Novel and traditional biomarkers of bone turnover in postmenopausal women.

Urinary markers of bone collagen degradation such as N-terminal telopeptide, deoxypyridinoline, hydroxyproline and proline-hydroxyproline dipeptide as a novel marker were measured in both morning and daily urine samples collected from 40 postmenopausal women on 10 consecutive days. In addition, osteocalcin, bone alkaline phosphatase and procollagen C-terminal propeptide were analyzed in one serum sample from each of the women. DXA densitometry was employed to differentiate between osteopenic and osteoporotic women. Spearman rank correlation, factor analysis and receiver-operating characteristics were computed to evaluate the results. The highest correlation with a single common factor was found between telopeptide assayed in daily urine, followed by the dipeptide and hydroxyproline assayed in morning urine. These markers also showed high sensitivity for the diagnosis of osteoporosis, while osteocalcin had a high sensitivity for the diagnosis of bone disease. The concentrations of telopeptide, dipeptide and osteocalcin differed significantly between the osteopenic and osteoporotic subjects. Because of the ease of non-hydrolyzed urine processing, the speed of chromatographic analysis and the negligible costs, the dipeptide assay opens new possibilities in the field.     

Comparison of the analytical and clinical performance characteristics of an N-MID versus an intact osteocalcin immunoradiometric assay

Osteocalcin is the most abundant non-collagenous protein in bone, reflecting its formation. It was reported that the instability of intact osteocalcin results from the cleavage of the C-terminal sequence of osteocalcin to produce a large N-terminal osteocalcin fragment. A two-site immunoassay for detecting both the N-terminal osteocalcin fragment and the intact osteocalcin was developed that were both independent of an unstable C-terminal sequence. The aim of this study is to investigate the performance of an N-MID osteocalcin immunoradiometric assay and to compare it with an intact osteocalcin assay. Ten serum samples were repeatedly frozen and thawed up to seven times. The variability of the values of N-MID osteocalcin was less than that of the intact osteocalcin. For stability of osteocalcin in serum after storage, the mean value of N-MID was 94. 3% of the initial value after 7 days at 4 degrees C, whereas the intact was 73.4%. The reduction of intact values were significantly larger than that of N-MID after 2, 5 and 7 days. At -30 degrees C, the values of N-MID did not change for up to 10 weeks. The concentrations of osteocalcin measured by an N-MID osteocalcin and an intact osteocalcin were investigated in 27 premenopausal subjects, 27 postmenopausal subjects, and 68 osteoporotic patients (23 with vertebral fractures and 45 with hip fractures). The percent mean increase of osteocalcin in postmenopausal subjects over premenopausal subjects was 98% in N-MID versus 42% in the intact assay. The z-scores of N-MID and intact showed similar results in all groups. N-MID osteocalcin significantly correlated with intact osteocalcin (r=0.755), and other biochemical markers for bone formation, such as bone specific alkaline phosphatase (r=0.606) and C-terminal propeptide of type I procollagen (PICP) (r=0.568). An N-MID IRMA had better stability during storage than intact and had the discriminative ability which is similar to the intact assay in postmenopause and osteoporosis. Therefore, an N-MID osteocalcin IRMA could improve the clinical utility and evaluation of osteocalcin.     

Bone metabolism during interferon-alpha treatment of essential thrombocythemia

In-vitro studies have demonstrated that interferon (IFN) has an inhibitory effect on bone formation. Changes in bone metabolism were investigated in 19 patients treated for essential thrombocythemia with IFN-alpha. Serum biochemical parameters of bone remodeling [total alkaline phosphatase, osteocalcin, type-I procollagen carboxy-terminal propeptide (PICP), cross-linked telopeptide type-I collagen (ICTP)] and mineral metabolism (total calcium, inorganic phosphate, parathyroid hormone, 25-hydroxyvitamin D) were measured before and after long-term IFN-alpha treatment. The effects of the cumulative IFN-alpha dose and duration of therapy on biochemical markers of bone metabolism were analyzed. No uniform trend or pattern was observed in the measured biochemical parameters except for ICTP, which decreased after treatment. Correlations indicated modulation of bone metabolism, i.e. remodeling with suppression of resorption, as a consequence of therapy with IFN-alpha.     

