Serum Levels Of Biochemical Markers Research Articles

The natural history of untreated prostate MRI lesions in an active surveillance prostate cancer population – 260 patient-years

Background: Hyperparathyriodism is associated with an increase risk of developing renal calculi. The aim of this study was to quantify the incidence of renal calculi in patients undergoing parathyroidectomy. Method: A retrospective study of 38 patients that have undergone parathyroidectomy between 2002 and 2009 was performed. Patient age, mode of discovery, serum levels of biochemical markers and types of renal imaging were evaluated. Results: 38 patients (7 male), median age 59 (range 31-79) were reviewed. All patients were diagnosed with primary hyperparathyroidism incidentally. Histology of parathyroids showed 9 nodular hyperplasias and 29 parathyroid adenomas. Median adjusted calcium is 2.87 (range 2.62 5.3), median parathyroid hormone level is 15.2 (range 6.6 114.8). 6 (15%) had a 24 hour urine calcium level test and 4 (10%) had renal stone. 13 (31%) out of 18 patients (USS1⁄45, CT KUB1⁄43, IVU1⁄43, abdominal x-ray1⁄42) who have undergone renal imaging had renal calculi. 6 (16%) had renal calculi detected before confirmatory blood test for hyperparathyroidism. Conclusion: Ultrasound scan of the kidneys could be recommended for all parathyroidectomy patients. A prospective study with 24 hours urinary metabolic work upmight help to answer the relationship between primary hyperparthyroidism and urolithiasis.

SUSTAINED-RELEASE RECOMBINANT HUMAN GROWTH HORMONE IMPROVES BODY COMPOSITION AND QUALITY OF LIFE IN ADULTS WITH SOMATOPAUSE

SUSTAINED-RELEASE RECOMBINANT HUMAN GROWTH HORMONE IMPROVES BODY COMPOSITION AND QUALITY OF LIFE IN ADULTS WITH SOMATOPAUSE

Changes in serum levels of biochemical markers of bone turnover during 10 years among Japanese men and women: associated factors and birth-cohort effect. The Taiji Study

We aimed to clarify changes in biochemical markers of bone turnover (BTMs) over 10 years, associations with changes in bone mineral density (BMD), and birth-cohort effects in a Japanese community. We randomly selected 400 individuals (age, 40-79 years; 50 of each gender and age stratum) from a list of registered residents in 1993. We measured BMD of the spine and hip, and serum concentrations of total osteocalcin (OC), beta-C-terminal cross-linking telopeptide of type I collagen (beta-CTX), and N-terminal cross-linking telopeptide of type I collagen (NTX), in 1993 and 2003. Of the 400 subjects, 322 (153 men, 169 women) completed the 10-year follow-up. Mean change rates (standard deviation) for serum total OC, beta-CTX, and NTX over 10 years were -1.00 (3.74)%/year, 5.10 (22.48)%/year, and 0.40 (3.41)%/year, respectively, in men, and 0.02 (5.32)%/year, 5.53 (14.54)%/year, and 0.62 (3.26)%/year, respectively, in women. Change rates of BTMs were higher for women in their forties than for women in their fifties to seventies (P < 0.05), and higher in the menstrual transition group than in pre- and postmenopausal groups (P < 0.001). Changes in levels of BTMs over 10 years in women were significantly associated with change rates of BMDs at L2-L4 and total hip after adjusting for potential confounders. A significant birth-cohort effect was observed among women in their fifties. We concluded that change rates of BTMs during the 10 years were influenced by menstrual transition, age, and sex and associated with bone loss at L2-L4 and total hip.

