Serum bone sialoprotein: a marker of bone resorption in postmenopausal osteoporosis

Thirty healthy perimenopausal women who had normal lumber spine bone mineral density (LS-BMD) measured by dual energy X-ray absorptiometry (DEXA) participated in this study as controls. The pathological group comprised 50 postmenopausal osteoporotic women who had LS-BMD more that 2 SD below the normal mean of healthy perimenopausal women. Postmenopausal osteoporotic patients were allocated to three different therapeutic modalities (hormone replacement therapy HRT, alendronate or combined HRT and alendronate). Blood and urine samples were collected from all groups before and 12 months after treatment. Serum bone sialoprotein (BSP) was measured by a specific radioimmunoassay and urinary pyridinoline N-telopeptide of type l collagen (NTX ) were determined as biomarkers of bone resorption. In addition, serum IL-11 and TGF &#103 2 were measured by enzyme immunoassays. The results obtained showed that serum BSP was significantly elevated in postmenopausal osteoporosis compared to that of healthy perimenopausal controls. Significant positive correlations exist between serum BSP and biomarkers of bone resorption (Pyr,DPyr,NTX ) as well as bone resorptive cytokines (IL-11,TGF &#103 2 ). Serum BSP decreased after different antiresorptive treatments and this decrease paralleled the decrease of bone resorption markers and the increase of LS-BMD. Based on these data, circulating BSP appears to be a valuable marker of bone resorption and monitoring therapy with antiresorptive drugs in postmenopausal osteoporosis. (Pyr), deoxy-pyridinoline (DPyr) and     

Serum bone sialoprotein: a marker of bone resorption in postmenopausal osteoporosis.

Thirty healthy perimenopausal women who had normal lumber spine bone mineral density (LS-BMD) measured by dual energy X-ray absorptiometry (DEXA) participated in this study as controls. The pathological group comprised 50 postmenopausal osteoporotic women who had LS-BMD more that 2 SD below the normal mean of healthy perimenopausal women. Postmenopausal osteoporotic patients were allocated to three different therapeutic modalities (hormone replacement therapy HRT, alendronate or combined HRT and alendronate). Blood and urine samples were collected from all groups before and 12 months after treatment. Serum bone sialoprotein (BSP) was measured by a specific radioimmunoassay and urinary pyridinoline (Pyr), deoxy-pyridinoline (DPyr) and N-telopeptide of type 1 collagen (NTX) were determined as biomarkers of bone resorption. In addition, serum IL-11 and TGFbeta2 were measured by enzyme immunoassays. The results obtained showed that serum BSP was significantly elevated in postmenopausal osteoporosis compared to that of healthy perimenopausal controls. Significant positive correlations exist between serum BSP and biomarkers of bone resorption (Pyr,DPyr,NTX) as well as bone resorptive cytokines (IL-11,TGFbeta2). Serum BSP decreased after different antiresorptive treatments and this decrease paralleled the decrease of bone resorption markers and the increase of LS-BMD. Based on these data, circulating BSP appears to be a valuable marker of bone resorption and monitoring therapy with antiresorptive drugs in postmenopausal osteoporosis.     

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.     

Bone turnover markers and sex hormones in men with idiopathic osteoporosis

BACKGROUND: In contrast to osteoporosis in postmenopausal women, osteoporosis in men has received much less attention. PATIENTS AND METHODS: We determined various biochemical parameters of bone metabolism and sex hormones in 31 men with idiopathic osteoporosis and 35 age matched control subjects. RESULTS: In the men with osteoporosis, a significantly increased urinary excretion of deoxypyridinoline (5.3 +/- 0.2 vs. 4.6 +/- 0.2 nmol mmol-1 creatinine; P = 0.033) in addition to increased serum levels of the c-terminal telopeptide of type I collagen (2677 +/- 230 vs. 2058 +/- 153 pmol; P = 0.037) were found. While parameters of bone formation were not significantly different in the patients and controls, serum bone sialoprotein levels were significantly decreased in the patients (3.7 +/- 0.8 vs. 12.4 +/- 4.0 ng mL-1; P = 0.021). Moreover, in men with idiopathic osteoporosis, lower levels of estradiol (91.3 +/- 5.8 vs. 114.6 +/- 7.8 pmol L-1; P = 0.044), higher levels of sex hormone binding globulin (31.5 +/- 3.1 vs. 24.2 +/- 1.4 nmol L-1; P = 0.034) and a decreased free androgen index (42.6 +/- 5.2 vs. 56.4 +/- 5.9; P = 0.016) were seen. Serum estradiol levels correlated negatively with several parameters of bone resorption. CONCLUSIONS: In men with idiopathic osteoporosis, bone resorption is increased and exceeds bone formation. The excessive bone resorption seen in idiopathic male osteoporosis may be due to decreased estradiol levels and low levels of bioavailable testosterone.     

