Biochemical Markers of Bone Turnover and Bone Loss at the Lumbar Spine and Femoral Neck: The Taiji Study

The purpose of this study was to ascertain whether biochemical markers of bone turnover predict bone loss. The survey was carried out in Taiji, Wakayama Prefecture, Japan. From a list of inhabitants aged 40–79 years, 400 participants (50 men and 50 women in each of four age groups) were selected randomly. Bone mineral density (BMD) was measured, and blood and urine samples of all participants were examined to obtain values for eight biochemical markers: alkaline phosphatase (ALP), bone Gla protein (BGP), type I procollagen (carboxyterminal peptide of type I procollagen; PICP), cross-linked carboxyterminal telopeptide region of type I collagen (ICTP), and urinary excretion of calcium (Ca), phosphate (P), pyridinoline (Pyr), and deoxypyridinoline (D-Pyr). Each marker was evaluated as a predictor of the rate of bone change in lumbar spine and femoral neck BMD over a 3-year period. The value of Pyr was significantly related to the change of lumbar spine BMD in men (P= 0.009), and that of BGP was found to be significant in women (P= 0.045). By contrast, none of the bone markers significantly correlated with bone loss at the femoral neck. The coefficient of determination at the lumbar spine was 5% and 7% at the femoral neck only. We conclude that biochemical markers of bone turnover cannot predict bone loss rates in middle-aged or elderly Japanese men and women over a 3-year period with sufficient accuracy for use in clinical decision making. Received: 26 January 1998 / Accepted: 9 July 1998     

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.     

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.     

Sexual differences in bone markers and bone mineral density of normal Chinese

We measured bone mineral density (BMD) at lumbar (L2–L4) vertebrae and proximal femurs of 385 healthy Chinese women aged 40–70 years and 156 healthy Chinese men aged 20–85, and four markers—bone alkaline phosphatase isozyme (BAP), procollagen-I C terminal propeptide (PICP), osteocalcin (BGP) in serum, and a bone resorption marker, urinary cross-linked N-telopeptide of type I collagen (NTX), of these subjects. The results indicate that in postmenopausal women, levels of all the markers increased with age. In men, serum BAP, PICP, and urinary NTX decreased significantly, and serum BGP decreased with borderline significance (P=0.08). With increasing age, bone density decreased at both sites in post-menopausal women and at the proximal femur in men. The lumbar bone density showed no significant age-related changes in men. In premenopausal women, BMD at either site showed no significant change with increasing age. Despite the different trends between men and women of agerelated changes in BMD and bone markers, bone density of both proximal femur and spine in both sexes correlated inversely with levels of the bone markers in a manner independent of age or body weight. The meaning of opposite age effects on bone markers in men and women needs further investigation. In addition, higher bone marker levels, implying faster bone turnover rate, are associated with lower BMD in both sexes.     

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     

Effects of Gestational Age, Maternal Diabetes, and Intrauterine Growth Retardation on Markers of Fetal Bone Turnover in Amniotic Fluid

Little is known about the dynamics of bone formation and bone resorption in utero, particularly the normal changes that occur throughout gestation and in clinical situations that result in low bone mass at birth. The objectives of this study were to describe the effects of gestational age on markers of fetal bone turnover, and to investigate whether the reported low bone mass at birth in small-for-gestational-age (SGA) infants and infants of diabetic mothers (IDMs) was associated with biochemical markers of decreased bone formation or increased bone resorption in utero. Bone formation and resorption were assessed by measurement of carboxyterminal propeptide of type I procollagen (PICP) and cross-linked carboxyterminal telopeptide of type I collagen (ICTP), respectively, in 201 amniotic fluid samples. These markers are by-products of type I collagen formation and degradation, respectively, and have been used in the assessment of bone metabolism ex utero. Both PICP and ICTP concentrations in amniotic fluid were inversely associated with gestational age (P < 0.0001). Amniotic fluid concentrations of PICP increased exponentially in relation to infant birthweight (P= 0.008), and SGA infants had lower amniotic fluid PICP concentrations than controls (P= 0.07). The presence of diabetes in the mother was not associated with alterations in amniotic fluid PICP or ICTP concentrations. Although maturational effects on clearance of bone markers from amniotic fluid cannot be excluded, these data are consistent with a high turnover of bone matrix early in fetal life, and a reduction in bone formation when fetal growth is compromised.     

