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.     

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.     

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.     

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.     

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

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

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。     

Assessment of four biochemical markers of bone metabolism in postmenopausal osteoporosis

In order to sudy the specificity and sensitivity of markers of bone metabolism in postmenopausal osteoporosis we investigated bone alkaline phosphatase, osteocalcin and carboxyl-terminal propeptide of procollagen type I in sera as markers of bone formation, and deoxypyridinoline in urine as a marker of bone resorption. The investigated parameters were determined in 53 women with confirmed osteoporosis and in a control group consisting of 45 healthy postmenopausal women without bone changes who were 40 to 79 years old. All biochemical markers were determined by monoclonal competitive enzyme immunoassay tests obtained by Metra Biosystems. The activity of bone alkaline phosphatase and the concentration of osteocalcin, procollagen type IVC-terminal propeptide (PICP), and deoxypyridinoline were grouped according to age of postmenopausal healthy and osteoporotic women. The values of all bone markers gradually increased with age, but significantly higher values were obtained in groups of postmenopausal osteoporotic women. By using receiver operator characteristic curve analysis, a very high specificity and sensitivity of the investigated biochemical markers in the diagnosis of postmenopausal osteoporosis were proven. The areas under the PICP curve and the osteocalcin curve were significantly higher than the area under the deoxypyridinoline curve, demonstrating a higher discriminating power of PICP and osteocalcin than deoxypyridinoline (p < 0.05).     

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.     

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.     

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.     

Evaluation of a fully automated serum assay for total N-terminal propeptide of type I collagen in postmenopausal osteoporosis

BACKGROUND: Biochemical markers of bone turnover can provide prognostic information about the risk of fracture and may be useful for monitoring efficacy of antiresorptive and anabolic therapy in osteoporosis. We evaluated the performance of a fully automated assay for serum total N-terminal propeptide of type I collagen (P1NP), a marker of bone formation. METHODS: Serum P1NP was measured on the Elecsys 2010 automated analyzer (Roche) in 230 healthy premenopausal women, age 30-49 years, 179 postmenopausal women with osteoporosis participating in the previously published 1 year randomized Parathyroid Hormone and Alendronate for Osteoporosis study of full-length parathyroid hormone (PTH 1-84, >100 microg/day subcutaneously; n = 119) or oral alendronate 10 mg/day (n = 60), and 64 healthy men, age 40 to 65 years. RESULTS: The within-run and between-run (total) imprecision (CVs) were < or =1.7% (n = 20) and 4.4% (n = 15), respectively. The median within-person variability of results (3 measurements over 3 months in 15 postmenopausal women) was 7.2%, resulting in a least significant change (LSC) value of 20%. Serum P1NP concentrations were 74% (P <0.0001) higher in postmenopausal women than in premenopausal controls. After 3 months of treatment, 83% and 88% of patients treated with PTH 1-84 and alendronate, respectively, demonstrated changes of serum P1NP that exceeded the LSC. CONCLUSION: The automated assay for serum total P1NP is precise and sensitive enough to detect changes that exceed the LSC in a majority of postmenopausal women after 3 months of treatment with PTH 1-84 or alendronate. Because of its convenience and high throughput, this bone formation marker may be useful for the monitoring of patients with osteoporosis.     

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.     

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.     

Unequal decrease in bone density of lumbar spine and ultradistal radius in Colles'' and vertebral fracture syndromes.

We measured bone mineral density (BMD) at the lumbar spine (LS-BMD) and ultradistal radius (UDR-BMD) in 42 postmenopausal normal women and in 108 postmenopausal osteoporotic women (55 with vertebral fracture, 34 with Colles' fracture, and 19 with both fractures). By receiver operating characteristic analysis, LS-BMD was better than UDR-BMD (P less than 0.01) as an indicator of vertebral fracture; the converse was true for Colles' fracture (P less than 0.01). Although UDR-BMD and LS-BMD were lower in each of the three fracture groups than in controls (P less than 0.01), the pattern of bone loss differed (P less than 0.001, analysis of variance): with vertebral fracture, LS-BMD decreased relatively more than UDR-BMD; with Colles' fracture, UDR-BMD decreased relatively more than LS-BMD; and with both fractures, decreases in LS-BMD and UDR-BMD were similar. We conclude that both types of fracture are caused by excessive bone loss but the difference in bone loss at the two sites is a major factor in determining which will fracture.     

