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Biomedical subjects

N Guañabens

Publications and source records attributed to N Guañabens.

At least 19 recordsLinked to original sources
PubMed2006

Biochemical response to bisphosphonate therapy in pagetic patients with skull involvement.

The aims of this study were to compare the response to therapy in disease activity in pagetic patients with and without skull involvement and the usefulness of bone markers in the evaluation of these patients. Forty patients with Paget's disease treated with tiludronate and 26 healthy controls were included. Serum total and bone alkaline phosphatases (TAP, BAP), procollagen I N propeptide (PINP), and urinary N- and C-terminal cross-linking telopeptides of collagen I (NTX, alpha-alpha CTX, and beta-beta CTX) were measured at baseline and 6 months after therapy. The extent of the disease was evaluated using the Coutris' index. Pagetic patients were classified into three groups: patients with skull involvement (G-I, n = 12), patients without skull involvement (G-II, n = 28), and a subgroup of patients from G-II without skull involvement but with similar disease extent to G-I (G-III, n = 10). At baseline, patients from G-I showed significantly higher values in most markers compared to G-II. alpha-alpha CTX was the marker with the highest values in all groups. Moreover, monostotic patients with skull involvement showed higher serum baseline values of TAP per unit of affected area than monostotic patients without skull involvement. After therapy, the percentage of patients with markers within the normal range was lower in G-I than in G-II and G-III. In conclusion, pagetic patients with skull involvement showed a marked increase in bone turnover and a lower response to therapy.

Adult↗
PubMed2006

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↗
PubMed2005

Camurati-Engelmann disease: review of the clinical, radiological, and molecular data of 24 families and implications for diagnosis and treatment.

Camurati-Engelmann disease (CED) is a rare autosomal dominant type of bone dysplasia. This review is based on the unpublished and detailed clinical, radiological, and molecular findings in 14 CED families, comprising 41 patients, combined with data from 10 other previously reported CED families. For all 100 cases, molecular evidence for CED was available, as a mutation was detected in TGFB1, the gene encoding transforming growth factor (TGF) beta1. Pain in the extremities was the most common clinical symptom, present in 68% of the patients. A waddling gait (48%), easy fatigability (44%), and muscle weakness (39%) were other important features. Radiological symptoms were not fully penetrant, with 94% of the patients showing the typical long bone involvement. A large percentage of the patients also showed involvement of the skull (54%) and pelvis (63%). The review provides an overview of possible treatments, diagnostic guidelines, and considerations for prenatal testing. The detailed description of such a large set of CED patients will be of value in establishing the correct diagnosis, genetic counselling, and treatment.

Camurati-Engelmann Syndrome↗
PubMed2004

Long-term biochemical response after bisphosphonate therapy in Paget's disease of bone. Proposed intervals for monitoring treatment.

OBJECTIVES: To monitor the long-term evolution of Paget's disease activity after treatment with tiludronate by using serum total alkaline phosphatase (TAP) and more sensitive markers such as bone alkaline phosphatase (BAP), procollagen type I N propeptide (PINP) and urinary N-terminal cross-linking telopeptide of type I collagen (NTX); to analyse the predictors of long-term response to therapy; and to study the most appropriate intervals of time for monitoring the response to therapy. METHODS: Thirty-two patients with Paget's disease were included in the study. All received 400 mg of oral tiludronate daily for 3 months. A total of 21 patients completed the study. In these patients, serum TAP, BAP and PINP and urinary NTX were measured at baseline and at 1, 6, 12 and 24 months after discontinuation of therapy. Quantitative bone scintigraphy was performed at baseline and at 6 and 24 months after the end of treatment, obtaining a scintigraphic activity index (SAI). Patients were classified into two groups depending on the long-term response to treatment: Group 1, patients who presented a persistent and significant decrease in disease activity at this time, n = 12 (57%) and Group 2, patients who presented a relapse in the activity of the disease at 24 months after treatment, n = 9 (43%). The relapse of disease activity was defined as a significant increase of SAI (>13%) between 6 and 24 months after the end of treatment, whereas the response to therapy was defined as a significant reduction in SAI (>13%) at 6 months after the end of treatment. In addition, these results were compared with the biochemical evolution of bone markers. RESULTS: Biochemical markers and SAI decreased significantly after therapy and the nadir response was observed at 6 months. At this time 100% of patients responded to therapy. The persistent long-term response was associated with lower baseline indices of bone turnover (serum BAP<60 ng/ml or TAP<600 IU/l). The intervals of time for monitoring depended on the marker used: no patient from Group 1 presented a biochemical relapse in serum TAP at 1 and 2 yr after the end of treatment whereas 33 and 45% of these patients showed relapsed serum BAP at these time points. Moreover, all patients from Group 2 presented a biochemical relapse of serum BAP at 2 yr whereas in only 33% of these patients did serum TAP relapse at this time. CONCLUSION: Most of the Pagetic patients treated with tiludronate presented a long-term response, which persisted 2 yr after the end of treatment. The nadir response to treatment was observed 6 months after discontinuation of therapy whereas the relapse of disease activity was already observed 1 yr after the end of therapy and depended on both the baseline disease activity and the bone marker used in the evaluation.

