Temporal, spatial and gender-based dietary differences in middle period San Pedro de Atacama, Chile: A model-based approach.

To explore the possible emergence and lived consequences of social inequality in the Atacama, we analyzed a large set (n = 288) of incredibly well preserved and contextualized human skeletons from the broad Middle Period (AD 500-1000) of the San Pedro de Atacama (Chile) oases. In this work, we explore model-based paleodietary reconstruction of the results of stable isotope analysis of human bone collagen and hydroxyapatite. The results of this modeling are used to explore local phenomena, the nature of the Middle Period, and the interaction between local situations and the larger world in which the oases were enmeshed by identifying the temporal, spatial, and biocultural correlates and dimensions of dietary difference. Our analyses revealed that: 1) over the 600-year period represented by our sample, there were significant changes in consumption patterns that may evince broad diachronic changes in the structure of Atacameño society, and 2) at/near 600 calAD, there was a possible episode of social discontinuity that manifested in significant changes in consumption practices. Additionally, while there were some differences in the level of internal dietary variability among the ayllus, once time was fully considered, none of the ayllus stood out for having a more (or less) clearly internally differentiated cuisine. Finally, sex does not appear to have been a particularly salient driver of observed dietary differences here. While we do not see any de facto evidence for complete dietary differentiation (as there is always overlap in consumption among individuals, ayllus, and time periods, and as isotopic analysis is not capable of pinpointing different foods items or preparations), there are broad aspects of dietary composition changing over time that are potentially linked to status, and foreignness. Ultimately, these stand as the clearest example of what has been termed "gastro-politics," potentially tied to the emergence of social inequality in the San Pedro oases.

Assessment of myocardial fibrosis by late gadolinium enhancement imaging and biomarkers of collagen metabolism in chronic rheumatic mitral regurgitation.

BACKGROUND: In chronic rheumatic mitral regurgitation (CRMR), involvement of the myocardium in the rheumatic process has been controversial. Therefore, we sought to study the presence of fibrosis using late gadolinium enhancement cardiac magnetic resonance imaging (LGE-CMR) and biomarkers of collagen turnover in CRMR. METHODS: Twenty-two patients with CRMR underwent CMR and echocardiography. Serum concentrations of matrix metalloproteinase- 1 (MMP-1), tissue inhibitor of MMP-1 (TIMP- 1), MMP-1-to-TIMP-1 ratio, procollagen III N-terminal pro-peptide (PIIINP) and procollagen type IC peptide (PIP) were measured. RESULTS: Four patients had fibrosis on LGE-CMR. PICP and PIIINP concentrations were similar to those of the controls, however MMP-1 concentration was increased compared to that of the controls (log MMP-1 3.5 ± 0.7 vs 2.7 ± 0.9, p = 0.02). There was increased MMP-1 activity as the MMP-1-to- TIMP-1 ratio was higher in CRMR patients compared to the controls ( -1.2 ± 0.6 vs -2.1 ± 0.89, p = 0.002). CONCLUSIONS: Myocardial fibrosis was rare in CRMR patients. CRMR is likely a disease characterised by the predominance of collagen degradation rather than increased synthesis and myocardial fibrosis.

Assessment of bone mineral density and bone metabolism in young male adults recently diagnosed with systemic lupus erythematosus in China.

Objective Systemic lupus erythematosus (SLE) is a chronic inflammatory autoimmune disease. However, the exact mechanism underlying SLE-related osteopenia and osteoporosis in patients newly diagnosed with SLE remains unknown. Methods 60 male subjects with SLE aged 20-30 years were enrolled. Serum osteocalcin was examined as a marker of bone formation and type I collagen degradation products (ß-crosslaps) as markers of bone resorption. Lumbar spine (L1-L4) and total hip bone mineral density (BMD) were determined by dual energy X-ray absorption (DXA). Results Among the 60 subjects with SLE at the time of diagnosis, the cohort showed a significant reduction of osteocalcin (12.62 ± 2.16 ng/mL), and serum ß-crosslaps level (992.6 ± 162.6 pg/mL) was markedly elevated. Univariate correlation analyses revealed negative correlations between osteocalcin and SLEDAI, dsDNA antibody and ß-crosslaps. A positive correlation was also observed between osteocalcin and C3, C4, 25-OH vitamin D, BMD L1-L4 and BMD total hip (see Table 3). Osteocalcin and ß-crosslaps were strongly associated with SLE disease activity by multiple stepwise logistic regression analysis. Conclusion Osteocalcin was negatively associated with SLE disease activity, and ß-crosslaps was positively associated with SLE disease activity, suggesting SLE disease activity itself directly contributed to the development of SLE-associated osteopenia and osteoporosis.

