Clinical usefulness of cross-linked N-telopeptide of type I collagen (NTx) as a bone metastatic marker in patients with prostate cancer--comparison with serum PICP, PINP and ICTP

Type I collagen cross-linked N-telopeptide (NTx) in urine, the degraded form of type I collagen cross-linked in bone, has been evaluated as a marker of bone resorption. In this study, the clinical usefulness of NTx as a marker of bone metastasis of prostate cancer was compared with that the carboxyterminal propeptide of type I procollagen (PICP), the aminoterminal propeptide of type I procollagen (PINP), and the pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) in serum. We assessed 37 cases of prostatic cancer in which the diagnosis had been confirmed pathologically. The patients were 15 patients with prostatic cancer with bone metastasis (before treatment or during a relapse) (Group 1); 11 patients, with bone metastasis, but for whom treatment was effective and condition had stabilized (Group 2); and 11 patients, with localized prostatic cancer and no evidence of bone metastasis (Group 3). The serum PICP, PINP, and ICTP levels and concentration of NTx in urine were compared among the three groups with the Mann-Whitney U test, with p values less than 0.05 considered significant. Urine NTx concentrations in Groups 1, 2 and 3 were 539.3 +/- 202.9, 160.6 +/- 97.6 and 48.6 +/- 7.6 nMBCE/mMCr, respectively. The differences between the Group 1 and Group 2 and between Group 1 and Group 3 were significant (p < 0.01 and p < 0.001). The differences between Group 1 and Group 3 and between Group 2 and Group 3 were significant for serum PICP, PINP and ICTP concentrations (p < 0.05). The correlation coefficient between urine NTx and each serum bone metabolic marker was 0.8 for PICP, 0.4 for PINP and 0.5 for ICTP. These bone metabolic markers are promising clinical markers of bone metastatic and may be useful for prediction of therapeutic efficacy and recurrence in bone and quantification of the extent of bone metastates.     

Serial markers of bone turnover in men with metastatic prostate cancer treated with zoledronic Acid for detection of bone metastases progression

OBJECTIVES: This study assessed the usefulness of serial measurements of bone turnover markers in men with metastatic prostate cancer treated with zoledronic acid to detect disease progression. METHODS: Serum measurements of total alkaline phosphatase (tALP), bone-specific alkaline phosphatase (bALP), cross-linked N-terminal (NTx) and cross-linked C-terminal (CTx) telopeptides of type I collagen, amino-terminal procollagen propeptides of type I collagen (PINP), C-terminal telopeptides of type I collagen (ICTP), and prostate-specific antigen (PSA) were performed in 77 prostate cancer patients suffering from bone metastases and treated with zoledronic acid up to 15 mo. Fifty patients were with and 27 patients without objective evidence of metastatic bone progression during the administration of zoledronic acid. RESULTS: The baseline bone marker concentrations were not significantly different between the groups. After administration of zoledronic acid all bone markers except of ICTP decreased compared with baseline. CTx showed the greatest decrease. In patients with metastatic bone progression PINP, tALP, bALP, and ICTP were significantly higher at weeks 24, 36, 48, and 60 after starting treatment with zoledronic acid compared with patients without progression. In addition to the information of prostate-specific antigen as a monitoring parameter, the bone formation marker showed a better distinction between patients with and without disease progression. CONCLUSIONS: Selected bone turnover markers provide valuable information regarding progression of bone metastasis in men with metastatic prostate cancer under bisphosphonate therapy. The clinical impact should be confirmed in prospective randomised studies.     

The serum level of the amino-terminal propeptide of type I procollagen is a sensitive marker for prostate cancer metastasis to bone

OBJECTIVE: To assess the level of a bone-formation marker, the amino-terminal propeptide of type I procollagen (PINP), for its utility in indicating bone metastasis in patients with prostate cancer. PATIENTS AND METHODS: Several bone formation markers, i.e. PINP, the carboxy-terminal propeptide of type I procollagen (PICP), bone-specific alkaline phosphatase (BALP), and bone Gla protein (BGP), a bone resorption marker (pyridinoline cross-linked carboxy-terminal telopeptide, ICTP), and prostate specific antigen (PSA) were measured in 40 patients without and 25 patients with bone metastasis. No patient had undergone previous treatment, except for six who developed bone metastasis while undergoing hormone therapy. RESULTS: All markers except BGP were significantly higher in patients with bone metastasis than in those without. The levels of PINP correlated best with the extent of disease, although the levels of PSA, BALP and ICTP also correlated well. While PINP had the largest area under the receiver-operator characteristic curve, PSA, BALP and ICTP also produced useful curves. CONCLUSION: The bone formation marker PINP seems to be useful for discriminating patients with and without bone metastasis. PINP may help in the early and accurate diagnosis of bone metastasis in such patients.     