Synthesis and biological activity of novel barbituric and thiobarbituric acid derivatives against non-alcoholic fatty liver disease

Forty-four barbituric acid or thiobarbituric acid derivatives were synthesized and evaluated for their effects on adipogenesis of 3T3-L1 adipocytes by measuring the expression of adiponectin in vitro. Four compounds (3a, 3o, 3s, 4t) were found to increase the expression of adiponectin and lower the leptin level in 3T3-L1 adipocytes at respective concentration of 10 μM. Among them, 3s showed the most efficacious. Oral administration of 3s effectively reduced body weight, liver weight, and visceral fat and regulated serum levels of biochemical markers in the high-fat/diet-induced Wistar rats. Histopathological evaluation of liver sections by Oil Red O and H&E staining confirmed 3s as a potent, orally active molecule for reducing fat deposition against non-alcoholic fatty liver disease.

A re‐evaluation of the influence of maternal insulin‐dependent diabetes on fetal nuchal translucency thickness and first‐trimester maternal serum biochemical markers of aneuploidy

To evaluate the influence of maternal insulin-dependent diabetes mellitus (IDDM) on maternal serum free ß-hCG, pregnancy-associated plasma protein-A (PAPP-A) and fetal nuchal translucency (NT) thickness from 11 weeks to 13 weeks 6 days of gestation in a large cohort of women screened prospectively for chromosomal anomalies. Information on maternal IDDM status, maternal serum biochemical marker levels and fetal NT were collected from the prenatal screening computer records. On total, the control group included 83,972 and the IDDM group included 489 pregnancies. The median-corrected free β-hCG and PAPP-A, expressed as MoM, and fetal NT, expressed as delta values, in the IDDM and non-IDDM groups were compared. There were no significant differences between the IDDM and non-IDDM groups in median-corrected free β-hCG (IDDM 1.01 MoM, non-IDDM 1.01 MoM; p = 0.970), or mean delta NT (IDDM 0.00 mm, non-IDDM 0.02 mm; p = 0.412). However, the median-corrected PAPP-A was significantly lower (IDDM 0.88 MoM, non-IDDM 1.03 MoM; p < 0.0001). In pregnancies with maternal IDDM, first-trimester screening for chromosomal defects does not require adjustments for the measured fetal NT and maternal serum free ß-hCG. However, for PAPP-A the 15% reduction is large enough to require correction in the calculation of risks for chromosomal defects.

Relationships among serum receptor of nuclear factor-κB ligand, osteoprotegerin, high-sensitivity C-reactive protein, and bone mineraldensity in postmenopausal women

The aim of this study was to investigate the correlations among circulating osteoprotegerin (OPG), the receptor activator of nuclear factor-kappaB ligand (RANKL), high-sensitivity C-reactive protein (hsCRP), and bone mineral density (BMD) in healthy postmenopausal women. In a population-based study, highly specific enzyme-linked immunosorbent assay methods were used to evaluate the sera of 382 healthy Iranian postmenopausal women (mean age +/- SD, 58.7 +/- 7.5 y) for RANKL, OPG, hsCRP, degradation products of C-terminal telopeptides of type I collagen, and osteocalcin. BMD was determined for the lumbar spine (L2-L4) and the proximal femur using dual-energy x-ray absorptiometry. Circulating levels of OPG (r = 0.30, P < 0.001) and the RANKL/OPG ratio (r = -0.17, P < 0.001) were significantly associated with age. The geometric mean of hsCRP was 1.89 mg/L (SE, 1.05) in the population studied. There was a significant correlation between log(hsCRP) levels and body mass index (BMI; r = 0.36, P < 0.001). Multivariate linear analyses revealed that age (beta = -0.295, P < 0.001), BMI (beta = 0.464, P < 0.001), RANKL (beta = -0.105, P = 0.014), and OPG (beta = 0.098, P = 0.029) were the independent determinants for lumbar BMD (R(2) = 0.35). Age (beta = -0.250, P < 0.001), BMI (beta = 0.486, P < 0.001), and RANKL (beta = -0.110, P = 0.009) were independently correlated with femoral neck BMD (R(2) = 0.36). Age- and BMI-adjusted analysis by quartiles of log-transformed hsCRP did not reveal an association with BMD, serum levels of biochemical markers of bone turnover, RANKL, or OPG. The circulating levels of the RANKL/OPG osteoimmunity system have an association with BMD, but subclinical systemic inflammation may not be involved in bone mass in healthy postmenopausal women.

