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C-terminal Telopeptide (c-terminal + telopeptide)
Selected AbstractsType I collagen markers in cord serum of appropriate vs. small for gestational age infants born during the second half of pregnancyEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 5 2001T. Saarela Background The serum concentration of the N-terminal propeptide of type I procollagen (PINP) reflects the synthesis rate of type I collagen, whereas the corresponding C-terminal telopeptide (ICTP) mirrors its degradation. Design PINP and ICTP were measured in a total of 690 cord serum samples from 592 appropriate-for-gestational-age (AGA) infants and 98 smal-for-gestational-age (SGA) infants. These markers were compared between AGA and SGA infants of different gestational ages, ranging from 23 to 41 weeks, and birth weights, from 620 to 4555 g. Results Both PINP and ICTP levels were very high in the preterm AGA infants and declined significantly with advancing gestational age, paralleling the shape of the fetal growth velocity curve. Regardless of the quite large interindividual variations observed in these markers, PINP was significantly lower in both the preterm and term AGA infants than in the SGA infants. This was also the case for ICTP in the preterm infants of gestational age less than 36 weeks. In stepwise multiple regression analyses, gestational age, being either AGA or SGA and head circumference were significant factors to explain the levels of PINP and ICTP. The levels of PINP and ICTP were correlated with each other highly significantly in both the AGA and SGA infants (rs = 0·700 and 0·692, respectively; P < 0·001 in both). Conclusions The levels of type I collagen markers seem to follow closely the shape of the fetal growth velocity curve during different stages of gestation. However, because of the large interindividual variations observed, further studies are needed before the significance of these markers for the assessment of normal and abnormal fetal growth can be established. [source] Head-to-head comparison of risedronate vs. teriparatide on bone turnover markers in women with postmenopausal osteoporosis: a randomised trialINTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 6 2008A. D. Anastasilakis Summary Aims:, We aimed to compare the effect of risedronate (RIS) and teriparatide (TPTD) (recombinant human parathyroid hormone 1,34) on bone turnover markers in women with postmenopausal osteoporosis. Methods:, Forty-four Caucasian women (age 65.1 ± 1.6 years) with postmenopausal osteoporosis were randomly assigned to receive either RIS 35 mg once weekly (n = 22) or TPTD 20 ,g once daily (n = 22) for 12 months. Serum N-terminal propeptide of type 1 collagen (P1NP), C-terminal telopeptide of type 1 collagen (CTx), total alkaline phosphatase (ALP) and intact parathyroid hormone (iPTH) were obtained from all women before, 3 and 6 months after treatment initiation. Lumbar spine bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry before and 12 months after treatment initiation. Results:, P1NP, CTx and total ALP levels decreased in RIS group (p < 0.001) and increased in TPTD group (p < 0.001) throughout the treatment. iPTH increased significantly in RIS group (p < 0.05) and decreased in TPTD group (p < 0.001). Finally, lumbar spine BMD increased significantly in both RIS (p = 0.003) and TPTD groups (p < 0.001) without significant differences between them. Conclusions:, Our data suggest that both serum P1NP and CTx are reliable markers of RIS and TPTD action in women with postmenopausal osteoporosis. In a similar way, serum total ALP can be used as an alternative marker for monitoring both RIS and TPTD action, while iPTH can be used only for TPTD-treated women. The increase in P1NP and CTx after 3 months of treatment with RIS or TPTD can predict the increase in BMD after 12 months of treatment. [source] Bioavailability and Biological Efficacy of a New Oral Formulation of Salmon Calcitonin in Healthy Volunteers,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 8 2002Thierry Buclin Abstract Salmon calcitonin (SCT) is a well-tolerated peptide drug with a wide therapeutic margin and is administered parenterally for long-term treatments of bone diseases. Its clinical usefulness would be enhanced by the development of an orally active formulation. In this randomized crossover double-blinded phase I trial, controlled by both a placebo and a parenteral verum, we have tested a new oral formulation of SCT associated with a caprylic acid derivative as carrier. Eight healthy volunteers received single doses of 400, 800, and 1200 ,g of SCT orally, a