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.     

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。     

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.     

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.     

Comparison of zinc excretion and biochemical markers of bone remodelling in the assessment of the effects of alendronate and calcitonin on bone in postmenopausal osteoporosis

OBJECTIVES: The aim of this study was to determinate the clinical usefulness of urinary bone resorption markers, urinary zinc excretion, and other biochemical markers in postmenopausal women with osteoporosis. We also evaluated the effects of alendronate and calcitonin therapies on biochemical markers of bone remodeling and urinary zinc excretion over a 6-month period. SUBJECTS AND METHODS: The study design was a randomized placebo controlled study. The patients were randomly assigned to receive alendronate (10 mg/day; 45 patients) or calcitonin (200 IU/day; 45 patients) or placebo (45 patients) for 6 months. All patients received supplemental calcium (1000 mg/day). To assess bone resorption, we measured excretion of cross-linked N-telopeptides of Type I collagen (uNTx); urinary zinc concentrations and standard chemistry determinations were also measured; and osteocalcin (sOC) was measured as a marker of bone formation. All parameters were measured before therapy and again after 1, 3, and 6 months in all groups. RESULTS: A statistically significant decrease occurred in the levels of sOC, uZn, and uNTx after 3 and 6 months in patients receiving calcitonin therapy (P < 0.05). sOC, uZn, and uNTx levels in the calcitonin group were significantly lower after three and 6 months from both placebo and baseline values of calcitonin group. In the alendronate group, a statistically significant decrease was observed in the levels of uNTx and uZn after 1 month and in the sOC, uZn, and uNTx after 3 and 6 months from both placebo and baseline values of alendronate group (P < 0.05). uNTx, sOC, and uZn decreased about 44%, 36%, and 33%, respectively, in the calcitonin group and about 53%, 51%, and 38%, respectively, in the alendronate group below baseline values 6 months after initiating treatment. In the placebo group, there was no significant decrease in sOC, uZn, and uNTx during the course of the study. CONCLUSION: Our study suggests that in postmenopausal women with osteoporosis, both alendronate and calcitonin reduce the concentrations of uNTx, uZn, and sOC, the effect of the alendronate dose administered being significantly earlier and more pronounced. Measurement of uNTx, uZn, and sOC might be a useful biochemical method of observing the positive clinical effect following alendronate or calcitonin therapy in postmenopausal women.     

Biochemical markers of bone turnover and response of bone mineral density to intervention in early postmenopausal women: an experience in a clinical laboratory

BACKGROUND: Markers of bone formation and resorption may be useful as early indicators of response to therapy. Our aim in this study was to investigate the use of bone markers for monitoring of intervention for bone loss in early postmenopausal women and to assess the relationships between these markers and changes in bone mineral density (BMD). METHODS: Subjects were randomly assigned to the following groups: a control group; a group receiving calcium alone; groups receiving calcium plus low or conventional doses of conjugated equine estrogen; and groups receiving calcium plus low or conventional doses of calcitriol. At baseline and at 1 and 3 months after intervention, we measured serum intact osteocalcin, serum N-terminal midfragment osteocalcin, serum C-terminal telopeptide of type I collagen (CTx), urinary deoxypyridinoline cross-links, and urinary CTX: The BMD of the lumbar spine and the femoral neck was measured at baseline and after 1 and 2 years of intervention. RESULTS: No marker changed significantly in the control group except urinary CTx, which increased at 3 months. Serum CTx decreased in all regimens at 1 or 3 months of intervention. In addition, the changes of all markers at 3 months were inversely associated with the change in the BMD of the lumbar spine at 1 or 2 years (r = -0.144 to -0.314), whereas only the changes of bone resorption markers at 3 months were inversely correlated with the changes in femoral BMD at 1 or 2 years (r = -0.143 to -0.366). CONCLUSIONS: Biochemical markers of bone turnover appear to be of use in assessing early response to therapy. Bone resorption markers, especially serum CTx, are better indicators than bone formation markers for estimating the response to intervention in early postmenopausal women. However, the early changes in bone markers were weakly related to the later changes in BMD.     

Metabolic markers of bone--post-guideline

Metabolic markers of bone are common clinical parameters for the evaluation of the pathophysiologic conditions and efficacy of the treatment, although they are not helpful for differential diagnosis of osteoporosis. The guideline published officially is helpful for practitioners and non-experts in the field. The distributions of urinary NTX and bone specific alkaline phosphatase are essentially same between primary osteoporotic postmenopausal women less than 70 years old and those over 70 years. No differences were found in the other metabolic markers between these groups. Although clinical evidence for patients over 85 years old is not enough, we do not have to think of age in the clinical application of metabolic markers of bone, if renal functions are within normal ranges.     