The assessment of bone metabolism in female elite endurance athletes by biochemical bone markers.

PURPOSE: Premature osteoporosis is a frequent problem in female athletes. Current concepts suggest that a disruption of the hypothalamic-pituitary axis leads to hypoestrogenism, which then causes amenorrhea and osteoporosis. However, the underlying mechanisms have been insufficiently investigated. Osteoprotegerin (OPG) and soluble TNF-alpha receptor antagonist ligand (sRANKL) regulate the balance of osteoblasts and osteoclasts. Their role in the pathogenesis of osteoporosis in female athletes has not been studied yet. METHODS: We measured OPG and sRANKL in relation to biochemical bone markers [osteocalcin (OC), bone alkaline phosphatase (BAP), serum beta-crosslaps (CTx)] and female sex hormones [estradiol (E2) and luteinizing hormone (LH)] in fastening blood samples from 25 female elite endurance athletes and 25 matched controls. RESULTS: Athletes exhibited significantly higher levels of the bone resorption marker CTx than controls (0.61 +/- 0.26 vs. 0.44 +/- 0.15 ng/ml). OPG and sRANKL were not changed. Subgroup analysis revealed that athletes using oral contraceptives [A-OCC(-)] had significantly higher levels of CTx (0.82 +/- 0.20 vs. 0.50 +/- 0.14 ng/ml), BAP [37.3 (23.2-54.4) U/l vs. 25.2 (20.3-35.6) U/l] and OPG (3.4+/-0.8 vs. 2.7+/-0.8 ng/ml) than controls who did not use oral contraceptives [C-OCC(-)]. While the difference for CTx exceeded the least significant change in this marker by approximately 30%, the differences for the bone formation markers OC and BAP were close to the least significant change. In athletes using oral contraceptives [A-OCC(+)] we found no differences compared to controls. CONCLUSIONS: A-OCC(-) athletes have increased bone turnover with a particular stimulation of bone resorption. The increased bone resorption is not accompanied by a shift of the OPG/sRANKL relationship towards an osteoclastogenic constellation. Since increased bone resorption was not detectable in A-OCC(+) athletes, it can be suggested that OCC use might protect bone health in female athletes.     

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.     

Serum concentrations of cross-linked N-telopeptides of type I collagen: new marker for bone resorption in hemodialysis patients

BACKGROUND: Urinary cross-linked N-telopeptide of type I collagen (NTX) is a reliable bone resorption marker in patients with metabolic bone disease. We assessed a clinically available serum NTX assay suitable for anuric patients on hemodialysis (HD). METHODS: Serum concentrations of NTX, C-terminal telopeptide of type I collagen (beta-CTX), pyridinoline (PYD), and deoxypyridinoline (DPD) were determined as bone resorption markers, and those of bone alkaline phosphatase (BAP) and intact osteocalcin (OC) as bone formation markers, in 113 male HD patients (mean age, 59.3 years; mean HD duration, 67.7 months). Each patient's bone mineral density (BMD) in the distal third of the radius was measured twice, with a 2-year interval between measurements, by dual-energy x-ray absorptiometry. RESULTS: Serum NTX correlated significantly with beta-CTX, PYD, DPD, BAP, and intact OC. NTX, as well as beta-CTX, PYD, DPD, BAP, and intact OC, correlated significantly with BMD at the time of measurement. NTX, beta-CTX, and DPD correlated significantly with the annual change in BMD during the 2-year period thereafter, in contrast to PYD, BAP, and intact OC. Patients in the highest quartile of serum NTX concentrations showed the fastest rate of bone loss. The sensitivity and specificity for detecting rapid bone loss were 48% and 83%, respectively, for serum NTX. CONCLUSION: Serum NTX may provide a clinically relevant serum assay to estimate bone turnover in HD patients.     

