Effect of Neoadjuvant Chemotherapy on the Serum Levels of Bone Turnover Markers in Women with Early-Stage Breast Cancer

Background

To evaluate effects of neoadjuvant chemotherapy on the bone turnover markers of preoperational breast cancer patients.

Methods

Forty-one breast cancer patients (29 premenopausal and 12 postmenopausal) and 60 healthy women (30 premenopausal and 30 postmenopausal) aged 30-64 years, were evaluated for their bone status. Serum levels of the bone formation markers PINP and BAP, as well as the resorption markers ICTP and β-Crosslaps in addition to E2, FSH, 25(OH)D and PTH were measured at the initial diagnosis and at 24 hours after each four chemotherapy cycles. BMD T-scores were determined in 12 patients 6 months after the neoadjuvant chemotherapies.

Results

The baseline levels of both bone formation and resorption markers in premenopausal patients were higher than in premenopausal healthy women (p<0.05), while no statistic difference was observed between postmenopausal patients and postmenopausal healthy women. Regardless of the menopausal status, chemotherapy increased the ICTP and β-Crosslaps levels (p<0.05), but decreased the BAP and PINP levels (p<0.05), the later one significantly more with Taxane medication (p<0.01, p<0.05). Chemotherapy caused significant decreases of 25(OH)D levels in premenopausal (p<0.01) and postmenopausal (p<0.05) patients, however, did not affect the PTH concentrations. In premenopausal patients the E2 level decreased, while the FSH level increased after chemotherapy (p<0.05). Patients with pronounced ICTP and β-Crosslaps combined with reduced BAP and PINP serum concentrations after neoadjuvant chemotherapies were prone to develop osteoporosis 6 month later.

Conclusions

Neoadjuvant chemotherapy appeared to promote bone resorption and inhibit bone formation in both postmenopausal and premenopausal early-stage breast patients.     

Analysis of bone mineral density and turnover in patients with cystic fibrosis: associations between the IGF system and inflammatory cytokines

BACKGROUND: Cystic fibrosis (CF) patients present an increased risk of osteoporosis, and increased fracture rate. Several factors have been identified as modulators of bone metabolism and bone mineral density (BMD). AIMS: To evaluate BMD and serum markers of bone turnover and establish their relationships with serum concentrations of interleukin (IL)-1beta, IL-6, tumour necrosis factor (TNF)-alpha, IGF-I, IGF-II, IGF binding protein (IGFBP)-2, IGFBP-3, and parathyroid hormone (PTH) in young adult CF patients. METHODS: Seventeen young adult CF patients (4 M, 13 F; mean age: 26.6 +/- 1.1 years) were enrolled in the study and analysed as a whole and as two subgroups according to the Shwachman-Kulczycki score. BMD was assessed at the lumbar spine (L1-L4) by dual energy X-ray absorptiometry (DXA Hologic QDR 2000). Bone turnover was assessed by measuring serum levels of osteocalcin (OC) and serum carboxyterminal propeptide of type I collagen (PICP) as markers of bone formation, and serum cross-linked carboxyterminal telopeptide of type I collagen (ICTP) as a marker of bone resorption. Serum IGFs, IGFBPs, and cytokines were assayed using special commercial kits. Daily calcium intake and weekly physical activity were estimated by questionnaires. Forced expiratory volume in one second was used to assess pulmonary function. RESULTS: Lumbar BMD was normal, although there was a tendency to be lower in the patients with a lower clinical score. Both OC and PICP were increased, whereas ICTP was normal. Lumbar BMD was positively correlated with pulmonary function. IL-6 and C-reactive protein (markers of inflammation) were inversely correlated with PICP. Serum ICTP levels were correlated with serum IGF-I levels.No significant relationship was detected among lumbar BMD, markers of bone turnover and PTH, IGF-I, IGF-II, IGFBP-2, IGFBP-3, TNF-alpha, IL-1beta, and body mass index Z-score. CONCLUSIONS: Bone turnover is abnormal in CF patients. Young adult CF patients with satisfying clinical status and nutritional conditions have normal BMD and increased serum OC and PICP levels.     

