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.     

Comparison of serum and urinary C-terminal telopeptide of type I collagen in aging, menopause and osteoporosis.

BACKGROUND: Urinary C-terminal telopeptide of type I collagen (u-CTx) has been reported to be a sensitive biochemical marker of bone turnover. There have been two assays for urinary CTx, which are alpha-CTx and beta-CTx. A newly developed immunoassay for serum CTx (s-CTx) is now available for assessment of bone resorption. We evaluated the effects of aging, menopause, and osteoporosis on the measurements of serum CTx and compared them to urinary CTx assays. Methods: In 79 premenopausal healthy women, 80 postmenopausal healthy women, 61 osteoporotic patients with vertebral fractures and 34 osteoporotic patients with hip fractures, s-CTx and urinary beta-CTx (u-betaCTx) were measured by ELISAs, and urinary alpha-CTx (u-alphaCTx) was measured by an RIA. RESULTS: In all subjects, s-CTx significantly correlated with both u-alphaCTx (r=0.54) and u-betaCTx (r=0.51). There was no significant difference among s-CTx, u-alphaCTx and u-betaCTx in the T-scores of the postmenopausal group over the premenopausal group. These findings indicate that the value of s-CTx, as well as urinary CTxs, reflected the increase of bone resorption associated with menopause with a high degree of sensitivity. Patients with vertebral fractures had moderately increased concentrations of bone resorption markers compared to age-matched healthy postmenopausal women (T-score; s-CTx: 0.8, u-alphaCTx: 0.9, u-betaCTx: 0.7), whereas bone resorption markers in hip fracture patients were greatly increased compared to healthy postmenopausal women (T-score; s-CTx: 1.1, u-alphaCTx: 1.3 u-betaCTx: 1.3). The T-scores of u-CTxs against the postmenopausal group in vertebral fracture group and in hip fracture group were not significantly different from those of s-CTx. CONCLUSIONS: s-CTx, as well as urinary CTxs, reflects the increase of bone resorption in patients with vertebral fractures and hip fractures.     

Measurements of urinary nonisomerized form of type I collagen degradation products (alpha-CTx) in aging, menopause, and osteoporosis with fractures

We have evaluated the effect of aging, menopause, and osteoporosis on the measurements of urinary nonisomerized form of type I collagen degradation products (alpha-CTx). In 18 children, 86 premenopausal healthy women, 144 postmenopausal healthy women, 74 patients with vertebral fractures and 61 patients with hip fractures, alpha-CTx excretions were measured by a RIA. The age-related changes of alpha-CTx in healthy females show that the values were extremely high before the age of 16 years and decreased between ages 16 and 29, and that after the age of 40 years, the values tended to increase and to vary widely with age. In menopause, alpha-CTx in postmenopausal subjects was significantly higher than those in premenopausal subjects. There was no significant correlation between alpha-CTx and years since menopause in 102 postmenopausal subjects. Alpha-CTx in the vertebral fracture group were higher than those in the postmenopause group, but not significantly. Alpha-CTx in the hip fracture group were significantly higher than those in postmenopause and vertebral fracture groups. In age-matched comparisons, the values of the patients with vertebral fracture and the patients with hip fracture were significantly higher than those of corresponded age-matched postmenopausal women. Alpha-CTx well reflects an increase of bone resorption associated with bone modeling at childhood and high bone resorption after the menopause and higher bone resorption in osteoporotic patients with fractures.     