placebo, and a 10-,g (50 IU) SCT intravenous infusion. SCT was reliably absorbed from the oral formulation, with an absolute bioavailability of 0.5,1.4%, depending on the dose. It induced a marked, dose-dependent drop in blood and urine C-terminal telopeptide of type I collagen (CTX), a sensitive and specific bone resorption marker, with the effects of 1200 ,g exceeding those of 10 ,g intravenously. It also decreased blood calcium and phosphate, and increased the circulating levels of parathyroid hormone (PTH) and, transiently, the urinary excretion of calcium. It was well-tolerated, with some subjects presenting mild and transient nausea, abdominal cramps, diarrheic stools, and headaches. This study shows that oral delivery of SCT is feasible with reproducible absorption and systemic biological efficacy. Such an oral formulation could facilitate the use of SCT in the treatment of osteoporosis and other bone diseases. [source] Cross-Sectional Evaluation of Bone Metabolism in Men,JOURNAL OF BONE AND MINERAL RESEARCH, Issue 9 2001P. Szulc Abstract There are relatively few data concerning age-related changes of bone turnover in men. The aim of the study was to evaluate age-related changes of the levels of serum and urinary biochemical markers of bone metabolism in a large cohort of 934 men aged 19,85 years and to investigate their association with bone mineral density (BMD). Bone formation was evaluated using serum levels of osteocalcin (OC), bone alkaline phosphatase (BAP), and N-terminal extension propeptide of type I collagen (PINP). Bone resorption was evaluated by measurement of urinary excretion of ,-isomerized C-terminal telopeptide of collagen type I (,-CTX) of free deoxypyridinoline (fDpyr) and total Dpyr (tDPyr) and of the serum level of ,-CTX. Levels of biochemical bone markers were very high in young men and decreased rapidly until the age of 40 years and then more slowly until 60 years of age. After the age of 60 years, markers of bone formation remained stable while resorption markers showed a moderate and variable increase with aging. Serum and urinary ,-CTX levels were elevated only in about 5% of elderly men. The age-related increase of urinary excretion of tDpyr and of its free and peptide-bound fractions was related to the presence of elevated levels in a subgroup of about 15% of elderly men. Before 60 years of age, levels of biochemical bone markers were not correlated with BMD, whereas after 60 years of age, they were correlated negatively with BMD. After adjustment for age and body weight, BMD in men with the highest levels of biochemical bone markers (i.e., in the upper quartile) was 1.8,12.5% (i.e., 0.25,0.89 SD) lower than in men with levels of biochemical bone markers in the lowest quartile. In conclusion, bone turnover in men is high in young adults and decreases to reach a nadir at 55,60 years of age. After the age of 60 years, bone resorption markers,but not bone formation markers,increase in some men and are associated with lower BMD, suggesting that this imbalance is responsible for increasing bone loss in elderly men. [source] Markers of bone destruction and formation and periodontitis in type 1 diabetes mellitusJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 8 2009David F. Lappin Abstract Aim: To determine plasma concentrations of bone metabolism markers in type 1 diabetes mellitus patients and non-diabetic and to evaluate the influence of periodontitis on biomarkers of bone formation in these patient groups. Methods: Plasma concentrations of receptor activator of nuclear factor- ,B ligand (RANKL), osteoprotegerin (OPG), C-terminal telopeptide of type 1 collagen and osteocalcin were measured in type 1 diabetes mellitus patients (n=63) and non-diabetics (n=38) who were also subdivided on the basis of their periodontal status. Results: Diabetics had significantly lower osteocalcin concentrations, lower RANKL to OPG ratios and higher OPG concentrations (as shown by other researchers) than non-diabetics. The ratio of RANKL to OPG was altered by the periodontal status. Osteocalcin had a negative correlation and OPG a positive correlation with the percentage of glycated haemoglobin in the blood. Conclusion: Because, osteocalcin, a biomarker of bone formation, is lower in patients with periodontitis and in patients with type 1 diabetes mellitus with and without periodontitis than in non-diabetics without periodontitis, this might indicate that diabetics are less able to replace bone lost during active bursts of periodontitis and explain the greater severity of disease seen in studies of patients with diabetes. [source] Local biochemical markers of