Assessment of vitamin D status and serum CrossLaps levels in adults with primary lactose malabsorption.

BACKGROUND/OBJECTIVES: Primary adult-type lactose malabsorption (PALM) is a widespread inherited autosomal recessive condition, which is considered to be associated with osteoporosis. This prospective study aimed at assessing the 25-hydroxy-vitamin D (25(OH)D) status and serum CrossLaps levels in individuals with PALM and normal controls. SUBJECTS/METHODS: All participants (n=210) underwent genotyping for the LCT C/T-13910 polymorphism, 25(OH)D and CrossLaps measurements and clinical examinations. In addition, the anthropometric data (that is, height, weight and body mass index) were determined. RESULTS: Fifty-five individuals with PALM (that is, LCT C/C-13910 homozygotes) showed lower 25(OH)D (mean: 24.95±10.04 vs 28.59±9.56 ng/ml, P=0.018) and higher CrossLaps serum levels (mean: 0.46±0.31 vs 0.43±0.49 ng/ml, P=0.251) compared with 155 normal controls (that is, LCT C/T-13910 hetero- or T/T-13910 homozygotes). Anthropometric data were similar between PALM probands and controls. CONCLUSIONS: Individuals with PALM were found to have lower 25(OH)D and higher CrossLaps serum levels compared with normal controls. In order to preserve life-long bone health, routine 25(OH)D and CrossLaps serum measurements should be performed in individuals with PALM.

Serotonin and the bone assessment.

INTRODUCTION: Lately, the in vitro and in vivo studies on serotonin metabolism have been pointing its influence in bone health. Also, there are no particular recommendations in performing the serum serotonin assessment in order to evaluate the skeletal status. AIM: We aimed to correlate the bone turnover markers and lumbar bone mineral density (BMD) with serotonin. MATERIAL AND METHODS: There is a cross-sectional study in Caucasian postmenopausal women. They were not diagnosed with carcinoid syndrome, or bone anomalies, and received no treatment (including antiresorptives). The following bone formation markers were performed: serum alkaline phosphatase (AP), serum osteocalcin (OC), and the bone resorption marker: serum CrossLaps (CL). Serum serotonin (high-pressure liquid chromatography), as well as central DXA (GE Prodigy) were assessed. RESULTS: 191 women of 57.1 years mean age were grouped according to DXA (WHO criteria). The linear regression analysis between serum serotonin and CL were not statistically significant (SS), between serotonin and OC was SS in the newly diagnosed osteoporosis group (N=40, r=0.4, p=0.03), between serotonin and AP SS was found in osteopenia group (N=88, r=0.24, p=0.03), with no changes when adjusting for age and BMI. The partial correlation between serotonin and BMD was not SS. DISCUSSION: The study raises the question of serotonin as a bone metabolism marker seeing that the results were not consistent. The main limit of our study was that we did not analyze the possible use of antidepressants to these women. Overall, this was a pilot study in clinical practice where few reports have been published, but still necessary, because the use of serum serotonin in current skeletal evaluation is still unclear.

The significance of carboxy-terminal telopeptide of type I collagen (ICTP) and osteocalcin (OC) in assessment of bone disease in patients with multiple myeloma.

Bone disease occurring in multiple myeloma is usually evaluated using radiological methods. These methods, however, provide not much information about the dynamic process of bone resorption and formation. This study analysed levels of serum markers of bone turnover (ICTP and OC), reflecting function of osteoclasts and osteoblasts. It demonstrates increased level of ICTP in 75 patients with MM compared to control group (8 persons) and patients with Waldenström's macroglobulinemia (10 persons). The level of ICTP was also higher in patients with more advanced bone disease and probably in higher stage of disease according to Salmon and Durie classification. This tendency was not observed in relation to OC. Result of the research confirms that ICTP may incur sensitive and specific markers of bone lesions in multiple myeloma.