Adult↗
PubMed2003

Immunocytochemical evidence on the effects of glucocorticoids on type I collagen synthesis in human osteoblastic cells.

The effects of glucocorticoids on DNA synthesis and cellular function were assessed in cultures of human osteoblastic cells by using indirect immunoperoxidase staining with a type I antiprocollagen antibody and by measuring procollagen type I N and C propeptides (PINP, PICP) in the culture medium by radiometric methods. Likewise, we analyzed the correlation between intracellular immunostaining and procollagen propeptides released into the culture medium, as well as the correlation between PINP and PICP. Human osteoblasts were cultured with and without addition of dexamethasone (DEX) at two supraphysiological concentrations, 10(-6) M and 10(-7) M, for 24 and 48 h. Treatment with DEX at 10(-6) M was associated with a significant decrease in the percentage of cells showing intracellular type I procollagen immunoreactivity at 24 and 48 h ( P < 0.05). Similar effects were observed with 10(-7) M DEX. Dexamethasone 10(-6) M and 10(-7) M also induced significant decreases in PINP and PICP values after 24 and 48 h of treatment ( P < 0.05). The decrease in intracellular procollagen immunoreactivity and propeptide secretion was not associated with a reduction in DNA synthesis. A highly significant correlation was observed between the values of PINP and PICP in the culture medium as well as between the values of intracellular immunostaining and PINP and PICP ( P < 0.001). In conclusion, our results suggest that supraphysiological doses of glucocorticoids produce a direct inhibition on osteoblastic function through their effect on type I procollagen synthesis. Immunoperoxidase detection of type I intracellular procollagen as well as the quantification of PINP and PICP in the culture medium are reliable methods of assessing osteoblast function.

Alkaline Phosphatase↗
PubMed2003

Serum osteoprotegerin and its ligand in Paget's disease of bone: relationship to disease activity and effect of treatment with bisphosphonates.

OBJECTIVE: To test the following hypotheses: 1) osteoprotegerin (OPG) and receptor activator of nuclear factor kappa B ligand (RANKL) serum levels in patients with Paget's disease are related to disease activity and are different from those in healthy individuals; 2) interleukin-6 (IL-6), a cytokine that has been shown to have higher levels in Paget's disease, modulates these factors; and 3) the antiresorptive effect of bisphosphonates in Paget's disease of bone may be mediated through these local factors. METHODS: The study group comprised 31 patients with Paget's disease who received 400 mg/day of oral tiludronate for 3 months. Serum levels of OPG, RANKL, IL-6, bone alkaline phosphatase (AP), N-terminal type I procollagen propeptide, urinary N-terminal crosslinking telopeptide of type I collagen, and urinary alpha-C-terminal crosslinking telopeptide of type I collagen were measured at baseline and 1 month after the end of therapy. In addition, the RANKL:OPG ratio was calculated, and disease activity was evaluated at baseline by quantitative bone scintigraphy. RESULTS: Mean baseline OPG values were higher in patients with Paget's disease than in healthy control subjects (P < 0.005), but RANKL and IL-6 values and RANKL:OPG ratios in the 2 groups were similar. OPG concentrations decreased significantly after treatment with tiludronate (P < 0.005), whereas no significant changes were observed in serum RANKL values. No correlation was found between either bone markers or quantitative scintigraphic indices and serum levels of OPG, RANKL, IL-6, and RANKL:OPG ratios. Serum OPG decreased significantly only in those patients with baseline OPG values >4.1 pM/liter. CONCLUSION: Serum OPG increases in Paget's disease and decreases after treatment with tiludronate, especially in patients with the highest OPG values. In contrast, RANKL serum levels and RANKL:OPG ratios are unmodified in patients with Paget's disease. Although serum OPG, RANKL, and IL-6 values were unrelated to disease activity, the increase in OPG may reflect a protective mechanism of the skeleton to compensate for increased bone resorption.

