[Serum beta-type I collagen carboxyterminal telopeptide (beta-CTXs) and bone involvement in chronic renal failure]. / Telopéptido carboxilo terminal del colágeno tipo I (beta-CTX) sérico y compromiso oseo en la insuficiencia renal crónica.

An increase in parathyroid hormone (PTH) levels in chronic renal failure (CRF) induces bone abnormalities known as renal osteodystrophy (ROD). The aim of the present study was to evaluate alternative biochemical methods to bone biopsy, to evaluate changes in bone remodeling in renal patients. Intact PTH (iPTH) and bone markers were measured in 43 predialysis (PD), 49 hemodialysis patients (HD) and 185 controls. betaCTXs, bone alkaline phosphatase (bAL), iPTH were higher and creatinine clearance (Ccr) was lower in PD and HD compared with controls (p < 0.0001). In both renal groups, a positive correlation was found between iPTH and both betaCTXs and bAL (p < 0.0001) and between betaCTXs and bAL (p < 0.002). PD patients with Ccr < 40 ml/min had higher iPTH, bAL and betaCTXs (p<0.004, p<0.05 and p<0.001, respectively) than patients with Ccr > 40 ml/min. betaCTXs (p < 0.05) in PD and betaCTXs and bAL in HD patients were higher than controls, even when iPTH was within normal range (< 65 pg/ml). Patients with severe secondary hyperparathyroidism showed higher bone markers than patients with normal or moderately increased iPTH (p < 0.001). These results suggest that even when there is no increase in iPTH, bone remodeling increases (possibly due to other factors) exhibiting higher bone resorption, and betaCTXs would seem to be an adequate non-invasive tool to assess early bone changes in CRF and prevent future fractures. Bone marker measurements in ROD would be useful to identify patients who may require bone biopsy. However, further studies comparing both methods must be performed before replacing bone biopsy with serum beta-CTX.

Effect of puberty on the relationship between bone markers of turnover and bone mineral density in Turner's syndrome.

It has been suggested that the appropriate timing of puberty is necessary for normal bone mineral acquisition which may not be achieved amongst patients with Turner's syndrome (TS). The aim of this study was to assess bone mineral density (BMD) and bone turnover in 34 patients with TS (age range 2.2-39.0 years). The areal BMD (aBMD) was determined by dual-energy X-ray absorptiometry, and the volumetric BMD was calculated. Blood and second voided urine samples were taken the morning after an overnight fast for evaluation of the biochemical markers of bone turnover: bone-specific alkaline phosphatase (BAP) and N-telopeptides of type I collagen (NTX), respectively. Both were determined by enzyme-linked immunosorbent assay. The patients were divided into three groups: group 1 (n = 13; prepubertal; age range 2.2-19.0 years), group 2 (n = 10; teenagers; age range 12.4-19.0 years), and group 3 (n = 11; adults; chronological age >20 years). They were also grouped by breast development according to Tanner stage into B1 (n = 12), B2-3 (n = 9), and B4-5 (n = 13). The aBMD was significantly lower in group 1 and was higher at Tanner stages 4 and 5 as compared with patients at Tanner stage 1. The bone turnover markers were significantly higher in group 1 (NTX: p = 0.002; BAP: p = 0.0005) and declined, as puberty progressed. A negative correlation was observed between aBMD and biochemical bone markers at the lumbar spine (NTX: r = -0.54, p = 0.05; BAP: r = -0.44, p = 0.01) and in the whole body (NTX: r = -0.60, p = 0.0008; BAP: r = -0.19, p = 0.002). We conclude that the negative relationships between aBMD and biochemical markers suggest a high bone turnover, mainly in prepubertal patients and that the results observed in relation to aBMD and puberty are imputed to the delayed puberty which occurs amongst TS patients.

Effect of intravenous pamidronate on bone markers and local bone mineral density in fibrous dysplasia.

