX were determined by electrochemiluminescence. RESULTS: Mean TBS of postmenopausal women in our region was 1.341 ± 0.111. Nearly 50 % of them had normal values. Only 11 % had scores compatible with a clearly degraded microarchitecture. TBS decreased with age, correlated negatively with BMI and was lower in current smokers than in non-smokers. An association was observed between TBS and QUS, although the association was weak and lower than that found between TBS and BMD or QUS and BMD. No association was found between TBS and 25(OH)D, PTH or bone turnover markers. CONCLUSIONS: Half of postmenopausal women in our region have TBS values that indicate a preserved microarchitecture. Only about 10 % have scores compatible with a clearly degraded microarchitecture. A weak association was observed between TBS and QUS, suggesting that the two techniques capture different aspects of bone microarchitecture. The absence of association with 25(OH)D, PTH, and bone turnover markers may be due to the fact that TBS assesses a specific (mostly trabecular) part of the skeleton, whilst the three serum factors are related to the whole skeleton.

Bone mineral density and trabecular bone score in treatment-naïve patients with non-cirrhotic hepatitis C virus infection.

We studied 112 treatment-naïve chronic HCV patients without cirrhosis, and we found that, especially HCV+ postmenopausal women, they had lower TBS and BMD values than healthy controls. This suggests that HCV infection is an independent risk factor for osteoporosis, and therefore, screening for osteoporosis in postmenopausal HCV+ women should be considered. PURPOSE: To know whether patients in earlier stages of chronic HCV infection are at increased risk of developing low bone mass and bone microarchitectural changes and whether there is an association between bone metabolism and the severity of the liver disease. METHODS: We studied 112 treatment-naïve chronic HCV outpatients and 233 healthy age- and sex-matched controls. Bone mineral density (BMD) and trabecular bone score (TBS) were assessed by DXA. Serum 25(OH)D, PTH, P1NP, and CTX were determined by electrochemiluminescence. RESULTS: TBS values were significantly lower in HCV patients than in controls, both considering the population as a whole (1.337 ± 0.119 vs. 1.377 ± 0.122; p < 0.005) and after stratifying by sex (1.347 ± 0.12 vs. 1.381 ± 0.13 in men and 1.314 ± 0.10 vs. 1.369 ± 0.11 in women). The difference remained significant (p < 0.0001 in all cases) after adjusting for confounders. BMD was also lower in HCV patients (lumbar spine, 0.935 ± 0.151 vs. 0.991 ± 0.143 g/cm2, p 0.001; femoral neck, 0.764 ± 0.123 vs. 0.818 ± 0.123 g/cm2, p 0.0001; total hip, 0.926 ± 0.148 vs. 0.963 ± 0.132 g/cm2, p 0.02), although, after adjustment, differences kept a clear trend towards statistical significance in women at the lumbar spine and femoral neck. However, in men and at the total hip in women, differences were no longer significant. We find no relationship between these parameters and the severity of the disease. No significant difference was observed in PTH and 25OHD status after adjustment. Finally, serum P1NP, but not CTX, was higher in HCV patients. CONCLUSIONS: Our findings suggest that HCV infection is an independent risk factor for osteoporosis, especially among postmenopausal women. Therefore, the appropriateness of screening for osteoporosis in postmenopausal HCV-positive women should be considered.

[Validation of an algorithm to calculate the absolute risk of non-vertebral fragility fractures in a cohort of postmenopausal women]. / Validación de un algoritmo para el cálculo del riesgo absoluto de fracturas no vertebrales por fragilidad en una cohorte de mujeres posmenopáusicas.

BACKGROUND AND OBJECTIVES: Absolute risk estimate for fractures in the individual subject provides meaningful information for interventions. Recently, we have described an algorithm to calculate the absolute risk for non-vertebral fractures in women from Spain, aged 65 years or older, that includes clinical parameters and quantitative bone ultrasound values of the calcaneus (URL: www.ecosap.info). We assessed the performance of the algorithm by means of the statistical analysis of the model calibration. SUBJECTS AND METHODS: The algorithm was the result of the prospective analysis of 5.201 [corrected] women who were attended for any reason in Primary Care Centres and followed-up for 3 years. Model calibration was evaluated by comparing number of estimated (E) cases predicted with the equation with the number of observed (O) cases, and its accuracy to discriminate women with and without a new fracture. RESULTS: No evidence of statistically significant miscalibration of the model was observed. The E/O ratio was 1,02 (CI 95%: 0,91-1,14). Calibration chi(2) value (difference between the estimated and observed cases) did not reach statistical significance. Area under the curve-ROC was approximately 0.67. CONCLUSIONS: These results suggest a good calibration of the proposed algorithm for non-vertebral fracture prediction. It would be desirable to calibrate it with an independent cohort to definitively test its external validity.