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.     

The effect of calcium citrate on bone density in the early and mid-postmenopausal period: a randomized placebo-controlled study

This placebo-controlled randomized trial was conducted to ascertain the value of calcium citrate supplementation in averting bone loss in 63 postmenopausal women, 57 of whom were early postmenopausal (five years after menopause) and six of whom were mid-postmenopausal (five to ten years after menopause). Bone density data were available for 25 women who took 800 mg of calcium citrate daily and 31 women who received placebo for one to two years. The two groups were similar in baseline age, years postmenopause (3.3 in the calcium citrate group vs 2.7 in the placebo group), height, weight, calcium intake, and L2-L4 bone density. L2-L4 bone density did not change during calcium citrate treatment (+ 1.03% after two years), whereas it declined significantly by -2.38% after two years on placebo (P < .001). Femoral neck bone density did not change in either group. Radial shaft bone density did not change in the calcium citrate group (-0.02% after two years), but it declined significantly in the placebo group (-1.79% after one year and -3.03% after two years, P < .01). The difference in bone density of the L2-L4 vertebrae and radial shaft after two years of treatment was significant between the two groups. An analysis of covariance disclosed no significant effect of calcium citrate on L2-L4 bone density during the first three years after menopause, but a protective effect after three years. Although serum PTH did not change, serum and urinary calcium increased and serum calcitriol and urinary phosphorus decreased in the calcium citrate group, indicative of parathyroid suppression. Serum bone-specific alkaline phosphatase and osteocalcin, and urinary hydroxyproline and N-telopeptide decreased during some calcium citrate treatment periods, indicative of a reduction in bone turnover. Thus, calcium citrate supplementation (400 mg of calcium twice daily) averted bone loss and stabilized bone density in the spine, femoral neck, and radial shaft in women relatively soon after menopause. This bone-sparing action was probably due to the inhibition of bone resorption from parathyroid suppression.     

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.     

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.     

Biomarkers of bone turnover and bone mineral density in hyperprolactinemic amenorrheic women.

We tested the hypothesis that biomarkers of bone resorption are increased in hyperprolactinemic amenorrheic patients with estrogen (E) deficiency, augmenting the possible risk of developing osteoporosis. Fifty hyperprolactinemic patients with amenorrhea of more than 12 months and with low serum E2, as well as 30 healthy fertile women (controls), matched for age and body mass index, participated in this study. Bromocriptine was administered orally to hyperprolactinemic patients and blood and urine samples were collected before and 12 weeks after treatment. Serum osteocalcin (OC) and bone-specific alkaline phosphatase (B-ALP), reflecting bone formation, and urinary deoxypridinoline (D-Pyr) and N-telopeptide of type 1 collagen (NTX) excretion, reflecting bone resorption, were measured using direct immunoassays. Hyperprolactinemic patients had higher (p < 0.0005) levels of all the biomarkers compared to control values: (OC, 22+/-1.2 [SE] vs. 14+/-.99 ng/ml (+57 %); B-ALP, 14.2+/-0.7 vs. 7.5+/-0.8 ng/ml (+89 %); D-Pyr, 8.8+/-0.6 vs. 3.2+/-0.3 nmol/mmol creatinine (+175%) and NTX, 65+/-5.1 vs. 25+/-3.2 nmol bone collagen equivalent (BCE)/mmol creatinine (+160%)). These results were associated with significantly decreased lumbar spine bone mineral density (LS-BMD), measured by dual energy X-ray absorptiometry (DEXA). Treatment of hyperprolactinemia with bromocriptine restored normal values of bone formation and resorption markers. In conclusion, hyperprolactinemia with estrogen deficiency exhibits a significant increase of bone resorption which is associated with a significant decrease of LS-BMD. These changes may subject the patient to the possible risk of developing osteoporosis.     

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.     

Parathyroid hormone treatment can reverse corticosteroid-induced osteoporosis. Results of a randomized controlled clinical trial.