Changes of Biochemical Markers of Bone Turnover and YKL-40 Following Hormonal Treatment for Metastatic Prostate Cancer Are Related to Survival

Elevated serum levels of biochemical markers of bone turnover and YKL-40 in patients with metastatic prostate cancer (PC) at the time of diagnosis are associated to poor prognosis. In this study, we evaluated the value of these biomarkers in monitoring the patients during hormonal treatment. Serum procollagen type I N-terminal propeptide (PINP), bone-specific alkaline phosphatase (BAP), CTX-I, and YKL-40 were determined by ELISA in a longitudinal study of 106 patients with metastatic PC during treatment with total androgen ablation or parenteral estrogen. Serum samples were collected with 3 months interval. Median observation time was 4.9 years (range, 3.6-6.2). A total of 78 patients died (64 within 7 months following the last blood sampling). After 6 months treatment, serum PINP, BAP, and YKL-40 decreased (P < 0.0001), but not serum CTX-I compared with baseline values. Univariate Cox analysis showed that serum PINP at 6 months [log transformed and treated as a continuous variable; hazard ratio (HR), 2.2; P < 0.0001], serum BAP (HR, 1.8; P < 0.0001), and serum CTX-I (HR, 2.4; P < 0.0001), but not serum YKL-40 (HR, 1.4; P = 0.16) were associated with survival. Multivariate Cox analysis including the biomarkers 6 months after the start of treatment showed that Soloway score (HR, 3.9; P = 0.013), WHO tumor grade (HR, 3.9; P = 0.004), and serum PINP (HR, 2.2; P < 0.0001) were independent prognostic variables of survival. Scoring the biomarkers during treatment as time-dependent covariates in univariate Cox regression analysis showed that increases in serum PINP (HR, 2.0; P < 0.0001), BAP (HR, 2.1; P < 0.0001), and YKL-40 (HR, 2.1; P < 0.0001) were predictors of early death. Serial monitoring of serum PINP, BAP, CTX-I, and YKL-40 in metastatic PC patients during hormonal treatment provided information of prognosis.

Changes in Serum Biochemical Markers of Bone Cell Activity in Growing Thoroughbred Horses

We studied the changes in biochemical markers of bone metabolism in growing Thoroughbred horses. Serum osteocalcin (OC), as a marker for bone formation, and carboxy-terminal propeptide of type-I collagen (PICP), as a marker for bone formation, carboxy-terminal telopeptide of type-I collagen (ICTP), as a marker for bone resorption, were determined in nine clinically healthy horses from 3 d to 17 mo of age. The BW and withers height (WH) increased during the study. On the other hand, a rapid reduction in body weight gain (BWG) was observed between 1 mo and 9 mo of age and a rapid reduction in withers height gain was observed between 1 mo and 5 mo of age. The serum markers decreased significantly with increasing age. In particular, dramatic changes in serum markers occurred between 3 d to 1 wk and 5 to 7 mo of age in these horses, which suggests that bone turnover rapidly decreased after birth. On the other hand, the ratio of PICP to ICTP decreased through the experiment. This result suggests that the reduction in bone formation exceeded that of bone resorption. There was a significant correlation between markers and growth parameters, except for the correlation between PICP and BWG on single linear regression analysis. Serum OC and ICTP were affected by the WH in multiple linear regression analysis. These results indicated that the age-related variation in serum biochemical markers of bone metabolism reflected bone growth, but neither BW nor BWG. Therefore, we consider that changes in bone modeling are the major factor affecting the levels of serum biochemical markers by 17 mo of age in horses.