Relationship of bone turnover parameters,endogenous hormones and vit D deficiency to hip fracture in elderly postmenopausal women

Hip fracture is one of the severest consequences of osteoporosis affecting elderly women, but abnormalities of bone turnover responsible for bone loss have not been clearly defined. This study evaluated the relationship of bone turnover parameters to hip fracture in postmenopausal elderly women. We also investigated the effects of endogenous hormones and vitamin D deficiency on osteoporotic hip fracture. The subjects were 21 osteoporotic patients with hip fracture (study group) and 20 healthy postmenopausal women (control group). We measured osteocalcin levels, total and bone alkaline phosphatase (T-ALP and B-ALP), calcitonin, intact parathyroid hormone (iPTH), serum 25 hydroxyvitamin D (25OHD), urinary free deoxypyridinoline (D-pyr) and cross-linked N-telopeptides of type 1 collagen (NTx) levels. Serum T-ALP and B-ALP levels in the study group were lower than those of the control group. The mean serum 25OHD levels in the study group were not significantly different from the control group, but in five cases the mean serum iPTH level was increased. The mean urinary NTx levels were significantly increased in the study group compared with the control group (p<0.05). There was no significant increase in urinary free D-pyr between the two groups. There was significant correlation between serum T-ALP levels and B-ALP levels and between serum iPTH levels and B-ALP levels. The mean serum SHBG level in the study group was higher than in the control group (p<0.05). These data suggest that postmenopausal hip fracture patients have biochemical evidence of decreased bone formation and increased bone resorption compared with postmenopausal healthy subjects. We suggest these abnormalities play a role in the decrease of bone mass and the consequent increase in bone fragility that characterises osteoporotic hip fracture.     

Circulating levels of osteoclast activating cytokines, interleukin-11 and transforming growth factor-beta2, as valuable biomarkers for the assessment of bone turnover in postmenopausal osteoporosis

The objective of this study was to evaluate the role of osteoclast activating cytokines, interleukin-11 (IL-11) and transforming growth factor-beta2 (TGF-beta2) in the assessment of bone turnover in postmenopausal osteoporosis (PO). Eighty postmenopausal osteoporotic women with lumbar spine bone mineral densities (BMD) as measured by DEXA that were more than 2.5 SD below the normal mean of healthy women (controls), participated in this study. Various therapeutic modalities (hormone replacement therapy, HRT, alendronate, calcitonin and 1alpha-hydroxyvitamin D (alfacalcidol) were administered for 12 months to 4 groups of postmenopausal osteoporotic patients. Fasting blood samples and two hour urine samples were collected from control subjects and from patients before and after treatment. Serum samples were assayed for IL-11, TGF-beta2, osteocalcin (OC) and bone alkaline phosphatase (B-ALP), whereas urine samples were assayed for N-telopeptide for type I collagen (NTX) and deoxypyridinoline (DPyr). The results demonstrated a significant increase of both IL-11 and TGF-beta2 in postmenopausal osteoporosis. Positive correlations exist between TGF-beta2 or IL-11 and markers of bone resorption (NTX and DPyr). Moreover, there was a significant positive correlation between TGF-beta2 and IL-11. Therapeutic modalities enhancing bone formation and/or with antiresorptive effect revealed a significant decrease in markers of bone resorption, formation and osteoclast activating cytokines, indicating a decrease in bone turnover. The decrease of IL-11 and TGF-beta2 may be attributed to a drug inhibitory effect of these cytokines on enhancing osteoblast mediated osteoid degradation. In conclusion, both serum IL-11 and TGF-beta2 determinations may be considered as biomarkers for the assessment of bone turnover and for monitoring antiresorptive therapy in postmenopausal osteoporosis.     