bone turnover: relationship to subsequent density of healing alveolar bone defectsJOURNAL OF CLINICAL PERIODONTOLOGY, Issue 3 2004Richard A. Reinhardt Abstract Objectives: This pilot study was designed to test whether biochemical markers of bone turnover in washes of periosteal or trabecular alveolar bone surfaces could be correlated with increases in bone density of an adjacent healing implant socket. Methods: Ten subjects had a canula inserted into the alveolar crest and sterile phosphate-buffered saline was washed over the periosteal and trabecular surfaces and collected. Surgical flaps were reflected, 5 mm diameter bone cores were removed from the bone wash site, and standardized radiographs were taken. The sites were allowed to heal for 12 weeks, and radiographs were repeated. Bone washes of the healing sites were also collected after 2 and 12 weeks. Washes were analysed for bone turnover markers osteocalcin (OC; radioimmunoassay) and C-terminal telopeptide of Type 1 collagen (ICTP; enzyme-linked immunosorbent assay (ELISA)), and blood component albumin (ALB; ELISA). Changes in bone density during healing were determined by radiographic absorptiometry. Results: OC/ALB and ICTP/ALB ratios were higher for trabecular than periosteal washes at baseline (p0.01). Trabecular OC/ALB and ICTP/ALB were inversely correlated with increasing bone density of the healing bone core socket (r=,0.72, p=0.03; Pearson's correlation coefficient). Conclusions: Biochemical markers of bone turnover in bone washes of specific alveolar bone sites may prove helpful in predicting how the bone density will increase around healing dental implants. [source] An open-label, phase 2 trial of denosumab in the treatment of relapsed or plateau-phase multiple myeloma,,AMERICAN JOURNAL OF HEMATOLOGY, Issue 10 2009Ravi Vij RANKL is a key mediator of osteoclast differentiation, activation, and survival. Preclinical data suggest that aberrant production and activation of osteoclasts may influence proliferation of multiple myeloma (MM) cells in the bone marrow. Reports have also shown that inhibiting RANKL may have a direct effect on RANK-expressing myeloma cells and a therapeutic role in treating the disease. In mouse myeloma models, inhibition of RANKL led to reduced serum paraprotein levels and tumor burden. Based on this hypothesis, this proof-of-concept, single-arm study investigated whether RANKL inhibition with denosumab could reduce serum M-protein levels in relapsed or plateau-phase myeloma subjects. All subjects received denosumab monthly, with loading doses on days 8 and 15 of month one, until disease progression or subject discontinuation. Results of this ongoing study demonstrated that no subjects in either cohort met the protocol-defined objective response criteria of complete response (CR) or partial response (PR), but that denosumab effectively inhibited the RANKL pathway regardless of previous exposure to bisphosphonates, as evidenced by suppressed levels of the bone turnover marker, serum C-terminal telopeptide of type 1 collagen (sCTx). Eleven (21%) subjects who relapsed within 3 months before study entry maintained stable disease for up to 16.5 months. Nineteen (46%) subjects with plateau-phase myeloma maintained stable disease for up to 18.3 months. The adverse event (AE) profile for denosumab and its dosing schedule in these populations was consistent with that for advanced cancer patients receiving systemic therapy. Additional controlled clinical studies of denosumab in subjects with both relapsed and plateau-phase MM are warranted. Am. J. Hematol. 2009. © 2009 Wiley-Liss, Inc. [source] Prevention of cartilage degeneration and restoration of chondroprotection by lubricin tribosupplementation in the rat following anterior cruciate ligament transectionARTHRITIS & RHEUMATISM, Issue 8 2010Gregory D. Jay Objective To investigate whether cartilage degeneration is prevented or minimized following intraarticular injections of lubricin derived from human synoviocytes in culture, recombinant human PRG4 (rhPRG4), or human synovial fluid (SF) in a rat model of anterior cruciate ligament (ACL) injury. Methods Unilateral ACL transection (ACLT) was performed in Lewis rats (n = 45). Nine animals were left untreated. The remaining rats were given intraarticular injections (50 ,l/injection) of either phosphate buffered saline (PBS) (n = 9), human synoviocyte lubricin (200 ,g/ml; n = 9), rhPRG4 (200 ,g/ml; n = 9), or human SF lubricin (200 ,g/ml; n = 9) twice weekly beginning on day 7 after injury. Joints were harvested on day 32 after injury. Histologic analysis was performed using Safranin O,fast green