The duration of exercise as a regulator of bone turnover

The relationship between duration of exercise and serum remodeling markers of bone turnover was evaluated by osteocalcin (OC), carboxy-terminal propeptide of type I collagen (PICP), total and bone-specific alkaline phosphatase (ALP) and carboxyterminal cross-linked telopeptide of type I collagen (ICTP) in 24 male premier league soccer players exercising 12 hours/week (range 8–18), 19 third league players exercising 8 hours/week (range 3–18) and 20 sixth league players exercising 6 hours/week (range 2–10). Twenty-seven volunteers served as controls. Forty-six former male soccer players (mean age 38 years, range 19–47), mean 15 years older than the current players, were compared with 41 matched controls. Data is presented as mean ± SEM. Active male players had 18 ± 4% higher OC, 37 ± 9% higher bone ALP and 36 ± 7% higher ICTP than controls (all P < 0.01). There were no differences in remodeling markers within the three groups of active players but each group had higher OC and ICTP than controls (both P < 0.05). Former players had no difference in bone remodeling markers compared to matched controls, but 39 ± 4% lower OC and 69 ± 8% lower ICTP than active players (both P < 0.001). Duration of activity was correlated with bone ALP and ICTP (both r = 0.3, P < 0.05) in individuals exercising 6 hours/week or less. No correlation was found in those exercising above this level. It seems as if the bone turnover, evaluated by serum bone remodeling markers, adapts to the current activity needed to maintain bone strength, and a duration of exercise above that level seems to confer no additional benefits.     

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.     

Pyridinoline cross-linked carboxyterminal telopeptide of type I collagen as a useful marker for monitoring metastatic bone activity in men with prostate cancer

PURPOSE: We investigated the clinical usefulness of measuring the serum concentrations of pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP) and carboxyterminal propeptide of type I procollagen (PICP) as markers for monitoring metastatic bone activity in patients with prostate cancer. MATERIALS AND METHODS: Serum levels of ICTP, PICP, alkaline phosphatase, prostatic acid phosphatase and prostate specific antigen (PSA) were analyzed in 104 untreated patients with prostate cancer, including 62 with and 42 without bone metastasis. Serial measurements of ICTP, PICP and PSA were performed during hormonal therapy in 35 of 62 prostate cancer patients with bone metastasis. RESULTS: Serum levels of all markers except prostatic acid phosphatase were significantly higher with than without bone metastasis. The median values of each marker increased according to the extent of bone metastasis. Serial ICTP, PICP and PSA in 19 patients with a partial response or no change in bone scans demonstrated a downward trend after treatment, while in 16 with progression they showed an upward trend after treatment. The rate of detecting bone metastasis and progression using ICTP were highest compared with other markers based on the percent clinical effectiveness and receiver operating characteristic curves. CONCLUSIONS: Measuring serum ICTP may be useful for detecting bone metastasis and prostate cancer progression, and may augment PSA and bone scan monitoring of metastatic bone activity.     