Assessment of soy phytoestrogens' effects on bone turnover indicators in menopausal women with osteopenia in Iran: a before and after clinical trial.

BACKGROUND: Osteoporosis is the gradual declining in bone mass with age, leading to increased bone fragility and fractures. Fractures in hip and spine are known to be the most important complication of the disease which leads in the annual mortality rate of 20% and serious morbidity rate of 50%. Menopause is one of the most common risk factors of osteoporosis. After menopause, sex hormone deficiency is associated with increased remodeling rate and negative bone balance, leading to accelerated bone loss and micro-architectural defects, resulting into increased bone fragility. Compounds with estrogen-like biological activity similar to "Isoflavones" present in plants especially soy, may reduce bone loss in postmenopausal women as they are similar in structure to estrogens. This research, therefore, was carried out to study the effects of Iranian soy protein on biochemical indicators of bone metabolism in osteopenic menopausal women. MATERIALS AND METHODS: This clinical trial of before-after type was carried out on 15 women 45-64 years of age. Subjects were given 35 g soy protein per day for 12 weeks. Blood and urine sampling, anthropometric measurement and 48-h-dietary recalls were carried out at zero, 6 and 12 weeks. Food consumption data were analyzed using Food Proccessor Software. For the study of bone metabolism indicators and changes in anthropometric data as well as dietary intake, and repeated analyses were employed. RESULTS: Comparison of weight, BMI, physical activity, energy intake and other intervening nutrients did not reveal any significant changes during different stages of the study. Soy protein consumption resulted in a significant reduction in the urinary deoxypyridinoline and increasing of total alkaline phosphatase (p < 0.05), although the alterations in osteocalcin, c-telopeptide, IGFBP3 and type I collagen telopeptide were not significant. CONCLUSION: In view of beneficial effect of soy protein on bone metabolism indicators, inclusion of this relatively inexpensive food in the daily diet of menopausal women, will probably delay bone resorption, thereby preventing osteoporosis.

The use of collagen-derived serum peptides for the clinical assessment of hypertensive heart disease.

Given the importance of fibrous tissue in leading to myocardial dysfunction and failure in hypertensive heart disease, non-invasive assessment of fibrosis could prove a clinically useful tool in hypertensive patients, particularly given the potential for cardioprotective and cardioreparative pharmacological strategies. In this regard, an emerging experimental and clinical experience holds promise for the assessment of various serum peptides arising from the metabolism of collagen types I and III in arterial hypertension. More specifically, the measurement of serum concentrations of procollagen type I carboxy-terminal propeptide (a peptide that is cleaved from procollagen type I during the synthesis of fibril-forming collagen type I) may provide indirect diagnostic information on both the extent of myocardial fibrosis and the ability of antihypertensive treatment to diminish collagen type I synthesis and reduce myocardial fibrosis in hypertensive patients. The available data set the stage for large and long-term trials to definitively validate this approach.

The assessment of bone metabolism in female elite endurance athletes by biochemical bone markers.

PURPOSE: Premature osteoporosis is a frequent problem in female athletes. Current concepts suggest that a disruption of the hypothalamic-pituitary axis leads to hypoestrogenism, which then causes amenorrhea and osteoporosis. However, the underlying mechanisms have been insufficiently investigated. Osteoprotegerin (OPG) and soluble TNF-alpha receptor antagonist ligand (sRANKL) regulate the balance of osteoblasts and osteoclasts. Their role in the pathogenesis of osteoporosis in female athletes has not been studied yet. METHODS: We measured OPG and sRANKL in relation to biochemical bone markers [osteocalcin (OC), bone alkaline phosphatase (BAP), serum beta-crosslaps (CTx)] and female sex hormones [estradiol (E2) and luteinizing hormone (LH)] in fastening blood samples from 25 female elite endurance athletes and 25 matched controls. RESULTS: Athletes exhibited significantly higher levels of the bone resorption marker CTx than controls (0.61 +/- 0.26 vs. 0.44 +/- 0.15 ng/ml). OPG and sRANKL were not changed. Subgroup analysis revealed that athletes using oral contraceptives [A-OCC(-)] had significantly higher levels of CTx (0.82 +/- 0.20 vs. 0.50 +/- 0.14 ng/ml), BAP [37.3 (23.2-54.4) U/l vs. 25.2 (20.3-35.6) U/l] and OPG (3.4+/-0.8 vs. 2.7+/-0.8 ng/ml) than controls who did not use oral contraceptives [C-OCC(-)]. While the difference for CTx exceeded the least significant change in this marker by approximately 30%, the differences for the bone formation markers OC and BAP were close to the least significant change. In athletes using oral contraceptives [A-OCC(+)] we found no differences compared to controls. CONCLUSIONS: A-OCC(-) athletes have increased bone turnover with a particular stimulation of bone resorption. The increased bone resorption is not accompanied by a shift of the OPG/sRANKL relationship towards an osteoclastogenic constellation. Since increased bone resorption was not detectable in A-OCC(+) athletes, it can be suggested that OCC use might protect bone health in female athletes.

