Biochemical markers of bone turnover predict bone loss in perimenopausal women but not in postmenopausal women-the Japanese Population-based Osteoporosis (JPOS) Cohort Study

Introduction The predictive value of biochemical markers of bone turnover for subsequent change in bone density in a population sample of healthy women with a wide range of ages has not been fully established. Methods We followed 1,283 women aged 15–79 years at baseline selected randomly from the inhabitants of three areas in Japan for 6 years, and examined 1,130 subjects with no disease or administration of drugs affecting bone metabolism. The annual change in bone density at the spine, total hip, and distal one third of the radius was determined during the follow-up period by dual x-ray absorptiometry and was compared among the groups using different levels of biochemical markers at baseline, including serum osteocalcin (OC) and bone-specific alkaline phosphatase (bone ALP), free and total (tDPD) forms of immunoreactive deoxypyridinoline, and type I collagen crosslinked C-terminal telopeptide (CTX) in urine. Results Premenopausal women aged 45 years or older with elevated levels of OC, bone ALP, CTX, or tDPD showed significantly greater bone loss at most skeletal sites during the follow-up period than those with lower levels, after adjustment for the effects of age, height, weight, dietary calcium intake, regular exercise, and current smoking. The greatest coefficient of determination of the model was observed in the association between CTX and bone loss at the hip during the first 3 years of follow-up (42.8%). These subjects were pooled with perimenopausal women at baseline, and those who still menstruated at follow-up in this pooled group showed significant but more modest associations, whereas those who entered menopause during the follow-up period showed clear associations. However, early postmenopausal women with less than 5 or 10 years since menopause showed an association that was limited mostly to the distal radius, and other postmenopausal groups had virtually no association. Conclusion Biochemical markers of bone turnover may predict bone loss in women undergoing menopausal transition but may not predict bone loss in postmenopausal women.     

Biochemical markers of bone turnover may predict progression to osteoporosis in osteopenic women: the JPOS Cohort Study

We evaluated the value of bone turnover markers, including osteocalcin (OC) and bone-specific alkaline phosphatase in the serum, and type I collagen C-terminal telopeptide and free and total deoxypyridinoline (tDPD) in the urine of fasting patients, in an attempt to predict which osteopenic women [i.e., those with ≥70% and <80% of the young adult mean (YAM) bone mineral density (BMD)] would progress to the osteoporosis level of BMD (<70% of YAM). Of the 1153 women without defects in bone metabolism who completed the 3-year follow-up, 147, 161, and 144 women were judged by dual X-ray absorptiometry to be osteopenic from baseline measurements of BMD in the spine (LS), hip (TH), and distal radius (DR), respectively. Progression to the osteoporotic level of BMD was noted for 23.8%, 16.1%, and 12.5% of the subjects with osteopenia of the LS, TH, and DR, respectively, while most of them were in the lower half of the osteopenic level of BMD at baseline. Among the subjects in this lower-level osteopenia category, a significantly higher OC level was observed for the subjects with osteoporosis progression at the LS than those without. The subjects with progression at DR showed a significantly higher tDPD level. The association between OC level and disease progression remained unchanged after adjustments for age, body size, and BMD at baseline. The subjects in the upper one-third category of OC levels showed a 6.4 fold greater risk of progression at LS (95% confidence interval, 1.8–23.1) compared with those in the lower one-third category after the adjustments for age, body size, and BMD at baseline. Receiver operating characteristics analysis showed that the area under the curve was 0.716 for the OC level in the prediction of osteoporosis progression at LS. The levels of OC and tDPD may be useful in predicting which osteopenic women will progress to osteoporosis.     

Bone mineral density and biochemical markers of bone turnover in aseptic loosening after total hip arthroplasty.

