Recovery of bone mass and normalization of bone turnover in long-term survivors of allogeneic bone marrow transplantation

Osteoporotic fractures are potential long-term complications of bone marrow transplantation (BMT). We previously reported that bone mineral density (BMD) of patients undergoing allogeneic BMT decreased by 6% to 9% during the first 6 months after BMT and that bone turnover rate was still increased 1 year after BMT. BMT patients do not need lifelong immunosuppressive treatment, which should offer favorable circumstances for the recovery of BMD. Thus, 27 (14 women, 13 men) of 29 long-term survivors of our previous study were invited to a follow-up study at a median of 75 months after BMT. From 12 months after BMT the BMD of the lumbar spine had increased by 2.4% (P = 0.002). The respective changes in femoral sites were +4.1% in the femoral neck (P = 0.087), 4.0% in the trochanter (P = 0.095), +4.7% in Ward's triangle (P = 0.072) and +1.4% in the total hip (P = 0.23). The markers of bone formation, serum osteocalcin and type I procollagen aminoterminal propeptide (PINP) had returned to control levels, but out of the markers of bone resorption the mean level of serum type I carboxyterminal telopeptide (ICTP) was 41% higher (P = 0.0001) and that of urinary type I collagen N-terminal telopeptide/creatinine (NTx) 41% lower (P = 0.0002) in patients than in controls. The mean serum 25-hydroxyvitamin D [25(OH)D] was 33% lower in patients (P = 0.0002), most of whom had hypovitaminosis D [serum 25(OH)D < or = 37 nmol/l]. Except for two, males had serum testosterone level lower than before BMT and four men had hypogonadism. In conclusion, in long-term survivors of allogeneic BMT BMD recovers and bone turnover state normalizes as compared to the situation 1 year after BMT. More attention should be paid to the vitamin D status of all recipients and to possible hypogonadism of male patients.     

Changes in serum levels of type I collagen-related proteins after surgically induced menopause and correlations with bone loss in the lumbar spine.

The purpose of this prospective study was to characterize the changes in serum levels of two proteins produced during the synthesis and degradation of type I collagen, i.e., the carboxyterminal propeptide of type I procollagen (PICP) and the pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), respectively, after oophorectomy, and to assess the degree of correlation between changes in the serum values of these proteins and changes in bone mineral density (BMD) of the lumbar spine. Serum levels of PICP, ICTP and bone gla protein (BGP) were determined in 18 women before oophorectomy (baseline) and at 7 days, and 1, 2, 3, 6, 9 and 12 months post-oophorectomy (PO). The BMD of the lumbar spine was measured at baseline, and at 6 months and 12 months PO. ICTP had increased significantly at 7 days PO and peaked between 1 and 3 months PO. PICP and BGP had increased significantly at 2 months PO and remained at high levels thereafter. The percent changes in lumbar BMD from baseline values (% CFB) at 6 months and at 12 months PO were significantly correlated with % CFB in ICTP, but not with % CFB in PICP or BGP. Accordingly, bone resorption is a main determinant of bone mineral loss after oophorectomy and the change in recently-developed bone resorption markers, such as ICTP, is of clinical utility in predicting a degree of subsequent bone loss after surgical menopause.     

56例甲状腺功能亢进症患者的骨代谢生化指标分析

目的探讨甲状腺功能对骨代谢的影响。方法对56例甲状腺功能亢进（简称甲亢）患者及56例健康对照者采用化学发光法和放射免疫法（RIA）测定血FT3、FT4、PINP、BGP、ICTP、B-ALP。结果甲亢患者血bFT3、FT4、PINP、BGP、ICTP、B-ALP活性较健康对照组明显增高（P〈0．01）,且甲亢患者血FT3、FT4分别与PINP、BGP、ICTP、B-ALP呈正相关（P〈0．01）。结论甲状腺激素可能直接参与加速骨转换及增加骨吸收,由此导致甲亢患者骨量丢失。     