Assessment of the bone status of Nigerian children and adolescents with sickle cell disease using calcaneal ultrasound and serum markers of bone metabolism.

Growth and skeletal maturation are impaired in sickle cell disease (SCD). SCD is also associated with decreased bone mineral density (BMD) as determined by dual X-ray and photon absorptiometry. Quantitative ultrasound (US), which is as good a predictor of fracture as absorptiometry, provides additional information about bone architecture and elasticity. It is not known if the quantitative US parameters, broadband ultrasound attenuation (BUA) and speed of sound (SOS), are affected in children and adolescents with SCD. We therefore compared the bones of 80 children with SCD in Nigeria to those of age- and gender-matched controls using calcaneal ultrasound and the serum bone markers N-telopeptide of type1 collagen (NTx) and bone-specific alkaline phosphatase (BSAP), which are indicators of bone resorption and formation, respectively. BUA, which is reflective of BMD, was significantly lower for both the male and female SCD subjects compared with controls (86 vs 113 dB/MHz, P < 0.001 and 87 vs 100 dB/MHz, P < 0.001, respectively). However, SOS, which is more indicative of bone elasticity, was significantly different only for the male SCD subjects. Both NTx and BSAP were significantly reduced in the serum of the male and female SCD subjects. Correlations between BUA and serum NTx were found for both female controls and SCD subjects (r = 0.58, P < 0.001 and r = 0.32, P = 0.05, respectively), but not for the male subjects or controls. Significant correlations between BUA and BSAP were observed only for the female controls. In summary, we have shown that US analysis, in combination with serum markers of bone metabolism, can be used to distinguish bone development in children with SCD from that of nonaffected controls.

Biochemical assessment of myocardial fibrosis in hypertensive heart disease.

Fibrous tissue accumulation is an integral feature of the adverse structural remodeling of cardiac tissue seen with hypertensive heart disease. Given the importance of fibrous tissue in leading to myocardial dysfunction and failure, noninvasive monitoring of myocardial fibrosis by use of serological markers of collagen turnover could prove a clinically useful tool, particularly given the potential for cardioprotective and cardioreparative pharmacological strategies. An emerging experimental and clinical experience holds promise for the use of radioimmunoassays of various serological markers of fibrillar collagen type I and type III turnover in arterial hypertension. More specifically, the measurement of serum concentrations of procollagen type I C-terminal propeptide (a peptide that is cleaved from procollagen type I during the synthesis of fibril-forming collagen type I) may provide indirect diagnostic information on both the extent of myocardial fibrosis and the ability of antihypertensive treatment to diminish collagen type I synthesis and reduce myocardial fibrosis. This approach represents an exciting and innovative strategy, and available data set the stage for larger trials, in which noninvasive measures of fibrosis in hypertensive heart disease could prove useful.

Assessment of the bone status of Nigerian women by ultrasound and biochemical markers.