The aims of this study were to determine whether subjects with aseptic loosening after total hip arthroplasty (THA) have regional differences in periprosthetic bone mineral density (BMD) and systemic biochemical markers of bone turnover compared to subjects with successful implants.Proximal femoral and pelvic BMD were measured by dual energy X-ray absorptiometry and bone turnover markers were assayed in 49 subjects 12.6+/-4.3 (mean+/-SD) years after cemented THA. Femoral BMD was lower in Gruen zones 2, 5, 6, and 7 in subjects with a loose femoral implant (n=17) compared to those (n=32) with fixed femoral implants (P<0.05 all comparisons). This BMD difference was greatest (-31%, P=0.02) in the proximal and medial region of the femur. Subjects with femoral loosening had higher levels of the bone resorption marker N-telopeptides of type-I collagen (P=0.02) than those with a fixed femoral implant. No differences in pelvic BMD or bone turnover markers were found between subjects with loose (n=18) versus fixed (n=31) pelvic implants.This study suggests that failure of femoral components after cemented THA is associated with region-specific decreases in BMD and an increase in urinary excretion of N-telopeptide cross-links of type-I collagen. These surrogate outcome markers may be of value in monitoring response to antiresorptive therapies used to treat periprosthetic osteolysis, although the diagnosis of aseptic loosening remains clinical and radiological.     

骨代谢生化指标随年龄的变化及其临床意义

本文收集了北京地区１９２８名不同年龄（０～８７岁）健康人及５３４５例２０余种疾病患者空腹尿及血，并对其骨代谢生化指标进行测定。结果表明：血清２５羟基维生素Ｄ（２５ＯＨＤ），碱性磷酸酶（ＡＬＰ），骨钙素（ＢＧＰ），甲状旁腺激素（ＰＴＨ），尿Ⅰ型胶原交联Ｎ末端肽与肌酐比值（ＮＴＸ／Ｃｒ）及羟脯氨酸与肌酐比值（ＨＯＰ／Ｃｒ）与年龄显著相关。血清２５ＯＨＤ，ＢＧＰ，尿ＮＴＸ／Ｃｒ及ＨＯＰ／Ｃｒ可用于预测骨量。１，２５（ＯＮ）２Ｄ３，２５ＯＨＤ，ＮＴＸ／Ｃｒ和ＮＯＰ／Ｃｒ可用于区分绝经前与绝经后骨质疏松妇女。与年龄有关的骨丢失可能与１，２５（ＯＨ）２Ｄ３的降低、ＰＴＨ的升高及肾功能减退有关；绝经后骨丢失与雌激素缺乏有关。     

Prevention of bone loss in early nonsurgical and nonosteoporotic high turnover patients with salmon calcitonin: The role of biochemical bone markers in monitoring high turnover patients under calcitonin treatment

Annual bone loss rate was estimated in a group of randomly selected 150 nonsurgical and nonosteoporotic early postmenopausal women, 42–56 years, with the use of the mathematical equation proposed by Christiansen et al. (OSTEOTREND-R) [1]. Fifty-six women were characterized as high turnover patients (estimated annual bone loss more than 2.7%). These high turnover patients were included in a double-blind, placebo-controlled clinical study. Patients were divided into two groups of 28 women each. The first group of patients received 100 IU of salmon calcitonin intranasally daily for 1 year and the second group intranasal spray of placebo daily. Blood and urine biochemical parameters as well as bone mineral content of the spine and proximal forearm were determined initially and at the end of 6 and 12 months. No other side effects were noted apart from discomfort of nasal mucosa in two patients (one in each group). The group of calcitonin-treated patients showed a dramatic decrease in bone loss rate as estimated with the use of biochemical bone markers at the end of 6 and 12 months (3.7% versus 0.8% and 0.0% at the end of 6 and 12 months, respectively, P<0.001) whereas in the placebo group, bone loss rate remained unchanged (4.2% versus 4.1% and 4.3% at the end of 6 and 12 months, respectively). The calcitonintreated patients showed a significant increase in bone mineral content of spine and proximal forearm (P<0.001 at the end of 6 and 12 months, respectively). On the other hand, a significant decrease in all measurement sites appeared in the placebo group. In conclusion, our results showed that nasal salmon calcitonin administration can prevent the increased postmenorpausal bone loss in selected high bone turnover patients. The predicted annual bone loss rate, as estimated with the combination of biochemical bone markers, is useful in monitoring the responsiveness of high turnover patients to calcitonin at short intervals.     

