Serum leptin concentration, bone mineral density and bone biochemical markers in a sample of Egyptian women: a possible relationship

Adipocytokines secreted by adipose tissue participate in bone metabolism; leptin is one of the circulating peptides secreted by adipose tissue. To determine the serum levels of leptin in obese postmenopausal women in order to correlate these levels with bone mineral density and bone biochemical markers to find out the role of leptin in bone metabolism. This was a cross-sectional study which included 37 obese postmenopausal women with body mass index [BMI] >30 kg/m[2]. Thirty-seven lean postmenopausal women with BMI <25 kg/m[2] were included as control group. Serum leptin, bone specific alkaline phosphatase [BAP], osteocalcin and urine C-telopeptide of type collagen [CTx] were assayed. Bone mineral density [BMD] and soft tissue body composition were determined using dual energy X-ray absorptiometry. There was a statistically highly significant increase in serum leptin levels in obese than lean postmenopausal women [p < 0.0001]. There was a highly significant decrease in BMD of spine and hip [p < 0.0001] in obese than lean postmenopausal women. After adjustment of fat mass, a highly significant positive correlation was found between leptin and BAP [r = 0.562, p < 0.0001], a significant positive correlation was found between leptin and each of osteocalcin and urine CTx [r = 0.423, 0.456 respectively, p < 0.05] but there was no statistically significant correlation between leptin and BMD. Our results support the hypothesis that leptin can act directly or indirectly on bone remodeling by modulating osteoblast activities. Leptin was found to be associated with decreased BMD at different sites of the body and was positively correlated with bone biochemical markers. However, leptin did not come out to be an independent predictor of BMD whereas; fat mass was found to have a role in bone metabolism in postmenopausal women. However these comparisons of a single measurement of leptin with BMD, does not exclude possible long-term strong relationships between leptin and BMD

High dietary calcium intake decreases bone mobilization during pregnancy in humans / Alto consumo de calcio en la dieta, disminuye la movilización ósea durante el embarazo en seres humanos

Calcium metabolism of the mother is modified during pregnancy because of the mineralization of the fetus skeleton. OBJECTIVE: To evaluate the association of calcium intake and bone demineralization during pregnancy. MATERIAL AND METHODS: At each trimester of pregnancy a validated food frequency intake questionnaire was administered to assess individual daily calcium intake in a cohort of 206 pregnant women, residents of Mexico City. Samples of urine were collected to measure levels of the cross-linked N-telopeptide of type I collagen (NTx), which is a biomarker of bone resorption. The association between calcium ingestion and bone resorption was analyzed using random effects models; non-linear associations were explored using generalized additive models. RESULTS: Progressive increases in NTx levels were observed during pregnancy; with mean and standard deviation (SD) values during the first, second and third trimester of 76.50 (SD=38), 101.02 (SD=48.86) and 144.83 (SD=61.33) nmol BCE/mmol creatinine, respectively. Higher dietary calcium intake was associated with lower bone resorption (β=-0.015; p<0.05). The association between age and NTx showed a non-linear trend with an inflexion point around 33 years: increase in maternal age below that point was associated with a decrease in bone resorption, while in older women the increase in age was associated with an increased resorption. CONCLUSIONS: Our results suggest that calcium ingestion, specifically from dairy products, reduces bone resorption during pregnancy. For each 300mg (a glass of milk) of calcium intake there is an estimated reduction in NTx level of 4.8 nmol BCE/mmol of creatinine (p<0.05).

El metabolismo de calcio es modificado durante el embarazo debido a la mineralización del esqueleto del feto. OBJETIVO: Evaluar la asociación entre la ingesta de calcio y la desmineralización ósea durante el embarazo. MATERIAL Y MÉTODOS: Se administró un Cuestionario de Frecuencia de Consumo de alimentos en cada trimestre del embarazo para evaluar el consumo de calcio en una cohorte de 206 mujeres residentes de la Ciudad de México. Se recolectaron muestras de orina para medir los niveles de N-telopéptido de colágeno tipo I (NTx), biomarcador de resorción. Se hicieron modelos de efectos aleatorios; se estudiaron asociaciones no lineales utilizando modelos aditivos generalizados. RESULTADOS: Se observó aumento progresivo en los niveles de NTx durante el embarazo. El mayor consumo de calcio se asoció con una menor resorción ósea (β=- 0.015, p<0,05). CONCLUSIONES: Los resultados sugieren que la ingestión de calcio reduce la resorción ósea en el embarazo.