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

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

Pretreatment levels of urinary deoxypyridinoline as a potential marker in patients with prostate cancer with or without bone metastasis

OBJECTIVE: To assess the predictive role of the bone markers alkaline phosphatase (ALP) and urinary deoxypyridinoline (DPD), as indicators of bone turnover, at baseline in patients with prostate cancer. PATIENTS, SUBJECTS AND METHODS: Urinary DPD, serum ALP and prostate-specific antigen (PSA) were evaluated in 23 patients with benign prostatic hyperplasia (BPH), 115 with prostatic carcinoma, of whom 21 had bone metastasis, and in 16 age-matched control subjects. RESULTS: Patients with newly diagnosed prostate cancer and bone metastasis had a higher urinary excretion of DPD, and a higher serum PSA and ALP than had patients with BPH and those with prostate cancer but no metastasis. Receiver operating curve analysis for PSA, ALP and DPD showed a significant discriminating ability for positive and negative bone scans (P = 0.0684). However, from logistic regression of the combinations, only serum ALP was a significant independent predictor of bone metastasis in patients with prostate cancer. CONCLUSION: Serum ALP or urinary DPD are the best predictors of bone metastasis in patients with prostate cancer; further studies with more patients are required.     

Influence of Osteoarthritis on Serum Marker Levels of Bone Formation and Resorption in Patients with Benign Prostatic Hypertrophy

Background :
The aim of this study was to investigate the influence of osteoarthritis of lumbar vertebrae on serum bone formation and resorption marker levels of patients with benign prostatic hypertrophy (BPH).
Methods :
Serum levels of carboxyterminal propeptide of type I procollagen (PICP), alkaline phosphatase (ALP), carboxyterminaltelopeptide of type I collagen (ICTP), and prostate-specific antigen (PSA) were examined in 40 patients with BPH, and the presence of osteoarthritis at the lumbar vertebrae of the patients was evaluated by plain x-ray-p.
Results :
Findings of osteoarthritis were observed in 23 of the 40 patients (58%), and 10 of the patients had severe osteoarthritis (involving at least 2 lumbar vertebral bodies). The serum levels of PICP, ALP, ICTP, and PSA of the patients without osteoarthritis findings were not different from those of the patients with osteoarthritis or severe osteoarthritis.
Conclusion :
The influence of osteoarthritis on serum bone formation and resorption marker levels of patients with BPH appears to be rather slight, if there is any influence at all.     

血清骨保护素诊断前列腺癌骨转移的初步研究

目的探讨骨保护素（OPG）对前列腺癌骨转移的诊断意义。方法健康男性和前列腺增生患者各30例;对前列腺癌66例患者,分为无骨转移组（M0）36例（局限性前列腺癌30例、淋巴结转移6例）和骨转移组（M1）30例,采用ELISA法测定血清OPG浓度,结合临床资料进行统计学分析。结果M,组血清OPG浓度明显高于其他各组,差异有统计学意义（P〈0．001）。血清OPG与前列腺特异性抗原和碱性磷酸酶浓度呈正相关（r=0．427,0．277;P〈0．001）;与Gleason评分和病理分级呈正相关（r=0．331,0．344;P=0．001）。受试者工作特征（ROC）曲线分析可见,OPG的曲线下面积（AUC）较碱性磷酸酶大,对骨转移的诊断价值高。结论血清OPG对前列腺癌骨转移具有重要诊断价值。     

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     

Variable efficacy of bone remodeling biochemical markers in the management of patients with Paget’s disease of bone treated with tiludronate