Hormone replacement therapy,calcium and vitamin D<Subscript>3</Subscript> versus calcium and vitamin D<Subscript>3</Subscript>alone decreases markers of cartilage and bone metabolism in rheumatoid arthritis: a randomized controlled trial [ISRCTN46523456]

This study aimed to evaluate the effects of hormone replacement therapy (HRT), known to prevent osteoporosis and fractures, on markers of bone and cartilage metabolism. Furthermore, we assessed whether changes in these markers corresponded to alterations in bone mineral density and radiographic joint destructions in postmenopausal women with rheumatoid arthritis. Eighty-eight women were randomized to receive HRT, calcium, and vitamin D3, or calcium and vitamin D3 alone, for 2 years. Bone turnover was studied by analyzing serum levels of C-terminal telopeptide fragments of type I collagen (CTX-I), C-terminal telopeptide of type I collagen (ICTP), bone sialoprotein, and C-terminal propeptide of type I procollagen (PICP) and cartilage turnover by urinary levels of collagen type II C-telopeptide degradation fragments (CTX-II) and cartilage oligomeric matrix protein (COMP) in serum. Treatment with HRT resulted in decrease in CTX-I (P < 0.001), ICTP (P < 0.001), PICP (P < 0.05), COMP (P < 0.01), and CTX-II (P < 0.05) at 2 years. Reductions in CTX-I, ICTP, and PICP were associated with improved bone mineral density. Of the markers tested, CTX-I reflected bone turnover most sensitively; it was reduced by 53 +/- 6% in the patients receiving HRT. Baseline ICTP (P < 0.001), CTX-II (P < 0.01), and COMP (P < 0.05) correlated with the Larsen score. We suggest that biochemical markers of bone and cartilage turnover may provide a useful tool for assessing novel treatment modalities in arthritis, concerning both joint protection and prevention of osteoporosis.     

Changes in serological biomarkers of liver function and connective tissue turnover in chronic hepatitis B during lamivudine therapy

Abstract

Assessment of hepatic damage associated with chronic hepatitis B (CHB) currently relies on measurement of serum transaminases and assessment of hepatic histology. It was determined serum hepatic function tests and the liver fibrosis biomarkers type IV collagen (CIV), amino-terminal propeptide of type I procollagen (PINP), amino-terminal propeptide of type III procollagen (PIIINP) and carboxy-terminal telopeptide of type I collagen (ICTP) were of value in monitoring the effect of lamivudine therapy for CHB. Thirty-nine patients received orally 100?mg lamivudine daily for 48 weeks. Blood samples were obtained at baseline, 24 and 48 weeks. At the end of the treatment period, the patients were then divided into four groups according to the pattern of HBs and HBe antigens. At baseline, alanine aminotransferase, aspartate aminotransferase, PIIINP and the PINP/ICTP ratio and at 24 weeks alanine aminotransferase, aspartate aminotransferase and the PINP/ICTP ratio had lower values in the complete response compared with complete failure groups. Using receiver-operated curve analysis, only the PINP/ICTP ratio at baseline (area under the curve 0.806) and ALT and the PINP/ICTP ratio at 24?weeks (areas under the curve 0.803 and 0.776, respectively) had significant diagnostic ability in detecting responders. In conclusion, the PINP/ITCP ratio is sensitive and specific in detecting responders to treatment.     

Changes in serological biomarkers of liver function and connective tissue turnover in chronic hepatitis B during lamivudine therapy