staining, and articular cartilage degeneration was graded using the Osteoarthritis Research Society International (OARSI),modified Mankin criteria. Histologic specimens were immunoprobed for lubricin and sulfated glycosaminoglycans. A 24-hour urine collection was performed on days 17 and 29 postinjury, and urinary C-terminal telopeptide of type II collagen (CTX-II) levels were measured. Results Treatment with human synoviocyte lubricin resulted in significantly lower OARSI scores for cartilage degeneration compared with no treatment or PBS treatment (P < 0.05). Increased immunostaining for lubricin in the superficial zone chondrocytes and on the surface of cartilage was observed in lubricin-treated, but not untreated or PBS-treated, joints. On day 17, urinary CTX-II levels in human synoviocyte lubricin, and human SF lubricin,treated animals were significantly lower than those in untreated animals (P = 0.005 and P = 0.002, respectively) and in PBS-treated animals (P = 0.002 and P < 0.001, respectively). Conclusion After treatment with any of the 3 types of lubricin evaluated in this study, a reduction in cartilage damage following ACLT was evident, combined with a reduction in type II collagen degradation. Our findings indicate that intraarticular lubricin injection following an ACL injury may be beneficial in retarding the degeneration of cartilage and the development of posttraumatic OA. [source] Effects of teriparatide versus alendronate for treating glucocorticoid-induced osteoporosis: Thirty-six,month results of a randomized, double-blind, controlled trial,ARTHRITIS & RHEUMATISM, Issue 11 2009Kenneth G. Saag Objective To compare the bone anabolic drug teriparatide (20 ,g/day) with the antiresorptive drug alendronate (10 mg/day) for treating glucocorticoid-induced osteoporosis (OP). Methods This was a 36-month, randomized, double-blind, controlled trial in 428 subjects with OP (ages 22,89 years) who had received ,5 mg/day of prednisone equivalent for ,3 months preceding screening. Measures included changes in lumbar spine and hip bone mineral density (BMD), changes in bone biomarkers, fracture incidence, and safety. Results Increases in BMD from baseline were significantly greater in the teriparatide group than in the alendronate group, and at 36 months were 11.0% versus 5.3% for lumbar spine, 5.2% versus 2.7% for total hip, and 6.3% versus 3.4% for femoral neck (P < 0.001 for all). In the teriparatide group, median percent increases from baseline in N-terminal type I procollagen propeptide (PINP) and osteocalcin (OC) levels were significant from 1 to 36 months (P < 0.01), and increases in levels of C-terminal telopeptide of type I collagen (CTX) were significant from 1 to 6 months (P < 0.01). In the alendronate group, median percent decreases in PINP, OC, and CTX were significant by 6 months and remained below baseline through 36 months (P < 0.001). Fewer subjects had vertebral fractures in the teriparatide group than in the alendronate group (3 [1.7%] of 173 versus 13 [7.7%] of 169; P = 0.007), with most occurring during the first 18 months. There was no significant difference between groups in the incidence of nonvertebral fractures (16 [7.5%] of 214 subjects taking teriparatide versus 15 [7.0%] of 214 subjects taking alendronate; P = 0.843). More subjects in the teriparatide group (21%) versus the alendronate group (7%) had elevated predose serum calcium concentrations (P < 0.001). Conclusion Our findings indicate that subjects with glucocorticoid-induced OP treated with teriparatide for 36 months had greater increases in BMD and fewer new vertebral fractures than subjects treated with alendronate. [source] The combination of the biomarkers urinary C-terminal telopeptide of type II collagen, serum cartilage oligomeric matrix protein, and serum chondroitin sulfate 846 reflects cartilage damage in hemophilic arthropathyARTHRITIS & RHEUMATISM, Issue 1 2009Nathalie W. D. Jansen Objective Hemophilic arthropathy, with characteristics of inflammatory (rheumatoid arthritis) and degenerative (osteoarthritis) joint damage, occurs at an early age, is associated with minor comorbidity, and is restricted to 3 pairs of large joints. The aim of this study was to determine whether commonly used serum and/or urinary biomarkers of cartilage and bone turnover for which assay kits are commercially available are associated with the severity of joint damage in patients with various degrees of hemophilic arthropathy and, thus, whether this disease could be useful in the identification and evaluation of such biomarkers. Methods Blood and urine samples were collected from 36 patients with various degrees