The aim of this work was to evaluate the response of different biochemical bone markers to tiludronate administration in Paget’s disease of bone. Ten patients (five men and five women), 56–77 years old (67 ± 6.5), were treated for 3 months with tiludronate tablets (400 mg/day). Bone formation markers: alkaline phosphatase (AP), bone alkaline phosphatase (bAP), osteocalcin (BGP), and procollagen I carboxyterminal propeptide (PICP) in serum; and bone resorption markers: serum cross-linked carboxyterminal telopeptides of type I collagen (ICTP), urinary hydroxyproline/creatinine (Hyp/Cr), pyridinoline/Cr (Pyr/Cr), and alpha-1 collagen chain products degradation (CrossLaps) were assessed. Samples were taken before and at monthly intervals for 3 months after treatment began. The results of the present work show that serum AP and bAP are sensitive and reliable biochemical markers of bone formation in the follow-up of tiludronate in this disease. Serum PICP shows less sensitivity than serum AP, and serum BGP is not indicated as biochemical marker in these types of studies. Urinary hydroxyproline seems to be the most reliable biochemical marker of bone resorption. More studies should be performed with urinary Pyr and CrossLaps determinations. Serum ICTP is not adequate for the follow-up of tiludronate treatment in Paget’s disease of bone.     

Prostate tumour markers as an aid in the staging of prostatic cancer.

Serum acid phosphatase activity (ACP), prostate specific phosphatase (PAP) and prostate specific antigen (PSA) were measured in 100 patients with prostatic cancer. The patients were divided into 4 groups: T1-2 MO, T3-4 MO and M1 patients with less than or equal to 10 or greater than 10 metastatic foci in bone scintigraphy. The mean serum ACP levels were almost identical in the T1-2 MO and T3-4 MO groups and there was no significant difference between the mean PAP values. Significantly higher PSA levels were observed in the MO patients in the extracapsular category compared with those in the intracapsular category. The mean serum levels of all 3 tumour markers were significantly higher in the M1 than in the MO category. PSA seems to be the marker of choice as a diagnostic aid for differentiating between patients with intracapsular and those with extracapsular tumour growth. In prostatic cancer patients with bone metastases these markers were of similar value for staging the disease.     

Urinary Pyridinoline and Deoxypyridinoline as Potential Markers of Bone Metastasis in Patients with Prostate Cancer

Purpose

The levels of probable markers of bony metastatic disease were measured to evaluate their efficacy as predictors of disease and therapeutic outcome.

Materials and Methods

Urinary pyridinoline, urinary deoxypyridinoline, serum alkaline phosphatase and serum osteocalcin were measured in patients with benign prostatic hyperplasia, clinically localized prostate cancer and prostate cancer with bone metastases. Also, urinary pyridinoline and deoxypyridinoline were compared in 2 groups of patients with metastatic prostate cancer of the bone who demonstrated progression or positive response to treatment. Urinary pyridinoline and deoxypyridinoline were determined by high performance liquid chromatography and were normalized to urinary creatinine.

Results

Levels of pyridinoline and deoxypyridinoline in urine, and the level of alkaline phosphatase in serum from patients with bone metastatic prostate cancer were significantly greater than levels in patients with benign prostatic hyperplasia or localized prostate cancer. Serum osteocalcin levels failed to separate the 3 groups. Serial measurement of urinary pyridinoline and deoxypyridinoline was correlated with a positive response to treatment (decreased) and with clinical progression of disease (increased) before detection of new bone lesions by bone scintigraphy.

Conclusions

Measurement of urinary pyridinoline and deoxypyridinoline may provide a useful marker of prostate cancer metastatic to bone and may be useful in monitoring the response to treatment.     

Prediction of bone metastases by combination of tartrate-resistant acid phosphatase, alkaline phosphatase and prostate specific antigen in patients with prostate cancer