Antioxidant Vitamin Supplements and Markers of Bone Turnover in a Community Sample of Nonsmoking Women

Whereas several epidemiological studies suggest that low dietary intake of vitamins C and E is linked to increased hip fracture in smokers and antioxidants (dietary and endogenous) are reduced in elderly osteoporotic women, none has demonstrated an effect of supplemental antioxidants on bone turnover. In an observational study of 533 randomly selected women, we investigated the associations among the use of antioxidant supplements, vitamins C and E, serum levels of biochemical markers of bone turnover (C-telopeptide [CTx] and bone-specific alkaline phosphatase [BSAP]), and whole body bone mineral density (BMD). Twenty-two women were identified as current users of supplemental vitamin C or E. Duration of antioxidant supplement use was negatively associated with age-adjusted and weight-adjusted serum CTx, such that mean CTx levels (natural log transformed) were 0.022 units lower for each year of exposure. No significant differences were detected for adjusted serum BSAP or whole body BMD. Our results suggest that antioxidant vitamin E or C supplements may suppress bone resorption in nonsmoking postmenopausal women. Coupling of bone formation and resorption may explain the absence of an effect on bone formation markers, given evidence of enhanced effects of antioxidants on osteoblast differentiation; this warrants further investigation. This work adds to the growing body of evidence that antioxidants may play a role in preventing osteoporosis.

Effects of autotransfusion of mediastinal shed blood on biochemical markers of myocardial damage in coronary surgery

Previous studies have shown conflicting results regarding the effect of autotransfusion of mediastinal shed blood after coronary artery bypass grafting (CABG) on the serum levels of myocardial band (MB) isoenzymes of creatine kinase (CK-MB) and cardiac troponins. The effect of autotransfusion on serum levels of human heart fatty acid binding protein (H-FABP), another marker of myocardial necrosis, has not been studied. The aim of the present study was to investigate the effects of autotransfusion of mediastinal shed blood on the serum levels of CK-MB, cardiac troponin T (cTnT), and H-FABP after uncomplicated primary CABG. Fifty patients were randomized to post-operative autotransfusion of mediastinal shed blood or no autotransfusion. Blood samples for the analysis of the biochemical markers of myocardial damage were drawn pre-operatively and 1, 4, 12, 24, 48, and 72 h after the termination of cardiopulmonary bypass. Samples from the mediastinal shed blood were collected after 1 and 4 h. The levels of the biochemical markers of myocardial injury were all markedly elevated in mediastinal shed blood. Autotransfusion did not significantly affect the serum levels of cTnT or H-FABP. However, during the early post-operative hours, there was a trend towards a higher level of cTnT and H-FABP in the autotransfusion group. During the first 24 h after surgery, the autotransfusion group had a significantly higher serum level of CK-MB. Post-operative autotransfusion of mediastinal shed blood may contribute to elevated serum levels of biochemical markers of myocardial injury.

The influence of maternal insulin‐dependent diabetes on fetal nuchal translucency thickness and first‐trimester maternal serum biochemical markers of aneuploidy

To evaluate the influence of maternal insulin dependent diabetes mellitus (IDDM) on maternal serum free beta-hCG, PAPP-A and fetal nuchal translucency (NT), thickness at 11 to 13(+6) weeks of gestation in a large cohort of women screened prospectively for chromosomal anomalies. Information on maternal IDDM status, maternal serum biochemical marker levels and fetal NT were collected from the prenatal screening computer records in two first-trimester screening centres. In total the control group included 33 301 pregnancies of which 16 366 had NT and maternal serum biochemistry results and 16 305 with NT only. The IDDM group included 195 pregnancies of which 79 had NT and maternal serum biochemistry results and 127 with NT only. The median maternal weight corrected free beta-hCG and PAPP-A, expressed as multiple of the median (MoM), and fetal NT, expressed as delta values, in the IDDM and non-IDDM groups were compared. There were no significant differences between the IDDM and non-IDDM groups in median maternal weight corrected free beta-hCG (IDDM 0.87 MoM, 95% Confidence Interval 0.75 to 1.16 MoM, non-IDDM 1.00 MoM), median maternal weight corrected PAPP-A (IDDM 1.02 MoM, 95% Confidence Interval 0.83 to 1.05 MoM, non-IDDM 1.01 MoM), or mean delta NT (IDDM 0.0358 mm, non-IDDM 0.0002 mm). In pregnancies with maternal IDDM, first-trimester screening for chromosomal defects does not require adjustments for the measured fetal NT. However, more data are required before the possible reduction in maternal serum free beta-hCG and the reduction of PAPP-A suggested by the published world series can be considered sufficiently important to take into account in the calculation of risks for chromosomal defects.