Factors influencing bone loss in rheumatoid arthritis: a longitudinal study

OBJECTIVES: To assess the occurrence of bone loss in rheumatoid arthritis (RA) and to determine the factors influencing bone loss (particularly the usefulness of bone turnover markers) over an 18-month period. METHODS: A total of 51 patients were studied, 6 men and 45 females (of whom 35 were menopausal). Their mean age was 56 +/- 10 years and the mean RA duration was 12 +/- 10 years. Twenty-eight (55%) were receiving corticosteroids (10 mg/day for a mean duration of 6 +/- 5 years). Several clinical and biological parameters reflecting disease activity or severity were recorded both at the 0 and 18-month investigations. Bone turnover was assessed at baseline by measuring the serum levels of 4 biological markers. Three of them reflected bone formation, i.e., procollagen type I C-terminal propepeptide (PICP), procollagen type I N-terminal propeptide (PINP) and osteocalcin (OC). The fourth, procollagen type I-C terminal telopeptide (ICTP), reflected bone resorption. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry both at the lumbar spine (LS) and femoral neck (FN) at baseline and 18 months later. RESULTS: Bone loss occurred both at the LS: 2.1%, [95% CI: 0.8%-3.4%, P < 0.005] and femoral neck: 3.1%, [95% CI: 1.1%-5.1%, P < 0.005]. Bone loss was markedly increased for postmenopausal women at the FN: 5.3% [95% CI: 2.9%-7.6%, P < 0.005]. Bone loss was not statistically significantly different between users and non-users of steroids. Bone loss at the LS was significantly correlated with both osteocalcin (r = 0.51, P < 0.01) and ICTP levels (r = 0.32, P < 0.05). FN bone loss was correlated with the osteocalcin level only (r = 0.34, P < 0.05). Fast losers (bone loss at the LS above the median) had higher OC (P < 0.01) and ESR (P < 0.05) levels at baseline as compared with slow losers (bone loss at the LS below the median). CONCLUSION: Bone loss occurs in RA particularly at the FN and seems to be influenced by increased bone turnover and high levels of inflammation.     

Assessment of bone metabolism in obese women

OBJECTIVE: To evaluate the bone metabolism in obese women by the estimation of selected markers of bone formation. METHODS: The concentration of plasma parathyroid hormone (PTH) and selected markers of bone formation [osteocalcin (BGP) in plasma, carboxyterminal propeptide of type I procollagen (PICP) and alkaline phosphatase (AP) activity in blood serum] and bone resorption [cross-linked carboxyterminal telopeptide of type I collagen (ICTP) in blood serum and urinary excretion of calcium (Ca)] in 18 extremely obese women (BMI>40 kg/m2) with android phenotype (WHR>0.8) and in 20 healthy women with normal body weight. The age range of all subjects was 25 to 42 years (mean: 36.82 + 3.95). RESULTS: All obese women showed significantly increased concentration of plasma PTH, BGP and serum PICP, ICTP and elevated urinary excretion of Ca. CONCLUSIONS: The obtained results show that in extremely obese women with android phenotype bone metabolism disturbances may occur pointing at increased bone formation and resorption.     

Effects of suppression of estrogen action by the p450 aromatase inhibitor letrozole on bone mineral density and bone turnover in pubertal boys

The essential role of estrogen (E) in regulation of developing peak bone mass in males was confirmed when young adult men were described who cannot respond to or produce E because of defective E receptor alpha or P-450 aromatase enzyme, respectively. These men had significantly reduced bone mineral density (BMD) despite normal or supranormal androgen concentrations, and E administration improved BMD in the men with aromatase deficiency, whereas testosterone (T) was ineffective. Because new P450 aromatase inhibitors may prove to be potential drugs in various growth disorders, the effect of suppression of E action on developing peak bone mass has to be closely evaluated. In this study, we explored the effects of suppression of E synthesis on bone metabolism in pubertal boys. A total of 23 boys with constitutional delay of puberty were randomized to receive T and placebo or T and a specific and potent P450 aromatase inhibitor, letrozole. We determined BMD in the lumbar spine and the femoral neck. Bone resorption was studied by measuring the serum concentration of cross-linked carboxyterminal telopeptide of type I collagen by two different methods (CTx and ICTP), and bone formation by determining the serum concentrations of carboxyterminal propeptide of type I procollagen (PICP), osteocalcin, and alkaline phosphatase. We demonstrated previously that, during treatment with T and placebo, the concentrations of androgens and E increased. During treatment with T and letrozole, the E concentrations remained at the pretreatment level, but the androgen concentrations increased; the increase in the T concentration was more than 5-fold higher than during treatment with T and placebo. We did not observe any significant differences in the changes in bone mineral content, BMD, or bone mineral apparent density, an estimate of true volumetric BMD, between the treated groups. Lumbar spine bone mineral apparent density increased in both treated groups; but in the T- plus letrozole-treated group, the increase was statistically significant only 6 months after discontinuation of letrozole treatment. All bone resorption and formation markers increased during treatment with T and placebo. During treatment with T plus letrozole, CTx, PICP, and osteocalcin remained unchanged, whereas ICTP and alkaline phosphatase increased. Thus, 1-yr treatment with this new P450 aromatase inhibitor in pubertal boys is unlikely to be associated with any major harmful effect on developing peak bone mass. However, to convincingly exclude such effects, particularly rare or minor ones, will require a study with a larger sample size; and thus, close follow-up of bone metabolism during treatment with P450 aromatase inhibitors is still warranted.     