Low bone mass is associated with carotid atherosclerosis in postmenopausal women: The Japanese Population-based Osteoporosis (JPOS) Cohort Study

Summary  We analyzed 609 women belonging to the JPOS study in a 10-year follow-up survey, to examine the association of osteoporosis with atherosclerosis. Osteoporosis or prevalent vertebral fracture at baseline was associated with increased intima-media thickness of the carotid bifurcation in postmenopausal women, adjusted for age, BMI, and other variables at baseline. Introduction  Whether low bone mass predicts increased carotid atherosclerosis has not been fully investigated. Methods  In 2006, we conducted a 10-year follow-up survey of 1,040 women (follow-up rate: 68.6%). We analyzed 609 women ≥50 years old in 2006 without a history of cardiovascular or connective tissue diseases at baseline. BMD and evaluation of vertebral fracture at baseline were used. The intima-media thickness of carotid bifurcation (BIF-IMT) was measured by B-mode ultrasonography in 2006. Results  Adjusted BIF-IMT values of subjects with spine T-score ≥-1, between-2.5 and -1, and <-2.5 or prevalent vertebral fracture were 1.19 mm, 1.34 mm, 1.57 mm, respectively, in women with less than 10 years since menopause (YSM) (n = 159), 1.30 mm, 1.32 mm, 1.53 mm, in women with YSM ≥10 without a history of hypertension at baseline (n = 144) (both with p < 0.05 for linear trend). Those values among no versus prevalent vertebral fracture in women with YSM ≥10 were 1.40 mm, 1.66 mm with p < 0.05 (n = 202). Those associations were independent of age, BMI, total cholesterol, smoking and drinking habits, history of diabetes mellitus, and hypertension (for women with YSM < 10) at baseline. Conclusion  Osteoporosis including prevalent vertebral fracture may be associated with carotid atherosclerosis in the first 10 years of postmenopausal women.     

Bone Mineral Density of the Spine, Hip and Distal Forearm in Representative Samples of the Japanese Female Population: Japanese Population-Based Osteoporosis (JPOS) Study

Low bone mineral density (BMD) is one of the most important elements for the diagnosis of osteoporosis and screening people with higher risk of fractures. To establish the criterion value of BMD for the diagnosis of osteoporosis and to estimate the prevalence rate of osteoporosis in Japanese women, we performed a Japanese population-based osteoporosis (JPOS) study. The subjects were 4550 women aged 15 through 79 years randomly selected from seven municipalities throughout Japan. The sample size was determined to ensure that the observed mean BMD would remain within 2.5% from the real value with a probability of 0.95 in each of the 5-year age groups. The study comprised bone mass measurements by dual-energy X-ray absorptiometry at the spine (L2–4), hip and distal forearm, body size measurements and detailed interviews on medical and gynecologic history. After excluding those subjects with apparent or suggested abnormalities affecting bone mass from 3985 women (87.6%) who completed the study, 3465 women remained and served as the subjects. We present 5-year age-specific mean values of BMD and cut-off values for the diagnosis of osteoporosis according to World Health Organization (WHO) and the Japanese Society of Bone and Mineral Research (JSBMR) criteria. The cut-off levels at the spine and the distal radius proposed in this study were similar to those proposed by the JSBMR but the cut-off level at the femoral neck in this study was 4.7% higher than that of the JSBMR. The prevalence rates of osteoporosis according to WHO criteria in the present subjects aged 50 through 79 years were calculated as 38.0% at the spine, 11.6% at the femoral neck and 56.8% at the distal one-third site of the radius, and those in the Japanese female population of the same age were estimated to be 35.1%, 9.4% and 51.2%, respectively. A fivefold difference was observed among the prevalence rates at different skeletal sites, which suggests that the different definitions of osteoporosis should be established for the different skeletal sites. The prevalence rate diagnosed at the femoral neck seemed to be lower in the present study than those reported for Caucasians. This might account for a lower incidence rate of hip fracture in Japanese women. Received: 6 June 2000 / Accepted: 5 January 2001     

Ultrasound bone densitometry of the calcaneus,determined with Sahara,in healthy Japanese adolescents: Japanese Population-based Osteoporosis (JPOS) Study