Adult↗
PubMed2002

Quantitative ultrasound calcaneus measurements: normative data and precision in the spanish population.

Quantitative ultrasound (QUS) assessment at the calcaneus has been found to be a safe and reliable method for evaluating skeletal status. In this study we have determined the normative QUS data in the Spanish population for the Sahara Clinical Sonometer (Hologic). Broadband ultrasound attenuation (BUA), speed of sound (SOS), quantitative ultrasound index (QUI) and estimated bone mineral density (BMD) were determined. We also studied the precision in vivo and in vitro. The short-term in vivo precision (CV) was 4.88% for BUA, 0.36% for SOS, 3.45% for QUI and 4.15% for BMD, while in vitro precision was 0.40% for SOS and 2.67% for BUA. Our results are comparable to reference population data previously published in other countries and may serve as reference normative data for both genders in Spain.

Adolescent↗
PubMed2001

Bone mass and mineral metabolism in liver transplant patients treated with FK506 or cyclosporine A.

The purpose of this study was to compare the effects of Cyclosporine A (CyA) and FK506 on bone mass and mineral metabolism in liver transplantation (LT) patients. A prospective study was performed on 18 male patients who underwent LT treated with CyA, and 7 LT patients who received FK506. Bone mineral density (BMD) of the lumbar spine and proximal femur (DPX-L) was measured before and at 6, 12, and 24 months after transplantation. Moreover, intact parathyroid hormone (PTH) and 25-hydroxyvitamin D (25OHD) levels were determined at the same time. The cumulative dose of glucocorticoids was calculated in all patients. At 6 months, lumbar BMD decreased 5.2 +/- 1.2% (P = 0.0005) and 2.9 +/- 2.1% (p = ns) in CyA and FK506 groups, respectively. Lumbar BMD reached baseline values at 1 year in the FK506 group and 2 years after LT in the CyA group. Moreover, significant intergroup differences in femoral neck BMD changes after 2 years of transplant were observed (CyA: -5.2 +/- 1.97 versus FK506: +1.55 +/- 2.2%; P = 0.039). In the first year posttransplant both groups showed a marked increase in PTH and 25OHD levels. The mean cumulative dose of glucocorticoids was higher in the CyA group (CyA group 11.06 +/- 0.46 g versus FK 506 group 6.71 +/- 0.42 g; P < 0.001), and multiple linear regression analysis showed a negative correlation between BMD changes at the lumbar spine and mean cumulative dose of glucocorticoids (P = 0.022). In conclusion, our data suggest that after liver transplantation treatment with FK506 shows a more favorable long-term effect on bone mass evolution than CyA therapy. These differences seem to be associated with the lower dose of glucocorticoids used in the FK506 group.

Absorptiometry, Photon↗
PubMed2001

Bone disease after liver transplantation: a long-term prospective study of bone mass changes, hormonal status and histomorphometric characteristics.