Objective:   The clinical value of serum tartrate-resistant acid phosphatase (TRACP), prostate specific antigen (PSA), alkaline phosphatase (ALP), and prostatic acid phosphatase (PACP) for the prediction of bone metastases in prostate cancer were investigated.
Methods:   TRACP, PACP, ALP, and PSA serum levels were measured in 215 patients with prostate cancer, including 160 without and 55 with bone metastases. Correlation of serum marker levels with bone metastases was assessed using receiver operating characteristics (ROC) analysis. Sensitivity, specificity, accuracy, positive and negative predictive values were calculated for each serum marker. Multivariate stepwise logistic regression analysis was used to identify independent predictors for the presence of bone metastasis.
Results:   Mean serum TRACP, PACP, ALP, and PSA levels were significantly elevated in patients with bone metastases compared with those without ( P  < 0.05). PSA and PACP levels increased significantly with clinical stage of the disease, whereas TRACP and ALP levels only increased significantly in stage D2. Serum TRACP levels correlated significantly with extent of disease on bone scans. ROC analyses showed no significant differences in area under the curve for these markers. Logistic regression analysis demonstrated that PSA, ALP, and TRACP were significant predictors of bone metastasis. Predicted and observed risks of bone metastasis were well correlated when TRACP, ALP, and PSA were combined and bone scan could have been omitted in 70% of patients by assessing these three markers.
Conclusions:   Serum TRACP can be considered a useful predictor of bone metastases in prostate cancer. A combination of TRACP, ALP, and PSA can obviate the need for a bone scan in 70% of cases.     

The efficacy of biochemical markers in patients with ossification of posterior longitudinal ligament of the spine

STUDY DESIGN: Serum levels of carboxyterminal propeptide of type I collagen (PICP), osteocalcin (OC), carboxyterminal telopeptide of type I collagen (ICTP) and urinary levels of pyridinoline (Pyr) and deoxypyridinoline (Dpyr) were measured in patients with ossification of posterior longitudinal ligament of the spine (OPLL) and age-matched control subjects. OBJECTIVES: To evaluate the efficacy of these biochemical markers of the patients with OPLL. SETTING: Department of Orthopedic Surgery, Hamamatsu University School of Medicine, Hamamatsu, Japan. METHODS: Spot urine and blood samples were obtained from 20 healthy males aged 45 - 78 (mean+/-SD; 63. 0+/-11.5) and 22 male patients with OPLL aged 46 - 77 (mean+/-SD; 59. 9+/-8.8), and serum levels of PICP, OC, ICTP and urinary levels of Pyr and Dpyr were measured. RESULTS: There were no significant difference in age, serum PICP, OC, ICTP, urinary Pyr and Dpyr levels between OPLL and control group. CONCLUSION: Neither bone formation nor bone resorption was accelerated in the patients with OPLL.     

Evaluation of bone loss and the serum markers of bone metabolism in patients with hyperparathyroidism

Bone loss and the serum markers of bone metabolism were studied in 22 patients with primary hyperparathyroidism and 108 patients with renal hyperparathyroidism. The parameters of bone loss were bone mineral density in the distal radius and lumbar vertebrae, measured by dual energy X-ray absorptiometry, and bone mass index (GS/D) and the metacarpal index, in the second metacarpal bone, measured by the digital image processing method. Alkaline phosphatase (AIP), intact osteocalcin (OC), and the carboxyterminal propeptide of type I procollagen (PICP) were measured as serum markers of bone formation, while tartrate-resistant acid phsophatase (TRACP) and the carboxyterminal pyridinoline cross-linked telopeptide of type I collagen (ICTP) were measured as serum markers of bone resorption. Bone loss and elevated markers of bone metabolism were observed both in patients with skeletal symptoms and in those without. Furthermore, the decrease in the cortical bone mass was more predominant than that of the trabecular bone. As markers of bone formation, AIP and OC seemed to be more sensitive than PICP, and as markers of bone resorption, ICTP appeared to be more sensitive than TRACP. Thus, a close correlation was observed between bone loss and the markers of bone formation and resorption.     

Correlations of new markers of bone formation and resorption in kidney transplant recipients