女性骨生化指标与髋部骨密度的关系

目的探讨血清Ⅰ型胶原N末端肽(sNTX)、血清碱性磷酸酶(sALP)与女性年龄、绝经和髋部骨密度(BMD)之间的关系。方法采用酶联免疫吸附法测定824名20-80岁女性志愿者的sNTX;用全自动生化分析仪测定sALP;采用双能X线骨密度仪测量左髋部BMD。结果(1)sNTX和sALP与年龄呈正相关(r分别为0.333和0.541,P<0.01);在30-39岁年龄段最低,自40-49岁明显升高,与30-39岁年龄段比较有显著差异(P<0.01);两者随年龄的变化以三次回归模型拟合最优(R2分别为0.142和0.343,P=0.000);sNTX和sALP在绝经后较绝经前明显升高,分别达25%和48%。(2)sNTX和sALP与BMD呈显著负相关(r=-0.300--0.492,P<0.01);控制年龄、绝经年限和体重指数后,这种负相关关系仍然存在(P<0.05-0.01);与骨量正常组比较,低骨量组和骨质疏松组妇女的sNTX和sALP显著升高(P<0.01),特别在骨质疏松组升高更显著。结论sNTX和sALP能反映女性随年龄和绝经变化的骨转换状态;高骨转换状态是绝经后女性髋部骨量丢失的重要原因之一。     

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.     

绝经后妇女骨代谢过程中血清基质金属蛋白酶3和骨桥蛋白的变化

背景：骨桥蛋白和基质金属蛋白酶3具有高度的亲和力,此二者的表达可能与骨代谢有关。目的：观察绝经后妇女血清基质金属蛋白酶3和骨桥蛋白水平,并观察其与骨保护蛋白、骨保护蛋白配体及骨代谢指标的关系。方法：将120名绝经后妇女分为骨密度正常组、低骨量组和骨质疏松组3组,对其血清基质金属蛋白酶3、骨桥蛋白、骨保护蛋白、骨保护蛋白配体及骨碱性磷酸酶、骨钙素、Ⅰ型胶原交联C端肽和尿Ⅰ型胶原交联N端肽进行测定,计算骨桥蛋白/基质金属蛋白酶3比值。结果与结论：骨质疏松组中血清骨桥蛋白和基质金属蛋白酶3的水平高于正常组（P〈0.05）。绝经后妇女血清基质金属蛋白酶3、骨桥蛋白和骨桥蛋白/基质金属蛋白酶3比值与血清骨保护蛋白配体、骨碱性磷酸酶和骨钙素水平呈明显负相关（P〈0.05）,与骨保护蛋白、尿尿Ⅰ型胶原交联N端肽/肌酐比值呈明显正相关性（P〈0.05）。骨质疏松组中血清基质金属蛋白酶3、骨桥蛋白和骨桥蛋白/基质金属蛋白酶3比值与血清骨保护蛋白配体、骨碱性磷酸酶和骨钙素水平呈明显负相关（P〈0.05）,与骨保护蛋白、尿尿Ⅰ型胶原交联N端肽/肌酐水平比值存在明显正相关性（P〈0.05）。提示绝经后妇女血清骨桥蛋白水平和骨桥蛋白/基质金属蛋白酶3比值升高与绝经后骨质疏松症伴随骨代谢转换过程增快有关。     

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     

Relation of parity and homocysteine to bone mineral density of postmenopausal women

Osteoporosis is a major problem in contemporary society. However, there is not enough data on multiparity and osteoporosis from developing and/or undeveloped countries on a large scale. Selection of participants in this study was aimed at the detection of bone status in healthy (normal bone mineral density) postmenopausal (n = 46, 55.3 +/- 6.7 years) and osteoporotic postmenopausal women (n: 33) of similar age. Bone mineral density (BMD) was evaluated using dual energy X-ray absorptiometry. At the DEXA evaluation, 33 women had osteoporotic (T score below -2.5) and 46 had normal BMD values. The number of pregnancies was found to range from 3 to 12 (with an overall mean of 6.7 +/- 2.5), while 2.6 +/- 1.9 (range, 1-7) were miscarriages in all of the 33 postmenopausal osteoporotic women. Serum homocysteine (t-Hcy) and urinary deoxypyridinoline (DPD) levels were significantly higher in osteoporotic postmenopausal women (11.96 +/- 3.84 micromol/L, 15.4 +/- 7.0 nM/mM cr) than in non-osteoporotic postmenopausal women (10.93 +/- 3.6 micromol/L, 10.6 +/- 9.1 nM/mM cr), p < 0.05, p < 0.01, respectively. Surprisingly, in postmenopausal osteoporotic women the homocysteine (t-Hcy) levels were positively associated with the number of deliveries (multiparity; 6.7 +/- 2.5), and positively associated with the number of curettages (2.6 +/- 1.9), r = 0.401, p < 0.038 and r = 0.520, p < 0.029, respectively. The mechanism linking serum t-Hcy to the number of pregnancies is unclear, and the relationship may only be by chance. In conclusion, the present study firstly suggests that the number of pregnancies has an effect on the t-Hcy levels. In addition, our study indicates that there is a significant negative correlation between the number of pregnancies and the lumbar spine BMD.     