Serum levels of cardiac troponin I and other marker proteins in patients with chronic renal failure.

Serum levels ob biochemical markers for acute myocardial infarction (AMI) can be increased in patients with chronic renal failure (CRF) or skeletal muscle injury, creating diagnostic confusion. We evaluated the clinical utility of cardiac troponin I (cTnI) as a marker of AMI, particularly in patients with CRF. Subjects consisted of 59 healthy volunteers and 102 patients: 61 with CRF undergoing hemodialysis (CRF-HD), 10 with CRF under conservative therapy (CRF-CT), 21 with renal disease (RD), and 10 with muscle disease (MD). Patients with RD, CRF, and MD were evaluated to verify the absence of myocardial injury. We developed an immunoradiometric assay to measure serum cTnI using monoclonal antibodies. The lower limit of detection was 0.33 micro g/l. Serum cTnI, creatine kinase (CK), CK-MB, cardiac troponin T (first-, second-, and third-generation assay: cTnT-I, cTnT-II, and cTnT-III), and cardiac myosin light chain 1 (cMLC1) were measured. cTnI was not detected in healthy volunteers or patients with CRF, RD, or MD. In patients with CRF-HD, elevated levels occurred in 4.9% (3/61) for CK, 0% (0/61) for CK-MB, 39.5% (15/38) for cTnT-I, 7.3% (3/41) for cTnT-II, 13.0% (3/23) for cTnT-III, and 77.0% (47/61) for cMLC1; and in patients with MD the levels were increased in 70% (7/10) for CK, 50% (5/10) for CK-MB, 44.4% (4/9) for cTnT-I, 20% (2/10) for cTnT-II, and 50% (5/10) for cMLC1. cTnI is a highly specific marker for AMI and is particularly useful for detecting AMI in patients with CRF or MD. Serum levels of biochemical markers for acute myocardial infarction (AMI) can be increased in patients with chronic renal failure (CRF) or skeletal muscle injury, creating diagnostic confusion. We evaluated the clinical utility of cardiac troponin I (cTnI) as a marker of AMI, particularly in patients with CRF.

The impact of correcting for smoking status when screening for chromosomal anomalies using maternal serum biochemistry and fetal nuchal translucency thickness in the first trimester of pregnancy.

To evaluate the influence of cigarette smoking status on maternal serum free beta-hCG, PAPP-A and fetal nuchal translucency (NT) thickness at 11 to 14 weeks of gestation in a large cohort of women screened prospectively for chromosomal anomalies. Information on maternal cigarette smoking status, maternal age, maternal serum biochemical marker levels and fetal NT were collected from the prenatal screening computer records in two OSCAR screening centres. Data was available from 32,730 unaffected pregnancies and from 124 with Down syndrome. Statistical analysis of the marker levels in the smoking and non-smoking group were carried out. The impact on false-positive rate of correcting for smoking status was assessed from a modelling exercise. Prevalence of smoking was significantly affected by maternal age with an overall incidence of 11.5%, which varied from 35% in women under 20 to 7% in women over 35. In the unaffected population, the median free beta-hCG MoM was significantly lower in the smoking group (0.97 vs 1.00) as was that for PAPP-A (0.84 vs 1.02). The standard deviation of the log(10) MoM free beta-hCG was lower in the smoking group and that for PAPP-A was higher in the smoking group. The difference in median marker levels did not seem to be related to the number of cigarettes smoked per day. In the group with Down syndrome, the median MoM free beta-hCG was not significantly different in the smokers (1.69 vs 1.86) as was that for PAPP-A (0.53 vs 0.57). Fetal delta NT was not significantly different in the unaffected smokers (0.11 vs 0.0 mm) or in those with Down syndrome (1.96 vs 2.25 mm). In the smoking group, when screening using maternal serum biochemistry and age alone, the false-positive rate was 6.17%, compared to 4.67% in an age-matched group of non-smokers. Correcting for smoking status by dividing the measured MoM by the median found in the smoking group resulted in the false-positive rate falling to 4.40%. When screening using NT, maternal serum biochemistry and age, the false-positive rate in smokers was 4.48%, which reduced to 3.46% after correction-in line with the 3.76% in the non-smoking group. The impact on detection rate was too small to be accurately measured. The impact of smoking on first-trimester biochemical marker levels does not seem to be dose related. Whilst correcting first-trimester biochemical markers for maternal smoking status has little impact at the population level for detection rates, a considerable reduction in false-positive rate can be achieved, reducing the level to that seen in non-smokers. However, the effect on the individual patient-specific risk can be substantial and could certainly make a difference to the patient's decision on whether to have an invasive test.