Ultrasound analysis of the calcaneus and serum markers of bone turnover were used to examine the bone status of healthy Nigerian women who reside in an area of the world where dietary calcium intake is generally low and estrogen replacement therapy is not widely available. A total of 218 women (108 premenopausal and 110 postmenopausal) between the ages of 16 and 95 years were enrolled in the study. Broadband ultrasound attenuation (BUA) and speed of sound velocity (SOS) were measured and used to calculate the stiffness index (SI) of the calcaneus. In this cross-sectional study, the Nigerian women exhibited a marked age-dependent decline in SI that was defined by the regression equation SI = 105.9 - 6.62E-3 x Age2. SI was significantly correlated with age (r = -0.41, P < 0.001) and with serum NTx concentrations (r = -0.26, P < 0.001), but not with serum levels of bone-specific alkaline phosphatase (BSAP). Years since menopause was also significantly correlated with SI (r = 0.40, P < 0.001). A significant increase in serum NTx concentration occurred at least a decade before a significant decline in SI was evident. In the total study group, 24% of the women had T-scores indicative of osteopenia and 9% had T-scores indicative of osteoporosis, based on US reference data. Although the reported current incidence of fracture is low in women in sub-Saharan West Africa, these data show that after menopause Nigerian women have a decline in bone quality and increase in bone turnover similar to North American Caucasian women.

Assessment of the relationship between dynamic pattern of nighttime levels of melatonin and chosen biochemical markers of bone metabolism in a rat model of postmenopausal osteoporosis.

BACKGROUND: Lately, there have been suggestions that bone mass changes occurring in postmenopausal women may remain related to melatonin. OBJECTIVE: To assess the relationship between the dynamic pattern of nighttime levels of melatonin and chosen biochemical markers of bone metabolism in ovariectomized rats--a model of postmenopausal osteoporosis. METHODS: Mature Wistar female rats were either ovariectomozed or underwent a sham operation. Following this they were killed at 02:00AM at weekly intervals for 8 weeks after surgery. Serum levels of MEL at death related to the chosen biochemical markers of bone formation (alkaline phosphatase--ALP; carboxyterminal propeptide of type I procollagen--PICP, both in serum) and resorption (cross-linked carboxyterminal telopeptide of type I collagen--ICTP in serum; hydroxyproline--HYP and total calcium--Ca, both excreted in urine). RESULTS: In all ovariectomized rats changes of examined indices of bone tissue metabolism were found to be dynamic and statistically significant relative to the control group; however the changes were more pronounced regarding resorption markers. Following ovariectomy, the increase in ALP and PICP values was found to begin at the 4th and the 1st week, while that in ICTP, HYP and Ca at the 2nd, the 1st and the 1st week, respectively. The ALP and PICP values remained at a similar level until the end of observation, whereas ICTP, HYP and Ca gradually decreased. MEL levels were decreased during the 2nd week following surgery and slightly increased 2 weeks later. The serum MEL levels in the ovariectomized group were significantly and negatively correlated with serum ICTP and both urinary HYP and Ca levels. CONCLUSION: Our findings in rats seem to corroborate the concept of secondary changes in MEL levels co-participating in the development of bone mass changes characteristic for postmenopausal osteoporosis.

The applicability of biochemical markers of bone metabolism for predicting the risk of bone fractures and for the assessment of bone tissue resorption in the course of osteoporosis.

The role of increased metabolism of bone tissue as a risk factor for bone fractures in the course of osteoporosis has been investigated. The importance of the assay of biochemical markers of bone remodelling for determining the degree of bone tissue resorption has been evaluated.

A detailed assessment of alterations in bone turnover, calcium homeostasis, and bone density in normal pregnancy.