After liver transplantation there is a high incidence of fractures, with important rates of bone loss during the first months. However, the long-term evolution of bone mass and metabolism parameters have been scarcely studied. In order to determine the incidence and risk factors involved in the development of skeletal fractures and to analyze the long-term evolution of bone mass, bone turnover and hormonal status after liver transplantation, a 3-year prospective study was performed in 45 patients following liver transplantation. Serum osteocalcin, parathyroid hormone (PTH), 25-hydroxyvitamin D (25-OH D) and testosterone levels (men), and bone mass at the lumbar spine and femur were measured before and sequentially at different time points during 3 years. Spinal X-rays were obtained during the first year. Histomorphometric analysis of bone biopsies obtained in 24 patients within the first 12 hours after surgery and 6 months after transplantation was performed. Fifteen patients (33%) developed fractures after liver transplantation, and pre-transplant risk factors for fractures were age and low bone mass (odd's ratio for osteoporosis, 95% confidence interval: 5.69, 1.32-24.53). Serum PTH, osteocalcin, 25-OH D, testosterone and creatinine levels increased after transplantation. Moreover, PTH correlated with creatinine and osteocalcin values. Bone mass decreased during the first 6 months and reached baseline values at the lumbar spine the second year, with posterior significant recovery at the femoral neck. Long term evolution of femoral neck BMD correlated with PTH levels. Six months after transplantation bone histomorphometric data showed an increase in bone formation parameters. After liver transplantation there is a high incidence of fractures, specially in elderly patients and those with osteoporosis. Bone mass decreased in the short-term period and improved, initially at the lumbar spine and later at the femur, according to histomorphometric evidences of an increase in bone formation. The increase in creatinine values induces a secondary hyperparathyroidism that influences the changes in femoral bone mass. Treatment of osteoporosis shortly after liver transplantation may be important in the prevention of bone fractures, particularly in patients with low bone mass.

Adult↗
PubMed2001

Usefulness of biochemical markers of bone turnover in assessing response to the treatment of Paget's disease.

The aim of this study was to investigate the usefulness of biochemical markers of bone turnover for monitoring treatment efficacy of Paget's disease of bone, and also to evaluate the utility of biological variation data in choosing the best markers for assessment of biochemical response to therapy. Thirty-eight patients with Paget's disease were included in a prospective study. All received 400 mg/day of oral tiludronate for 3 months. In 31 patients that completed treatment, biochemical markers were measured at baseline and at 1 and 6 months after treatment ended. In serum we determined the levels of total alkaline phosphatase (tAP), bone alkaline phosphatase (bAP), procollagen type I N-terminal propeptide (PINP), and C-terminal telopeptide of type I collagen (sCTx). Urine samples were analyzed for hydroxyproline (Hyp) and for C- and N-terminal telopeptides of type I collagen (CTx and NTx, respectively). Quantitative bone scintigraphy was performed at baseline and at 6 months after discontinuation of therapy. A ratio for monitoring response to treatment was obtained for each marker. This ratio reflected the size of treatment response of the marker in relation to the value of its critical difference. Thus, ratio values of >1 indicated a significant decrease of the marker after therapy. In addition, response to therapy was evaluated according to disease activity. Mean values of all markers of bone turnover decreased significantly after therapy. Serum bAP and PINP and urinary NTx showed the highest percentage reduction (between 58% and 68%). Furthermore, serum bAP and PINP showed the highest ratios for monitoring changes induced by treatment, followed by serum tAP and urinary NTx. sCTx and urinary CTx as well as Hyp showed mean ratios for monitoring changes of <1, indicating a low sensitivity for monitoring treatment. Patients with polyostotic disease showed a continuous decrease in mean values for all markers at 6 months from the end of therapy, whereas, in monostotic patients, there was a trend toward increased levels at this timepoint. In conclusion, serum bAP and PINP were the most sensitive markers for monitoring treatment efficacy in Paget's disease, although serum tAP and urinary NTx were also sensitive markers for monitoring changes. Data on biological variation are useful for assessing actual changes induced by treatment.

Adult↗
PubMed2001

Collagen type Ialpha1 and vitamin D receptor gene polymorphisms and bone mass in primary biliary cirrhosis.