Estrogen receptor beta dinucleotide (CA) repeat polymorphism is significantly associated with bone mineral density in postmenopausal women.

Significant associations between the lengths of a highly polymorphic dinucleotide (CA) repeat located within the human estrogen receptor beta (ESR2) gene on chromosome 14, bone mineral density (BMD) and androgen levels have been reported previously in premenopausal women. We measured the size of this microsatellite repeat in 226 healthy women (60-98 years). After adjustment for age, body mass index, hormone replacement status, and other variables known to influence BMD, women with < 25 CA repeats had significantly higher BMD measured in the total skeleton, lumbar spine, and femoral neck when compared with women having longer alleles. Women with shorter alleles also had higher circulating estrone and estradiol levels that approached statistical significance as compared with women harboring longer alleles after appropriate adjustments were performed in linear regression models. Women having both short and long CA repeats had BMD values in all regions of the skeleton that were midway between those found in women homozygous for longer or shorter repeat sizes. Because the ESR2 CA repeat size was neither associated with change in BMD nor serum levels of biochemical markers of bone turnover, it is likely that ESR2 CA repeat genotype is significantly linked to the attainment of peak bone mass in women.

Serum prealbumin predicts survival in hemodialysis and peritoneal dialysis: 10 years of prospective observation

Malnutrition is a major factor contributing to the high mortality rate in hemodialysis (HD) and peritoneal dialysis (PD) patients. We and others have reported previously that single enrollment levels of serum biochemical markers, such as albumin, cholesterol, creatinine, and prealbumin, are correlated directly with mortality in HD and PD patients. We have studied prospectively the relationship of enrollment prealbumin levels, demographic characteristics, and other biochemical markers to all causes of mortality in 130 HD and 128 PD patients who were monitored for 10 years. The Kaplan-Meier method was used to compute observed survival, and the Cox proportional hazards model was used to identify independent predictors of mortality risk. For HD patients, enrollment serum prealbumin remained a strong independent predictor of long-term survival after adjusting for age, race, gender, months on dialysis, diabetic status, and other nutritional markers. In PD and HD patients, observed and adjusted survivals (after adjusting for aforementioned confounding variables) of patients with prealbumin greater than 30 mg/dL were significantly higher than survivals of patients with prealbumin less than 30 mg/dL. For HD and PD patients, age and diabetes were associated inversely with prealbumin concentration, whereas levels of albumin, creatinine, and total cholesterol were associated directly with prealbumin concentration. In this study, prealbumin was the best biochemical predictor of mortality for HD patients and a useful tool to assess nutritional risk in HD and PD patients. © 2001 by the National Kidney Foundation, Inc.

