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X Nogués

Publications and source records attributed to X Nogués.

At least 19 recordsLinked to original sources

COL1A1, ESR1, VDR and TGFB1 polymorphisms and haplotypes in relation to BMD in Spanish postmenopausal women.

INTRODUCTION AND HYPOTHESIS: Genetic studies of osteoporosis have focused on analysing single polymorphisms in individual genes - with inconclusive results. An alternative approach may involve haplotypes and gene-gene interactions. The aim of the study was to test the association between the COL1A1, ESR1, VDR and TGFB1 polymorphisms or haplotypes and bone mineral density (BMD) in Spanish postmenopausal women. METHODS: Sixteen polymorphisms were analysed in 719 postmenopausal women. ANOVA, ANCOVA and Xi2 tests were used to perform the statistical analysis. RESULTS: COL1A1 -1997G > T (p=0.04) and TGFB1 Leu10Pro (p=0.02) were found to be associated with adjusted lumbar spine (LS) BMD. Interactions were observed between: the COL1A1 -1997 G/T and Sp1 polymorphisms (p < 0.01 for LS BMD) and the COL1A1 -1663 indelT and VDR ApaI polymorphisms (p < 0.01 for femoral neck (FN) BMD). The COL1A1 GDs and ESR1 LPX haplotypes were associated with FN BMD (p=0.03 and p=0.03). CONCLUSIONS: Polymorphisms at COL1A1 and TGFB1 and haplotypes at COL1A1 and ESR1 were found to be associated with BMD in a cohort of postmenopausal Spanish women. Moreover, COL1A1 polymorphisms showed significant interactions among them and with the VDR 3' polymorphisms.

Bone Density↗

Inhaled steroids do not decrease bone mineral density but increase risk of fractures: data from the GIUMO Study Group.

Although the negative effect of systemic steroids on bone is well documented, there is not clear evidence about possible adverse effects of inhaled steroids on bone metabolism and fractures. A cross-sectional study was performed on 105 women suffering from bronchial asthma treated with inhaled steroids and 133 controls. Bone mineral density (BMD) was measured by quantitative ultrasonography (QUS) at the calcaneus and by dual X-ray absorptiometry (DXA), at both the lumbar spine and proximal femur. Patients suffering from bronchial asthma showed no statistically significant changes in BMD as measured by DXA or QUS, compared with controls. A higher prevalence of fractures was found in the group of women with bronchial asthma, with an age-adjusted odds ratio of 2.79 (95% CI: 1.19-6.54). Inhaled steroids do not appear to decrease BMD, but are associated with an increased risk of fracture in women.

Absorptiometry, Photon↗

Timing of follow-up densitometry in hormone replacement therapy users for optimal osteoporosis prevention.

The objectives of the study were (1) to determine the time interval for repeat dual-energy X-ray absorptiometry (DXA) to detect significant bone loss, i.e., greater than the coefficient of variation (CV) of the center (2.8 x CV%) and (2) to assess how long hormone replacement therapy can be maintained to avoid undetected development of low bone mass and to not unduly delay appropriate treatment. A total of 3,826 healthy women, aged 40-65 years, participated in a prospective cohort study, 807 of whom were treated with transdermal estrogen replacement therapy and 626 with transdermal estrogen/progesterone regimens. The untreated group included the remaining 2,393 women. Between 1996 and 2002 they underwent a baseline DXA scan, and DXA scans were then repeated annually. There were no differences among the study groups at entry into the study. Treatment with estrogen was a protective factor for loss of bone mass at the lumbar spine (odds ratio [OR] =0.431, 95% confidence interval [CI] 0.344 to 0.522) and at the femoral neck (OR =0.433, 95% CI 0.352 to 0.521). Treatment with estrogen/progesterone also showed a protective effect against significant changes in follow-up BMD (>2.8 x 1.05% CV of densitometry at L1-L4, >2.8 x 2.3% CV at the femoral neck). In the treated group, significant differences in BMD at the lumbar spine (OR =1.593, 95% CI 1.423 to 2.355) did not appear within the first 3 years, and differences in BMD at the femoral neck (OR =3.555, 95% CI 2.782 to 4.905) did not appear within the first 4 years. It is concluded that in women aged 45-65 years, receiving transdermal hormone replacement therapy without risk factor for loss of bone mass, such as age < 55 years and body mass index <25 kg/m(2), periodical follow-up densitometries would not be necessary, provided that the duration of estrogen or estrogen/progesterone therapy is shorter than 3 years.

Absorptiometry, Photon↗

Relationship among densitometry, bone histomorphometry, and histologic stage in idiopathic myelofibrosis.