老年男性吸烟与骨转换标志物、骨密度和骨质疏松性骨折风险的关系

目的 调查老年男性吸烟与骨转换标志物、骨密度和骨质疏松性骨折风险的关系.方法 调查576例60～97岁老年男性吸烟等情况,按照是否吸烟分成吸烟组31例和非吸烟组545例.检测两组骨转换标志物[包括I型胶原羧基末端肽交联(CTX)、I型前胶原氨基端前肽(P1NP)和骨钙素(OC)]、骨密度[包括股骨颈骨密度(FNBMD)...     

Evaluation of a fully automated serum assay for C-terminal cross-linking telopeptide of type I collagen in osteoporosis

BACKGROUND: Biochemical markers of bone turnover can provide prognostic information about the risk of osteoporotic fracture and are useful tools for monitoring efficacy of antiresorptive therapy. A serum-based automated assay may be of better clinical value than urinary markers because of lower imprecision and day-to-day within-person variability. Our aim was to evaluate the technical and clinical performances of a new, fully automated assay for serum C-terminal cross-linking telopeptide of type I collagen (CTX), a marker of bone resorption. METHODS: Serum CTX was measured on the Elecsys 2010 automated analyzer (Roche). Results were compared with those of the manual ELISA. We measured serum CTX concentrations in 728 healthy women, ages 31-89 years. We investigated the ability of this assay to predict the rate of postmenopausal forearm bone loss evaluated by four repeated bone mineral density measurements using dual-x-ray absorptiometry in 305 women followed prospectively for 4 years. Finally, in a cohort of healthy, untreated, postmenopausal women, we compared baseline serum CTX in 55 women who subsequently had a fracture (20 vertebral and 35 peripheral fractures) with values in the 380 women who did not fracture during a mean 5 years of follow-up. RESULTS: The within- (n = 21) and between-run (n = 21) CVs were <4.1% and 5.7%, respectively. In 728 healthy women, serum CTX concentrations (automated) correlated with those of the manual ELISA (r = 0.82; P<0.0001). The median long-term within-person variability assessed by four repeated measurements over 3 months in 18 postmenopausal women was 9.4%. Compared with 254 premenopausal women, serum CTX was 39% (P<0.0001) higher in 45 perimenopausal women and 86% (P<0.0001) higher in 429 postmenopausal women (mean age, 64 years). Baseline serum CTX correlated negatively with changes of bone mass measured at the mid (r = -0.23; P<0.0001) and distal (r = -0.27; P<0001) radius. Postmenopausal women with serum CTX greater than the mean + 2 SD values in premenopausal women accounted for 42% of the population, lost bone at the mid radius on average eightfold more rapidly than the other women (-0.27% +/- 2.92% vs. -2.25% +/- 3.95%; P<0.0001), and had increased risk of fracture with a relative risk (95% confidence interval) of 1.8 (1.01-3.1) after adjustment for physical activity. CONCLUSIONS: The automated assay for serum CTX is precise and predicts rate of bone loss and fracture risk in postmenopausal women. Because it is convenient to use and has high throughput, this serum bone resorption marker may be useful for the investigation of patients with osteoporosis.     

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.     

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.     