To establish the reference values for quantitative ultrasound (QUS) indices (speed of sound [SOS]), and broadband ultrasonic attenuation [BUA]) in healthy Japanese adolescents, and to evaluate the effects of age and body size on QUS in comparison with their effects on bone mineral density (BMD), 632 healthy adolescents aged 12 through 17 years recruited from a larger cohort study (Japanese Population-based Osteoporosis [JPOS] Study), were examined in terms of bone mass measurements by QUS at the calcaneus (Sahara; Hologic) and by dual-energy X-ray absorptiometry at the distal one-third radius and ultradistal forearm. We present sex- and age-specific mean values of the QUS and BMD indices. BMD increased significantly up to 17 years of age in males and up to 16 years in females. However, the age-related change in the QUS indices in males was not as clear as that seen for BMD and no age-related change in the QUS indices was observed in females. Significant positive correlation coefficients between BMD and body size were observed in both sexes even after adjusting for the effect of age. SOS showed no correlation with body size and BUA showed a positive but weak correlation with body size in both sexes. Thus, the relationships of age and body size to BMD and QUS were different from each other, even though the QUS indices had significant positive correlations with BMD, allowing for the effect of age.Fumiaki Marumo for JPOS Study Group     

Effects of the Cdx-2 Polymorphism of the Vitamin D Receptor Gene and Lifestyle Factors on Bone Mineral Density in a Representative Sample of Japanese Women: The Japanese Population-based Osteoporosis (JPOS) Study

Using a large-scale representative sample of the Japanese female population, we examined the effects of a single nucleotide polymorphism within a binding site of Cdx-2 in the promoter region of the vitamin D receptor gene on bone mineral density (BMD), and the interactions between this polymorphism and lifestyle factors on BMD. Fifty women were randomly selected from each of the 5-year age-stratified populations (15–79 years) in each of three chosen municipalities as a part of the Japanese Population-based Osteoporosis Study. BMD at the lumbar spine, hip, and distal forearm was measured using dual-energy X-ray absorptiometry at baseline and again in a follow-up study conducted 3 years later. Information on lifestyle factors was collected in a questionnaire and followed up in interviews. The G-to-A polymorphism within the Cdx-2 binding site was determined by a TaqMan allelic discrimination assay. At baseline, 1,340 women were analyzed. The baseline BMD in the ultradistal forearm in premenopausal women with the GG genotype was significantly lower than in those with other genotypes. There was no association between the Cdx-2 genotype and the change in BMD at any of the skeletal sites. We found significant associations between daily milk consumption and baseline BMD at some skeletal sites but only in subjects with the GG genotype. In conclusion, the Cdx-2 polymorphism alone did not have a substantial effect on BMD in Japanese women. However, this polymorphism might have some effect in women with low calcium intake.     

骨转换标志物与骨密度预测老年女性骨质疏松性骨折的对比研究

目的探讨骨密度与骨转换标志物(bone turnover markers,BTMs)在老年女性骨质疏松患者中的检测意义,对比两者对骨质疏松性骨折(osteoporotic fracture,OF)的预测能力。方法收集2017年10月至2019年2月于成都医学院第一附属医院骨科住院的OF患者96例和骨质疏松患者107例,分为骨折组和非骨折组。通过双能X线吸收仪(DXA)测定骨密度,电化学发光检测BTMs:I型前胶原N端前肽(PINP)、I型胶原β-异构化C末端肽(β-CTX)、骨钙素N端分子片段(N-MID),同时测定骨代谢相关指标:碱性磷酸酶(alkaline phosphatase,ALP)、钙(Ca)、磷(P),t检验对比两组间的计量资料,采用二分类Logistic回归分析骨密度和BTMs与OF的相关性。结果骨折组的骨密度低于非骨折组,差异有统计学意义(P 0. 05);PINP、β-CTX高于非骨折组,70～90岁患者N-MID低于非骨折组,差异均有统计学意义(P0. 05);而ALP、P、Ca在两组之间相比,差异无统计学意义(P0. 05)。二分类Logistic回归分析提示腰椎及髋部骨密度、β-CTX与OF具有显著相关性,OR分别为-4. 182、-6. 929和7. 572,差异均有统计学意义(P0. 05)。PINP、N-MID与OF呈正相关,OR分别为4. 213和2. 510,差异均无统计学意义(P0. 05)。结论低骨密度、高β-CTX的骨质疏松老年女性更容易发生OF,β-CTX比骨密度预测OF的能力更强,可适时对高危人群进行相关干预管理。     