Assessment of hepatic damage associated with chronic hepatitis B (CHB) currently relies on measurement of serum transaminases and assessment of hepatic histology. It was determined serum hepatic function tests and the liver fibrosis biomarkers type IV collagen (CIV), amino-terminal propeptide of type I procollagen (PINP), amino-terminal propeptide of type III procollagen (PIIINP) and carboxy-terminal telopeptide of type I collagen (ICTP) were of value in monitoring the effect of lamivudine therapy for CHB. Thirty-nine patients received orally 100 mg lamivudine daily for 48 weeks. Blood samples were obtained at baseline, 24 and 48 weeks. At the end of the treatment period, the patients were then divided into four groups according to the pattern of HBs and HBe antigens. At baseline, alanine aminotransferase, aspartate aminotransferase, PIIINP and the PINP/ICTP ratio and at 24 weeks alanine aminotransferase, aspartate aminotransferase and the PINP/ICTP ratio had lower values in the complete response compared with complete failure groups. Using receiver-operated curve analysis, only the PINP/ICTP ratio at baseline (area under the curve 0.806) and ALT and the PINP/ICTP ratio at 24 weeks (areas under the curve 0.803 and 0.776, respectively) had significant diagnostic ability in detecting responders. In conclusion, the PINP/ITCP ratio is sensitive and specific in detecting responders to treatment.     

Relationships of serum leptin levels with biochemical markers of bone turnover and with growth factors in normal weight and overweight children

Objective: To examine the hypothesis of an influence of leptin on growth factors and on biochemical markers of bone turnover of prepubertal overweight children. Design and Methods: 395 prepubertal children, 6-13 years of age, were selected and the relationships between circulating serum levels of leptin and insulin-like growth factor I (IGF-I), insulin growth factor binding protein-3 (IGFBP-3) and some biochemical markers of bone turnover (osteocalcin, OC; carboxyterminal propeptide of type I procollagen, PICP, and carboxyterminal propeptide of type I collagen, ICTP) were analyzed. The subjects were subdivided into normal weight (NW, n = 163) and weight excess (WE, n = 232) subjects. Results and Conclusions: Significant differences between the two groups were found for leptin (p < 0.01), IGF-I (p < 0.01) and IGFBP-3 (p < 0.01), with higher values in WEs, and for OC (p < 0.01) with higher values in NWs. A significant reduction of leptin (p < 0.01) and IGFBP-3 (p < 0.01) serum values and an increase of those of OC (p < 0.01) and PICP (p < 0.05), but not of ICTP, were registered in 103 WEs who showed a drop in weight excess during a weight-excess reduction program. No variations were observed in 26 non-responsive subjects. In a multivariate analysis in which leptin, corrected by BMI and sex, was the independent variable, a significant negative correlation was found with PICP (beta = -0.235, p < 0.01), IGF-I (beta = -0.180, p < 0.01) and height velocity (beta = -0.155, p < 0.01). There was no correlation with OC, ICTP and IGFBP-3. The results demonstrate that nutritional status and leptin levels are involved in the regulation of growth factors and biochemical markers of bone formation.     

The correlation of serum immunoglobulin free light chain levels and selected biological markers in multiple myeloma

Aims: the presented study is aimed at the evaluation of correlation of free light chains serum levels - kappa, lambda and their relation (K/L ratio) and serum levels of selected biological markers in a group of patients with multiple myeloma examined at the time of the diagnosis. Methods: 102 patients with multiple myeloma were included in this prospective study. Free light chains serum levels were determined by Freelite Binding Site system, for determination of serum levels of selected parameters the following methods were used: REA thymidinekinase (TK), RIA (beta(2)microglobulin (beta(2)m), ICTP, PINP), enzymoimmunoassay (sIL-6R, sVCAM-1, sICAM-1, sOPG) and quantitative enzymatic immunoassay (sHGF, sVEGF, sSyndecan-1 (sSyn-1) a sFas). Results: There was found a correlation in the kappa-group of the dominant kappa chain and serum readings of beta(2)m (r = 0.344, p = 0.005), TK (r = 0.263, p = 0.035), ICTP (r = 0.402, p = 0.001), PINP (r = 0.264, p = 0.039), sOPG (r = 0.328, p = 0.028), sSyn-1 (r = 0.255, p = 0.046) and sFas (r = 0.418, p = 0.001). In case of K/L ratio there was found a statistically significant association of levels of beta(2)m (r = 0.316, p = 0.01), TK (r = 0.274, p = 0.027), ICTP (r = 0.346, p = 0.006), PINP (r = 0.261, p = 0.042), sSyn-1 (r = 0.283, p = 0.026) and sFas (r = 0.377, p = 0.002). In the lambda-group the analysis confirmed mutual dependence of the dominant lambda chain levels on beta(2)m (r = 0.476, p = 0.003), ICTP (r = 0.375, p = 0.022), sVCAM-1 (r = 0.383, p = 0.019), sHGF (r = 0.441, p = 0.006) and sFas (r = 0.334, p = 0.040). In addition we ascertained a correlation of L/K ratio and levels of beta(2)m (r = -0.473, p = 0.003), TK (r = -0.412, p = 0.011), ICTP (r = -0.331, p = 0.045), PINP (r = -0.409, p = 0.012), sHGF (r = -0.357, p = 0.028), sSyn-1 (r = -0.449, p = 0.005) a sFas (r = - 0.371, p = 0.022). Conclusions: The study confirmed mutual correlation of FLC serum levels and the levels of several selected biological markers, in particular beta(2)m, TK, ICTP, PINP, sSyn-1 a sFas at time of the diagnosis. It referred to the mutual relation of bone marrow microenvironment, biological qualities of clonal plasmocytes and the intensity of the free light chains production by the tumour cell population.     