Critical differences in the serial measurement of three biochemical markers of bone turnover in the sera of pre- and postmenopausal women

Objectives: The purpose of this investigation was to quantify the biologic, day-to-day variability and critical differences in serum levels of crosslinked collagen N-telopeptides (NTx), procollagen aminoterminal extension propeptides (PINP) and bone specific alkaline phosphatase (bAP) in healthy women.

Design and methods: Seven blood samples were collected from12 pre- and 15 postmenopausal women over 4 to 6 months. NTx, PINP and bAP levels were determined utilizing enzyme- and radioimmunoassay techniques.

Results: The within-subject coefficient of variation (C.V.) in serum bAP, NTx and PINP levels was 7.1, 10.6 and 12.4% respectively. These variances did not differ significantly among premenopausal women when compared with postmenopausal subjects. Combining terms for analytical and biologic variability revealed that a critical difference between 2 successive serial measurements is 24% for bAP, 34% for NTx and 38% for PINP.

Conclusion: Circulating levels of NTx, PINP and bAP are stable over time periods of several months, allowing for the determination of significant changes in skeletal metabolism of women.     

Assessment of urinary bone markers for monitoring treatment of osteoporosis

BACKGROUND: The usefulness of urinary markers of bone turnover in monitoring therapy depends on their within-person variability compared with their responses to therapy. The aim of this study was to assess the performance of two such markers on this basis. METHODS: We measured variation, during a whole year, of cross-linked N-terminal telopeptide of collagen I (NTx) and urinary deoxypyridinoline (DPD) as ratios to creatinine concentration and after log-transformation of the ratios in untreated women stratified into three bone density classes, of which the lowest was osteoporotic. We also measured changes in bone mineral density at the lumbar spine (LSBMD) and hip (FNBMD) in untreated women with normal bones and in those with moderate osteopenia and calculated the reference change value (RCV; or least significant change) at P <0.05 for all of these measures. We made the same measurements on women treated with bisphosphonates, estrogen replacement (HRT), or calcium and examined their individual responses to treatment compared with RCV. RESULTS: After 12 months on bisphosphonates, LSBMD changed more than RCV (2.55%) in 47% of women compared with 44% of those on HRT and 13% of those on calcium. Response of FNBMD was less. Log NTx (RCV= -28%) responded to bisphosphonates in 78%, regardless of BMD, but less often to HRT (67%). Log DPD (RCV= -30%) responded to bisphosphonates less frequently (31% at 12 months). CONCLUSIONS: NTx has advantages over DPD in monitoring therapy for osteoporosis when mailed urine samples are used.     

Urinary bone resorption markers in monitoring treatment of symptomatic osteoporosis

We have studied the clinical usefulness of urinary bone resorption markers in postmenopausal women with symptomatic osteoporosis. The study design is a randomised double-blind placebo controlled study, in which the subjects were daily treated for 24 months either with a hormone analogue (2.5 mg Livial, generic name Tibolone, Organon, Amsterdam, Holland) plus 800 mg calcium (n = 14, age 63+/-5 years, range 52-68 years), or with placebo plus 800 mg calcium (n = 19, age 66+/-7 years, range 50-75 years). The laboratory methods for urinary bone resorption markers were enzyme immunoassays (EIA) for urinary pyridoline (PYD) and deoxypyridoline crosslinks (DPD), and for cross-linked N-telopeptides of Type I Collagen (NTx), and an HPLC assay for urinary hydroxyproline (HOP). All the urine assay results were calculated per mmol creatinine. All the resorption markers decreased during the two-year study period in both groups. The Z scores (discriminating power, i.e. ability of the different tests to distinguish the hormone treated subjects from the placebo treated subjects) for HOP and PYD were rather low: 0.06-1.52 for HOP and 0.68-1.47 for PYD. The differences between the two treatment groups were statistically significant for DPD at 12 and 24 months of treatment (P = 0.0471 and P = 0.0466, respectively), the Z scores ranging 0.45-1.90. NTx showed the most prominent decrease from the beginning of the study especially in the hormone treatment group: the differences between the two treatment groups were statistically highly significant for NTx already at 6 months of treatment (P = 0.0015), and the Z scores remained high ranging 2.11-3.82 throughout the two-year study period. Dual X-ray absorptiometry (DXA) of the lumbar spine and femoral neck did not show statistically significant differences between the two treatment groups throughout the two-year study period. After 2 years there was, however, a significant increase in bone density both in the spine (+ 6.6%, P = 0.0002) and in the femoral neck (+ 3.4%, P = 0.0389) in the women with hormone treatment. In the control group a significant increase (+ 5.1%, P = 0.0012) in the spine, whereas a non-significant decrease (-1.5%, n.s.) in the femoral neck was observed. We suggest that measurement of urinary cross-linked peptides derived from Type I collagen (NTx and DPD) might be a useful biochemical method of observing the positive clinical effect (i.e. reduction in bone resorption) following hormone replacement therapy in postmenopausal fracture patients.     