The effects of pregnancy on bone turnover and the potential risk of developing an osteoporotic fracture in pregnancy are controversial. Utilizing biochemical markers of bone formation and resorption and dual-energy X-ray absorptiometry (DEXA), bone turnover before, during, and after pregnancy was studied in detail. Ten women (mean age 30 years; range 23-40) were recruited. Prepregnancy data were obtained and then a review was performed at 2-week intervals , once pregnancy was confirmed, until 14 weeks of gestation and thereafter monthly until term. Bone mineral density (BMD) was estimated by DEXA scanning of hip, spine, and forearm preconception and postpartum. In addition, BMD of the forearm at 14 weeks and 28 weeks gestation was obtained. All pregnancies had a successful outcome. Urinary free pyridinium cross-links, free pyridinoline (fPyr) and free deoxypyridinoline (fDPyr), were normal prepregnancy (mean [+/-SD]) 14.6 nmol/mmol (1.8) and 5.0 nmol/mmol (1.0) creat, respectively. By 14 weeks, they had increased to 20.8 nmol/mmol (4.3) and 6.1 nmol mmol (1.4) (both p < 0.02) and by 28 weeks to 26.3 nmol/mmol (5.6) and 7.4 nmol/mmol (1.6) (both p < 0.01). The ratio of fPyr to fDPyr remained constant. A similar significant increase was observed in N-telopeptide (NTx). Bone formation was assessed by measurement of carboxyterminal propeptide of type 1 collagen (P1CP) and bone-specific alkaline phosphatase (BSAP). Neither were altered significantly before 28 weeks, but subsequently mean P1CP increased from 110 microg/liter (23) to 235 microg/liter (84) at 38 weeks and mean BSAP increased from 11.1 U/liter (5.0) to 28.6 U/liter (11.1) (p < 0.01 for both variables). Lumbar spine (L1-L4) BMD decreased from a prepregnancy mean of 1.075 g/cm (0.115) to 1.054 g/cm2 (0.150) postpartum (p < 0.05). Total hip BMD decreased from a prepregnancy mean of 0.976 g/cm2 (0.089) to 0.941 g/cm2 (0.097) (p < 0.05). Forearm BMD at midradius, one-third distal and ultradistal decreased but did not reach statistical significance. As assessed by these bone markers, in the first 2 trimesters of pregnancy, bone remodeling is uncoupled with a marked increase in bone resorption. A corresponding increase in formation markers is not observed until the third trimester. Spinal BMD exhibits a significant decrease from prepregnancy to the immediate postpartum period with a mean reduction in BMD of 3.5 % in 9 months.

External quality assessment of bone metabolism marker assays. initial experiences in a UK NEQAS programme.

This paper reports on a pilot external quality assessment scheme for bone markers including serum bone alkaline phosphatase and procollagen 1-carboxy terminal propeptide together with urine deoxypyridinoline, N- and C-telopeptides. The data shows poor numerical agreement between commercial assays, between-laboratory imprecision that could be improved, and the need for international standardisation of assays.

Novel serum markers of bone resorption: clinical assessment and comparison with established urinary indices.

Although urinary measurements of collagen degradation provide valid estimates of bone resorption, their clinical application is hampered by pronounced analytical and biological variability. Therefore, immunoassays for the determination of such parameters in serum have been developed. In this study, we assessed the performance of three new serum markers of bone turnover, i.e., C-terminal and N-terminal telopeptides of type I collagen (S-CTX and S-NTX) and bone sialoprotein. Results were compared with urinary total pyridinoline, total deoxypyridinoline, and urinary C-terminal telopeptides of type I collagen (U-CTX) and urinary N-terminal telopeptides of type I collagen (U-NTX). The study population included healthy men (n = 27), premenopausal (n = 30) and postmenopausal (n = 31) women, patients with hepatic dysfunction (HF, n = 24), renal failure (RF, n = 30), breast cancer without (BC-, n = 24) and with (BC+, n = 30) bone metastases, primary vertebral osteoporosis (OPO, n = 27), primary hyperparathyroidism (PHPT, n = 16), active Paget's disease of bone (n = 18), multiple myeloma (MM, n = 18), and patients with hypercalcemia of malignancy before and after treatment with pamidronate (HOM, n = 28). Changes in urinary and serum markers were similar in most metabolic bone diseases. However, differentiation between healthy controls and OPO, or PHPT, was improved by the serum markers. In MM, all serum and urinary markers were elevated (p < 0. 05 vs. controls). In BC+, skeletal involvement was reflected by significant increments in all indices (p < 0.01 vs. BC-), except U-CTX and S-CTX. In HOM, pamidronate-induced changes in biomarkers were most pronounced for U-CTX and S-CTX and S-NTX. HF and RF were associated with elevated levels of all serum markers (p < 0.05 vs. controls). In conclusion, measurements in serum reflect bone resorption to the same extent as the urinary indices. Since serum markers circumvent some of the limitations of urinary measurements, their use potentially improves the assessment of skeletal disorders.

Use of bone turnover marker, pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), in the assessment and monitoring of bone metastasis in prostate cancer.