Renal osteodystrophy is a common complication of chronic renal failure and renal replacement therapy. Successful kidney transplantation reverses many of these abnormalities, but the improvement is often incomplete. The evaluation of renal osteodystrophy in everyday practice is based on noninvasive measurements. Taking this into consideration the aim of the present study was to assess new markers of bone metabolism: serum CrossLaps degradation products of C-terminal telopeptides of type I collagen tartrate-resistant acid phosphatase (TRAP) and bone-specific alkaline phosphatase (bALP), as well as their correlations with bone mineral disease (BMD) in kidney transplant recipients. Twenty-six patients (aged 26 to 54 years) receiving a triple immunosuppressive regimen with stable graft function were enrolled in the study. Serum parathormone (PTH) osteocalcin type collagen C-terminal peptides (ICTP), and procollagen type I carboxyterminal extension peptide (PICP) concentrations were measured by radioimmunoassay (RIA), Serum CrossLaps, bALP, beta2-microglobulin, TRAP 5b by enzyme-linked immunoassay (ELISA), and deoxypyridinoline (DPD) in urine immunochemiluminescence. BMD, as measured by dual-energy X-ray absorptiometry (DEXA), correlated negatively with markers of bone formation (bALP, osteoclacin, and PICP) and resorption (TRAP, ICTP, and beta2-microglobulin). The only positive correlation was between urine DPD and BMD at the femoral neck. Interestingly, BMD correlated negatively with CsA concentration. TRAP 5b correlated positively with serum creatinine, ALP, bALP, osteocalcin, iPTH, ICTP, and serum beta2-microglobulin, and negatively with CsA concentration, and azathioprine and prednisone dose. DPD did not correlate with any parameters. Serum CrossLaps correlated with markers of both bone formation and resorption. Because TRAP and serum CrossLaps correlated with markers of both bone formation and or resorption, additional studies are needed to establish the value of these markers of bone resorption to assess renal osteodystrophy.     

Angiogenic peptides in prostatic disease

OBJECTIVE: To determine the value of measuring serum concentrations of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in patients with benign prostatic hyperplasia (BPH), advanced and localized prostate cancer, and thus assess the role of angiogenesis factors as markers of malignancy and the formation of metastasis. PATIENTS AND METHODS: Serum was obtained from 106 suitable patients who attended a routine clinic during the study period. A histological diagnosis was confirmed for each patient and a bone scan was positive in those with metastatic disease. The level of serum prostate specific antigen (PSA) was measured and the serum concentrations of VEGF and bFGF measured using a quantitative sandwich immunoassay technique. RESULTS: There was a significant difference (1.6-fold) in the serum concentration of bFGF between patients with local and advanced prostate cancer (P=0.006), but there was no significant difference for either of the growth factors between patients with BPH and metastatic prostate cancer (Mann-Whitney test). CONCLUSION: The serum levels of VEGF and bFGF could not be used to distinguish benign from malignant prostatic disease; the serum PSA level is of more value than either, but the serum concentration of bFGF may be of some value in differentiating patients with local and advanced malignancy.     

Quantitative evaluation of bone metastases in patients with advanced prostate cancer during systemic treatment

OBJECTIVE: To assess the clinical usefulness of quantifying the extent of disease on bone scans in monitoring treatment response in patients with advanced prostate cancer, using computer-assisted image analysis. PATIENTS AND METHODS: The percentage of the positive area on the bone scan (%PABS) was quantified automatically using a personal computer with an image-analysis program. Serial measurements of %PABS in 42 patients with bone metastasis from prostate cancer followed for a mean (range) of 33 (4-72) months with hormonal therapy were compared with those of the extent of disease (EOD) grades in bone lesions and serum prostate specific antigen (PSA) levels according to treatment response. RESULTS: Serial values of EOD grades and %PABS decreased during treatment in 11 patients with a partial response and in 12 with progressive disease who had no bone metastasis progression. However, EOD grades and %PABS increased in the remaining 19 patients with progressive disease who had bone metastatic progression. Estimated survival curves showed that %PABS was a useful prognostic indicator, in that patients with a > 25% decline in %PABS survived longer than those with a < 25% decline after treatment (P = 0.0207). CONCLUSIONS: The %PABS is a simple and reproducible estimate of the proportion of the skeleton involving tumours in patients with advanced prostate cancer, and serial measurements of %PABS can assist in monitoring the treatment response in patients with bone metastatic prostate cancer.     

Biochemical Markers of Bone Turnover in Camurati–Engelmann Disease: A Report on Four Cases in One Family

