Usefulness of Bone Metabolic Markers in the Diagnosis of Bone Metastasis from Lung Cancer

Bone metastasis is common in lung cancer patient and the diagnosis of bone metastasis is usually made by using imaging techniques, especially bone scintigraphy. However, the diagnostic yield from bone scintigraphy is limited. The aim of this study is to assess the clinical usefulness of urinary pyridinoline cross-linked N-telopeptides of Type I collagen (NTx), urinary deoxypyridinoline (DPD), and serum alkaline phosphatase (ALP) in the assessment of bone metastasis in patients with lung cancer. Urinary NTx, DPD, and serum ALP were measured in 151 lung cancer patients (33 with and 118 without bone metastasis). Lung cancer patients with bone metastasis had a higher urinary excretion of NTx and DPD, and a higher serum ALP than those without bone metastasis. NTx had a better receiver operating characteristic (ROC) curve than DPD and ALP, since the areas under the ROC curve were 0.82, 0.79, and 0.71, respectively. Although correlation coefficients among NTx, DPD and ALP were significantly positive (p < 0.005), the strongest relationship was appeared between NTx and DPD (R=0.616). In conclusion, our results showed the utility of the new bone markers in detecting bone metastasis and suggested that measurement of urinary NTx was valid diagnostic method of bone metastasis from lung cancer.

Determinants of One-year Response of Lumbar Bone Mineral Density to Alendronate Treatment in Elderly Japanese Women with Osteoporosis

The purpose of this study was to determine factors that could predict the one-year response of the lumbar bone mineral density (BMD) to alendronate treatment in elderly Japanese women with osteoporosis. Eighty-five postmenopausal women with osteoporosis, all of whom were between 55-88 years of age, were treated with alendronate (5 mg daily) for 12 months. Serum calcium, phosphorus, and alkaline phosphatase (ALP) and urinary NTX levels were measured at the baseline and 6 months, and lumbar (L1-L4) BMD was measured by dual energy X-ray absorptiometry at the baseline and 12 months. Multiple regression analysis was used to determine factors that were correlated with the percent change in lumbar BMD at 12 months. Lumbar BMD increased by 8.1 % at 12 months with a reduction in the urinary NTX level by 51.0 % at 6 months. Baseline lumbar BMD (R2=0.226, p< 0.0001) and percent changes in serum ALP and urinary NTX levels (R2=0.044, p< 0.05 and R2=0.103, p< 0.001, respectively) had a negative correlation with the percent change in lumbar BMD at month 12, while the baseline number of prevalent vertebral fractures (R2=0.163, p< 0.001), serum ALP level, and urinary NTX level (R2=0.074, p< 0.05 and R2=0.160, p< 0.001, respectively) had a positive correlation with it. However, baseline age, height, body weight, body mass index, years since menopause, serum calcium and phosphorus levels, and percent changes in serum calcium and phosphorus levels at 6 months did not have any significant correlation with the percent change in lumbar BMD at 12 months. These results suggest that lumbar BMD was more responsive to one-year of alendronate treatment in elderly osteoporotic Japanese women with lower lumbar BMD, more prevalent vertebral fractures, and higher bone turnover, who showed a greater decrease in bone turnover at 6 months, regardless of age, years since menopause, and physique. Alendronate may be efficacious in elderly Japanese women with evident osteoporosis that is associated with high bone turnover, and the percent changes in serum ALP and urinary NTX levels at 6 months could predict the one-year response of lumbar BMD to alendronate treatment.

The Effects of Sulphasalazine on Urinary Excretion of the Hydroxypyridinium Crosslinks of Collagen in Patients with Rheumatoid Arthritis

Secondary osteoporosis is a feature of rheumatoid arthritis (RA). In recent years, several attempts have been made to develop specific markers for monitoring connective tissue metabolism in arthritic diseases. Our purpose, in this study was to assess pyridinium crosslinks (PYD and DPYD) excretion in relation to the activity of RA (changes related to sulphasalazine treatment). Fourty premenopausal female patients with active RA (mean age; 36.0 7.2 years), 20 postmenopausal women with active RA (mean age; 60.0 6.8 years), 23 postmenopausal women with OA (mean age; 56.1 6.6 years) and 17 premenopausal healthy subjects (mean age; 28.3 4.28 years) were enrolled in our study. All of the 40 premenopausal female patients with active RA were given sulphasalazine. The mean follow up period for these patients was 10.3 1.1 months. In all of these patients, urine samples were collected both in the active and in the inactive periods. Urine PYD and DPYD levels were measured by ELISA. Urine PYD levels were significantly higher in the active period (14.01 3.16 nmol/mmol cr) than in the inactive (8.25 4.23 nmol/mmol cr) period in patients with premenopausal RA (p 0.05). Urine PYD levels were significantly high in postmenopausal active RA patients (19.06 3.26 nmol/mmol cr) compared to premenopausal active and ind inactive, postmenopausal inactive RA patients, osteoarthritis and healthy controls. Urine DPYD excretion was similar in patients with premenopausal RA in the active (7.46 2.13 nmol/mmol cr) and inactive periods (5.08 0.87 nmol/mmol cr) (p 0.05). In active premenopausal RA patients, a correlation was found between PYD excretion and RAI, ESR, CRP and functional capacity (r=0.5729 p 0.01, r=0.5953 p 0.01, r=0.6125 p 0.01 and r=0.6232, p 0.01 respectively). But in the inactive period, no such correlation was was evident. In disease activity parameters did not correlate with DPYD excretion in either the active or the inactive period. As a result, urine PYD excretion was significantly high in patients with active RA. During sulphasalazine treatment, urine PYD levels decreased. This is attributed to improvement in bone destruction.

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

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.