Characteristics of bone tissue metabolism in adolescents with undifferentiated connective tissue dysplasia

Biochemical markers of bone metabolism, including osteocalcin, total aminoterminal propeptide type I collagen (PINP), and the product of degradation of carboxy-terminal telopeptide type I collagen (β-CrossLaps) were studied in 17 adolescents 11–14 years of age with undifferentiated connective tissue dysplasia (UDCT). Decreased serum concentrations of bone formation markers (PINP and osteocalcin) against the background of normal levels of the bone resorption marker (β-CrossLaps) indicated that the processes of bone remodeling were disturbed and characterized by low-intensity bone-tissue formation with the relative predominance of resorption. The detected bone metabolism disturbances contributed to the development of osteopenia, which gives us grounds to include adolescents with UDCT to the risk group for early-onset osteoporosis.     

Monitoring of bone resorption and bone formation in multiple myeloma

The article deals with the clinical value of monitoring of serum markers of osteoresorption (ICTP) and bone formation (PICP) in multiple myeloma. In a group of patients treated by conventional chemotherapy and group of patients treated by high dose chemotherapy with autologous peripheral blood stemm cell transplantation (APBSTC).     

Increased bone turnover is associated with protein and energy metabolism in adolescents with sickle cell anemia

Contribution of bone turnover to the hypercatabolic state observed in sickle cell anemia is unknown. We examined the association between markers of bone turnover and basal rates of whole body protein turnover and energy expenditure in 28 adolescents with homozygous sickle cell anemia (HbSS) and in 26 matched controls with normal phenotype (HbAA). Whole body protein breakdown and synthesis were measured using a stable isotope of [15N]glycine, resting energy expenditure was measured by whole room indirect calorimetry, and the rate of pyridinoline cross-link (PYD) excretion in urine and fasting serum levels of the type I procollagen carboxy-terminal propeptide (PICP) were measured with commercial kits. Urinary PYD and serum PICP were significantly elevated in HbSS patients. The increase in procollagen synthesis, indicated by high levels of PICP, was significantly correlated with increased whole body protein synthesis. The increase in type I collagen degradation, indicated by high PYD excretion, was significantly correlated with increased protein breakdown. We conclude that increased rates of bone turnover contribute to the increased rates of protein turnover and energy expenditure observed in adolescents with homozygous sickle cell anemia.     