of hemophilic arthropathy. Commercially available assays for the most frequently investigated serum and urine biomarkers were performed: urinary C-terminal telopeptide of type I collagen (CTX-I), urinary CTX-II, serum CTX-I, serum CTX-II, serum cartilage oligomeric matrix protein (COMP), serum cartilage cleavage products C1,2C and C2C, and serum chondroitin sulfate 846 (CS-846). Radiographs of the ankles, knees, and elbows in all patients were evaluated for the degree of joint damage according to the Pettersson score, which is based on cartilage and periarticular bone changes and is specific for hemophilic arthropathy. Results Urinary CTX-II, serum C1,2C, and serum CS-846 levels correlated with the overall Pettersson score and with the joint space narrowing component. Regression analysis showed that combined indexes of different markers increased the degree of correlation for the combination of urinary CTX-II, serum COMP, and serum CS-846. Bone-specific markers (urinary/serum CTX-I and serum C1,2C) did not correlate with specific bone-related items of the Pettersson score (osteoporosis and erosions). Conclusion These results support the idea that a combination of biomarkers relates significantly better to the severity of joint damage than do individual biomarkers. The combination of urinary CTX-II, serum COMP, and serum CS-846 correlated best with the degree of arthropathy. Because of its specific characteristics and restricted involvement, hemophilic arthropathy may prove useful in the screening of newly developed biomarkers of joint damage. [source] Increases in collagen type I synthesis in asthma: the role of eosinophils and transforming growth factor-b,CLINICAL & EXPERIMENTAL ALLERGY, Issue 6 2002A. Nomura Summary Background Collagen type I is one of the major deposits in thickening of the reticular basement membrane of asthma. Objective and Methods In this study, we assessed turnover of collagen type I in asthma by measuring procollagen type I C-terminal peptide (PICP) and collagen type I C-terminal telopeptide (ICTP) in induced sputum. Results PICP but not ICTP was found to be significantly higher in asthma subjects than in normal volunteers (P < 0.05). In asthma, PICP was inversely correlated with %FEV1.0 (r = ,0.539), and its levels significantly increased upon exacerbation (P < 0.05), indicating that collagen synthesis increases during asthma exacerbation. Additionally, PICP was found to significantly correlate with eosinophil counts in sputum (r = 0.539), indicating that eosinophils stimulate collagen turnover. Because eosinophils can produce TGF-,, a potent stimulator of collagen synthesis, we immunocytochemically examined TGF-,-positive cells in sputum. TGF-,-positive cells significantly correlated with eosinophil counts (r = 0.811) and PICP (r = 0.569), suggesting that TGF-, released from eosinophils is involved in collagen synthesis. Conclusions The results of the present study suggest that collagen synthesis is stimulated in asthmatic airways by eosinophils through TGF-,, while collagen degradation is not, and that PICP in sputum can act as a new marker for airway inflammation in asthma. [source] Circulating leptin levels and bone mineral density in children with biliary atresiaACTA PAEDIATRICA, Issue 2 2008Sittisak Honsawek Abstract Aim: To investigate circulating leptin levels in biliary atresia (BA) patients and the association of leptin with bone mineral density (BMD) and the severity of BA. Methods: We have examined 50 patients with BA and 15 matched healthy controls. Serum leptin, osteocalcin and C-terminal telopeptide of type I collagen (CTX) levels were measured by sandwich enzyme-linked immunosorbent assay (ELISA). BMD of the lumbar spine was measured by dual energy X-ray absorptiometry. Results: Serum leptin levels of BA patients were lower than those of healthy controls (2.7 ± 0.3 vs. 7.1 ± 1.7 ng/mL, p = 0.0001). Among the BA patients, serum leptin levels were significantly lower in patients with jaundice than patients without jaundice (1.7 ± 0.2 vs. 3.4 ± 0.4 ng/mL, p = 0.001). BMD of BA patients was correlated (p < 0.001) with leptin levels, age and BMI (r = 0.55, r = 0.75 and r = 0.58, respectively). The serum CTX levels were significantly higher in jaundice patients compared with jaundice-free patients and the healthy controls (0.6 ± 0.2 vs. 0.2 ± 0.1 ng/mL, p = 0.01), whereas the serum osteocalcin levels in BA patients were not different from those in the controls. Conclusion: Circulating leptin levels are correlated with BMD and the presence of jaundice in BA, suggesting that the leptin may play a physiological role in maintaining bone mass of