Bone density change and biochemical indices of skeletal turnover

Although biochemical markers of skeletal turnover cannot replace bone density scanning for the diagnosis of osteoporosis, it is thought that they may help add to prediction of fracture risk and help determine adequacy of osteoporosis therapy. Nevertheless, whether biochemical markers in the serum or urine can predict individual rates of bone loss in the spine or hip region is unknown. We studied a heterogeneous group of women (n=81) who were premenopausal, untreated postmenopausal, and estrogentreated postmenopausal with baseline determination of body mass index (BMI), calcium intake, biochemical measurements, and serial bone densitometry over 3 years. Serum assays included bone Gla protein (BGP), total and bonespecific specific included bone Gla protein (BGP), total and bone-specific alkaline phosphatase (AP, BSAP), carboxyterminal propeptide of type I procollagen (PICP), carboxyterminal telopeptide of type I collagen (ICTP) and tartrate-resistant acid phosphatase (TRAP). Urine assays included hydroxyproline (OHP), calcium, total pyridinoline, and total deoxypyridinoline. Individual biochemical markers and calcium intake were modestly correlated with bone density changes but were inconsistent regarding the spine versus the hip. All of the formation variables were significantly correlated to spine density change (r=−0.24 to −0.49) whereas the only resorption variable that correlated was urine OHp/Cr (r=−0.31). The only formation variable that correlated with hip density change was serum PICP whereas all of the resorption variables except serum TRAP were correlated (r=−0.23 to −0.35). “High turnover” individuals were defined as those with levels of biochemical variables at least 1 SD above the mean young normal for each variable. Higher bone loss rates were seen in this group for several of the turnover markers compared with bone loss rates in all other individuals. However, the sensitivity of this “high turnover” status for identifying high bone losers did not exceed 60% for any of the variables. In untreated postmenopausal women, a model using urine OHp, serum ICTP, serum BSAP, and calcium intake was able to predict 42% of the variance of change in BMD of the lumbar spine. A model using BMI, serum ICTP, and serum BGP could predict 32% of the variance of change in BMD of the femoral neck. No combination of markers could predict variance in bone density change at either site in estrogenized women (premenopausal and estrogen-treated postmenopausal). We conclude that measuring individual serum and urine markers of bone turnover cannot accurately predict bone loss rates in the spine and hip; however, combinations of demographic and biochemical variables could predict some of the variance in untreated postmenopausal women. Biochemical markers cannot replace serial bone densitometry for accurate determination of change in bone mass at the most clinically relevant sites.     

Bone Turnover Responses to Changed Physical Activity

The aim of the study was to compare bone turnover in male soccer players with controls and to follow bone turnover with changes in activity level. Serum-osteocalcin (OC), carboxy-terminal propeptide of type I collagen (PICP) and total alkaline phosphatases (tALP) were measured to assess bone formation. Bone resorption was detected by carboxyterminal cross-linked telopeptide of type I collagen (ICTP). Bone turnover of 12 male premier league soccer players (mean age 23 years, range, 17–34) exercising 12 hours/week (range, 8–15) were at the last day of the soccer season compared with 27 age- and gender-matched controls. Bone turnover was followed weekly during a 4-week resting period between two seasons, and a further 10 days following resumption of full training. Data are presented as mean ± SEM. Both OC (22 ± 12%) and ICTP (34 ± 17%) were higher in the players compared with the controls at the end of the season (both P < 0.05, respectively). After 2 weeks of reduced physical activity among the athletes, the PICP levels were 21 ± 4% (P < 0.05) lower and the ICTP levels 8 ± 12% higher (P = 0.07) compared with baseline. OC, PICP, and tALP was then no different compared with controls and ICTP was higher than controls (P < 0.001). Ten days within the new season, there was a 23 ± 5% increase in PICP (P < 0.001) and a 4 ± 4% decrease in ICTP (P < 0.05) compared with the end of the resting period. In summary, male soccer players have higher bone turnover compared with age- and gender-matched controls. Changes in physical activity level were associated with changes in bone formation and resorption as evaluated by bone markers within weeks, and after 2 weeks rest, ICTP was higher in the athletes than the controls. We conclude that the higher age-related diminution in BMD, previously reported in former soccer players compared with age- and gender-matched controls, may be the result of increased bone resorption, evaluated by ICTP, compared with the controls.     