Osteoprotegerin serum levels in women: correlation with age,bone mass,bone turnover and fracture status

Pre-clinical data have shown that osteoprotegerin (OPG) inhibits osteoclast function and therefore plays an important role in bone remodelling. This study aimed to evaluate the clinical value of serum OPG. Do higher OPG serum levels reflect decreased bone resorption and perhaps higher bone mass in women? Serum OPG levels were measured in 177 healthy women (aged 17-85 years) and in 48 untreated patients (mean age 71 +/- 5) with established osteoporosis, and related to age, bone mass, markers of bone turnover and, in the case of patients with osteoporosis, to pre-existing vertebral fractures. In healthy women OPG levels showed a positive correlation with age (r = 0.25, p < 0.001) but not to bone mass or markers of bone turnover. In women with osteoporosis, however, there was a strong relationship between serum OPG and markers of bone turnover (serum c-terminal crosslinked telopeptides of thpe I collagen (sCTX): r = +0.82, p < 0.0001; osteocalcin (OC): r = +0.69, p < 0.0001), with patients who had higher levels of bone-turnover markers showing higher serum levels of OPG. After adjustment for bone mass and bone markers, patients with pre-existing vertebral fractures had significantly lower serum OPG levels than patients without fractures (57 +/- 8 vs. 97 +/- 10 pg/ml, [mean +/- SE], p < 0.01). The age-dependent increase of OPG as an antiresorptive factor may reflect an insufficient paracrine mechanism of bone cells to compensate for bone loss in older age. In patients with osteoporosis, however, OPG correlated strongly with markers of bone turnover; this may point toward a higher level of RANKL/OPG expression in these patients. Finally, low OPG serum levels seem to be associated with vertebral fractures. We hypothesise that low OPG levels in preset conditions of bone turnover may indicate a higher risk of fracture in patients with osteoporosis.     

Increased bone resorption in the critically ill: association with sepsis and increased nitric oxide production

OBJECTIVE: Cytokines stimulate nitric oxide production in bone, and high concentrations of cytokine-induced nitric oxide inhibit bone resorption in vitro. This has led to the suggestion that nitric oxide may protect against bone loss in inflammatory and infectious diseases. In this study, we sought to determine whether nitric oxide generated as the result of sepsis was associated with suppression of bone resorption in vivo. DESIGN: Observational study. SETTING: Adult intensive care unit of a university hospital. PATIENTS: We studied 20 consecutive patients who had been admitted to the intensive care unit because of sepsis and three who had been admitted because of trauma. Controls were 29 patients with noninflammatory musculoskeletal conditions. INTERVENTIONS: Standard clinical care. MEASUREMENTS AND MAIN RESULTS: Bone resorption was assessed by measurement of urinary pyridinoline and deoxypyridinoline as a ratio to urinary creatinine. Nitric oxide production was assessed by measuring the ratio of the nitric oxide breakdown products nitrate and nitrite to urinary creatinine. Urinary nitrate and nitrite/creatinine values were significantly higher in intensive care patients with sepsis (mean +/- sem, 0.164 +/- 0.053 micromol/mmol) than in intensive care patients with trauma (0.066 +/- 0.008) and controls (0.079 +/- 0.007; p =.007 between groups). Urinary pyridinoline/creatinine values were increased in intensive care patients with sepsis (553.8 +/- 193 nmol/mmol) and trauma (238 +/- 32) compared with controls (44.7 +/- 2.6; p =.001 between groups), and similar differences between the groups were observed for deoxypyridinoline/creatinine values: intensive care patients with sepsis, 86.4 +/- 24.0; intensive care patients with trauma, 46 +/- 4.2; and controls, 10.3 +/- 0.7 (p =.001). CONCLUSIONS: Critically ill patients with sepsis have increased nitric oxide production and increased bone resorption, whereas trauma patients have increased bone resorption in the presence of normal nitric oxide production. High concentrations of nitric oxide generated during the course of infection do not afford significant protection against accelerated bone resorption.     

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.     