绝经后妇女血清基质金属蛋白酶与骨转换生化指标及骨密度的关系

目的探讨绝经后妇女血清基质金属蛋白酶(MMP)-1和MMP-2与骨密度及骨转换生化指标之间的关系。方法采用酶联免疫吸附法测定297名48~80岁女性志愿者的血清MMP-1、MMP-2和血清骨碱性磷酸酶(BAP)、血清骨钙素(OC)及血清Ⅰ型胶原氨基末端肽(NTX),用双能X线吸收法测定腰椎正位1~4总体、股骨颈、华氏区、髋部总体的骨密度。结果MMP-1与骨密度及骨转换生化指标无明显相关性;MMP-2与骨密度呈较弱的负相关,校正年龄与体重指数后,MMP-2与股骨颈、髋部骨密度的相关性消失;MMP-2与BAP、OC、NTX正相关(P<0.01);绝经后骨质疏松症患者血清MMP-2水平高于年龄匹配的正常对照组和骨量减少组(P<0.01)。结论绝经后妇女血清MMP-2与骨转换生化指标相关联,血清MMP-2水平升高可能为高骨代谢转换过程(如绝经后骨质疏松症)中的一种伴随表现。     

The effect of smoking on bone metabolism: maternal and cord blood bone marker levels

BACKGROUND: To clarify the effect of smoking on bone metabolism in the fetus, we measured osteocalcin (OC), bone isoenzyme of alkaline phosphatase (BALP), procollagen type 1 C-terminal propeptide (PICP) in maternal serum and umbilical cord blood. METHODS: 15 active smoker, 14 passive smoker, 15 nonsmoker women and their newborn were included in this study. OC, BALP, PICP were determined by enzyme immunoassay. RESULTS: Of the bone markers tested only OC was different in the serum of the three groups of women. Infants of smoker women have significantly lower umbilical cord blood OC levels than those of infants from both passive smoker and nonsmoker women.(25.6 +/- 6.6, 35.8 +/- 10.4, 37.2 +/- 16.1 ng/mL respectively, p < 0.05). Infants of smoker women have significantly lower umbilical cord blood BALP levels than those of infants from nonsmoker women. (46 +/- 12, 57 +/- 15 U/L p < 0.05). All bone markers except total ALP were significantly higher in umbilical cord blood as compared to maternal blood levels (p < 0.001 for all). CONCLUSION: High umbilical cord blood bone marker levels may reflect the altered bone metabolism of fetus. Moreover, chronic hypoxia due to smoking may cause the suppression of bone matrix synthesis or placental synthesis as reflected by low OC and BALP levels in umbilical cord blood of infants from smoker women.     

Changes in biochemical markers after lower limb fractures

BACKGROUND: The bone remodeling sequence after bone fracture changes the concentrations of biochemical bone markers, but the relationships of fracture size and of healing time to changes in biomarkers are unclear. The present pilot study was undertaken to determine the changes found in serum bone markers after plate osteosynthesis of closed distal tibial and malleolar fractures during a study period of 24 weeks. METHODS: We measured tatrate-resistant acid phosphatase (TRACP 5b), collagen type I C-terminal telopeptide (ICTP), bone-specific alkaline phosphatase (bone ALP), osteocalcin (OC), procollagen type I C-terminal propeptide (PICP), procollagen type III N-terminal propeptide (PIIINP), and human cartilage glycoprotein 39 (YKL-40) in 20 patients with lower limb fractures (10 malleolar, 10 tibia). A physical examination and radiographs were completed to assess evidence of union. RESULTS: All malleolar fractures healed within 6 weeks, whereas 2 tibial fractures did not show complete bone healing after 24 weeks. Changes were comparable but more pronounced in the tibia group, and marker concentrations remained increased at the end of study (bone ALP, 86 vs 74 U/L; OC, 14.9 vs 7.7 microg/L; ICTP: 5.6 vs 3.3 microg/L at day 84 after osteosynthesis, P <0.05 in tibia; 80 vs 70 U/L, 8 vs 5.2 microg/L, and 3.5 vs 3.2 microg/L, respectively, in the malleolar fracture group). CONCLUSIONS: In normal bone healing, changes in bone turnover markers were primarily dependent on the fracture size. Delayed tibia fracture healing may involve a disturbance in bone remodeling.     