Serum levels of bone GLA protein (osteocalcin,BGP) and carboxyterminal propeptide of type I procollagen (PICP) in acromegly: Effects of long-term octreotide treatment

Summary We measured serum concentrations of bone Glaprotein (osteocalcin, BGP) and carboxyterminal propeptide of type I procollagen (PICP) in 14 patients with active acromegaly. Blood was collected at 0800 for measurement of bone Gla-protein (BGP), carboxyterminal propeptide of type I procollagen (PICP), and insulin-like growth factor I (IGF-I); growth hormone (GH) was then determined at 15-minute intervals for 3 hours and the integrated mean was calculated. The same protocol was repeated at regular intervals during treatment with the long-acting somatostatin analog, octreotide, 150–450 g/day for 6–33 months (median 15). In a case-control analysis, serum BGP concentrations recorded in the acromegalic patients were significantly elevated (14.2±4.2 g/liter versus 8.0±3.3 g/liter, P<0.001). Octreotide treatment induced a roughly parallel reduction in serum GH, IGF-I, and BGP. We found a significant positive correlation between BGP levels recorded before and during therapy and the logarithm of corresponding mean GH levels (r=0.67, P<0.001). Also IGF-I concentrations were positively correlated with BGP (r=0.66, P<0.001). On the other hand, PICP levels recorded in the acromegalics did not differ from control subjects (146±46 g/liter versus 127±44 g/liter, NS) and no correlation was found between either GH and PICP or IGF-I and PICP. To conclude, the present data are compatible with the view that GH and IGF-I play an important role in the control of BGP but not PICP production. It could be that BGP and PICP are submitted to different hormonal modulation.     

Increased bone turnover as reflected by biochemical markers in patients with potentially unstable fixation of the tibial component

Introduction Whether biochemical markers of bone metabolism can be used in assessing the conditions of implant fixation is unknown. In this study, the serum levels of three bone markers were measured prospectively in patients undergoing total knee arthroplasty (TKA) to determine if patients with different fixation conditions of the tibial component showed any differences in the levels of the markers.Materials and methods The fixation of the tibial component in 40 knees (40 patients, 14 male and 26 female, average age 71 years) was assessed by radiostereometric analysis (RSA), and based upon the pattern of migration, implants with stable fixation (n=25) and potentially unstable fixation (n=15) were identified. Serum levels of carboxyterminal propeptide of type I procollagen (PICP), osteocalcin (OC) and cross-linked carboxyterminal telopeptide of type I collagen (ICTP) were assessed and compared between the two fixation groups. Blood samples were obtained preoperatively (baseline) and repeated postoperatively at 1 week, 3, 6, 12, and 24 months.Results The baseline levels of the markers were statistically the same (p>0.05) between the two fixation groups. Postoperatively, ICTP levels in the unstable group were significantly higher than in the stable group from 6 to 24 months (p=0.02). Levels of OC in the unstable group were higher at 12 and 24 months compared with the stable group, reaching statistical significance only at 12 months (p=0.03). No difference in the levels of PICP was found between the two groups.Conclusion The findings indicate a more active bone turnover probably at the bone-cement/implant interface in knees with potentially unstable fixation. It reveals the potential value for biochemical markers in monitoring implant fixation and aseptic loosening and suggests a possibility for improving implant fixation by drugs which inhibit osteolysis.     

New biochemical markers of bone resorption derived from collagen breakdown in the study of postmenopausal osteoporosis