Influence of pinealectomy and long-term melatonin administration on bone metabolism in orchidectomized rats

INTRODUCTION: The aim of the study was to demonstrate whether pinealectomy and long-term MEL administration can affect bone metabolism (as evaluated on the basis of serum concentrations of PICP and ICTP) in orchidectomized rats. MATERIAL AND METHODS: The study included 248 adult male Wistar rats; 6 remained intact, 120 were orchidectomized (Orch), and the remaining ones underwent a sham operation (SOrch). Two weeks after surgery, the rats were divided into 8 groups: 1) SOrch + SPx; 2) SOrch + SPx + MEL; 3) Orch + SPx; 4) Orch + SPx + MEL; 5) SOrch + Px; 6) SOrch + Px + MEL; 7) Orch + Px; 8) Orch + Px + MEL. Animals from 5(th), 6(th), 7(th) and 8(th) groups were pinealectomized (Px) while the remaining ones underwent a sham operation (SPx). Two weeks after surgery rats in the 2(nd), 4(th), 6(th) and 8(th) groups were administered MEL (50 microg/100 g of bm) intraperitoneally while the remaining animals were administered solvent only (daily between 5 and 6 pm during a month). The animals were decapitated before the experiment (intact rats), after 2 weeks from Orch and SOrch, Px and SPx, after 4 weeks from MEL or solvent administration and after 4 and 8 weeks from discontinuing administration of MEL, and blood was collected for PICP and ICTP concentrations assays with the use of RIA method. DISCUSSION: In Orch rats, a distinct tendency to increase the studied bone markers, especially ICTP was shown. Pinealectomy had inducing, while MEL suppressing effect upon the level of PICP and ICTP; these changes were more pronounced in Orch + Px and SOrch + Px + MEL groups, respectively. After discontinuing administration of MEL distinct tendency to increase of PICP and ICTP level was shown. CONCLUSIONS: Our findings indicate that MEL is an important modulator of bone tissue metabolism in male rats and that deficiency of MEL concentration may be a co-factor in osteoporosis development.     

Changes of collagen metabolism predict the left ventricular remodeling after myocardial infarction

Objectives: To analyze the predictive value of cardiac collagen metabolism “in vivo" in patients with myocardial infarction (MI) treated with percutaneous coronary intervention (PCI). Design: Forty-five patients (age 66 ± 8.27) underwent biochemical analysis for cardiac collagen metabolism (groups A, B and C); 30 patients with their first MI were treated with successful PCI (group A; n = 30), group B (n = 5) were MI patients with unsuccessful PCI. Group C were patients without MI (n = 10), they underwent elective diagnostic coronary angiography only. The collagen metabolism was analyzed in acute and subacute MI phases by using serum blood markers: the carboxy-terminal propeptide of type I procollagen (PICP), amino-terminal propeptide of type III procollagen (PIIINP) and carboxy-terminal telopeptide of type I collagen (ICTP). Furthermore, the ejection fraction (EF) and left ventricular end-diastolic volume maximal changes in the course of 6 months were measured by echocardiography. Results: A significant increase of both PICP and PIIINP on day 4 following MI was detected. Furthermore, PICP and PIIINP level assessed on the 30th day was significantly higher in the PCI unsuccessful group versus successful group. PICP level on day 4 above 110 ug/l and PIIINP level above 4 ug/l was significantly often found in the subgroup of patients with the EF improvement less than 10% or worsening and with significant left ventricular dilatation during 6 months follow-up. Cardiac catheterization itself does not affect collagen metabolism. Conclusion: We concluded that collagen metabolism markers enable to study in vivo the MI healing and to predict left ventricular functional and volume changes.     

Immobilization-dependent bone collagen breakdown appears to increase with time: evidence for a lack of new bone equilibrium in response to reduced load during prolonged bed rest.

The purpose of this study was to evaluate the effect of prolonged immobilization on bone, in order to investigate how skeletal turnover adapts to bed rest. We examined indices of bone formation and bone resorption in the serum and urine of fifty-four patients (26 males and 28 females) immobilized after an episode of paralytic stroke. The length of immobilization ranged from 30 to 180 days. A significant, time-dependent increase in markers of resorption - urinary pyridinoline (Pyr) and deoxypyridinoline (D-Pyr), serum Type I collagen cross-linked C-telopeptide (ICTP) - was observed in immobilized patients, as compared to free-living healthy subjects. The positive correlation between resorption markers increase and the length of immobilization suggests that the rate of bone resorption did not decrease with time. On the other hand, the levels of markers of bone formation - bone-specific alkaline phosphatase (B-ALP), and the carboxyl-terminal propeptide of Type I procollagen (PICP) - remained within the normal range in all patients, regardless the length of immobilization. Our results would indicate an uncoupling between bone formation and bone resorption during bed rest, and suggest that the bone collagen break-down was not a self-limiting process in immobilized patients, and that a new equilibrium or "steady state" in response to the reduced load was not reached in the skeleton.     