Biochemical markers of bone metabolism in growing thoroughbreds: a longitudinal study

This study describes longitudinal changes in serum levels of biochemical markers of bone cell activity in a group of 24 thoroughbred foals from birth to 18 months of age. The markers of bone formation included the type I collagen carboxy-terminal propeptide (PICP), the bone-specific isoenzyme of alkaline phosphatase (BAP), and osteocalcin (OC). Levels of the cross-linked telopeptide of type I collagen (ICTP), a marker of bone resorption, and the N-terminal propeptide of type III collagen (PNIIIP), a marker of soft tissue turnover, were also measured. Levels of all markers fell significantly between birth and 18 months of age (70–80 per cent); this decrease being most marked between 0 and 6 months. However, a transient increase in levels of the markers then occurred between 6 and 14 months of age. The timing of this increase was specific for each parameter. ICTP and OC concentrations increased between October and December.PICP concentrations increased between December and April whereas the increase in PIIINP was coincident with the peak in weight gain between April and June. Changes in BAP concentration were less distinct at this time. Season was shown to have significant effects on the biochemical markers independent from the effect of age. Concentrations of all markers decreased with increasing body weight and at any given age heavier horses had lower marker levels. These results show that biochemical markers of bone cell activity and soft tissue turnover follow characteristic patterns of change in growing thoroughbreds influenced by age, season and bodyweight. The demonstration that the reference ranges for the biochemical markers change from month to month means that single samples from individuals are of little value for monitoring bone cell activity in growing thoroughbreds.

Effect of Therapy with Recombinant Human Growth Hormone on Insulin-Like Growth Factor System Components and Serum Levels of Biochemical Markers of Bone Formation in Children After Severe Burn Injury

Burn injury in children is associated with low bone formation and long-term bone loss. Because recombinant human GH (rHGH) may accelerate burn wound healing, and because rHGH increases bone formation and density in GH-deficient patients, we studied the short-term effects of rHGH on bone fomation, reflected by osteocalcin and type I procollagen propeptide levels in a randomized, double-blind, placebo-controlled study. Nineteen patients were enrolled and received either rHGH (0.2 mg/kg.day) or an equal volume of saline. Mean burn size and age were not different between the groups, and test substances were given from admission to time of wound healing (mean: 43 +/- 22 days). At wound healing, serum levels of insulin-like growth factor (IGF)-1 and IGF binding protein (IGFBP)-3 in the rHGH group rose to mean values of 229% and 187% of the respective means of the placebo group (P < 0.025). Serum osteocalcin concentrations remained below normal in both groups, and type I procollagen propeptide levels achieved a low normal level IGFBR-4 levels were twice that of normal on admission and doubled further at wound healing; IGFBP-5 levels were low on admission but rose to normal at wound healing. We conclude that large doses of rHGH were ineffective in improving disordered bone formation despite increasing serum IGF-1 and IGFBP-3. The rHGH-independent rise in serum levels of the inhibitory binding protein IGFBP-4 suggests a mechanism by which improved bone formation is prevented despite successful elevation of IGF-1 and IGFBP-3 in the burned child.

High incidence of significant bone loss in patients with severe congenital neutropenia (Kostmann’s syndrome)