Dynamics of bone turnover in children with GH deficiency treated with GH until final height

OBJECTIVE: To examine the dynamics of bone turnover in children with growth hormone deficiency (GHD) during long-term treatment. DESIGN: We longitudinally measured growth velocity and serum concentrations of osteocalcin (OC), carboxyterminal propeptide of type I procollagen (PICP), and cross-linked carboxyterminal telopeptide of type I collagen (ICTP) in 24 patients with GHD during long-term GH treatment until final height (age: 7.7+/-0.7 and 16.9+/-0.5 years at baseline and at final height respectively). RESULTS: At baseline, OC, PICP, and ICTP levels were significantly (P<0.0001) reduced in comparison with prepubertal bone age-matched controls (10.2+/-2.3 microgram/l and 22.5+/-7.6 microgram/l; 187.8+/-26.2 microgram/l and 328. 4+/-74.3 microgram/l; 7.7+/-2.0 microgram/l and 14.2+/-1.3 microgram/l respectively). During the first year of treatment mean levels of the bone markers increased significantly (P<0.0001) with a peak at 12 months. After the first year of treatment, OC and PICP levels progressively declined, whereas ICTP levels remained stable until the final height; in any case, bone marker levels remained significantly higher (P<0.03-P<0.0001) than baseline. The change in bone marker levels at 6 and 12 months of treatment with respect to the baseline values was not related to growth rate during long-term treatment or final height. CONCLUSIONS: The results show that children with GHD have reduced bone turnover at baseline, and that long-term GH treatment is associated with a stimulation of bone turnover. OC, PICP, and ICTP do not predict growth rate during long-term treatment or final height in children with GHD.     

Age-related changes in bone mineral density and serum bone-related proteins in premenopausal and postmenopausal Japanese women

The purpose of this cross-sectional study was to characterize the age-related change in bone metabolism during the pre- and postmenopausal periods, and to define the standard levels of three serum markers of bone metabolism, pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), carboxyterminal propeptide of type I procollagen (PICP), and bone gla protein (BGP), in Japanese adult women. The bone mineral density (BMD) of the lumbar spine (L2-L4) and the serum levels of ICTP, PICP and BGP were determined in a total of 207 healthy Japanese women (108 premenopausal and 99 postmenopausal). The lumbar BMD decreased significantly with increasing age not only in postmenopausal women (P<0.001) but also in premenopausal women (P=0.014). There was a clear gap in the serum levels of ICTP, PICP and BGP between the premenopausal and postmenopausal group (P<0.001), but those were absolutely the same within each group except for ICTP in the postmenopausal women. These findings and the values of serum ICTP, PICP and BGP in pre- and postmenopausal women obtained in this study are expected to be very useful for treatment of postmenopausal osteoporosis.     