Idiopathic myelofibrosis (IMF) induces dramatic changes in bone. Bone remodeling and densitometric alterations in a series of nine patients with IMF and their relationship with the histologic stage of the disease were assessed. Patients were included at diagnosis and a bone marrow biopsy, dual-energy X-ray absorptiometry, and transiliac bone biopsy for histomorphometric analysis were performed. Five cases were classified as IMF histologic stage 1, one as stage 2, and three as stage 3. Compared with 40 age- and sex-matched controls, the following histomorphometric parameters were significantly higher in our patients: bone volume (BV/TV), osteoblast surface (Ob.S/BS), eroded surface (ES/BS), osteoclast surface (Oc.S/BS), osteoclast number (N.Oc/TA), mineralizing surface (MS/BS), reversal period (Rv.P), and remodeling period (Rm.P). Mineral apposition rate (MAR) and erosion depth (E.Depth) were significantly decreased (P < 0.05 for all comparisons). Bone mineral density (BMD) measurements showed high values for patient age and sex both at femur neck (Z score range +0.19 to +7) and total femur (Z score range -0.09 to +6.48). When densitometric values were analyzed according to IMF histologic stage, patients in stages 1 and 2 had significantly lower BMD values than to those in stage 3 (P = 0.024). In conclusion, patients with IMF present a characteristic bone histomorphometric pattern with increased bone volume and bone cells but low apposition and decreased erosion depth, suggesting a positive balance in bone remodeling units. This balance would produce the increase in bone mass observed in this disease. Given the increase in BMD observed with more advanced stages of IMF, this noninvasive method could be useful tool for assessing IMF progression.

Biomechanical Phenomena↗

Alendronate and etidronate do not regulate interleukin 6 and 11 synthesis in normal human osteoblasts in culture.

Bisphosphonates exert a potent inhibitory effect on bone resorption. Several studies have been performed, with contradictory results, to ascertain whether the effect of bisphosphonates on osteoclasts could be produced, at least in part, by modulation of the synthesis of resorption-promoting factors by osteoblasts. The aim of this study was to evaluate the effect of etidronate (10-4-10-9 M) and alendronate (10-7-10-12 M) on the production of IL-6 and IL-11 using human osteoblast cultures. Cytokines were quantified by ELISA, and mRNA expression was tested. Treatment with alendronate and etidronate had no effect on the synthesis of IL-6 or IL-11, and IL-6 and IL-11 mRNA levels. These results were obtained both in nonstimulated cultures and in cultures stimulated by means of TNF-a, IL-1b, and TNF-a+IL-1b, with or without FCS. In conclusion, a possible indirect osteoclast-mediated effect of alendronate and etidronate on bone resorption would not be exerted through reduction in osteoblastic synthesis of IL-6 and IL-11.

Aged↗

[Screening for bone disease risk with clinical factors in women after physiologic menopause].

BACKGROUND: Densitometric screening for osteoporosis in postmenopausal women has not been demonstrated cost-effective. We have tried to identify clinical factors for screening previous to densitometry avoiding unnecessary explorations. PATIENTS AND METHODS SETTING: outpatient clinics of a menopausal unit in a 450-bed general hospital. Cross-sectional study, in two steps, of two groups of 140 and 284 women attending for physiological menopause. A clinical questionnaire, physical data and lumbar densitometry (Hologic QDR 1000) were obtained classifying the cases as "normal" or "low bone mass" (osteopenia or osteoporosis) according with the WHO criteria. In the first group a logistic regression analysis was done to identify predictive factors for abnormal densitometry, then validated in the second group. Sensitivity, specificity, predictive values (PV) and classification ability of clinical factors were analyzed. RESULTS: Four factors were independent predictors of abnormal densitometry: age > 51 (odds ratio [OR] = 6.64; 95% CI, 2.36-18.7); body weight < 70 kg (OR = 4.32; 95% CI, 1.71-10.09); years of fertility < 32 (OR = 3.77; 95% CI, 1.36-10.04), and number of live births > 2 (OR = 3.47; 95% CI, 1.27-9.53). Presence of one factor offers: sensitivity 91.9%; specificity 15%; positive PV 66.6%, and negative PV 50%, whereas the presence of two factors offers: sensitivity 62.7%; specificity 70%; positive PV 79.9%, and negative PV 50.3%. Clinical screening allows, when two factors are present, to avoid a 35.5% of densitometries and the false-negative cases represent 18%. CONCLUSIONS: Detection of bone-risk clinical factors (abnormal densitometry) yields a screening, previous to densitometry, that avoids at least one third of explorations in women with physiological menopause, improving the efficiency of the test.

Cross-Sectional Studies↗

Effect of alendronate on cultured normal human osteoblasts.