骨代谢标志物与绝经后妇女骨质疏松症的相关性研究

目的探讨绝经后骨质疏松及其引起的骨折与骨代谢标志物之间的关系。方法应用单能X线骨密度仪测量绝经期妇女脚跟骨骨密度（BMD）,并根据有无骨质疏松和骨折将108例绝经后妇女分为无骨质疏松（NOP）组,骨质疏松无骨折（OP1）组和骨质疏松伴骨折（OP2）组,测定各组受试者BMD和骨代谢标志物骨钙素（N—MID）,总骨Ⅰ型前胶原N端肽（P1NP）和口胶原特殊序列（β-Crosslaps）水平。结果血清N—MID、PINP和β-Crosslaps水平：NOP组低于OP1组,OP1组低于OP2组,且差异均有统计学意义（P〈0．05）。结论绝经后骨质疏松患者血清骨代谢标志物水平与骨质疏松及骨折存在密切的相关性;血清N—MID、P1NP和β-Crosslaps是诊断绝经后妇女骨质疏松症、预测骨折风险的理想指标。     

Preventing osteoporotic fractures in older people

While fractures at the spine, wrist and hip are regarded as classical osteoporotic fractures, all fragility fractures in the elderly should be considered as osteoporotic once pathological fracture (e.g. metastatic disease) has been excluded. The assessment of fracture risk should take account of specific risk factors in addition to bone mineral density (BMD). The WHO has produced FRAX, a well validated tool that estimates the probability of a major osteoporotic fracture in the next 10 years. The algorithm is specifically designed for primary care. After age and prior fragility fracture, BMD is the next major determinant of fracture risk. Rather than scanning all individuals with a risk factor, measurements should be targeted to those whose probability of fracture lies close to the intervention threshold where knowledge of BMD will influence management. Individuals with a low trauma vertebral fracture or low BMD for age should be investigated for underlying causes of osteoporosis. Secondary causes account for up to 40% of cases of osteoporosis in women and 60% in men. The goal of osteoporosis management is to reduce the future risk of fracture. Lifestyle modification includes measures to reduce falls risk and bone loss such as exercise, adequate dietary calcium and avoidance of smoking and excessive alcohol consumption. All patients with an osteoporotic fracture and those at high risk should be assessed for falls risk. Combined therapy, with calcium and vitamin D, has been shown to reduce hip fracture risk in the frail elderly and should be considered in all older patients who are housebound or in residential care. Alendronate and risedronate are available as once-weekly preparations with evidence for significant reductions in vertebral and non-vertebral fractures. Denosumab is approved for osteoporosis in postmenopausal women at increased risk of fractures. Strontium ranelate has been shown to reduce fracture risk significantly in postmenopausal women.     