Corticosteroid-induced osteoporosis is the most common secondary cause of osteoporosis. We conducted a 12-mo, randomized clinical trial of human parathyroid hormone 1-34 (hPTH 1-34) in postmenopausal women (mean age was 63 yr) with osteoporosis who were taking corticosteroids and hormone replacement therapy. Response to the treatment was assessed with bone mineral density (BMD) measurements of the lumbar spine by quantitative computed tomography (QCT); BMD measurements of the lumbar spine, hip, and forearm by dual-energy x-ray absorptiometry (DXA); and biochemical markers of bone turnover. The mean (+/-SE) changes in BMD of the lumbar spine by QCT and DXA in the PTH group were 35+/-5.5% and 11+/-1.4%, respectively, compared with a relatively small change of 1.7+/-1.8% and 0+/-0.9% in the estrogen-only group. The differences in mean percentage between the groups at 1 yr were 33.5% for the lumbar spine by QCT (P < 0.001) and 9.8% for the lumbar spine by DXA (P < 0.001). The changes in the hip and forearm were not significantly different between or within the groups. During the first 3 mo of PTH treatment, markers of bone formation increased to nearly 150%, whereas markers of bone resorption increased only 100%, suggesting an early uncoupling of bone turnover in favor of formation. These results suggest that parathyroid hormone dramatically increases bone mass in the central skeleton of postmenopausal women with corticosteroid- induced osteoporosis who are taking hormone replacement.     

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.     

Relationships between serum adiponectin,leptin concentrations and bone mineral density,and bone biochemical markers in Chinese women

BackgroundAdiponectin and leptin, as the main circulating peptides secreted by adipose tissue, are potential contributors to bone metabolism. However, their association with bone mineral density (BMD) is unknown. We investigated whether these serum adipocytokines concentrations are associated with BMD and bone turnover markers.MethodsSerum adiponectin, leptin concentrations, bone turnover biochemical markers, and BMD were determined in 265 premenopausal and 336 postmenopausal Chinese women.ResultsIn postmenopausal Chinese women, the multiple linear stepwise regression analysis showed that year since menopause, lean mass, estradiol, and adiponectin, but not fat mass, leptin, were independent predictors of BMD in postmenopausal Chinese women. However, in premenopausal Chinese women, adiponectin was not the predictor of BMD. The significant positive correlations between adiponectin and bone-specific alkaline phosphatase (BAP), bone cross-linked N-telopeptides of type I collagen (NTX) were found only in postmenopausal women. Serum BAP, and NTX, but not adiponectin, decreased in response to alendronate therapy.ConclusionsAdiponectin was an independent predictor of BMD, and positively correlated with bone turnover biochemical markers in postmenopausal Chinese women, but not premenopausal women. It suggested that adiponectin may exert a negative effect on bone mass by promoting excessive bone resorption associated with bone loss. However, these effects may be mediated by menopausal status.     

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.     

Levels of C-telopeptide fragments of collagen type I enable the monitoring and early adjustment of clodronate therapy in patients with postmenopausal osteoporosis.

We monitored the efficacy of therapy with clodronate, a bisphosphonate drug, in women with postmenopausal osteoporosis, using urinary immunoenzymatic assay of C-telopeptide of collagen type I, an eight amino acid fragment (collagen fragment) of the C-telopeptide of the alpha1-chain of collagen type I (EKAHDGGR). The analysis of the dynamics of collagen fragment concentrations (a marker of bone resorption) during treatment suggests the possibility of early modulation and customization of therapy based on the levels of this marker. This could enable improved control over secondary effects and side effects of clodronate therapy. Pharmacologic inhibition of bone resorption by osteoclasts could be indirectly responsible for the increase in parathyroid hormone found during treatment with clodronate. Increased levels of parathyroid hormone are probably necessary to stimulate residual osteoclast activity and are sufficient for the maintenance of calcium-phosphate homeostasis in a new pharmacologically-induced equilibrium. Outside this context the levels of parathyroid hormone of certain patients would be considered pathologic.     

Bone turnover markers and estradiol level in postmenopausal women.

It has been found recently that women with estradiol (E) levels < 5 pg/ml were more likely to suffer osteoporotic fractures. We evaluated the relationships between biomarkers of bone turnover and changes in hormone levels in early or late postmenopausal women without any replacement therapy. Follicle stimulating hormone (FSH), luteinizing hormones (LH), estradiol and serum resorption (crosslaps) and formation (osteocalcin) markers were assayed. Bone densities in the spine and femoral neck were also measured. Elevated FSH, LH and decreased estradiol in postmenopausal women were accompanied by higher osteocalcin (9.1-9.7 ng/ml) and crosslaps level (3305-3458 pmol/l) compared to premenopausal women (6.8 ng/ml and 2087 pmol/l). Bone density was lower in elderly women. A significant inverse correlation was found between estradiol and crosslaps level; FSH and LH were also correlated with bone markers. Estradiol levels < 9 pg/ml were associated with increased bone resorption, decreased hip bone density and higher frequency of osteopenia and osteoporosis. Over 57% of women with an estradiol < 9 pg/ml could be identified as having "a high turnover" compared with 30% with estradiol above 9 pg/ml. Our results indicate that changes in bone density may not be very clear but an increase in bone turnover is distinctly apparent in women with severe estradiol deficiency.