Increased autocrine production of insulin-like growth factor II (IGF-II) alters serum sensitivity of MCF-7 human breast cancer cell proliferation

Abstract. Regulation of the growth of breast cancer cells is the result of a complex interaction between steroid hormones and growth factors, and in particular of oestrogen and insulin-like growth factors (IGF). Alteration of any one mitogenic component can affect the cell response to other pathways. Previous work has shown that increased autocrine production of IGF-II from a transfected inducible expression vector can result in reduced oestrogen sensitivity of growth of MCF-7 human breast cancer cells. This report describes alterations to non-oestrogen regulated pathways of cell growth following enhanced IGF-II expression in these transfected MI7 cells. Serum sensitivity of cell growth in the absence of oestrogen was found to differ between MI7 and untransfected MCF-7 cells, in that growth of MI7 but not MCF-7 cells was strongly inhibited by high serum levels. Increased serum had no effect on levels of IGF-II mRNA, IGFIR, IGFBP4 mRNA, or IGFBP secreted in MI7 cells. However, growth inhibition by serum in MI7 cells could be overcome by increasing levels of IGF-II in the serum or by removal of IGFBP onto polycarbonate membranes. Thus, the growth inhibition by serum in MI7 cells is concluded to result from the increased levels of IGFBP added with higher serum. This would support an inhibitory role for IGFBP on growth of breast cancer cells when cell growth is being driven by IGF pathways in the absence of oestrogen, and would suggest that cellular sensitivity to such factors can depend on levels of endogenous IGF production.     

Serum interleukin-6 in renal osteodystrophy: relationship with serum PTH and bone remodeling markers.

Interleukin-6, synthesized by osteoblasts in response to PTH, stimulates osteoclastogenesis and bone resorption in vitro, and it has been implicated in the pathogenesis of bone loss in several clinical situations. The aim of this study was to evaluate whether serum levels of interleukin-6 were increased in patients with renal osteodystrophy, and to investigate the possible relationships between serum interleukin-6 and PTH levels on one hand, and serum interleukin-6 and bone remodeling markers on the other. Serum interleukin-6 (IL-6), intact PTH, osteocalcin, bone alkaline phosphatase (BAP) and carboxyterminal telopeptide of Type 1 collagen (ICTP) were measured in 86 uremic patients. IL-6 (median [range] 16.5 [1.0-430] pg/ml), PTH (279.8 [11-2004] pg/ml), osteocalcin (143.8 [8-921] ng/ml), BAP (20.9 [6-169] U/I) and ICTP (38.8 [1.5-181.5] microg/l) were higher than normal. IL-6 levels correlated with PTH (r= 0.22, p = 0.04) and with ICTP (r = 0.31, p = 0.004). A stronger correlation was found between PTH and circulating bone remodeling markers (r = 0.66 for osteocalcin, r = 0.56 for BAP, and r = 0.39 for ICTP). The correlation between PTH and IL-6 was stronger in those patients (n = 15) with severe secondary hyperparathyroidism (r= 0,71, p = 0.003). On the other hand, in the group of patients (n = 41) with PTH lower than 250 pg/ml, there was no correlation between IL-6 and PTH, while IL-6 correlated with ICTP (r = 0.44, p = 0.006). Serum IL-6 correlates with ICTP which suggests that it may mediate bone resorption in renal osteodystrophy.     