Bone turnover in hyperthyroidism before and after thyrostatic management

Hyperthyroidism is associated with enhanced osteoblastic and osteoclastic activity, and patients frequently have low bone mineral density and high bone turnover. The aim of this study was to examine the bone formation and resorption markers trend in 12 female patients, before and after normalization of thyroid activity. The following measurements were made at baseline and 1 and 6 months after hormone normalization induced by methimazole treatment: total alkaline phosphatase (ALP), bone alkaline phosphatase (BALP), collagen type C-terminal propeptide (PICP), osteocalcin (BGP), telopeptide (ICTP), urinary-hydroxyproline/urinary creatinine (uOHP/uCreat), urinary calcium/urinary creatinine (uCa/uCreat) and deoxypyridinoline crosslinks (D-Pyr). Compared with controls, all of these parameters were significantly increased (ALP p = 0.014; BALP p = 0.0001; PICP p = 0.013; BGP p = 0.009; ICTP p = 0.0001; uOHP/uCreat p = 0.002; uCa/uCreat p = 0.044; crosslinks p = 0.0001). After treatment the values of ALP, BALP and PICP in hyperthyroid patients showed an initial slight increase and then a significant downwards trend (ALP p = 0.008, BAP p = 0.001, PICP p = 0.026). Furthermore, resorption markers showed a significant decrease (uOHP/ uCreat p < 0.005 and D-Pyr p < 0.008). As regards lumbar BMD patients, measurements were significantly reduced in comparison with the control group (p = 0.005). Six months after serum thyroid hormones level normalization, we observed a significant increase (p=0.014 vs baseline). Both neoformation and resorption markers are useful to assess pathological bone turnover and bone involvement in hyperthyroidism. They could also be employed to monitor the effect of antithyroid treatment on bone and to indicate if bone antiresorption therapy should be considered.     

Immediate fall of bone formation and transient increase of bone resorption in the course of high-dose, short-term glucocorticoid therapy in young patients with multiple sclerosis

Glucocorticoid (GC)-induced osteoporosis is the leading form of secondary osteoporosis. Bone loss can be rapid. However, longitudinal studies at the very beginning of treatment are scarce. Patients relapsing from multiple sclerosis are treated with high-dose, short-term iv GCs. A number of them are young, without concomitant disease affecting bone and with no substantial impairment of mobility. Such patients were selected for the present study. Thirteen patients suffering from multiple sclerosis [11 females, two males; age 32 +/- 2 yr (mean +/- se)] and receiving iv methylprednisolone 15 mg/kg daily for 10 d completed the study. We measured serum osteocalcin (OC), aminoterminal propeptide of type I collagen (PINP), bone isoform of alkaline phosphatase (bALP), carboxyterminal telopeptide of type I collagen (CTX), and urinary calcium/creatinine ratio (uCa/Cr) during the 10-d cycle and 3 months later. Dual-energy x-ray absorptiometry and calcaneal quantitative ultrasonometry were performed before and 6 months after therapy. We found an immediate, impressive fall of OC and PINP (-80 +/- 3 and -54 +/- 5% at d 2, respectively), which persisted throughout the whole treatment period (P < 0.0001 for both markers). bALP levels showed only a modest decrease at d 6 (-19 +/- 7%, P < 0.05), with subsequent return to baseline in d 7-10. After 3 months, OC, PINP, and bALP levels rose to +51 +/- 22, +37 +/- 16 (not significant), and +61 +/- 17% (P < 0.01) with respect to baseline, respectively. uCa/Cr and CTX showed a progressive, marked increase during treatment, peaking at d 7-9 (+92 +/- 44 and +149 +/- 63%, respectively), with subsequent decrement at d 10 (P < 0.01 and P < 0.05, respectively) despite continuing GC administration. After 3 months, uCa/Cr and CTX levels were also higher than baseline. No change in quantitative ultrasonometry parameters and bone mineral density was observed 6 months after therapy. In conclusion, high-dose, short-term iv GC regimens cause an immediate and persistent decrease in bone formation and a rapid and transient increase of bone resorption. Our data also support the concept that discontinuation of such regimens is followed by a high bone turnover phase.     