The aim of this work was to perform a comparative study between three recently developed biochemical markers of bone resorption derived from collagen metabolism — (1) total urinary free pyridinolines (Pyr), (2) serum pyridinoline cross-linked carboxy-terminal telopeptides of type I collagen (ICTP) and (3) a urinary-specific sequence for a part of the C-telopeptide of the ₁ chain of type I collagen (CTX) — in the diagnosis and follow-up of postmenopausal osteoporosis. Results were also evaluated relative to the classical biochemical marker urinary hydroxyproline (Hyp). The study included 20 untreated osteoporotic postmenopausal women (OSP), age 60 ±6 years, range 46–69 years; 27 osteoporotic postmenopausal women treated (OSP-T) by cyclic therapy with disodium etidronate, 25-hydroxyvitamin D and calcium for a period between 3 months and 4 years (25±15 months), age 59±7 years, range 41–67 years; 17 osteopenic postmenopausal women, age 57±6 years, range 46±68 years; and 29 healthy control postmenopausal women, age 56±7 years, range 41–70 years. The diagnostic criterion for postmenopausal osteoporosis was a bone mineral density (BMD) (Hologic QDR-1000) in lumbar spine and/or femoral neck more than 2 SD below the mean value corresponding to an age- and sex-matched healthy control group. For inclusion in the osteopenic group BMD values had to be between 1 and 2 SD below the mean BMD value corresponding to the control group. We found a significant increase (p<0.01) in the levels of Pyr/Cr and CTX/Cr (Cr=creatinine) in OSP patients with respect to the control group and we did not obeserve any significant difference between control and OSP-T or osteopenic women. It is interesting to note that there was a mean increase in CTX/Cr in OSP patients of 101% of the control values, while the mean increase found in Pyr/Cr concentration was only 33%. However, we did not find significant differences in the concentrations of ICTP and Hyp/Cr between groups. In a comparison of Pyr/Cr and CTX/Cr, urinary CTX showed the higher diagnostic accuracy, as can be deduced from the receiver operating characteristic (ROC) curves. CTX sensitivity was 40% with a specificity of 100%, whereas the sensitivity was 25% for urinary Pyr/Cr. In conclusion, the results of the present work suggest that in osteoporotic women CTX has the highest diagnostic accuracy among the markers of bone resporption studied.     

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.     

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.     

Biochemical markers of bone formation in the study of postmenopausal osteoporosis

A comparative study was performed on the sensitivity of the determination of the available biochemical markers of bone formation — total and bone alkaline phosphatase (TAP and bAP, respectively), osteocalcin (BGP), procollagen I aminoterminal propeptide (PINP) and procollagen I carboxyterminal propeptide (PICP) — in the study of postmenopausal osteoporosis. The comparison between PINP and PICP, due to the recent development of the amino-terminal assay, is of special interest. The study included 26 untreated osteoporotic postmenopausal women, age 59±6 years (range 46–69 years) and 17 healthy control postmenopausal women, age 56±7 years (range 48–70 years). We found a significant increase in the levels of bAP (p=0.0021), BGP (p=0.041), PINP (p=0.0001) and PICP (p=0.0073), but not in the levels of TAP (p=0.3389), in osteoporotic patients with respect to the control group. Serum PINP and bAP showed the highest diagnostic accuracy among the markers of bone formation studied, as can be deduced from the receiver operating characteristics (ROC) curves. In spite of their similar origin (amino-terminal and carboxy-terminal release from a procollagen molecule), the results obtained by measuring levels of PINP are significantly better than those found with PICP.     

Activity of rheumatoid arthritis and urinary pyridinoline and deoxypyridinoline

The aims of this study were to examine levels of the crosslinking components of collagen, pyridinoline (Pyr) and deoxypyridinoline (D-Pyr) which are bone resorption markers, in patients with rheumatoid arthritis (RA), and to determine their association with disease activity and bone mineral density (BMD). These bone resorption markers were measured in 35 postmenopausal women with RA, 30 age-matched female patients with osteoarthritis of the knee (controls), and 47 patients with bone fracture. The mean BMD in the RA patients was lower than that in the control group, and the Z-score (number of standard deviations above and below the normal mean after comparison with age and sex matched normal control values) was significantly lower. Mean levels of Pyr and D-Pyr were significantly higher in the RA patients than in the control group, and the Pyr/D-Pyr ratio was also higher in the RA patients than in the other groups. Regarding the relationship between the bone resorption markers and RA activity, Pyr increased as the Lansbury's joint score (number of swollen joints corrected for joint size according Lansbury) rose, showing a normal correlation; D-Pyr also showed a normal correlation. Pyr and D-Pyr were high in patients with a high erythrocyte sedimentation rate, showing a normal correlation. Only Pyr increased with increases in C-reactive protein (CRP), showing a normal correlation. These findings suggested that a high value for Pyr (which includes a large amount of collagen type II) indicated that RA activity was affected more by synovitis, rather than by systemic osteoporosis.     