Oestrogen receptor content of normal breast cells and breast carcinomas throughout the menstrual cycle

To examine the presence and distribution of oestrogen receptors in the normal breast during the menstrual cycle cytological samples obtained by fine needle aspiration from 69 premenopausal women with normal breasts were analysed immunocyto-chemically with a monoclonal antibody to oestrogen receptor; samples from 15 postmenopausal women were also analysed. The receptor content of breast cancers from 83 premenopausal women was also determined in relation to when during the menstrual cycle excision was performed. In the normal premenopausal women oestrogen receptors were detected in the nuclei of epithelial cells in 21 out of 68 (31%) assessable samples. All 21 of these samples were obtained from the 35 women who were studied during the first half of their menstrual cycle (days 28 to 14). None of the 33 samples obtained during the second half of the cycle contained oestrogen receptors. Samples were assessable in eight of the postmenopausal women, six giving a positive result for oestrogen receptor. Fifty one of the 83 carcinomas were positive for oestrogen receptor, 24 having been excised during the first half of the cycle and 27 during the second half.Production of oestrogen receptor protein is suppressed at the time of ovulation in the normal breast epithelium of premenopausal women. In contrast, breast carcinoma cells either synthesise this protein continuously throughout the cycle or fail to express it despite fluctuations of serum hormone concentrations.     

Interleukin-6: a growth factor stimulating collagen synthesis in human tendon

Human connective tissue, e.g., tendon, responds dynamically to physical activity, with collagen synthesis being increased after both acute and prolonged exercise or training. Markers of collagen synthesis and degradation as well as concentration of several potential growth factors have been shown to increase markedly in the peritendinous tissue around the human Achilles tendon following exercise. Of these potential growth factors interleukin-6 (IL-6) showed the largest fold increase, suggesting that IL-6 may be involved in transforming mechanical loading into collagen synthesis in human tendon tissue. In the present study the tissue levels of type I collagen turnover markers [procollagen type I NH(2)-terminal propeptide (PINP) and C-OOH terminal telopeptide of type I collagen (ICTP)] were measured by the use of microdialysis in peritendinous tissue of the Achilles tendon in 14 male volunteers, who had recombinant human IL-6 (rhIL-6) infused into the peritendinous tissue of the Achilles' tendon in one leg, with the other leg serving as control. Subjects were randomly assigned to either a resting group or an exercise group performing a 1-h treadmill run (12 km/h, 2% uphill) before infusion. In addition to IL-6, serum concentrations of collagen turnover markers PINP, ICTP, and COOH-terminal telopeptide of type I collagen (ICTX) were measured. The peritendinous concentration of PINP rose markedly in response to rhIL-6 infusion in both the exercise and the rest group, demonstrating that infusion of IL-6 significantly stimulates collagen synthesis in the peritendinous tissue in humans. Exercise alone did not result in an increased collagen synthesis. This indicates that IL-6 is involved in the collagen synthesis and supports the hypothesis that IL-6 is an important growth factor of the connective tissue in healthy human tendons.     

Effects of long-term immobilization and recovery on human triceps surae and collagen turnover in the Achilles tendon in patients with healing ankle fracture.

The aim of the present study was to analyze how human tendon connective tissue responds to an approximately 7-wk period of immobilization and a remobilization period of a similar length, in patients with unilateral ankle fracture, which is currently unknown. Calf muscle cross-sectional area (CSA) decreased by 15% (5,316 to 4,517 mm2) and strength by 54% (239 to 110 N.m) in the immobilized leg after 7 wk. During the 7-wk remobilization, the CSA increased by 9% (to 4,943 mm2) and strength by 37% (to 176 Nm). Achilles tendon CSA did not change significantly during either immobilization or remobilization. Local collagen turnover was measured as the peritendinous concentrations of NH2-terminal propeptide of type I collagen (PINP) and COOH-terminal telopeptide region of type I collagen (ICTP), markers thought to be indexes of type I collagen synthesis and degradation, respectively. Both markers were increased (PINP: 257 vs. 56 ng/ml; ICTP: 9.8 vs. 2.1 microg/l) in the immobilized leg compared with the control leg after the 7 wk of immobilization, and levels decreased again in the immobilized leg during the recovery period (PINP: 103 vs. 44 ng/ml; ICTP: 4.2 vs. 1.9 microg/l). A significant reduction in calf muscle CSA and strength was found in relation to 7 wk of immobilization. Immobilization increased both collagen synthesis and degradation in tendon near tissue. However, it cannot be excluded that the facture of the ankle in close proximity could have affected these data. Remobilization increased muscle size and strength and tendon synthesis and degradation decreased to baseline levels. These dynamic changes in tendon connective tissue turnover were not associated with macroscopic changes in tendon size.     