The potential influence of two gene polymorphisms, vitamin D receptor gene (VDR) and the gene encoding collagen type Ialpha1 (COLIA1) Sp1 polymorphisms, in the reduced bone mass observed in patients with primary biliary cirrhosis (PBC) was assessed in 61 women with PBC (age, 54.1 +/- 1.1 years) by restriction enzyme digestion of polymerase chain reaction (PCR)-amplified DNA extracted from whole blood. Bone mineral density (BMD) of the lumbar spine (L2-L4) and proximal femur were measured by X-ray absorptiometry. The severity of liver disease and cholestasis was also evaluated, and changes in BMD were calculated after a mean period of 2.9 +/- 0.3 years in 41 patients. Sixteen patients (26 %) had the BB, 20 the bb (33 %), and 25 Bb (41%) VDR genotypes. There were no significant baseline BMD differences among the 3 VDR genotypes. Forty-one patients (68%) had the SS, 16 the Ss (27%), and 3 the ss (5%) COLIA1 genotypes. The baseline lumbar BMD was significantly lower in patients having the s allele than in the homozygote SS patients (Z-score, -0.76 +/- 0.24 vs. -0.10 +/- 0.17, P =.02). The severity of cholestasis was not related to the VDR or COLIA1 1 polymorphisms. Lumbar bone loss was independent of VDR and COLIA1 genotypes, but it was associated with cholestasis. In conclusion, the COLIA1 but not VDR polymorphism is a genetic marker of peak bone mass in patients with PBC, although the severity of cholestasis is the main factor for osteoporosis since it is associated with the rate of bone loss.

Bone Density↗
PubMed2000

Cyclical etidronate versus sodium fluoride in established postmenopausal osteoporosis: a randomized 3 year trial.

To compare the effects of sodium fluoride and etidronate in severe postmenopausal osteoporosis, we conducted a 3 year, prospective, trial in 118 postmenopausal osteoporotic women with at least one vertebral fracture, who were randomly assigned to receive sodium fluoride (25 mg twice daily, as enteric-coated tablets) plus calcium (1000 mg/day) or intermittent etidronate (400 mg/day for 14 days) followed by calcium (1000 mg/day for 76 days). Lateral spine X-ray films and dual-energy X-ray absorptiometry (DXA) measurements of the lumbar spine and proximal femur were performed at enrollment and yearly. Nonvertebral fractures were recorded every 6 months. Thirty-one women in the fluoride group and 47 in the etidronate group completed the trial. At 36 months, the mean change from baseline of the lumbar bone density in the fluoride group was 8.5 +/- 2.04% (p = 0.001) and in the etidronate group was of 3.6 +/- 0. 84% (p < 0.001). The changes in the fluoride group were significantly higher than in the etidronate group (p = 0.01). Both groups showed nonsignificant changes in femoral neck bone density. There was no significant difference between groups in the cumulative proportion of women with new vertebral fractures, with an incidence in the fluoride group of 16% vs. 17% in the etidronate group. However, the number of new vertebral fractures was significantly lower in the fluoride group (6 fractures) than in the etidronate group (19 fractures) (p = 0.05). The number of patients with nonvertebral fractures was similar in both groups. A high incidence of side effects, mainly gastrointestinal symptoms and lower extremity pain syndrome, was observed in the fluoride group. Etidronate was well tolerated. We conclude that, in women with severe osteoporosis, although sodium fluoride is more favorable than cyclical etidronate for increasing lumbar bone mass, no differences were observed in the incidence of fractures.

Administration, Oral↗
PubMed2000

Mutations in the gene encoding the latency-associated peptide of TGF-beta 1 cause Camurati-Engelmann disease.

Camurati-Engelmann disease (CED; MIM 131300), or progressive diaphyseal dysplasia, is a rare, sclerosing bone dysplasia inherited in an autosomal dominant manner. Recently, the gene causing CED has been assigned to the chromosomal region 19q13 (refs 1-3). Because this region contains the gene encoding transforming growth factor-beta 1 (TGFB1), an important mediator of bone remodelling, we evaluated TGFB1 as a candidate gene for causing CED.