Alendronate is an aminobisphosphonate with a potent anti-reabsorptive action that does not appear to interfere with bone mineralization, and is even able to increase bone mineral density in osteoporotic postmenopausal women through a still not fully understood mechanism. This study was conducted to assess the direct effect of alendronate on diverse aspects of normal human osteoblast physiology. For that purpose, the in vitro effect of a wide range of concentrations [from 10(-1) to 10(-12) mol/L] of alendronate on cell viability, proliferation, collagen synthesis, and the mineral-depositing capacity of normal human osteoblasts was tested. Alendronate effects were examined at 48 and 96 h of culture in the presence or absence of fetal calf serum. In vitro alendronate affected osteoblast viability at concentrations equal to or higher than 10(-4) mol/L. At concentrations equal to or higher than 10(-3) mol/L, no viable cells were observed in cultures. In vitro alendronate at concentrations between 10(-5) and 10(-12) mol/L did not have any effect on the proliferative capacity of normal human osteoblasts determined by two different techniques: (1) tritiated thymidine incorporation to DNA and (2) cell counting. Collagen synthesis by normal human osteoblasts showed a tendency to decrease following incubation with alendronate supplemented with fetal calf serum. This decrease was only statistically significant after 96 h of culture; however, a dose-response effect could not be documented. Finally, no effect of alendronate was observed on calcium deposition in vitro by normal human osteoblasts at concentrations equal to or lower than 10(-5) mol/L. In conclusion, the present study shows that alendronate in vitro does not affect viability, proliferation, and mineral deposit capacity of normal human osteoblasts at the concentration at which it inhibits by 50% the resorptive capacity of osteoclasts that for this drug has been reported as 2 x 10(-9) mol/L.

Adult↗

Piroxicam fast-dissolving dosage form vs diclofenac sodium in the treatment of acute renal colic: a double-blind controlled trial.

OBJECTIVE: To assess the possible therapeutic effect of 40 mg sublingual piroxicam (fast-dissolving dosage form, FDDF) compared with intramuscular 75 mg diclofenac, as a reference drug, on acute renal colic in a randomized, double-blind controlled clinical trial. PATIENTS AND METHODS: Eighty patients were assigned to one of two treatment groups; one received an intramuscular injection with 0.2 mL distilled water and two sublingual tablets of 20 mg piroxicam FDDF, and the other received an intramuscular injection with 75 mg diclofenac sodium and two sublingual tablets of placebo. Pain intensity was evaluated by the patient using a visual analogue scale and by the observers. Vital signs at baseline and 30 min after the administration of the study drugs were also recorded. RESULTS: The overall efficacy of the treatment was 81%; nine patients in the piroxicam and six in the diclofenac group (no significant difference) required rescue treatment. Compared with baseline levels, the pain relief was significant (P < 0.001) at 30 min in both groups. Twenty-two patients in the piroxicam and 25 in the diclofenac group attained complete pain relief at 30 min, as evaluated by the observer (no significant difference). Both treatments were similarly effective in decreasing vital signs, mainly systolic blood pressure, heart and respiratory rates. However, when the percentage change was compared between the groups, piroxicam significantly decreased the respiratory rate (P < 0.03). CONCLUSION: Piroxicam FDDF is as effective as parenteral diclofenac in emergency renal colic treatment. Furthermore, its ease of self-administration increases patient compliance and potential use in general practice.

Acute Disease↗

Acute effects of ethanol on mineral metabolism and trabecular bone in Sprague-Dawley rats.

In order to assess the effects of acute ethanol intoxication on bone, 45 female Sprague-Dawley rats were studied. Five rats were sacrificed at baseline. The remainder received either ethanol (2 g/kg of body weight) intraperitoneally or isotonic saline. Rats were sacrificed in groups of 10 (5 intoxicated and 5 placebo) at 1, 4, 8, and 24 hours after injection. At the time of sacrifice, a blood sample was obtained and the 4th vertebra was excised for histomorphometric analysis of undecalcified bone. Effect of ethanol was assessed by an analysis of variance test using a Scheffé procedure. In ethanol-treated rats we observed (mean +/- SD, ethanol versus controls, maximum difference point, P value) a significant decrease in osteiod surface with osteoblasts (42.86 +/- 15.61% versus 64.57 +/- 6.24%, P < 0.05); osteoclast number (0.05 +/- 0.02 n/mm2 versus 0.17 +/- 0.09 n/nm2, P < 0.05), and osteocalcin (36.9 +/- 2.21 ng/ml versus 45.8 +/- 5.1 ng/ml, P < 0.05). Osteoclast surface was initially reduced (0.129 +/- 0.09% versus 0.425 +/- 0. 26%, P < 0.01) but showed a subsequent increase (0.765 +/- 0.24% versus 0.226 +/- 0.17%, P < 0.01) attributable to alcohol. There was also a significant decrease in serum Ca (8.51 +/- 0.23 mg/dl versus 9.10 +/- 0.29 mg/dl, P < 0.01) and parathyroid hormone values (23.51 +/- 5.72 pg/ml versus 76.39 +/- 11.66 pg/ml, P < 0.001). We conclude that acute alcohol intoxication in rats induces early striking changes in bone histology and analytical parameters, not completely reversed after 24 hours. These data are consistent with a toxic effect induced by alcohol on bone.