Role of urinary biomarkers in the diagnosis of congenital upper urinary tract obstruction

Congenital obstructive uropathy constitutes a significant cause of morbidity in children. Currently, there is no reference standard for the diagnosis of renal obstruction in children. The con-invasive measurement of biomarkers in voided urine has considerable appeal as a potential application in children with congenital obstructive nephropathy. The aim of the present review is to explore the current role of biomarkers in the diagnosis and follow-up of obstructive uropathy in children. The literature data [PubMed] was scarched from inception to May 2007, regarding the role of urinary biomarkers in the diagnosis and follow-up of children with congenital obstructive uropathy. The review included 23 experimental and 33 prospective controlled clinical studies. Several cytokines, peptides, enzymes and microproteins were indentified as major contributors to, or as biomarkers ensuing from obstruction-induced renal fibrosis and apoptosis. The most important biomarkers were transforming growth factor-beta1 [TGF- beta1], epidermal growth factor [EGF], endothelin-1 [ET-1], urinary tubular enzymes [N-acetyI- beta-D-glucosaminidase [NAG], gamma-glutamyI transferase [GGT] and alkaline phosphatase [ALP]], and microproteins [beta2-microglobulin [beta2M], microalbumin [M.AIb] and micrototal protein [M.TP]. All biomarkers showed different degrees of success but the most promising markers were TGF- betaI, ET-I and a panel of tubular enzymes. These biomarkers showed a sensitivity of 74.3% to 100%, a specifity of 80% to 90% and an overall accuracy of 81.5% to 94% in the diagnosis of congenital obstructive uropathy in children. Moreover, come of the markers were valuable in differentiation between dilated non-obstructed kidneys qualifying for conservative management and obstructed kidneys requiring surgical correction. Some studies demonstrated that urinaty biomarkers are helfpul in evaluating the success of treatment in children with congenital renal obstruction. Some limitations of the previous studies include lack of controls and small sample size. Larger controlled studies are necessary to confirm the clinical usefulness of biomarkers in the diagnosis and follow-up of children with congenital obstructive uropathy. Urinary biomarkers are a promising tool that could be used as a non-invasive assessment of congenital renal obstruction in children

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.

Serum beta[2]-microglobulin concentration correlates with urinary concentrations of type 1 collagen cross- linked N-telopeptides and deoxypyridinoline in rheumatoid arthritis

Determination of serum BETA[2]-microglobulin concentration, an invasive procedure, has been advocated for monitoring patients' response to treatment in rheumatoid arthritis. The object of this study was to find out if serum BETA[2]-microglobulin concentration correlated with urinary excretions of type 1 collagen cross-linked N-telopeptides [NTx] and deoxypyridinoline [Pyrilinks-D] in rheumatoid arthritis [RA]. Using chemiluminiscent assay, serum BETA[2]-microglobulin concentrations were estimated in 25 female patients with active RA, 25 female with inactive disease, and 25 age-matched healthy female controls. Concentrations of NTx and Pyrilinks-D were also determined by immunoabsorbent assays in spot urine samples from these subject groups. The serum concentration of BETA[2]-microglobulin in patients with RA [7.45 +/- + +/- 2.10 mg/L] was significantly higher [P<0.001] than the concentrations in patients with inactive disease [3.33 +/- 0.76 mg/L], or than in normal healthy controls [2.74 +/- 0.52 mg/L]. Similarly, in patients with active RA, the spot urinary concentrations of NTx [123.08 +/- 25.53 nmol BCE/mmol creatinine] and Pyrilinks-D [15.08 +/- 3.29 nmol/mmol creatinine] were significantly higher [P<0.01] than those in patients with inactive disease [58.42 +/- 12.65 nmol BCE/mmol creatinine and 10.10 +/- 2.43 nmol/mmol creatinine, respectively]. In patients with active RA, serum concentration of BETA[2]-microglobulin correlated positively with spot urinary NTx concentrations [r=0.9910, P=0.0001], and Pyrilinks-D concentration [r=0.6177, P=0.001]. In patients with active RA, the spot urinary concentrations of NTx and Pyrilinks-D correlated positively with serum BETA[2]-microglobulin. Therefore, the estimations of these urinary markers may take the place of serum BETA[2]-microglobulin estimation in monitoring the patient's response to treatment in rheumatoid arthritis

El proceso digestivo y la regulación de la función excretora renal: pepsanuria y procininas inhibidoras de la acción diurética del péptido natriurético auricular / Digestive process and regulation of renal excretory function: pepsanurin and prokinin inhibitors of diuretic action of atrial natriuretic peptide

In order to clarify the blunting effect of peptides released by pepsin from blood plasma on ANP diuretic action, 2 prokinins designated PU-16 were tested. Both of them were able to inhibit in nanomolar doses the diuretic-saluretic action of 0.5 ug i.v. bolus of ANP given to anesthetized rats either by intravenous route or introduced in the duodenal lumen. PU-16 in doses of 0.5 ug and 1 ug were able to reduce in 72 and 96.5 per cent respectively the natriuresis induced bu 0.5 ug intravenous bolus of ANP. The data support the hypothesis that prokinins liberated in the digestive tract, could be physiological factors involved in hydrosaline homeostasis, moderating the ANP mediated increase of water, Na and K excretion during digestion