Bone Remodeling↗
PubMed2000

Collagen type Ialpha1 gene polymorphism in idiopathic osteoporosis in men.

OBJECTIVE: To analyse the distribution of polymorphism of the collagen type Ialpha1 gene (COL1A1) and its relationship with bone metabolism and bone turnover in men with idiopathic osteoporosis. METHODS: A total of 35 male patients with idiopathic osteoporosis, aged 50.4 +/- 10.3 yr, and 60 healthy males (controls), aged 47 +/- 17 yr, were included in the study. Serum osteocalcin, 25-hydroxyvitamin D and parathyroid hormone were determined in all patients. The COL1A1 Sp1 genotypes (SS, SS:, ss) were assessed by restriction enzyme digestion (BAL:1) of DNA amplified by the polymerase chain reaction. RESULTS: Patients with idiopathic osteoporosis had a higher frequency of the s allele than men in the control group (29 vs 11%, P: = 0.003) and a higher frequency of the SS: genotype (patients, 48% SS, 46% SS:, 6% ss; controls, 80% SS, 18% SS:, 2% ss; P: = 0.003). No significant differences between genotypes were observed in serum concentrations of osteocalcin, vitamin D or parathyroid hormone among either the patients or the controls. CONCLUSION: This study suggests that, in men with idiopathic osteoporosis, there is a high prevalence of the s allele and the SS: genotype that is unrelated to other parameters of bone metabolism.

Adult↗
PubMed2000

Localisation of the gene causing diaphyseal dysplasia Camurati-Engelmann to chromosome 19q13.

Camurati-Engelmann disease, progressive diaphyseal dysplasia, or diaphyseal dysplasia Camurati-Engelmann is a rare, autosomal dominantly inherited bone disease, characterised by progressive cortical expansion and sclerosis mainly affecting the diaphyses of the long bones associated with cranial hyperostosis. The main clinical features are severe pain in the legs, muscular weakness, and a waddling gait. The underlying cause of this condition remains unknown. In order to localise the disease causing gene, we performed a linkage study in a large Jewish-Iraqi family with 18 affected subjects in four generations. A genome wide search with highly polymorphic markers showed linkage with several markers at chromosome 19q13. A maximum lod score of 4.9 (theta=0) was obtained with markers D19S425 (58.7 cM, 19q13.1) and D19S900 (67.1 cM, 19q13. 2). The disease causing gene is located in a candidate region of approximately 32 cM, flanked by markers D19S868 (55.9 cM, 19q13.1) and D19S571 (87.7 cM, 19q13.4).

Camurati-Engelmann Syndrome↗
PubMed1999

High bilirubin levels interfere with serum tartrate-resistant acid phosphatase determination: relevance as a marker of bone resorption in jaundiced patients.

Serum tartrate-resistant acid phosphatase (TRAcP) activity is considered to be a biochemical marker of bone resorption. Recently, a lack of specificity of collagen-related markers for assessing bone turnover has been observed in patients with chronic liver disease. Thus, it could be of great interest to determine serum TRAcP activity in such patients. However, nonspecificity of the analytical reaction could occur when hemolyzed, lipemic, or icteric specimens are analyzed. Therefore, we have studied the interference caused by bilirubin in the measurement of serum TRAcP activity using the Hillmann method. The interference was assessed in two pools of serum containing different bilirubin concentrations but with similar total AcP levels. Mixing proportional parts of the two pools, 10 samples were also obtained. Serum activities of total AcP and TRAcP, and the concentration of bilirubin were measured in the 10 samples. Both the actual and the expected values obtained by theoretical calculations were compared. Serum bilirubin values of 2.4 mg/dl showed a negative interference of 15% in the determination of serum TRAcP activity, whereas values of bilirubin higher than 10 mg/dl interfered totally with the measurement of serum TRAcP. Bilirubin did not interfere with the total AcP determination. This study clearly shows the interference of bilirubin in the determination of serum TRAcP. This finding should be considered when bone metabolism disorders are evaluated in jaundiced patients.

Acid Phosphatase↗