Bisphosphonates have proven to be effective in patients with fibrous dysplasia of the bone (FD) as shown by their effect on bone pain, markers of bone turnover, or radiological changes. The aim of this study was to evaluate the usefulness of measuring bone mineral density (BMD) of affected bones to assess the efficacy of bisphosphonate treatment. Seven patients (mean age 26 years) received courses of 180 mg intravenous infusion of pamidronate every 6 months (60 mg/day during 3 days). Clinical symptoms, serum alkaline phosphatase, and urinary C-terminal cross-linking telopeptide of type I collagen were assessed every 3 months. BMD of total skeleton and X-rays of FD areas (FDa) were performed at baseline and at 12 months. BMD of FDa was compared with the contralateral side (CL) using the region of interest program on the total skeleton scan. BMD of total skeleton was normal at baseline. Average BMD of FDa was -11.4% compared with CL, a significantly greater difference than that observed between the left and right sides in healthy controls, -0.7% (P < 0.02). At 12 months bone pain diminished in all patients. Bone turnover markers decreased. Mean total skeleton BMD increased 3.3% (P < 0.02). Subregions of the total skeleton scan presenting FD lesions augmented: arms +9.6% (P < 0.02), legs +4.2%, and pelvis +3.5% (P < 0.05). The increase in mean BMD of FDa was +6.8% compared with +2.6% in CL. No changes were observed on the X-ray. These results indicate that simultaneous determination of markers of bone turnover and BMD of FDa is useful in short-term follow-up to determine the efficacy of intravenous pamidronate.

Relationship between serum vitamin d status and clinical manifestations of primary hyperparathyroidism.

OBJECTIVE: To compare vitamin D status represented by serum 25-hydroxyvitamin D (25-OHD) levels in a group of patients with primary hyperparathyroidism, stratified by clinical manifestations. METHODS: We studied 22 patients (18 women and 4 men) with primary hyperparathyroidism--5 patients with severe osteitis fibrosa cystica, 10 symptomatic patients with active renal stone disease without overt bone disease, and 7 asymptomatic patients. Bone mineral density (BMD) measurements (T-scores) were done at the lumbar spine, femoral neck, and distal radius, and laboratory data for the three subgroups were analyzed. RESULTS: Although considerably younger than the asymptomatic group, patients with osteitis fibrosa had significantly lower mean serum 25-OHD levels (16.7 +/- 1.1 ng/mL versus 29.9 +/- 2.9 ng/mL; P = 0.003). Moreover, patients with osteitis fibrosa had significantly lower BMD in comparison with patients who had renal stone disease as well as asymptomatic patients for all sites measured. Serum parathyroid hormone levels were significantly higher in patients with osteitis fibrosa than in asymptomatic patients (1,352.8 +/- 297.2 pg/mL versus 145.0 +/- 43.7 pg/mL; P<0.02) as well as in comparison with patients who had renal stone disease (P<0.02). Patients with osteitis fibrosa had urinary N-telopeptide levels that were significantly higher than those in asymptomatic patients (501.5 +/- 201.7 versus 51.3 +/- 6.4 nmol/mmol creatinine; P = 0.02) and those in patients with renal stone disease (P = 0.01). CONCLUSION: The findings in this study demonstrate that vitamin D deficiency or insufficiency may contribute to disease severity in primary hyperparathyroidism.

Utilidad clínica de los marcadores de formación y resorción ósea / Clinical utility of biochemical merkers of bone turnover

Se evaluó el recambio óseo en distintas situaciones fisiológicas y patológicas que alteran el metabolismo óseo. A tal fin se analizó la utilidad de un marcador bioquímico de formación como la fosfatasa alcalina ósea (FAO) y uno de resorción ósea, como la fracción carboxilo terminal del telopéptido del colágeno tipo I (CTX). En la población adulta normal los hombres y mujeres premenopáusicas no presentaron diferencias significativas. Contrariamente, las mujeres posmenopáusicas tuvieron niveles de FAO y CTX significativamente mayores que éstos dos grupos (p<0,01). Entre el segundo y tercer trimestre de embarazo ambos marcadores aumentaron significativamente (FAO: p<0,009 y CTX: p<0,0003). Mientras la FAO no varió en posmenopáusicas ante el tratamiento hormonal de reemplazo (THR), el CTX disminuyó significativamente (p<0,001). Mujeres posmenopáusicas osteopénicas y osteoporóticas presentaron niveles de CTX y FAO significativamente menores luego de THR o tratamiento con bifosfonatos respecto de las no tratadas (FAO: p<0,05 y 0,03 y CTX: p<0,02 y 0,0001 respectivamente). Pacientes con insuficiencia renal en hemodiálisis presentaron niveles séricos de FAO y CTX significativamente mayores que los controles sanos por edad y sexo (p<0,05). Pacientes hipertiroideos, pagéticos o con patología ósea secundaria a enfermedad celíaca disminuyeron los niveles de FAO y CTX en forma significativa (p<0,05) luego del tratamiento específico. Como se esperaba, el marcador de resorción respondió más rápidamente a cambios en el remodelamiento óseo. Si le sumamos la alta especificidad y sensibilidad del CTX, se sugiere que éste marcador sería de utilidad en todas aquellas patologías en que se sospeche alteración o se quiera determinar el grado del remodelamiento óseo (AU)