Bone metabolism in patients more than five years after bone marrow transplantation

We investigated the bone metabolism of 22 patients (median age 38 years) over 6 years after allogeneic bone marrow transplantation (BMT). Biplanar roentgenograms of the thoracic and lumbar spine were used to diagnose vertebral deformities caused by fractures. The actual bone mineral density (BMD) of the lumbar spine and the femoral neck were measured. Laboratory tests included calcium, phosphate, parathyroid hormone, a marker of bone resorption (beta-crosslaps, CTX), markers of bone formation (osteocalcin, bone-specific alkaline phosphatase), osteoprotegerin (OPG)--antagonist of the osteoclast differentiation factor RANKL, and sex hormone status. One patient had a vertebral fracture. Seven patients (28%) had osteopenia in the lumbar spine while 12 patients (48%) had osteopenia in the femoral neck. Bone resorption was increased in nine patients (43%) and bone formation was increased in four patients (20%). BMT recipients had significantly increased serum levels of OPG (P=0.029). Three women (75%) and four men (25%) were hypogonadal. The data showed that BMD is reduced and bone metabolism is still disturbed more than 6 years after BMT. The RANKL/osteoprotegerin system appears to play an important role in the pathophysiology of late post transplantation osteoporosis.     

Relationship between biochemical markers of bone turnover and bone scintigraphic indices in assessment of Paget's disease activity

Objective. To evaluate the relationship between biochemical markers of bone turnover and bone scan indices of disease activity, as well as to analyze their variations based on skeletal involvement, in Paget's disease. Methods. Serum samples were obtained from 51 patients with Paget's disease to determine the levels of total alkaline phosphatase (total AP), bone alkaline phosphatase (bone AP), propeptide carboxyterminal of type I procollagen (PICP), propeptide aminoterminal of type I procollagen (PINP), osteocalcin, tartrate-resistant acid phosphatase, and telopeptide carboxyterminal of type I collagen. Urine samples were analyzed for levels of hydroxyproline (HYP), pyridinoline (PYR), deoxypyridinoline (DPYR), C-terminal telopeptide of type I collagen (CTx), and N-terminal telopeptide of type I collagen (NTx). In addition, 2 semiquantitative scintigraphic indices, disease activity (AI) and disease extent (EI), were obtained. Pagetic skeletal locations were evaluated individually, with special attention to skull involvement. Results. All biochemical markers correlated with the AI and the EI. Serum PINP, bone AP, and total AP showed the highest proportions of increased values among the bone formation markers (94%, 82%, and 76%, respectively). Among the bone resorption markers, urinary NTx showed the highest proportion of increased values in patients with Paget's disease (96%), compared with PYR (69%), DPYR (71%), CTx (65%), and HYP (64%). In patients with mild disease activity, serum PINP was the marker with the highest proportion of increased values (71%). In contrast, serum PICP and urinary CTx were the most discriminative markers for skull involvement. Except for higher values for most of the biochemical markers of bone turnover in flat bones, no major differences in other skeletal locations were observed. Conclusion. The determination of serum PINP as a marker of bone formation and urinary NTx as a marker of bone resorption provided the best biochemical profile to ascertain the extent and activity of Paget's disease. In patients with skull involvement, serum PICP and urinary CTx were shown to be the most discriminative markers.     

The relationship between leptin concentration and bone metabolism in the human fetus

This study investigates the relationship between leptin and fetal bone metabolism by measuring fetal blood levels of leptin, carboxy-terminal pro-peptide of type I pro-collagen (PICP; a marker of bone formation) and cross-linked carboxy-terminal telopeptide of type I collagen (ICTP; a marker of bone resorption). The median gestational age at the time of sampling was 23 weeks (range, 18-35). There was a positive correlation between leptin concentration and gestational age (r = 0.543, P < 0.001) and a negative correlation between both PICP and ICTP and gestational age (r = -0.592 and r = -0.550, respectively, and P < 0.001 for both). Also, there was a negative correlation between the concentrations of leptin and both PICP (r = -0.260, P = 0.022) and ICTP (r = -0.622, P < 0.001). Using multiple regression analysis, fetal leptin concentration was positively correlated to the gestational age (r = 0.240, P = 0.042) and negatively correlated to ICTP (r = -0.420, P = 0.001). The increase in leptin concentration with gestational age is consistent with adipose tissue development and the subsequent accumulation of fat mass. The negative correlation between fetal leptin and ICTP suggests that leptin may decrease bone resorption with the overall effect of increasing bone mass. Therefore, leptin may play a role in fetal bone metabolism as part of its effect on fetal growth and development.     