Higher efficacy of urinary bone resorption marker measurements in assessing response to treatment for osteoporosis in postmenopausal women

Osteoporosis has reached epidemic proportions. This situation has stimulated the development of biochemical markers to assist in assessing osteoporotic risk and monitoring treatment efficacy. Biochemical markers for assessing the level of bone resorption have been developed during the last few decades. One of the most widely used bone resorption markers is cross-linked N-terminal telopeptides (NTX). Measurements of urinary and serum NTX provide indications of the level of bone resorption during osteoporosis treatment. However, it remains unclear whether urinary or serum NTX measurements show better efficacy for assessing osteoporosis treatment effects during the early phase of treatment. Therefore, the primary aim of the present study was to compare the efficacies of urinary and serum NTX measurements for assessing the level of bone resorption during the early stage of osteoporosis treatment. We enrolled 43 postmenopausal Japanese women in an open-label randomized placebo-controlled trial. Overall, 21 women in the osteoporosis treatment group and 19 women in the placebo group completed the study. There was a significant reduction in urinary NTX in the treatment group, which was detectable as early as 4 weeks and maintained until 16 weeks, compared with the placebo group. On the other hand, serum NTX did not show a significant reduction in the treatment group compared with the placebo group until 16 weeks. These results indicate that urinary NTX measurements are more sensitive and show higher efficacy than serum NTX measurements for assessing treatment effect during the early phase of osteoporosis treatment in postmenopausal women.     

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。     

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.     

血清白细胞介素6及骨代谢生化指标变化与骨质疏松症发生发展的关系

背景绝经期妇女雌激素水平下降后出现骨吸收增强,同时伴有细胞因子增多,骨代谢紊乱.进一步观察骨质疏松患者血清中白细胞介素6(IL-6)、骨钙素、尿胶原吡啶酚(pyridinoline,PYD)、雌二醇的水平,有利于判定上述因子是否与骨质疏松发生发展有关.目的探讨女性骨质疏松患者的血清中IL-6,骨钙素与雌二醇,尿液中PYD的水平与骨代谢的关系,寻找骨质疏松症发生发展的可能有关因素.设计以患者和健康体检者为研究对象,病例-对照,观察对比研究.单位深圳市南山人民医院骨科中心实验室.对象选择1999-01/2001-12深圳市南山人民医院骨科收治的25例绝经期女性骨质疏松患者为实验组,年龄42～69岁.选择同期本院健康体检女性10例为对照组.方法空腹抽取实验组和对照组研究对象静脉血2 mL,分离血清,同时收集晨尿2 mL,分别测IL-6,骨钙素,PYD和雌二醇的含量.主要观察指标两组血清IL-6,骨钙素,雌二醇水平及尿液中PYD比较.结果实验组的25例患者IL-6[(201.0±79.9)ng/L],骨钙素[(25.5±16.2)μg/L],PYD[(41.3±9.7)nmol/mmol肌酐]均明显高于对照组(t=2.159～2.953,P<0.05～0.01);实验组血清雌二醇水平[(79.8±73.2)ng/L]明显低于对照组(t=2.071,P<0.05).结论IL-6,骨钙素,PYD,雌二醇在骨质疏松的发生、发展的过程中起着很重要的作用.在骨质疏松患者治疗和康复过程中调节IL-6,骨钙素,PYD,雌二醇的水平是非常必要的.     

Induction of de novo bone formation in the beagle. A novel effect of aluminum.

To define the primary effects of aluminum on bone in the mammalian species, we examined the dose/time-dependent actions of aluminum in normal beagles. Administration of low dose aluminum (0.75 mg/kg) significantly elevated the serum aluminum (151.7 +/- 19.9 micrograms/liter) compared with that in controls (4.2 +/- 1.35 micrograms/liter) but did not alter the calcium, creatinine, or parathyroid hormone. After 8 wk of therapy, bone biopsies displayed reduced bone resorption (2.6 +/- 0.63 vs. 4.5 +/- 0.39%) and osteoblast covered bone surfaces (2.02 +/- 0.51 vs. 7.64 +/- 1.86%), which was indicative of low turnover. In contrast, prolonged treatment resulted in increased bone volume and trabecular number (38.9 +/- 1.35 vs. 25.2 +/- 2.56% and 3.56 +/- 0.23 vs. 2.88 +/- 0.11/mm) which was consistent with uncoupled bone formation. Administration of higher doses of aluminum (1.20 mg/kg) increased the serum aluminum further (1242.3 +/- 259.8 micrograms/liter) but did not affect calcium, creatinine, or parathyroid hormone. However, after 8 wk of treatment, bone biopsies displayed changes similar to those after long-term, low-dose therapy. In this regard, an increased trabecular number (3.41 +/- 0.18/mm) and bone volume (36.5 +/- 2.38%) again provided evidence of uncoupled bone formation. In contrast, in this instance poorly mineralized woven bone contributed to the enhanced bone volume. High-dose treatment for 16 wk further enhanced bone volume (50.4 +/- 4.61%) and trabecular number (3.90 +/- 0.5/mm). These observations illustrate that aluminum may stimulate uncoupled bone formation and induce a positive bone balance. This enhancement of bone histogenesis contrasts with the effects of pharmacologic agents that alter the function of existing bone remodeling units.     