Utilidad clínica de los marcadores de formación y resorción ósea / Clinical utility of biochemical merkers of bone turnover

Se evaluó el recambio óseo en distintas situaciones fisiológicas y patológicas que alteran el metabolismo óseo. A tal fin se analizó la utilidad de un marcador bioquímico de formación como la fosfatasa alcalina ósea (FAO) y uno de resorción ósea, como la fracción carboxilo terminal del telopéptido del colágeno tipo I (CTX). En la población adulta normal los hombres y mujeres premenopáusicas no presentaron diferencias significativas. Contrariamente, las mujeres posmenopáusicas tuvieron niveles de FAO y CTX significativamente mayores que éstos dos grupos (p<0,01). Entre el segundo y tercer trimestre de embarazo ambos marcadores aumentaron significativamente (FAO: p<0,009 y CTX: p<0,0003). Mientras la FAO no varió en posmenopáusicas ante el tratamiento hormonal de reemplazo (THR), el CTX disminuyó significativamente (p<0,001). Mujeres posmenopáusicas osteopénicas y osteoporóticas presentaron niveles de CTX y FAO significativamente menores luego de THR o tratamiento con bifosfonatos respecto de las no tratadas (FAO: p<0,05 y 0,03 y CTX: p<0,02 y 0,0001 respectivamente). Pacientes con insuficiencia renal en hemodiálisis presentaron niveles séricos de FAO y CTX significativamente mayores que los controles sanos por edad y sexo (p<0,05). Pacientes hipertiroideos, pagéticos o con patología ósea secundaria a enfermedad celíaca disminuyeron los niveles de FAO y CTX en forma significativa (p<0,05) luego del tratamiento específico. Como se esperaba, el marcador de resorción respondió más rápidamente a cambios en el remodelamiento óseo. Si le sumamos la alta especificidad y sensibilidad del CTX, se sugiere que éste marcador sería de utilidad en todas aquellas patologías en que se sospeche alteración o se quiera determinar el grado del remodelamiento óseo

Short-term therapy with oral olpadronate in active Paget's disease of bone.

One of the aims of the treatment of Paget's disease with bisphosphonates should be the normalization of the activity of the disease with the shortest possible exposure to the drug. Olpadronate (OPD) is a new bisphosphonate characterized by the dimethylation of the amino group, its potency is near to alendronate, and more soluble in the digestive media than other aminobisphosphonates. We treated 46 patients (28 men and 18 women, mean age 70 years) with active Paget's disease with oral OPD, 200 mg/day for 12 +/- 2 days, except 2 patients who received 400 mg/day. Eight patients had never been treated before, and 38 had previously received antiosteolytic drugs. The period without treatment prior to OPD was (X +/- 1 SD) 14 +/- 12 months. Baseline bone alkaline phosphatase (BALP) (levels fell from (X +/- 1 SD) 54.0 +/- 62.7 IU/ml (range 22-396) to a lowest mean value of 16.2 +/- 6.4 IU/ml (range 8-45) (normal range 5-21 IU/ml). Forty patients normalized BALP values, in most of the cases within the first 3 months after OPD treatment. Two patients showed partial response (> 50% decrease from baseline), three patients presented poor response (< 50% decrease from baseline), and one patient did not respond at all. Two patients complained of gastric discomfort, and one patient had diarrhea, which disappeared after discontinuation of the drug. Follow-up was carried out on 36 patients; 22 patients are still in remission, with an average length of 9.0 +/- 2.6 months. Fourteen patients experienced relapse after 9 +/- 2 months remission. In conclusion, a 12-day treatment with 200 mg/day of OPD proved to be a very effective and well tolerated therapy of Paget's disease and induced biochemical remissions in the vast majority of patients, even in those with very active disease.

O papel dos marcadores bioquímicos do metabolismo ósseo no diagnóstico e seguimento laboratorial das doenças ósteo-metabólicas / The role of bone biochemical markers in the diagnosis and follow-up bone metabolic diseases

Os novos marcadores bioquímicos do metabolismo ósseo säo um novo recurso laboratorial com aplicaçöes cada vez mais amplas. Podem ser divididos em dois grupos principais: os de formaçäo óssea, representados principalmente pela fosfatase alcalina óssea e pela osteocalcina, e os de reabsorçäo óssea, representados basicamente pelos métodos que avaliam a excreçäo de fragmentos específicos produzidos pela hidrólise do colágeno tipo 1 (piridinolina, deoxipiridinolina, NTX, CTX). Suas aplicaçöes práticas se estendem desde a avaliaçäo da resposta terapêutica obtida pela introduçäo de terapêutica específica.