Gaucher disease and bone: Laboratory and skeletal mineral density variations during a long period of enzyme replacement therapy

Summary The usefulness of bone turnover markers in Gaucher disease is still unclear and their utility in monitoring the effects of enzyme replacement therapy (ERT) on bone metabolism has not yet been investigated exhaustively. Skeletal involvement seems to improve slowly during ERT, but only a few studies evaluating bone mineral density (BMD) changes during a long follow-up period have been reported. The aim of this study was to assess the efficacy of ERT on bone involvement in a group of 12 type I Gaucher disease (GD I) patients by monitoring biochemical indices of bone resorption/formation and BMD measured by dual energy x-ray absorptiometry (DEXA). Serum (calcium, phosphorus, bone alkaline phosphatase isoenzyme, carboxyterminal propeptide of type I procollagen (PICP), carboxyterminal telopeptide of type I collagen (ICTP), osteocalcin, intact parathyroid hormone) and urinary (calcium, phosphorus, hydroxyproline and free deoxypyridinoline) markers of bone metabolism and lumbar BMD were measured at baseline, after 6 and 12 months, and then every year for a mean ERT follow-up period of 4.5 years (range 4.4–6 years). Twelve healthy adult subjects matched for age and sex were tested as negative controls. A significant decrease of PICP was detected in the patient group at baseline (mean value 100.52 ng/ml vs 142.45 ng/ml, p = 0.017), while ICTP was remarkably higher: mean value 3.93 ng/ml vs 2.72 ng/ml, p = 0.004 (two-sided Student’s t-test). No changes in bone formation indices were observed during the follow-up period, while urinary calcium excretion increased significantly from 0.065 to 0.191 mg/mg creatinine (p = 0.0014) (repeated measures ANOVA). A significant BMD improvement was also detected after an average ERT period of 4.5 years: Z-score increased from −0.81 to −0.56 (p = 0.005) (two-sided Student’s t-test). These data evidenced the ineffectiveness of the biochemical markers used in monitoring ERT efficacy in GD I skeletal involvement, whereas DEXA was demonstrated to be a reliable method with which to follow up BMD improvement.     

Effects of inflammation and treatment on bone turnover and bone mass in polymyalgia rheumatica

Objective. Polymyalgia rheumatica (PMR) has an abrupt onset of inflammatory symptoms, making it a useful model for studying the effects of inflammation in bone. PMR requires corticosteroid treatment, which may itself have a detrimental effect on bone. This study used serially measured biochemical markers of bone turnover and bone density to address the relative contributions of systemic inflammation and corticosteroid therapy to bone loss. Methods. Fifty untreated patients with PMR were randomized to receive oral prednisolone or intramuscular methylprednisolone. Biochemical bone markers (pyridinoline [PYR], deoxypyridinoline [DPYR], procollagen type I carboxy-terminal peptide [PICP]) and bone mineral density (BMD) were measured at baseline and at 6, 12, and 24 months. Results. The median disease duration at presentation was 12 weeks (range 5–32 weeks). Levels of urinary crosslinks were increased in patients with untreated PMR compared with controls (PYR 74.9 ± 30.0 nmole/mmole creatinine, DPYR 14.6 ± 6.4 nmoles/mmole creatinine [mean ± SD]; P = 0.0001); the PICP level was normal (115.0 ± 39.0 μg/liter). With treatment, the crosslinks levels fell and PICP levels rose within 6 months (P = 0.01). Bone resorption (PYR) correlated with untreated disease activity (erythrocyte sedimentation rate [ESR]) (r = 0.5, P = 0.003) and with interleukin-6 levels (r = 0.48, P = 0.05). There was a significant reduction in BMD of both the hip and the spine after 12 months of treatment (P = 0.0002), with no difference between treatment groups. As the steroid dosage was reduced, bone mass improved. Initial ESR influenced the percent change in BMD at 1 year (r = 0.35, P = 0.05), while cumulative steroid dose, mean ESR, and type of steroid used did not. Conclusion. Inflammation in PMR increases bone resorption and appears to have a more detrimental effect on bone than does low-dose corticosteroid. If corticosteroids can be tapered and discontinued, bone loss in PMR can be a transient phenomenon.     

Biochemical markers of bone turnover during pregnancy: a longitudinal study.