High bone turnover of type I collagen depends on fetal growth

The bone metabolic processes of proliferation and differentiation in preterm and term newborns have yet to be fully elucidated. Seventy-four umbilical cord blood samples were collected from preterm and term newborns delivered at 27 to 42 gestational weeks (GWs). Carboxy-terminal propeptide of type I procollagen (PICP), pyridinoline cross-linked telopeptide domain of type I collagen (ICTP), alkaline phosphatase (ALP), and bone-specific alkaline phosphatase (BAP) were measured. Calcitonin (CT), estrogen (E2), intact parathyroid hormone, and insulin-like growth factor-I (IGF-I) were also examined in 20 or 23 randomly selected samples. We conducted cross-sectional regression analyses for bone metabolic markers, fetal growth markers including GWs, birth weight (BW), height (BH) and head circumference (HC), and bone related hormones. PICP and ICTP activities were very high, but decreased significantly with fetal growth based on GWs, BW, BH, and HC changes (GWs, BW, and BH to both PICP and ICTP, P < 0.0001; HC to ICTP, P < 0.0001; HC to PICP, P < 0.05), while BAP and ALP did not change significantly. E2 and CT both showed a significant positive correlation with Ca (P < 0.05), but neither hormone had any apparent correlation with PICP, ALP, BAP, or ICTP. These results suggest very active bone formation and resorption of type I collagen to be dependent on fetal growth and that fetal osteoblasts dominate the proliferation phase of development rather than the maturation phase. However, factors contributing to high bone turnover in the fetus remain to be elucidated.     

Collagen type I metabolism after bone surgery

This study follows the postoperative course of serum collagen type I metabolites in patients after uncomplicated implantation of a cemented total hip endoprothesis (TEP; n = 12, mean age: 69.3 years), a cemented hemiendoprothesis (HEP; n = 13, mean age 79.7 years), a dynamic condylar or hip screw (DCS/DHS; n = 12, mean age 75.1 years) and osteosynthetic treatment of a Weber B or C fracture (OS; n = 17, mean age 54.3 years). The course of the propeptide of human type I procollagen (PICP) as an anabolic marker as well as of I-carboxyterminal telopeptide (ICTP) as a catabolic marker of bone metabolism was characterized. Measurements were done preoperatively and weekly for 3 weeks after surgery. The concentrations of both markers increased and reached a maximum in the 2nd or 3rd week after surgery. However, the PICP values differed, depending on the kind of surgical intervention and the type of bone healing. Secondary fracture healing with formation of callus occurred in the DCS/DHS group, which developed the highest median PICP concentrations (initial 83 μ g/l, second week 337 μg/l; P < 0.001). In contrast, the primary bone healing in the OS group showed increasing ICTP but unchanged PICP concentrations. Patients in the cemented TEP and HEP groups as a kind of artificial bone healing had comparable concentrations. To consider the effective metabolism of collagen type I, the PICP/ICTP ratio was calculated. Although the median PICP and ICTP concentrations of the studied groups differed, the PICP/ICTP ratios were similar. In comparison to 54 young and healthy volunteers (median PICP/ICTP ratio: 37), the ratios of the studied groups were still normal but low (median ratios: < 20). This could be an effect of decreasing collagen type I metabolism with age. Although the results are in agreement with animal studies and histomorphometric investigations, the clinical use of PICP and ICTP determination as a tool for the detection of complicated bone healing is limited by the marked interindividual variability and the uncertain bone specificity. Received: 2 April 1998