新疆老年男性骨转化生化标志物及性激素与骨质疏松症的相关性研究

目的探讨新疆老年男性骨转换生化标志物及性激素水平与原发性骨质疏松症的关系。方法采用双能X线骨密度仪检测146例老年男性患者腰椎、左侧股骨骨密度(BMD),平均年龄:72.4±7.9岁,基于骨密度T值分为骨量正常组(75例)和骨量异常组(71例),采用酶联免疫法测定Ⅰ型前胶原氨基端原肽(PINP)和Ⅰ型胶原C末端肽(CTX),放射免疫法测定雌二醇(E2)和睾酮(T),比较两组骨转换生化指标和性激素水平是否存在差异及其与骨密度的相关性。结果 1 PINP与CTX在骨量正常组和骨量异常组差异均无统计学意义(P0.05);两者偏相关分析呈显著正相关(r=0.746 P=0.000)。2雌二醇、睾酮在两组中比较,差异有统计学意义(P0.05)。骨量异常组雌二醇(17.48±7.61)低于骨量正常组(21.31±11.43),t=2.391,P=0.018;骨量异常组睾酮(3.50±1.02)低于骨量正常组(3.98±1.43),t=2.331,P=0.021。3汉族人群左侧髋关节骨密度高于维吾尔族人群,除Inter Tro部位外,差异均有统计学意义(P0.05);年龄与髋关节各部位骨密度呈显著负相关。结论性激素水平降低可能是影响男性骨量减少的一个重要危险因素,而雌激素可能占主要地位;随着年龄的增加,老年男性髋关节骨密度呈下降趋势,测定左侧髋关节骨密度对诊断骨质疏松症有着重要意义。     

Age-specific reference values of hip geometric indices from a representative sample of the Japanese female population: Japanese Population-based Osteoporosis (JPOS) Study

Summary  

We analyzed 2,107 hip dual-energy X-ray absorptiometry (DXA) images from the Japanese Population-based Osteoporosis Study with the Hip Structure Analysis (HSA) program to obtain age-specific reference values of HSA indices for the Japanese female population. These references may help physicians accurately assess HSA results and aid researchers in making interracial comparisons of the indices.     

Association between weight changes and changes in hip geometric indices in the Japanese female population during 10-year follow-up: Japanese Population-based Osteoporosis (JPOS) Cohort Study

Summary  

During a 10-year follow-up of 893 women of various ages from the Japanese Population-based Osteoporosis Cohort Study, we evaluated the relationship between weight changes and hip geometric strength assessed by hip structure analysis. Our findings suggest that maintaining weight may help retain geometric strength and reduce hip fracture risk.     

The effect of 1-year transdermal estrogen replacement therapy on bone mineral density and biochemical markers of bone turnover in osteopenic postmenopausal systemic lupus erythematosus patients: a randomized,double-blind,placebo-controlled trial

We studied the effect of 1-year transdermal estrogen replacement therapy (ERT) on bone mineral density (BMD) and biochemical markers of bone turnover in osteopenic postmenopausal systemic lupus erythematosus (SLE) patients in a randomized, double-blind, placebo-controlled trial. SLE patients were randomly allocated to treatment (estradiol; 50 g transdermal 17-estradiol; n=15) or placebo (n=17) group. Both groups received 5 mg continuous oral medroxyprogesterone acetate, 500 mg calcium and 400 IU vitamin D₃. L₁–L₄ spine (LS), left femur and total hip BMD were measured at baseline and at 6 and 12 months. Serum osteocalcin (OC) and degradation products of C-terminal telopeptides of type-I collagen (CTx) levels were measured at baseline and 3, 6, 9, and 12 months. There was a significant difference in the percentage change of LS BMD at 6 months between the two groups (103.24±3.74% (estradiol group) vs 98.99±3.11% (placebo group); P<0.005). There was a significant decrease within the estradiol group in the CTx levels between baseline and all subsequent visits (P<0.05). There was no significant difference in SLE disease activity index, Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) damage index and corticosteroid dose during the study period. Transdermal estradiol may prevent bone loss in postmenopausal SLE women at the lumbar spine and femur, with no increase in disease activity among postmenopausal SLE women receiving transdermal ERT. The high dropout rate (8/15) leads us to the conclusion that efficacy of HRT in a high-risk group such as SLE women can be attained only in a small number of patients, provided all inclusion/exclusion criteria are strictly adhered to.     