New evidence that serum β2-microglobulin behaves as a biological marker of bone remodelling in women

Abstract. Having observed that serum β ₂-microglobulin concentration correlates with serum tartrate-resistant acid phosphatase (TRAP) concentration in postmenopausal osteoporosis, and that metacarpal endosteal diameter is dependent on bone resorption, we correlated the two biochemical parameters with the radiographic parameter to determine if β ₂-microglobulin behaves like a biological marker of bone remodelling. In 105 women (mean age 68±4 years) consisting of 60 normal postmenopausal women and 55 osteoporotic postmenopausal women, there was a significant positive correlation between metacarpal endosteal diameter and these two biochemical values ( r = 0.66 with β ₂-microglobulin and r = 0.68 with TRAP in the osteoporotic postmenopausal women: r = 0.48 with β ₂-microglobulin and r = 0.56 with TRAP in the normal postmenopausal women: P < 0.001 for all comparisons). All three measurements were significantly higher ( P < 0.001) in the osteoporotic postmenopausal women than in the normal postmenopausal women. These findings show that serum β ₂-microglobulin behaves like a biological marker of remodelling.     

Bone mass and biochemical parameters of bone metabolism in men with spinal osteoporosis

With advancing age both sexes have an increased incidence of osteoporotic fractures, although fractures are more common in women than in men. Whereas in women several potential risk factors have been identified, less is known about osteoporosis in men. A total of 27 Austrian men (mean age: 65 +/- 2 years) with atraumatic spine fractures were studied. In all patients, medical history gave no evidence of disease or medications causing osteoporosis. Peripheral bone mass was determined by single-photonabsorptiometry on the distal non-dominant forearm; lumbal bone density was measured by quantitative computed tomography. Serum levels of calcium, phosphate, alkaline phosphatase, osteocalcin, testosterone, estrogen, parathyroid hormone and 25-hydroxy-vitamin D as well as 2-h-urinary-OH proline and calcium excretion were measured. All data were compared with those of an age and sex matched control group consisting of 19 healthy males. A significant difference in mean peripheral and axial bone mass (SPA: P less than 0.004; QCT: P less than 0.0001) was observed between osteoporotic men and controls. When compared to controls, serum levels of alkaline phosphatase (P less than 0.012), urinary OH proline (P less than 0.05) and urinary calcium excretion (P less than 0.003) were significantly higher in the osteoporotic males. Additionally, there was a significant positive correlation between serum alkaline phosphatase and urinary OH proline excretion (r = 0.32; P less than 0.04) in the osteoporotics. All other biochemical parameters showed no significant differences. Our results may lead to the assumption that osteopenia in men is related to increased bone turnover.     

Diagnostic efficacy of serum cross-linked N-telopeptide (NTx) and aminoterminal procollagen extension propeptide (PINP) measurements for identifying elderly women with decreased bone mineral density

The purpose of this study was to determine the diagnostic sensitivity, specificity, predictive value and overall efficiency of serum cross-linked N-telopeptides of bone collagen (NTx) and aminoterminal procollagen extension propeptide (PINP) measurements for identifying women with decreased spine, femoral neck and total body bone mineral density (BMD). Serum NTx and PINP levels and dual X-ray absorptiometry were performed on 196 healthy elderly women, aged 60-90 years. Twelve women were classified as having decreased BMD on the basis of regional and total skeletal densitometric values that were 1.5 to 2.5 standard deviations (SD) below the respective, age-stratified means and were compared with 184 women with BMD values greater than 1.5 SD below the mean. The results of receiver operating characteristic analysis revealed that a cutoff level of more than 15.0 nmol BCE/L for serum NTx, as measured by the Osteomark assay (Ostex International, Seattle WA USA) was associated with a 100% sensitivity and 70% specificity rate for identifying postmenopausal women with low BMD. The positive likelihood ratio was 3.3 and the negative predictive value was 1.0 using the 15.0 nmol decision level for NTx. The overall diagnostic efficiency of a single NTx measurement for identifying women with low BMD was 89%. A cutoff level of >45.0 microg/L for PINP as measured by the Orion Diagnostica RIA assay (Espoo, Finland) had a diagnostic sensitivity of 83% and specificity of 64% for identifying women with decreased BMD. The positive likelihood ratio was 2.3. the negative predictive value 0.98 and the overall diagnostic efficiency 73% using the 45.0 microg/L decision level for PINP. These results warrant future studies using larger populations that are inclusive of more women with low bone mineral density.