Biochemical markers of bone metabolism and bone tissue losses after allotransplantation of the cadaveric kidney: a cross-sectional

The biochemical markers of bone metabolism (osteocalcin (OC), C- and N-terminal procollagen I propeptides (PICP) and PINP), bone alkaline phosphatase (BALP), deoxypyridinoline (DPD), beta-crosslaps (beta-CL), bone acid phosphatase (BAP), osteoprotegerin (OPG), insulin-like growth factor I (IGF-I), and parathyroid hormone (PTH)), daily urinary calcium excretion (DUCE) (intestinal calcium absorption), and lumbar and hip bone mineral density (BMD) were determined in 195 patients (78 females and 74 males with normal function of the grafted kidney and 11 females and 31 males with chronic renal failure (CRF) 40 +/- 33 months after renal transplantation (RT). All RT recipients received triple immunosuppressive therapy (cyclosporin, prednisolone, and azathioprine). All groups showed a significant increase in resorption markers and a moderate increase in bone formation markers (except BALP), which suggested bone remodeling dissociation, as well as elevated levels of PTH and OPG and decreased DUCE and BMD in the vertebral column and hip. Increased bone metabolism and decreased intestinal calcium absorption were largely pronounced in CRF. In the majority of recipients, the BMD reduction in the vertebral column and hip was moderate (osteopenia) and only in male recipients with CRF, axial osteopenia was concurrent with peripheral osteoporosis. The main predictor of accelerated bone metabolism and BMD losses following RT was hyperparathyroidism mainly caused by decreased renal graft function. Decreased IGF-I may be a cause of bone remodeling dissociation after RT/ and the increase in OPG seems to be compensatory, which suppresses bone resorption and reduces bone losses.     

Activity or mass concentration of bone-specific alkaline phosphatase as a marker of bone formation.

BACKGROUND: Recently published data identified bone-specific alkaline phosphatase (BALP) as a good marker of bone formation in different bone diseases and osteoporosis. Two methods are available for BALP determination: one measures enzyme activity, the other its mass concentration. We compared results for BALP activity and its mass concentration in a group of 88 healthy pre- and postmenopausal women to identify which is a more useful marker for detecting early menopausal bone remodelling changes. METHODS: We measured BALP activity and BALP mass concentration in relation to femoral neck (FN) and lumbar spine (LS) bone mineral density (BMD) and some other widely used bone markers: osteocalcin (OC), procollagen type I N-terminal propeptide (PINP) and serum C-terminal telopeptide cross-links of type I collagen (CTx) in serum samples from 50 premenopausal (age 45.9+/-4.6 years) and 38 postmenopausal (age 54.4+/-4.5 years) women. RESULTS: Healthy postmenopausal women exhibited 34.2% (p<0.01) and 27.3% (p=0.000) higher levels of BALP activity and mass concentration than premenopausal women, respectively. At the same time, FN and LS BMD were not significantly different between the groups. CTx values were significantly higher in postmenopausal women (p=0.018), while OC and PINP were not. We observed significant correlation between BALP activity and mass concentration (r=0.85, p<0.01). The correlation between BALP activity and FN BMD or LS BMD was insignificant. BALP mass correlated significantly with LS BMD (r=-0.370, p=0.033) but not with FN BMD. As expected, we proved a significant positive correlation for both BALP methods with the other bone markers measured in our study. CONCLUSIONS: Postmenopausal women have slightly higher bone turnover. Since LS and FN BMD were not significantly lower in our group of healthy postmenopausal women, but BALP and CTx were markedly higher, we suggest that measurements of BALP and CTx might be useful as early markers of higher bone turnover. Finally, our results did not show any differences between the clinical utility of BALP activity and BALP mass concentration measurements.     

External quality assessment of bone metabolism marker assays. initial experiences in a UK NEQAS programme.

This paper reports on a pilot external quality assessment scheme for bone markers including serum bone alkaline phosphatase and procollagen 1-carboxy terminal propeptide together with urine deoxypyridinoline, N- and C-telopeptides. The data shows poor numerical agreement between commercial assays, between-laboratory imprecision that could be improved, and the need for international standardisation of assays.     

Effects of rhIGF-I administration on bone turnover during short-term fasting.