OBJECTIVE: The objective of this study was to prospectively investigate the effect of pregnancy on biochemical markers of bone turnover in healthy pregnant women. METHODS: During the course of our longitudinal study, biochemical markers of bone remodeling were measured in all three trimester of pregnancy (first trimester: 12.5+/-1.8 SD, second trimester: 21.6+/-1 SD, third trimester: 34.8+/-1.6 SD weeks of gestation). Serum type I collagen C-telopeptides (CTX) and a crosslinked peptide of the carboxy-terminal telopeptide of type I collagen (ICTP) were used as markers of bone resorption. Bone alkaline phosphatase (BAP) and the N-terminal propeptides of type I collagen (PINP) were used as biochemical markers of bone formation. Blood samples for the analysis of all 4 biochemical markers according to each trimester of pregnancy were available in 49 patients. RESULTS: The main changes for all biochemical markers were seen between the second and the third trimester. According to the markers of bone resorption, both serum CTX and ICTP showed a significant increase from the first to the third and from the second to the third trimester (p<0.001; median percentage change: CTX=101.5% and ICTP=40%). Concerning markers of bone formation, PINP showed a significant decrease from the first to the second trimester (p=0.001) followed by a significant increase from the second to the third trimester (p<0.001, 63.8%) and an overall increase from the first to the third trimester (p<0.001). BAP also showed a significant increase from the second to the third trimester (p<0.001; 51.7%) and an overall increase from the first to the third trimester (p<0.001). CONCLUSION: Markers of bone resorption were significantly increased during pregnancy. In contrast to bone resorption, markers of bone formation showed an increase as well as a decrease during pregnancy indicating a state of high bone turnover. This might coincide with the change in bone mineral density that was observed in some, but not all, studies using "dual-energy x-ray absorptiometry" (DXA) as well as "quantitative ultrasonometry" (QUS).     

Impact of circulating bone-resorbing cytokines on the subsequent bone loss following bone marrow transplantation

Cytokines including IL-6 and TNF-alpha play an important role in the pathogenesis of postmenopausal osteoporosis. However, the relationship between changes in the cytokine levels and subsequent bone loss in patients undergoing a bone marrow transplantation (BMT) is unclear. A total of 46 patients undergoing an allogeneic BMT were prospectively investigated. The bone turnover markers and the serum cytokines were measured before BMT and serially after BMT. Bone mineral density (BMD) was measured before and 1 year after BMT. At 1 year after BMT, the lumbar spine BMD had decreased by 4.8%, and the total proximal femoral BMD had decreased by 12.3%. The serum IL-6 and TNF-alpha levels increased until 2 and 3 weeks after BMT, respectively. The lumbar BMD was significantly decreased as the serum IL-6 and TNF-alpha levels increased by post-BMT 3 weeks. The lumbar BMD decreased significantly as the cumulative prednisolone and cyclosporine dose increased. Patients with GVHD > or =grade II had higher lumbar bone loss than patients with GVHD 相似文献   

Increased degradation of type I collagen in patients with inflammatory bowel disease.

To assess the mechanisms of osteopenia in inflammatory bowel disease (IBD), the serum markers of bone formation (osteocalcin and carboxyterminal propeptide of type I procollagen (PICP)) and bone degradation (carboxyterminal telopeptide of type I collagen (ICTP)), the bone mineral density (BMD) of the lumbar spine and the proximal femur and calcium intake of 150 unselected IBD patients and 73 healthy controls were investigated. The patients had higher ICTP values (3.69 (SD 1.40) microgram/l) than the healthy controls (3.25 (1.00) microgram/l, p = 0.035), but no differences in serum PICP and osteocalcin between these groups were detected. In the patients, the ICTP, PICP, and osteocalcin values did not have any significant correlation with BMD, but the patients with ICTP values above 3.6 microgram/l had significantly lower Z scores than those with lower ICTP. In the controls, however, a positive correlation between serum ICTP and BMD was found. The ulcerative colitis patients with total colitis had higher values of ICTP (3.96 (1.58) microgram/l) than those with a left sided disease (3.04 (0.86) micrograms/l, p = 0.009). The patients with a history of clinically active disease (n = 20) had higher ICTP (4.58 (1.55) microgram/l) and osteocalcin (12.56 (5.64) microgram/l) values than the patients (n = 130) with quiescent disease (ICTP 3.56 (1.33), p = 0.002, and osteocalcin 9.76 (3.62), p = 0.017). Increased serum osteocalcin, PICP, and ICTP concentrations and reduced BMD Z scores were found in a subgroup of Crohn's disease patients with a history of an active disease (n = 11). Raised serum ICTP and normal values of osteocalcin and PICP in IBD patients show increased breakdown of type I collagen without a compensatory increase in its synthesis suggesting an increased rate of bone degradation as a probable mechanism for osteopenia in IBD. Raised ICTP values are related to reduced bone mineral densities.     