Genetic polymorphisms are associated with serum levels of sex hormone binding globulin in postmenopausal women.

BACKGROUND: Estrogen activity plays a critical role in bone homeostasis. The serum levels of sex hormone binding globulin (SHBG) influence free estrogen levels and activity on target tissues. The objective of this study was to analyze the influence of common polymorphisms of the SHBG gene on serum SHBG, bone mineral density (BMD), and osteoporotic fractures. METHODS: Four biallelic polymorphisms of the SHBG gene were studied by means of Taqman assays in 753 postmenopausal women. BMD was measured by DXA and serum SHBG was measured by ELISA. RESULTS: Age, body weight, and two polymorphisms of the SHBG gene (rs6257 and rs1799941 [A/G]) were significantly associated with serum SHBG in unadjusted and age- and weight-adjusted models. Alleles at the rs1799941 locus showed the strongest association with serum SHBG (p=0.0004). The difference in SHBG levels between women with AA and GG genotypes at the rs1799941 locus was 39%. There were no significant differences in BMD across SHBG genotypes. The genotypes showed similar frequency distributions in control women and women with vertebral or hip fractures. CONCLUSION: Some common genetic variants of the SHBG gene, and particularly an A/G polymorphism situated in the 5' region, influence serum SHBG levels. However, a significant association with BMD or osteoporotic fractures has not been demonstrated.

Mineral metabolism in obese patients following vertical banded gastroplasty.

BACKGROUND: Bone disease has been described in patients after surgical treatment for obesity, but few studies have dealt with the impact of vertical banded gastroplasty on mineral metabolism. We have examined bone mineral metabolism in morbidly obese patients before and after 3 months after vertical banded gastroplasty without vitamin D supplementation. METHODS: Sixteen morbidly obese patients (14 women, 2 men) with a mean (+/-SD) age of 38 +/- 9 years and a body mass index (BMI) of 47.1 +/- 8.1 kg/m2 were studied. No vitamin D supplementation was given. Body weight, fat mass, calcium, 25OHD, iPTH, bone remodeling markers, and leptin levels were measured at baseline and after weight loss. RESULTS: Mean weight loss was 28 +/- 11 kg; BMI and body fat mass decreased by 20 and 35%, respectively. Bone resorption markers and albumin-corrected serum calcium increased after operation, whereas iPTH fell. Serum 25OHD levels rose. Leptin levels decreased. Serum iPTH was positively correlated with weight, BMI, and fat mass before operation (p < 0.05), and its decline after weight reduction was negatively associated with the increase in bone resorption markers (p < 0.01). Leptin concentration was correlated with BMI and body fat mass (p < 0.05) both before and after surgery. CONCLUSIONS: Weight reduction obtained in morbidly obese subjects 3 months after vertical banded gastroplasty increases bone turnover markers and decreases PTH secretion. Serum 25OHD levels rose. Therefore, no reasons for a metabolic bone disease related to hypovitaminosis D were readily apparent. However, an increase in bone turnover, which is generally regarded as a potential risk factor for osteoporosis, was observed. Further work is needed to clarify the importance of this turnover increase in the long run.

Vascular cognitive impairment: prodromal stages of ischemic vascular dementia.

BACKGROUND/AIMS: To describe the natural history of the prodromal stages of ischemic vascular dementia (pVaD). METHODS: A sample of 314 inpatients with pVaD or a clini- cal diagnosis of vascular dementia (VaD; lacunar state, Binswanger's disease, pure cortical VaD, corticosubcortical and strategic infarctions) admitted to a teaching tertiary center during a 13-year period was assessed (retrospectively n = 88, prospectively n = 226). Prospective neuropsychological assessment consisted of Mini Mental State Examination, Revised Wechsler Adult Intelligence Scale, Exit-25, Trail Making tests, Blessed Dementia Scale and Camdex H, Global Depression Scale and Hamilton Depression Rating Scale tests. Univariate analysis and logistic regressions are displayed. RESULTS: An unrecognized pVaD was related with a clinical onset with cognitive impairment no dementia (CIND) versus symptomatic cerebrovascular events (p < 0.0001), and with being under therapy with anticoagulant or antiplatelet agents (p < 0.01). Age <85 years at diagnosis of VaD (p < 0.01) correlated with a delayed pVaD diagnosis. CIND onset was associated with a longer prodromal stage (p < 0.01), no clinical strokes during pVaD (p < 0.001), silent ischemia (p < 0.01) and Binswanger's disease (p < 0.01). CONCLUSIONS: Vascular cognitive impairment remains an underdiagnosed, yet treatable entity. A brief neuropsychological examination and informant interviews should become standard practice in elderly populations with vascular risk factors. Small-vessel disease is a prevalent condition with a distinct natural history.