Insulin-like growth factor-I (IGF-I) is a nutritionally dependent bone trophic hormone which stimulates osteoblast function and collagen synthesis in vivo and in vitro. We hypothesized that in the fasting state, IGF-I levels would decline significantly and would establish a model in which we could investigate the effects of IGF-I administration on bone turnover. We therefore studied 14 normal women ages 19-33 (mean, 24 +/- 4 [SD] years) during a complete 10-d fast. After 4 d of fasting, subjects were randomized to receive rhIGF-I or placebo subcutaneously twice a day for 6 d. Bone turnover was assessed using specific markers of formation (osteocalcin and type I procollagen carboxyl-terminal propeptide [PICP]) and resorption (pyridinoline, deoxypyridinoline, type I collagen crosslinked N-telopeptide [N-telopeptide] and hydroxyproline). Serum levels of PICP and osteocalcin decreased from 143 +/- 52 to 60 +/- 28 ng/ml (P = 0.001) and from 7.6 +/- 5.4 to 4.2 +/- 3.1 ng/ml (P = 0.001) respectively with 4 d of fasting. Urinary excretion of pyridinoline and deoxypyridinoline decreased from 96 +/- 63 to 47 +/- 38 nmol/mmol creatinine (P < 0.05) and from 28 +/- 17 to 14 +/- 11 nmol/mmol creatinine (P < 0.05) respectively. Mean IGF-I levels decreased from 310 +/- 81 to 186 +/- 78 ng/ml (P = 0.001). In the second part of the experimental protocol, serum osteocalcin and PICP levels increased 5- and 3-fold, respectively with rhIGF-I administration and were significantly elevated compared with the placebo group at the end of treatment (20.9 +/- 17.3 vs. 5.9 +/- 6.4 ng/ml for osteocalcin [P < 0.05] and 188 +/- 45 vs. 110 +/- 37 ng/ml for PICP [P < 0.05]). In contrast, all four markers of bone resorption, including urinary pyridinoline, deoxypyridinoline, N-telopeptide and hydroxyproline were unchanged with rhIGF-I administration. This report is the first to demonstrate that bone turnover falls rapidly with acute caloric deprivation in normal women. RhIGF-I administration uncouples bone formation in this setting by significantly increasing bone formation, but not resorption. These data suggest a novel use of rhIGF-I to selectively stimulate bone formation in states of undernutrition and low bone turnover.     

Biochemical markers of bone turnover in women with surgically treated carcinoma of the breast

Abstract. Biochemical markers of bone turnover were measured in fasting urine and blood samples obtained from 38 postmenopausal women with previous surgi cal treatment of breast cancer combined with adjuvant chemotherapy, tamoxifen, or placebo. Significantly elevated urinary pyridinoline as nmol mmol^-1 creatinine (47.5 and 42.5 in tamoxifen and placebo treated patients compared with 26.3 in normal controls, both P <0.001) and deoxypyridinoline (11.9 and 10.5 com pared with 6.3, P <0.001 and P =0.002 respectively) were found with unchanged urinary hydroxyproline, serum alkaline phosphatase and procollagen I carboxyterminal peptide (PICP). These findings suggest enhanced bone resorption resulting from the humoral osteoclast activating effect of the previous breast cancer or underlying carcinoma recurrence. Alternatively the raised pyridinium excretion might indicate an altered cross linking composition of bone collagen. No specific effect on bone metabolism was found with tamoxifen treatment as all measured parameters were similar in both tamoxifen ex-users and non-users. This confirmed the safety of tamoxifen therapy with respect to bone.     

Changes of biochemical bone markers during the menopausal transition.

We present data on the changes of the bone formation markers osteocalcin (OC), bone-specific alkaline phosphatase (bone ALP) and bone sialoprotein (BSP), as well as the resorption markers pyridinoline (PYD), deoxypyridinoline (DPD), C- and N-terminal telopeptide cross-linked collagen type I (CTX, NTX), and tartrate-resistant acid phosphatase type 5b (TRACP) at five time points during the course of two years in healthy premenopausal, perimenopausal and early postmenopausal women. The prospective study showed that CTX (p<0.001), NTX (p=0.001) and TRACP (p=0.001), as well as bone ALP (p=0.009) and OC (p=0.052), were significantly increased already in the transition period from peri- to postmenopause. The pyridinium crosslinks indicated an increased collagen degradation rate already in the perimenopause (PYD, p=0.017; DPD, p=0.054). Significant inverse correlations with the two years changes of the bone mineral density were found for bone ALP, CTX, OC and DPD in the perimenopausal group. The measurement of a comprehensive panel of biochemical bone markers clearly shows that metabolic changes in bone metabolism appear pronounced in the perimenopause, a period still presenting satisfactory estrogen supply. Thus, the perimenopause is an important phase for a contingent development of osteoporosis.     