Bone turnover markers are correlated with quantitative ultrasound of the calcaneus: 5-year longitudinal data

Summary  Associations between bone turnover markers and calcaneal ultrasound (quantitative ultrasound, QUS) were studied in a population-based sample of 810 elderly women. Baseline bone turnover markers correlated with baseline QUS as well as with 5-year prospective changes in QUS. Introduction  Bone turnover markers are associated with areal bone mineral density, but the knowledge on the association with QUS is limited. Methods  Eight hundred ten women, all 75 years old, were investigated at baseline. Five hundred six completed a 5-year follow-up. Bone turnover markers and calcaneal QUS [speed of sound (SoS), broadband ultrasound attenuation (BUA), stiffness] were investigated at baseline. QUS was investigated at follow-up. Results  All bone turnover markers were correlated with baseline QUS [standardized regression (Beta_std) values from −0.07, p < 0.05 to −0.23, p < 0.001], with the exception of bone-specific alkaline phosphatase (S-Bone ALP) which was not correlated with BUA and stiffness index. When the correlations between baseline bone turnover markers and 5-year changes in QUS were analyzed, three serum osteocalcins were correlated with changes of SoS and stiffness index (Beta_std = −0.11, p < 0.05 to −0.17, p < 0.001). Also S-CTX-I correlated with changes of SoS and stiffness index (Beta_std = −0.10 and −0.09, respectively, p < 0.05). S-TRACP5b, urinary deoxypyridinoline/crea, and U-MidOC/crea correlated with changes of SoS (Beta_std = −0.10 and p < 0.05 for all). S-Bone ALP did not correlate with change of QUS. None of the bone turnover markers correlated with changes of BUA. Conclusions  Bone turnover markers correlate with concomitantly assessed QUS as well as with longitudinal change in QUS.     

Short-term effects of glucocorticoid therapy on biochemical markers of bone metabolism in Japanese patients: a prospective study

Glucocorticoid (GC) therapy induces rapid bone loss, but the early changes in calcium and bone metabolism in patients treated with GC have not been clarified. To investigate the changes in calcium and bone metabolism during the early stage of GC therapy, we analyzed various biochemical markers of bone metabolism. The serum levels of calcium (Ca), phosphorus, parathyroid hormone (PTH), osteocalcin (OC), bone alkaline phosphatase (BAP), and type I collagen cross-linked N-telopeptide (NTx), as well as the urinary levels of Ca, creatinine, and NTx, were measured on days 0, 3, 7, and 28 of GC therapy. The subjects were divided into the following four groups: 9 patients receiving pulse therapy (P), 18 patients receiving prednisolone (PSL) at doses ≥40 mg/day (H), 9 patients receiving PSL at doses ≥20 mg/day (M), and 11 patients receiving PSL at doses ≤10 mg/day (S). The serum OC level showed a marked decrease on day 3 of GC therapy (−41.2% ± 6.6%, P < 0.01), while the BAP level decreased gradually. Both serum and urinary NTx levels significantly increased on day 7 of GC therapy (9.9% ± 4.5%, P < 0.05, and 42.2% ± 10.6%, P < 0.01, respectively). Urinary Ca excretion was increased on day 3 of GC therapy and continued to increase until 4 weeks, while intact PTH showed an increase on day 3 and then remained constant until 4 weeks. In groups P and H, there were significant early changes in OC, BAP, NTx, and intact PTH levels, as well as urinary Ca excretion. Even a PSL dose of <10 mg/day caused a decrease in the serum OC level. In conclusion, the biochemical markers of Ca and bone metabolism showed different kinetics depending on the dose of GC, and it is important for patients on high-dose GC therapy to receive prophylaxis for bone loss from the start of GC treatment.     