BACKGROUND: We investigated whether a new marker of bone turnover, pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), could be useful in the assessment of bone metastasis and in monitoring of the response to treatment in patients with prostate cancer with bone metastasis. METHODS: In all, 58 patients with prostate cancer (25 with bone metastasis and 33 without bone metastasis) and 52 patients with benign prostate hypertrophy who were treated between June 1994-August 1997 were included in this study. All patients were newly diagnosed. RESULTS: Serum ICTP levels in patients with prostate cancer with bone metastasis were significantly higher than those in patients with prostate cancer without bone metastasis (P<0.0001) or with benign prostate hypertrophy (P<0.0001). No significant differences were observed in serum ICTP levels between patients with prostate cancer without bone metastasis and those with benign prostate hypertrophy. Serum ICTP levels correlated significantly with Soloway's grading system for bone scans. Serum ICTP levels in patients with bone metastasis showed a significant downward trend in response to hormonal treatment. CONCLUSIONS: The determination of serum ICTP levels is useful in the assessment of bone metastasis and in monitoring the response of bone metastasis to treatment to prostate cancer.

Uncoupling of bone metabolism in rheumatoid arthritis patients with or without joint destruction: assessment with serum type I collagen breakdown products.

In this study we investigate bone metabolism in patients with rheumatoid arthritis (RA), with or without joint destruction, using serum biochemical markers of bone turnover. Three hundred eighteen patients (disease duration >2 years; mean 9 years) were divided into those with joint destruction, that is, with Larsen wrist X-ray index > or =2 (n = 173) and those without joint destruction, that is, with Larsen wrist X-ray index <2 (n = 145). Bone formation was assessed by serum osteocalcin levels and bone resorption by a new assay for serum type I collagen C-telopeptide breakdown products (serum CTX). Osteocalcin levels were significantly lower in both destructive (-17%) and nondestructive (-22%) groups compared with 319 healthy gender- and age-matched control subjects (p < 0.001 for both groups), but were similar in the two arthritis groups. CTX levels were increased in patients with destructive arthritis compared with controls (+35%, p < 0.001), but were not different between those with nondestructive arthritis and controls. In patients with joint destruction, decreased bone formation rate was amplified in those on steroids (n = 72) compared with nonusers (n = 101) as demonstrated by lower osteocalcin levels (p = 0.02). CTX levels, but not osteocalcin levels, were positively correlated with indices of disease activity and, moreover, of joint destruction (p < 0.002-0.0001). These results indicate that bone metabolism is uncoupled in patients with RA. Bone formation appears to be reduced both in patients with and without joint destruction, whereas resorption is increased only in patients with joint destruction in relation to disease activity.

Application of a new serum assay for type I collagen cross-linked N-telopeptides: assessment of diurnal changes in bone turnover with and without alendronate treatment.

Biochemical markers of bone turnover are finding increased application in the investigation and management of skeletal diseases such as osteoporosis. The present study assessed for the first time the diurnal variation of serum type I collagen cross-linked N-telopeptides (NTx), a new serum-based marker of bone resorption, and the effect of antiresorptive therapy with alendronate on this marker in elderly osteopenic women. The concentrations of serum NTx were monitored over 24 hours in a randomly selected subset of 38 women (placebo n = 13, 69 +/- 3 (SD) year; alendronate n = 25, 69 +/- 3 year), who had completed 12-15 months of a larger (n = 120) randomized, double-blind, parallel group, placebo-controlled trial with alendronate 5 mg/day. Blood was obtained every 4 hours for measurement of serum NTx using a new chemiluminescent-based immunoassay. There was a significant diurnal variation of serum NTx (p = 0.001) in both the placebo and alendronate groups. Mean peak levels occurred at approximately 0504 h with a mean nadir at approximately 1320 h in the placebo group, with no significant difference on alendronate. Serum NTx was approximately 25% lower in the alendronate group over the entire 24-hour period. Mean (SE) daytime (0800-2000) and nighttime (2200-0800) serum NTx values were 6.40 +/- 0.30 versus 8.45 +/- 0.58 nmol BCE/liter, and 7.42 +/- 0.23 versus 10.01 +/- 0.53 nmol BCE/liter for alendronate versus placebo, respectively (P < or = 0.003 for both comparisons). Combining the data of both treatment groups, serum NTx was significantly (P < 0.05) correlated with serum osteocalcin (r = 0.753) and urine NTx (r = 0.628) measurements previously obtained over the entire 24-hour period. Serum NTx has a significant diurnal variation and is responsive to antiresorptive therapy with alendronate. Alendronate reduces the amplitude but maintains the pattern of the 24-hour serum NTx profile. These data suggest that serum NTx may be a useful new marker of bone resorption.