Changes in the serum growth factors and osteoprotegerin after bone marrow transplantation: impact on bone and mineral metabolism

The loss of bone mass often occurs after bone marrow transplantation (BMT), particularly during the early posttransplant period. There are few reports on the role of growth factors and osteoprotegerin (OPG) in the post-BMT bone loss. This study prospectively investigated 110 patients undergoing BMT and analyzed 36 patients who had dual-energy x-ray absorptiometry performed before BMT and 1 yr after BMT. The biochemical markers of bone formation and resorption were measured at the short-term intervals during the year-long follow-up. The serum IGF-I, IGF binding protein (IGFBP)-3, fibroblast growth factor-2, macrophage-colony stimulating factor (M-CSF), and OPG levels were measured before and 1 wk, 3 wk, and 3 months after BMT. The mean bone loss in the lumbar spine and the total proximal femur, which was calculated as the percent change from the baseline to the level at 1 yr, was 5.2% (P < 0.05) and 11.6% (P < 0.01), respectively. During the immediate post-BMT period, bone formation decreased, whereas bone resorption increased, which was indicated by the biochemical markers of bone turnover. The serum IGF-I levels also decreased progressively until 3 wk and then increased to the basal values at 3 months. The serum IGFBP-3 levels decreased progressively until 3 months. The serum fibroblast growth factor-2 levels decreased to the nadir at 1 wk and gradually recovered to the basal values at 3 months. The serum M-CSF levels increased immediately after BMT, which declined to its baseline level by 3 months. The serum OPG levels increased progressively, reached a peak at 3 weeks, and declined thereafter. There were significant correlations between the IGF-I and osteocalcin levels before BMT and at 3 wk after BMT (r = 0.45, P < 0.01; r = 0.54, P < 0.01). During the observation period, the serum IGFBP-3 and M-CSF levels showed positive correlations with the osteocalcin and serum collagen I carboxyl-terminal telopeptide levels, respectively. Although statistically not significant, the OPG levels tended to be positively associated with the serum collagen I carboxyl-terminal telopeptide levels. Significant correlations were observed between the percent changes from the baseline to 1 yr in the bone mineral density at the proximal femur and the serum IGF-I levels at 3 wk and 3 months after BMT (r = 0.52, P < 0.01; r = 0.41, P < 0.05).     

The carboxy-terminal propeptide of type I procollagen in serum as a marker of bone formation: the effect of nandrolone decanoate and female sex hormones

Seventy-nine osteoporotic (prior forearm or vertebral fracture), but otherwise healthy, postmenopausal women (aged 55 to 75 years) were allocated to two double-blind trials: (1) 39 women received either nandrolone decanoate (anabolic steroid) 50 mg as an intramuscular depot injection or a placebo injection every 3 weeks for 1 year; and (2) 40 women received either 2 mg 17 beta-estradiol plus 1 mg norethisterone acetate or placebo tablets daily for 1 year. Sixty-seven (85%) completed the 1 year of treatment. Serum concentration of type I procollagen carboxy-terminal propeptide (PICP) was measured before and at 3, 6, 9, and 12 months of therapy. In addition, 32 of the women had an iliac bone biopsy taken after double tetracycline labeling. Initial serum PICP correlated significantly with histomorphometrically measured rate of bone formation (r = .4; P less than .05) and plasma bone Gla protein (r = .6; P less than .001), but not with histomorphometrically measured bone resorption or biochemical estimates of bone resorption (fasting urinary hydroxyproline and calcium). Estrogen-progestogen therapy significantly decreased (P less than .001) serum PICP by about 30%, whereas anabolic steroid therapy hardly affected it. We conclude that serum PICP may be used as a noninvasive measurement of bone formation on a group basis. Whereas bone formation is clearly decreased during estrogen-progestogen therapy, it is not affected by long-term therapy with anabolic steroids.