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.     

The effect of B-vitamins on biochemical bone turnover markers and bone mineral density in osteoporotic patients: a 1-year double blind placebo controlled trial.

BACKGROUND: Hyperhomocysteinemia is a new risk factor for osteoporosis. This study analyzed the effect of a homocysteine (HCY)-lowering treatment in osteoporotic individuals. METHODS: Osteoporotic subjects (n=47, 55-82 years) were treated with either a combination of 2.5 mg folate, 0.5 mg vitamin B(12) and 25 mg vitamin B(6) or placebo. Bone mineral density (BMD) at lumbar spine and hip was measured at baseline and after 1 year. Urinary desoxypyridinoline cross-links (DPD) and plasma levels of tartrate resistant acid phosphatase (TRAP), C-terminal cross-links of collagen I (CTx), pro-collagen type I N-terminal peptide (PINP) and osteocalcin (OC) were measured after 0, 4, 8 and 12 months. RESULTS: B-vitamin supplementation significantly reduced HCY (0 vs. 12 months: 13.6+/-4.8 vs. 8.9+/-2.4 micromol/L). Placebo treatment had no effect on HCY (0 vs. 12 months: 12.0+/-3.4 vs. 12.7+/-3.9 micromol/L). BMD, TRAP, CTx, OC and PINP did not change throughout the study in both groups. Vitamin treatment decreased urinary DPD by -13% (p<0.01) after 8 and 12 months. In a sub-group analysis of hyperhomocysteinemic subjects (HCY>15 mumol/L, n=8), B-vitamin treatment tended to increase BMD at the lumbar spine, with a t-score from -2.7 to -1.7, and to decrease OC and PINP by approximately 50%. CONCLUSIONS: B-vitamin supplementation had no consistent effects on bone turnover or BMD. However, the situation may be different in patients with hyperhomocysteinemia.     

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.     

Effective utilization of metabolic markers of bone

Although long-term treatment is essential to reduce osteoporotic fracture, the treatment is often interrupted, because patients or even physicians cannot recognize the effects of the treatment. The less power of the drugs to increase BMD, low precision of BMD measurement, and/or deformity of lumbar spine are responsible for the low recognition. Bisphosphonate and estrogen replacement therapy reduce the resorption of bone, which can be recognized by the measurement of resorption markers, such as NTX or deoxypyridinoline. Measuring these markers before and after the treatment, patients and physicians can recognize the effect within 1-3 months, which magnitude is usually more than the least significant levels. Confirmation of the effectiveness of the treatment through these markers may reduce the dropout rate of the treatment.     

Excretion of sweat and urine pyridinoline crosslinks in healthy controls and subjects with established metabolic bone disease.

Convenient techniques for measuring rates of bone turnover have been developed in recent years with the advent of biochemical markers of bone metabolism. One recent of these techniques is a collection method and quantitative enzyme immunoassay for free pyridinoline crosslinks in human sweat. The concentrations of pyridinoline crosslinks in 5-day sweat collections and first morning void and 24-hour urine collections from healthy subjects and subjects with established metabolic bone disorders were determined. T-scores were higher in the sweat system than in the urine system by up to 10-fold in postmenopausal subjects, women with hyperparathyroidism, and subjects with postmenopausal osteoporosis. For subjects with postmenopausal osteoporosis, receiver-operating characteristic curve analysis yielded areas under the curve of 0.699, 0.629, and 0.520 for sweat pyridinoline, first morning void urine pyridinoline, and 24 hour urine pyridinoline respectively. The areas under the curve of the sweat and first morning void urine measurements were significantly greater (p<0.05) than the 24-hour pyridinoline measurements. Healthy postmenopausal subjects and subjects with postmenopausal osteoporosis were monitored before and during estrogen replacement therapy or alendronate therapy. Sweat pyridinoline values declined by 49.0 +/- 12.4% and 19.4 +/- 19.9% for estrogen and alendronate subjects respectively. We conclude that this non-invasive technique is a sensitive and specific measure of bone resorption and is appropriate as an adjunct to techniques such as bone density and may also be useful in monitoring of response to anti-resorptive therapies.