Objective: Clinical observation of bone pain, unusual fractures in two patients, and diffuse osteopenia/osteoporosis led us to assess bone mineral content and density in 30 patients with severe congenital neutropenia who were treated with recombinant-methionyl-human granulocyte colony-stimulating factor (r-metHuG-CSF). Study design: We reviewed roentgenograms in 29 of these 30 patients to evaluate bone loss before and during treatment. In addition, in 17 of the 30 patients, bone mineral status could be assessed by both quantitative computed tomography (Q-CT; n = 16) and dual energy x-ray absorptiometry (DXA; n = 1). In one patient, Q-CT was not possible because of severe vertebral fractures. Results: Of the 30 patients investigated, 15 had evidence of osteopenia/osteoporosis observed on spine radiographs ( n = 5), on Q-CT/DXA ( n = 1/ n = 1), or on radiographs and Q-CT ( n = 8). In 13 of the 30 patients, only a lateral radiograph of the lumbar spine was available, 5 of 13 showing either increased kyphosis and wedging of the vertebrae or compression fractures of the vertebral bodies, indicating severe established osteoporosis. In eight patients, the findings of the spinal radiographs were normal. In nine patients, spinal radiographs were taken before r-metHuG-CSF treatment. Osteoporotic vertebral deformation ( n = 3) or reduced bone mass ( n = 3) was seen in six of these nine patients. The levels of serum biochemical markers of bone metabolism were all within normal ranges except for mild elevation of the serum alkaline phosphatase level. The degree of spinal bone mineral loss did not correlate with dose and duration of r-metHuG-CSF treatment or with the age or sex of the patients. Conclusions: These data indicate a high incidence of bone mineral loss in children with severe congenital neutropenia. The underlying pathogenesis of bone demineralization is not clear. It is more likely that the bone loss was caused by the pathophysiologic features of the underlying disease, but it is possible that r-metHuG-CSF accelerates bone mineral loss. (J Pediatr 1997;131:592-7)

Significance of serum levels of type I procollagen peptide and intact osteocalcin and bone mineral density in patients with ossification of the posterior longitudinal ligaments.

This study was performed to evaluate the correlation between serum biochemical marker levels of bone metabolism and bone mineral density (BMD) in patients with ossification of the posterior longitudinal ligaments (OPLL). In addition, the efficacy of these markers in the prediction of the progression of OPLL was also examined. In 40 patients with OPLL, and in age- and gender-matched controls (n = 36), the levels of C-terminal extension peptide of type I procollagen (PICP) and intact osteocalcin were quantitated by a sandwich enzyme-linked immunosorbent assay as serum markers of bone formation. BMD of the whole body was measured using dual-energy X-ray absorptiometry. Serum PICP and intact osteocalcin levels were significantly increased in patients with OPLL. There was a significant correlation between serum bone formation marker levels and BMD in both the OPLL and the control groups. Patients with radiological progression of OPLL showed a level higher than the mean + 2 SD of controls in PICP, intact osteocalcin, and BMD. In addition, the levels of serum PICP and intact osteocalcin increased in correspondence with the progression of OPLL without statistical significance. In patients without any growth of OPLL, however, all the parameters were below the mean + 2 SD of controls. Thus, aggravation of bone formation activity was suggested to be closely correlated with the development of OPLL. In addition, serial measurements of these parameters might be useful for estimating the progression of OPLL.

Effects of 3 months of non-weight-bearing cycle ergometric exercise on bone metabolism

We evaluated the effect of non-weight-bearing exercise on bone metabolism by measuring serum levels of biochemical markers, N-terminal osteocalcin (OC), and intact OC. N-terminal assay using the radioimmunoassay (RIA) method is considered to be a marker of bone turnover. Intact OC was measured as a marker of bone formation by the sandwich enzyme-linked immunosorbent assay (ELISA) method. As is commonly known, the cycle ergometer is a very popular and useful tool for aerobic exercise used world wide to improve health. In this study, we evaluated the effect of such common exercise on N-terminal OC and intact OC using a cycle ergometer. N-terminal OC was not significantly changed after 30min of aerobic training with a cycle ergometer three times a week for 3 months, whereas intact OC decreased significantly. No changes in bone mineral density of weight-bearing or non-weight-bearing bones were found. These results suggest that the type and duration of exercise using the current training method were insufficient to produce a favorable effect on bone. The current training method consisted of aerobic, non-weight-bearing exercise alone using a cycle ergometer. It is unknown whether the non-weight-bearing form of exercise was responsible for our results, or whether the aerobic exercise itself was insufficient. The 3-month period may have been insufficient to stimulate osteogenesis, and it is possible that an exercise period of this duration may instead result in a tendency to suppress bone formation. At any rate, we believe it is significant that we were able to demonstrate, on the basis of changes in bone metabolism markers and bone mineral density, that the nature of this exercise was insufficient to stimulate osteogenesis.