BA patients with jaundice. [source] Erythropoietin administration does not influence the GH,IGF axis or makers of bone turnover in recreational athletesCLINICAL ENDOCRINOLOGY, Issue 3 2005A. E. Nelson Summary Objective, Measurement of biochemical markers of the IGF-system and of collagen turnover is a potential approach to detect GH abuse in sport. These markers are increased in patients on dialysis treated with recombinant human erythropoietin (r-HuEPO), mimicking the effects of GH. The aim was to determine whether r-HuEPO induces similar effects on the IGF-system and collagen turnover in healthy athletes. Subjects and measurements, Young male Caucasian recreational athletes were administered 50 U/kg r-HuEPO (n = 14) or placebo (n = 16) three times a week for 25 days, followed by a 4-week wash-out period. IGF-I, IGFBP-3, the acid labile subunit (ALS), N-terminal propeptide of type I collagen (PINP), C-terminal telopeptide of type I collagen (ICTP) and N-terminal propeptide of type III collagen (PIIINP) were measured in samples collected at baseline (two samples), after 10, 22 and 24 days of r-HuEPO treatment and at the end of the 4-week wash-out period. Results, Treatment with r-HuEPO resulted in approximately threefold elevation of serum EPO and marked elevation of markers of erythropoiesis. There was no significant treatment effect of r-HuEPO compared to baseline on IGF-I, IGFBP-3, ALS, PINP, ICTP or PIIINP. Conclusions, r-HuEPO administration did not change markers of the IGF-system and of collagen turnover in young healthy male athletes. Therefore, use of r-HuEPO in athletes should not affect the validity of a GH doping test using these GH-responsive markers. [source] Potent and Selective Inhibition of Human Cathepsin K Leads to Inhibition of Bone Resorption In Vivo in a Nonhuman PrimateJOURNAL OF BONE AND MINERAL RESEARCH, Issue 10 2001George B. Stroup Abstract Cathepsin K is a cysteine protease that plays an essential role in osteoclast-mediated degradation of the organic matrix of bone. Knockout of the enzyme in mice, as well as lack of functional enzyme in the human condition pycnodysostosis, results in osteopetrosis. These results suggests that inhibition of the human enzyme may provide protection from bone loss in states of elevated bone turnover, such as postmenopausal osteoporosis. To test this theory, we have produced a small molecule inhibitor of human cathepsin K, SB-357114, that potently and selectively inhibits this enzyme (Ki = 0.16 nM). This compound potently inhibited cathepsin activity in situ, in human osteoclasts (inhibitor concentration [IC]50 = 70 nM) as well as bone resorption mediated by human osteoclasts in vitro (IC50 = 29 nM). Using SB-357114, we evaluated the effect of inhibition of cathepsin K on bone resorption in vivo using a nonhuman primate model of postmenopausal bone loss in which the active form of cathepsin K is identical to the human orthologue. A gonadotropin-releasing hormone agonist (GnRHa) was used to render cynomolgus monkeys estrogen deficient, which led to an increase in bone turnover. Treatment with SB-357114 (12 mg/kg subcutaneously) resulted in a significant reduction in serum markers of bone resorption relative to untreated controls. The effect was observed 1.5 h after the first dose and was maintained for 24 h. After 5 days of dosing, the reductions in N-terminal telopeptides (NTx) and C-terminal telopeptides (CTx) of type I collagen were 61% and 67%, respectively. A decrease in serum osteocalcin of 22% was also observed. These data show that inhibition of cathepsin K results in a significant reduction of bone resorption in vivo and provide further evidence that this may be a viable approach to the treatment of postmenopausal osteoporosis. [source] Alendronate prevents femoral periprosthetic bone loss following total hip arthroplasty: Prospective randomized double-blind studyJOURNAL OF ORTHOPAEDIC RESEARCH, Issue 7 2006Mohammad Arabmotlagh Abstract Following total hip arthroplasty (THA), femoral periprosthetic bone undergoes a remodeling process that results in bone loss in its proximal regions that may compromise the long-term outcome of THA. Periprosthetic bone loss mainly occurs during the first postoperative months. The question is whether a postoperative treatment with alendronate is effective in reducing periprosthetic bone loss and which doses and duration of treatment are required. In a 12-month prospective, randomized double-blind study, 51 patients undergoing cementless THA were treated postoperatively either with a daily dose of 20 mg alendronate for 2 months and 10 mg for 2 months thereafter (group I), with 20 mg