阿仑磷酸钠联合复方丹参片治疗绝经后骨质疏松症患者的效果评价

目的 探讨复方丹参片联合福善美(阿仑磷酸钠)治疗妇女绝经后骨质疏松症,评价其疗效及安全性.方法 将180例绝经后骨质疏松症患者随机分为福善美组、丹参组和复方丹参片联合福善美组(简称联合组).分别采用相应药物进行治疗,疗程6个月,比较2组碱性磷酸酶、骨钙素、尿钙、尿肌酐、尿羟脯氨酸含量及腰1～5骨密度值.结果 联合组的碱性磷酸酶、骨钙素、尿钙、尿肌酐、尿羟脯氨酸、腰1～5骨密度值与其他2组比较差异显著.结论 福善美联合复方丹参片治疗绝经后妇女骨质疏松症安全有效.

Abstract：

Objective To assess whether treatment with compound danshen tablets plus alendronate would be safe and effective in women with postmenopausal osteoporosis. Methods 180 women with postmenopausal osteoporosis were randomized to receive combination therapy and independent therapy with compound danshen tablets and alendronate for 6 months. Scores of VRS were assessed,mean serum alkaline phosphatase, serum osteocalcin, urinary creatinine, urinary hydroxyproline, urinary calcium were detected. Bone mineral density of lumbar vertebra 1 ~5 was determined by dual X - ray absorptiometry. Results Mean serum alkaline phosphatase, serum osteocalcin, and urinary creatinine, urinary hydroxyproline, urinary calcium were statistically different between the combination therapy group and the independent therapy group, and bone mineral densities increased in all therapy groups while there was higher elevated level in the combination therapy group. Conclusions The combination therapy of compound danshen tablets with alendronate has a favorable influence on women with postmenopausal osteoporosis.     

Bone alkaline phosphatase measured with a new immunoradiometric assay in patients with metabolic bone diseases

We have investigated the clinical utility of a new quantitative two-site radioimmunometric assay specific for bone alkaline phosphatase (B-ALP) in 219 healthy control subjects and in 264 patients with various metabolic bone diseases. B-ALP was compared with total alkaline phosphatase (T-ALP) and with osteocalcin (BGP). B-ALP increased linearly with age in both sexes. In postmenopausal normal women B-ALP increased by 82% compared with premenopausal normal women, whereas the differences between pre- and postmenopausal women for T-ALP and BGP were 18% and 30% respectively. As assessed by Z -score, the highest values of B-ALP were found in patients with Paget's disease of bone, bone metastases or hyperparathyroidism and in patients on maintenance haemodialysis. In osteoporotic patients, B-ALP, but not T-ALP, showed a slight but significant ( P  < 0.05) difference compared with normal women. On the basis of bone turnover, osteoporotic patients were divided into two groups: high turnover and low turnover; B-ALP, like BGP, was significantly ( P  < 0.01) higher in patients with high turnover. In conclusion, B-ALP, measured by this new method, can be considered a sensitive marker of bone turnover and could be especially useful in identifying women at risk of developing osteoporosis.     

Use of bone alkaline phosphatase to monitor alendronate therapy in individual postmenopausal osteoporotic women.

BACKGROUND: Biochemical bone markers are sensitive to the changes in bone turnover that result from treatment of postmenopausal osteoporotic women with antiresorptive therapies. Although information is available on the use of bone markers in monitoring therapy in groups of subjects, less is known regarding how these markers perform in individual patients. METHODS: Serum bone alkaline phosphatase (bone ALP) concentrations, measured with the Tandem(R) Ostase(R) assay, were used to monitor the biochemical response of bone in postmenopausal women with osteoporosis receiving either 10 mg/day alendronate therapy (n = 74) or calcium supplementation (n = 148) for 24 months. RESULTS: Bone ALP decreased significantly from baseline at 3 months (P 相似文献   

Comparison of biochemical markers of bone remodelling in the assessment of the effects of alendronate on bone in postmenopausal osteoporosis.