Biochemical markers for the detection of bone metastasis in patients with prostate cancer: diagnostic efficacy and the effect of hormonal therapy

In the present study, we investigated the diagnostic effectiveness of biochemical markers of bone turnover for the detection of bone metastasis from prostate cancer and changes in the levels of these markers caused by hormonal therapy. Ninety-five patients with prostate cancer were divided into one of three groups: 26 patients with bone metastasis (BM(+)), 35 patients without bone metastasis on nonhormonal therapy (BM(−)HT(−)) and 34 patients without bone metastasis on hormonal therapy (BM(−)HT(+)). All patients in the BM(+) group had received hormonal therapy. Serum or urinary levels of the following biochemical markers of bone turnover were examined: bone-specific alkaline phosphatase (B-ALP), osteocalcin (OC), type I procollagen C-propeptide (PICP), type I collagen cross-linked C-telopeptide (ICTP), C-telopeptide fragment (CTx), N-telopeptide fragment (NTx), total pyridinoline (T-Pyr), total deoxypyridinoline (T-D-Pyr) and free deoxypyridinoline (F-D-Pyr). The BM(+) group showed significantly higher values than the BM(-)HT(-) group for B-ALP, PICP, NTx, CTx, T-Pyr, T-D-Pyr, and F-D-Pyr. Compared with the BM(−)HT(+) group, the BM(+) group showed significantly higher values for B-ALP, ICTP, NTx, T-Pyr and T-D-Pyr. The levels of B-ALP, NTx, CTx, T-D-Pyr and F-D-Pyr were significantly different between the BM(−)HT(−) and BM(−)HT(+) groups. All markers, except OC and CTx, significantly were correlated with the extent of bone metastasis on bone scintigraphy. Of all markers, receiver operating characteristic (ROC) analyses revealed B-ALP and F-D-Pyr to be the most sensitive and specific for differentiation between the BM(+) and BM(−)HT(−) groups with regard to bone formation and resorption, respectively. In contrast, B-ALP and ICTP were most sensitive and specific for differentiation between the BM(+) and BM(−)HT(+) groups. The results suggest that hormonal therapy greatly affects the efficacy of PICP, CTx and F-D-Pyr in the diagnosis of bone metastasis, whereas its effects on ICTP are small. Although bone metabolic markers would be useful in the diagnosis of bone metastasis from prostate cancer, the effects of hormonal therapy on bone metabolism should be kept in mind in their evaluation. Received: November 18, 1999 / Accepted: June 12, 2000     

Oncological validation of bone turnover markers c-terminal telopeptide of type I collagen (1CTP) and peptides n-terminal propeptide of type I procollagen (P1NP) in patients with prostate cancer and bone metastases

BackgroundBone formation markers c-terminal telopeptide of type I collagen (1CTP) and peptides n-terminal propeptide of type I procollagen (P1NP) were reported to be increased in patients with prostate cancer (PC) and bone metastases. The objective of the presented study was to investigate the utility of serum 1CTP and P1NP values in the diagnosis of bone metastases and in predicting oncological outcome in patients with PC.MethodsIn total, serum samples of 186 patients were included retrospectively including 53 (28.50%) benign prostatic hyperplasia (BPH) patients and 133 (71.50%) PC-patients. The group of patients with PC consisted of 58 patients with non-metastatic PC (cM0) (43.61%) and 70 (52.63%) patients with bone metastases (cM1b). Serum 1CTP and P1NP were measured by radioimmunoassay (RIA). Results were compared to clinical variables including oncologic follow-up data by univariate and multivariate analyses.ResultsMedian 1CTP concentrations were significantly higher in patients with PC compared to the BPH group [5.08 (range, 1.73–158.00) vs. 4.00 (range, 2.18–34.19) µg/L, P=0.019]. However, no significant difference of P1NP levels could be shown for these groups. With median values of 6.04 (1.73–158.00) and 3.91 µg/L (2.04–34.51) for 1CTP and 48.60 (9.12–1,074.37) and 33.90 (8.72–149.30) for P1NP both markers were altered in cM1b patients compared to cM0 patients (P=0.001 each). Furthermore, cancer-specific survival (CSS) and overall survival (OS) were significantly shorter in cM1b patients with higher 1CTP concentrations (P=0.037 and P=0.019, respectively), whereas no associations of P1NP and outcomes were observed.ConclusionsThe present study confirms that increased levels of 1CTP and P1NP concentrations are associated with presence of metastatic disease in the bone. Moreover, these markers are able to predict clinical course in PC patients with bone metastases. The potential use of these markers for treatment selection in advanced PC remains to be determined.