of alendronate for 2 months and 10 mg for 4 months thereafter (group II), or treated with placebo (group III). Proximal femoral bone mineral density (BMD) was measured with dual-energy X-ray absorptiometry (DEXA) and serum biochemical markers of bone turnover bone specific alkaline phosphatase, osteocalcin, and C-terminal telopeptides (CTX-I) were assayed. Six months of alendronate treatment significantly reduced (p,<,0.001) bone loss in proximal medial region (,10%) compared with placebo (,26%). All biochemical markers of bone turnover were suppressed by alendronate. These data suggest that alendronate administered for the first 6 postoperative months following THA was effective in preventing early periprosthetic bone loss. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:1336,1341, 2006 [source] Diurnal variation of serum and urine biomarkers in patients with radiographic knee osteoarthritisARTHRITIS & RHEUMATISM, Issue 8 2006S. Y. Kong Objective To evaluate diurnal variation of biomarkers in subjects with osteoarthritis (OA) of the knee. Methods Twenty subjects with radiographic knee OA were admitted to the General Clinical Research Center of Duke University for an overnight stay to undergo serial blood and urine sampling. Biomarkers measured included serum hyaluronan (HA), cartilage oligomeric matrix protein (COMP), keratan sulfate (KS-5D4), aggrecan neoepitope (CS846), high-sensitivity C-reactive protein (hsCRP), osteocalcin, transforming growth factor ,1 (TGF,1), and type II collagen (CII),related epitopes (neoepitope from cleavage of CII [C2C], carboxy-terminus of three-quarter peptide from cleavage of CI and CII [C1,2C], and type II procollagen carboxy-propeptide [CPII] in serum, and C-terminal telopeptides of CII [CTX-II] and C2C in urine). Results Levels of serum HA, COMP, KS-5D4, and TGF,1 increased significantly from T0 (before arising from bed) to T1 (1 hour after arising). More diurnal variation in HA was observed in patients with higher daily mean HA concentrations. CPII increased significantly from T0 to T2 (4 hours after arising). Urinary concentrations of CTX-II were also found to vary with morning activity, decreasing significantly from T0 to T2. Urinary C2C concentrations increased significantly from T0 until T3 (early evening). No diurnal variations in CS846, hsCRP, osteocalcin, serum C2C, or C1,2C were observed. Six biomarkers (serum C2C, C1,2C, COMP, KS-5D4, TGF,1, and urinary CTX-II) were associated with radiographic knee OA (expressed as the sum of Kellgren/Lawrence radiographic severity grades), with the strongest correlations observed with measurements obtained at later time points (either T2 or T3). Conclusion Our study results suggest that serum and urine sampling for HA, COMP, KS-5D4, TGF,1, CPII, urinary CTX-II, and urinary C2C should be standardized in future OA clinical trials. Serum and urine sampling at late midday time points may be the optimal approach for OA studies, although this result should be validated in a larger cohort. [source] Bone turnover markers and sex hormones in men with idiopathic osteoporosisEUROPEAN JOURNAL OF CLINICAL INVESTIGATION, Issue 5 2001P. Pietschmann Background In contrast to osteoporosis in postmenopausal women, osteoporosis in men has received much less attention. Patients and We determined various biochemical parameters of bone metabolism and sex hormones in 31 men with idiopathic osteoporosis and 35 age matched control subjects. Results In the men with osteoporosis, a significantly increased urinary excretion of deoxypyridinoline (5·3 ± 0·2 vs. 4·6 ± 0·2 nmol mmol,1 creatinine; P = 0·033) in addition to increased serum levels of the c-terminal telopeptide of type I collagen (2677 ± 230 vs. 2058 ± 153 pmol; P = 0·037) were found. While parameters of bone formation were not significantly different in the patients and controls, serum bone sialoprotein levels were significantly decreased in the patients (3·7 ± 0·8 vs. 12·4 ± 4·0 ng mL,1; P = 0·021). Moreover, in men with idiopathic osteoporosis, lower levels of estradiol (91·3 ± 5·8 vs. 114·6 ± 7·8 pmol L,1; P = 0·044), higher levels of sex hormone binding globulin (31·5 ± 3·1 vs. 24·2 ± 1·4 nmol L,1; P = 0·034) and a decreased free androgen index (42·6 ± 5·2 vs. 56·4 ± 5·9; P = 0·016) were seen. Serum estradiol levels correlated negatively with several parameters of bone resorption. Conclusions In men with idiopathic osteoporosis, bone resorption is increased and exceeds bone formation. The excessive bone resorption seen in idiopathic male osteoporosis may be due to decreased estradiol levels and low levels of bioavailable testosterone. [source] | ||||||||||