甲状腺癌术后短期甲状腺功能低下对骨代谢的影响

目的:观察分化型甲状腺癌(DTC)患者手术后、碘131(131I)清甲治疗前停用甲状腺素造成的短期甲减对骨代谢的影响。方法:选择DTC术后患者53例作为试验组,50例健康人作为对照组,试验组于停服甲状腺素第二天空腹采血行游离甲状腺素(FT4)、游离三碘甲状腺原氨酸(FT3)、促甲状腺激素(TSH)、血钙(Ca)、血磷(P)、血清碱性磷酸酶(ALP)、血清骨钙素(BGP),I型前胶原羧基末端前肽(PICP)、I型胶原交联羧基末端肽(ICTP)等各项检查,停服甲状腺素4周后于131I治疗前再行上述检查,对照组于体检当日采空腹血测相同项目。结果:试验组患者停药前血清FT3、FT4水平明显高于对照组,差异有统计学意义(P0.05)。停服甲状腺素后,试验组患者血清TSH升高,T3、T4水平降低,血BGP、血Ca、PICP、ICTP水平降低,与停药前及对照组的检验结果相比均有明显差异(P0.05)。停药后,骨密度与停药前比较差异无统计学意义(P0.05)。停服甲状腺素前后血磷水平无明显变化,与对照组相比也没有明显差异(P0.05)。结论:甲状腺癌术后造成甲状腺功能低下可明显影响患者骨代谢,应于131I后及时给予甲状腺激素,及时纠正甲低状态,同时也可适量补充钙剂。     

骨科损伤控制救治对四肢骨折患者血清骨代谢和炎症反应的影响

为探究骨科损伤控制(damage control orthopaedics, DCO)救治对四肢骨折患者血清骨代谢及炎症反应的影响,本研究选取40例四肢骨折患者,随机分为治疗组和对照组,各20例。治疗组采用骨科损伤控制救治四肢骨折患者,对照组则采用常规骨折治疗方法。酶联免疫法检测试剂盒检测骨代谢指标:骨钙素(bone gla protein, BGP)、Ⅰ型前胶原羧基端前肽(propeptide carboxy-terminal procollagen, PICP)水平、血清碱性磷酸酶(alkaline phosphatase, ALP),骨愈合相关指标:可溶性细胞间粘附分子-1 (soluble intercellular adhesion molecule 1, s ICAM-1)、胰岛素样生长因子-1 (insulin like growth factor-1, IGF-1),以及炎症反应相关因子白细胞介素-1 (interleukin-1, IL-1)、白细胞介素-6 (interleukin-6, IL-6)、肿瘤坏死因子-α(tumor necrosis factor-alpha, TNF-α);统计分析各组患者手术后疼痛程度以及肿胀程度评分。结果表明,骨科损伤控制治疗组的血清骨钙素(BGP)、Ⅰ型前胶原氨基酸末端前肽(PICP)水平、血清碱性磷酸酶(ALP)、可溶性细胞间粘附分子-1 (sICAM-1)和胰岛素样生长因子-1 (IGF-1)水平明显高于对照组;炎症反应因子IL-1、IL-6和TNF-α水平明显低于对照组;骨科损伤控制救治可明显降低四肢骨折患者术后的疼痛程度以及肿胀程度评分。综上所述,骨科损伤控制救治可明显提高四肢骨折患者血清骨代谢和骨愈合水平、降低炎症反应、疼痛以及肿胀程度。