The effects of alendronate treatment on biochemical markers of bone remodelling and bone mineral density (BMD) were studied in 30 Caucasian women (postmenopausal for at least 3 years, age 42-76 years, with BMD of the lumbar spine at least 2 S.D. below the mean for mature, premenopausal women). The patients were randomly assigned to receive alendronate (10 mg/day) or placebo for 12 months (double blind). The study was subsequently extended to a second year of open alendronate treatment. The treatment with alendronate resulted in a significant and progressive increase in BMD of the lumbar spine and femoral neck. Under the treatment, the maximal decrease of biochemical markers of bone remodelling (osteocalcin in plasma, bone-specific alkaline phosphatase, N-terminal propeptide of type I procollagen and C-terminal telopeptide of type I collagen in serum, and cross-linked amino-terminal N-telopeptide and total hydroxyproline in urine) was observed at 6 months with no further change during the 2-year period. There were no significant differences in discriminating between patients treated for 1 year with alendronate or placebo using either the percentage change in spine BMD at month 12, or a single measurement of the marker at month 6, or log (percent of baseline at month 6 of value of the marker). In this respect, the power of all the biochemical markers were comparable. The markers are a valuable adjunct to the measurements of BMD, especially in the patients not showing an increase of 3% or more at the lumbar spine BMD after 1 year of treatment.     

Biochemical markers of bone formation in hemodialysis and after allotransplantation of cadaveric kidney

AIM: To ascertain informative value of estimation of bone forming markers in patients on chronic hemodyalisis (CHD) and recipients of cadaveric kidney (CK). MATERIAL AND METHODS: Parathyroid hormone (PTH), beta-crosslaps (CTX), osteocalcin (OC), amino-terminal procollagen propeptide 1 (PINP), bone alkaline phosphatase (BAP), bone mineral density (BMD) were determined in 152 patients on CHD (89 males and 63 females aged 49 +/- 13 years) and 195 CK recipients (106 males and 89 females aged 42 +/- 12 years) 30 +/- 38 months after kidney transplantation. RESULTS: PTH, CTX and BAP determination specifies skeletal disease (secondary hyperparathyroidism or adynamic bone disease) in CHD patients. In patients with CK recipients osteoporosis differed from osteopenia by higher levels of PTH, CTX, OC in the absence of any differences in BAP, PINP. All bone forming markers were lower than CTX showing suppression of bone forming. Bone fractures in CK recipients' anamnesis were associated with OC and BAP decrease in men and low border of normal OC in women. Determination of bone formation and resorption markers in patients on CHD and CK recipients is of great clinical importance.     

Effects of low- and conventional-dose transcutaneous HRT over 2 years on bone metabolism in younger and older postmenopausal women

The minimum dosage of transcutaneous hormone replacement therapy (HRT) able to exert protective effects on postmenopausal bone mass, especially in older women, is uncertain. This study investigates the effects of transcutaneous HRT at two different doses of oestradiol [Estraderm 25 and 50 (E25, E50)] over 2 years in 44 postmenopausal women younger than 67 years and 27 of 67 years and older. Circulating biochemical markers of bone and connective tissue turnover, collagen type I (intact PINP, PICP) and type III (PIIINP) propeptides and type I telopeptide (ICTP), osteocalcin (OC) and alkaline phosphatase (AP) were measured. The responses of the biochemical markers in all the groups were very similar, and most of the observed changes occurred within the first year of treatment. E25 had an effect on the bone markers similar to that of E50, and there was little difference in response according to the patient's age. PINP fell markedly after 1 year in all groups to about half the pretreatment level, with a smaller drop in the second year. PICP responded more variably, and mean values were little changed. There was a slight fall at the higher dose in the younger women, and also in the older women (whose baseline level was higher) on the lower dose. The correlation between PINP and PICP was 0.52 at pretreatment and 0.84 after 2 years of treatment. PIIINP showed no changes. OC and AP both fell in all groups by the first year, but less markedly than PINP. Their response was slightly less pronounced in the older women. ICTP fell marginally in the younger women, and only after 2 years, regardless of dose. Postmenopausal serum oestradiol levels increased after HRT and were associated with decreased binding globulin (SHBG) levels in all groups. After E25 patch application individual serum oestradiol levels were variable and peaked between 13 and 36 h with a median value of 83.8 pmol L^–1. Our data suggest that low-dose transcutaneous HRT restores circulating oestradiol levels in postmenopausal osteopenic women of all ages as effectively as conventional-dose HRT and is associated with decreased circulating markers of bone and connective tissue turnover.