Moderate increases in ``classical' biochemical markers of bone turnover have been described only in some patients with Camurati–Engelmann disease. However, the determination of the following ``new' markers has not been previously performed: serum osteocalcin (BGP), bone alkaline phosphatase (BAP), carboxyterminal propeptide of type I procollagen (PICP), aminoterminal propeptide of type I procollagen (PINP), tartrate-resistant acid phosphatase (TRAP), telopeptide carboxyterminal of type I collagen (ICTP), urinary pyridinoline (PYR), crosslinked N-telopeptides of type I collagen (NTX), and Crosslaps (CL). Such a determination may improve the evaluation of the disease activity. To evaluate the usefulness of biochemical markers of bone turnover reflecting Camurati–Engelmann disease activity we measured the levels of all these markers in four affected patients. The results were compared with bone scintigraphic indices of disease activity. Except for PICP and TRAP, bone formation and resorption markers were abnormal in all patients and were related to bone scan indices of disease activity. Among the markers of bone formation PINP, BAP, and BGP showed the highest values, whereas NTX and CL were the most sensitive markers of bone resorption. These results suggest that the determination of NTX or CL, and PINP or either BAP and BGP, associated with bone scan evaluation, provides the best assessment of Camurati–Engelmann disease activity. Received: 14 June 1996 / Accepted: 31 December 1996     

Clinical Efficacy of Bone Alkaline Phosphatase and Prostate Specific Antigen in the Diagnosis of Bone Metastasis in Prostate Cancer

Purpose

We investigated the usefulness of bone alkaline phosphatase isoenzyme and prostate specific antigen (PSA) determined by radioimmunoassay to predict bone scan evidence of metastasis in newly diagnosed untreated and treated prostate cancer.

Materials and Methods

We analyzed bone alkaline phosphatase enzyme concentrations in 350 men, including 150 controls, 100 with benign prostatic hyperplasia and 100 with prostate cancer (52 with stage T1 to 4, M0 and 48 with stages T1 to 4, M1 to 4). We also analyzed bone alkaline phosphatase enzyme concentrations in 61 stages T1 to 4, M0 prostate cancer cases during followup after radical prostatectomy or hormonal therapy, and 17 had clinical progression (9 with local, 5 with lymph node and 3 with bone metastases). Simultaneously, we analyzed PSA concentrations.

Results

Average bone alkaline phophatase enzyme levels were 12, 11.1 and 10.0 ng./ml. in the control, benign prostatic hyperplasia and stage M0 prostate cancer groups, respectively (p not significant), and 83.2 ng./ml. in patients with stage M1 to 4 disease (p less than 0.001). Considering that to diagnose bone metastasis the cutoff for bone alkaline phosphatase enzyme and PSA is 30 ng./ml. and 100 ng./ml., respectively, clinical effectiveness was 93.7 percent and 81.8 percent, respectively. Finally, measurement of both substances at the same time increased clinical effectiveness to 97.9 percent. During followup a bone alkaline phosphatase enzyme level that becomes greater than 30 ng./ml. (0 percent in the local and lymphatic progression groups, and 100 percent in the bone metastasis group) indicates the need to perform a bone scan.

Conclusions

We recommend the clinical use of bone alkaline phosphatase enzyme determined by radioimmunoassay and PSA measurement for the diagnosis of bone metastases and progression of prostate cancer because of the good sensitivity and specificity.     

Palliative treatment of bone metastases in hormone-refractory prostate cancer: effects of pamidronate on the carboxyterminal telopeptide of type-I collagen level in patients with increasing prostate-specific antigen levels

PURPOSE: Bisphosphonates have been reported to be effective in reducing bone pain and skeletal-related events associated with bone metastases in hormone-refractory prostate cancer (HRPC). However, whether bone resorption is reduced primarily by these particular drugs is difficult to evaluate because patients with HRPC are usually treated with secondary or tertiary hormonal manipulations including second-line antiandrogens, high-dose diethylstilbestrol, or low-dose dexamethasone therapies, some of which may also be effective. Thus, we assessed changes in the level of the carboxyterminal telopeptide of type-I collagen (ICTP), a bone resorption marker, before and after pamidronate administration in HRPC patients with increasing prostate-specific antigen (PSA) levels. PATIENTS AND METHODS: Twenty-one HRPC patients with bone metastases and increasing PSA levels were intravenously treated with pamidronate at a dose of 30 mg either every 2 or every 4 weeks. Pamidronate administration was started immediately after confirmation of three consecutive increases in the PSA level. RESULTS: In 14 patients (67%), the ICTP levels decreased after the administration of pamidronate, despite increasing PSA levels. In 7 of these cases, the ICTP levels were lower than those recorded for 6 months or longer before the start of pamidronate administration. The characteristics of the responders were compared with those of the non-responders. CONCLUSION: In 67% of the HRPC patients with increasing PSA levels, pamidronate reduced the accelerated turnover of bone metabolism caused by metastases of prostate cancer.