Acid Phosphatase↗

[Multicenter comparative study on safety, tolerance, and effectiveness of lovastatin combined or not with cholestyramine, and gemfibrozil combined or not with cholestyramine in the treatment of primary hypercholesterolemia].

BACKGROUND: The well-known relationship between high plasma cholesterol levels and coronary heart disease makes the treatment of primary hypercholesterolemia an important issue. PATIENTS AND METHODS: A randomized, double-blind 12 week study to compare lovastatin (20-80 mg/day) and gemfibrozil (600 mg b.i.d.) was performed in 59 patients with primary hypercholesterolemia. Resincholestyramine was started on week 12, at a dose of 8-16 g/day for the next 12 weeks in any patient whose LDL-cholesterol exceeded 165 mg/dl at week 12. RESULTS: Total cholesterol, triglycerides and LDL-cholesterol decreased significantly (23.8%, 16.4% and 30.9%, respectively) after lovastatin therapy, whereas HDL-cholesterol increased (13.9%). The figures for the group treated with gemfibrozil were 12.8%, 30.3%, 17.2% and 14.6%, respectively. Mean changes between the two groups were statistically significant for all parameters except for HDL-cholesterol. LDL-cholesterol decreased below 165 mg/dl in 69% of patients receiving lovastatin and 36.7% of patients treated with gemfibrozil (p < 0.05). During the second phase there were no additional significant changes in the 9 patients of the lovastatin group and the 20 patients of the gemfibrozil group after cholestyramine, but LDL-cholesterol decreased below 165 mg/dl in 5 patients (55%) and 6 patients (30%), respectively. Side-effects were more prevalent in patients treated with gemfibrozil alone or in combination with cholestyramine. CONCLUSIONS: In patients with primary hypercholesterolemia, lovastatin alone or in combination with cholestyramine was more effective than gemfibrozil alone or in combination with cholestyramine to lower total cholesterol and LDL-cholesterol. The effect of both drugs on HDL-cholesterol was similar.

Adolescent↗

Bone remodeling alterations in myelodysplastic syndrome.

There is a close relationship between hematopoietic bone marrow and bone cells. Thus, the profound derangement of hematopoiesis in myelodysplastic syndromes (MDS) might be expected to affect bone cell function. We studied the dynamic histomorphometric changes in bone in 22 MDS patients to examine this relationship and analyze the influence of hematological disease on bone remodeling. Bone-regulating hormones and histomorphometry of undecalcified transiliac bone biopsies, after double tetracycline labeling, were studied. Serum calcium, phosphorus, creatinine, alkaline phophatase, osteocalcin, iPTH, 25(OH)D3, 1,25(OH)2D3, hydroxyprolinuria, and calcium/creatinine ratio in urine were normal compared with controls. Histomorphometry showed a significant decrease in osteoblast surface (Ob.S/BS) (0.30 +/- 0.40 vs. 0.8 +/- 1.1, p = 0.031), wall thickness (W.Th), (22.03 +/- 5.5 vs. 31.8 +/- 5.8, p < 0.005), osteoclast number (N.Oc/T.Ar) (0.004 +/- 0.01 vs. 0.017 +/- 0.01, p = 0.03), mineral apposition rate (MAR) (0.16 +/- 0.15 vs. 0.53 +/- 0.19, p < 0.005), bone formation rate, surface referent (BFR/BS) (0.004 +/- 0.10 vs. 0.016 +/- 0.016, p = 0.009), and activation frequency (Ac.f) (0.06 +/- 0.07 vs. 0.21 +/- 0.23, p = 0.008). An increase in mineralization lag time (MLT) (119.2 +/- 78.6 vs. 29.6 +/- 77, p < 0.005), (mean +/- SD, unpaired Student t-test) was observed. Bone volume (BV/ TV), eroded surfaces (ES/BS), and osteoid thickness (O.Th) remained unchanged. This picture of adynamic bone with decreased mineral apposition rate and markedly decreased osteoclast number is a characteristic finding in MDS patients. Thus, bone histomorphometric finding in MDS patients show the relationships and interactions between hematopoietic and bone cells.

Aged↗