Assessment of bone turnover in postmenopausal osteoporosis by measurement of serum bone Gla-protein

Controversy persists regarding the abnormality of bone turnover responsible for bone loss in women with postmenopausal osteoporosis. To evaluate this, we measured serum bone Gla-protein (BGP), a specific marker for bone turnover, in 62 untreated patients with postmenopausal osteoporosis. Results were compared with those in 142 normal women and were expressed as standard deviations from the age-adjusted predicted mean (Z score). Serum BGP was increased (+0.48 S.D., p = 0.002) in the osteoporotic patients; 9.7% of patients were greater than 2 S.D. above but none were greater than 2 S.D. below the normal mean. Moreover, when data from normal postmenopausal women (ages 51 to 75 years) and the osteoporotic patients were merged, significant negative correlation existed (r = -0.36, p less than 0.001) between serum BGP and bone density of the lumbar spine assessed by dual photon absorptiometry. Serum alkaline phosphatase, a less specific marker for bone formation, was also increased (+0.96 S.D., p less than 0.001) in the osteoporotic patients. The data suggest that overall bone turnover is increased in patients with postmenopausal osteoporosis and do not support the concept that an absolute decrease in bone formation is the major cause of the bone loss.     

Influence of type 2 diabetes mellitus on bone mineral density response to bisphosphonates in late postmenopausal osteoporosis

Bisphosphonates are effective agents for postmenopausal osteoporosis, but their efficacy in patients with type 2 diabetes mellitus (DM) is not known. The investigators evaluated bone mineral density (BMD) response to alendronate in women with concurrent late postmenopausal osteoporosis and type 2 DM. In a retrospective, matched case-control study, 26 late postmenopausal osteoporotic women with type 2 DM (age, 67.6±7.3 y; type 2 DM duration, 12.8±6.8 y; duration of menopause, 10.9±7.4 y; time on alendronate: 4.8±2.3 y; body mass index [BMI], 31.4±6.3 kg/m²) were matched with 26 controls according to age, BMI, duration of menopause, and alendronate treatment received. All subjects were given alendronate 10 mg/d or 70 mg/wk, along with sufficient vitamin D (≥400 IU) and calcium (≥1 g/d) intake, for 4.8 y. Response to alendronate therapy was determined by assessment of mean percent change in BMD of total hip, femoral neck, forearm, and lateral spine. The presence of type 2 DM resulted in no difference in spinal BMD response to alendronate therapy. In contrast, BMD in the total hip (mean percent change in BMD, −5.6% vs +1.4%;P=.096), femoral neck (−8.1 % vs +1.1 %;P=.015), and forearm (−3.6% vs +12.7%;P=.013) fell progressively from baseline in subjects with type 2 DM who were taking alendronate for 4.8 y, compared with controls. Elderly, postmenopausal, osteoporotic obese women with type 2 DM are resistant to long-term bisphosphonates, especially in regions of the hip, femoral neck, and forearm compared with the spine. The efficacy of bone resorption inhibitors in patients with type 2 DM, especially in comparison with anabolic agents, should be considered in additional studies.     

Association between serum soluble membrane type matrix metalloproteinase-1 (MT1-MMP) levels and bone mineral density, and biochemical markers in postmenopausal women

BACKGROUND: Recently, membrane type matrix metalloproteinase-1 (MT1-MMP) was found to participate in bone metabolism. We investigated the relationship between serum MT1-MMP and bone mineral density (BMD) as well as bone metabolic markers in 206 Chinese postmenopausal women aged 43-80 years. METHODS: Western analysis and ELISA were performed to detect serum soluble MT1-MMP levels. BMD was measured by dual energy X-ray absorptiometry (DXA). Serum alkaline phosphatase (BAP) and N-telopeptides of type I collagen (NTX) were assayed using ELISA. RESULTS: We found that soluble MT1-MMP abundantly existed in human serum as protein lack of transmembrane domain. Serum MT1-MMP levels were detectable in all participants and the range of value was 221.2-863.0 ng/ml (435.6+/-98.2 ng/ml). We found a significant negative weaker correlation between MT1-MMP and BMD at lumbar spine, total hip (Thip), and femoral neck (FN) (all P<0.05). After adjustment for age and BMI, the correlation with BMD at FN and Thip disappeared (all P>0.05). Multiple linear stepwise regression analysis showed that MT1-MMP was not a determinant factor for BMD. The significant positive correlations between MT1-MMP and BAP, NTX were found, and remained significant after adjustment for age and BMI (all P<0.05). Moreover, serum MT1-MMP, BAP, and NTX decreased in response to alendronate therapy. CONCLUSION: Circulating MT1-MMP and bone turnover markers are correlated, and serum MT1-MMP levels may rise with increase in bone turnover.     

Teriparatide (rhPTH 1-34) for the treatment of osteoporosis

Osteoporosis is a skeletal disorder characterised by compromised bone strength predisposing a person to an increased risk of fracture. Osteoporosis develops through an imbalance between bone resorption by osteoclasts and bone formation by osteoblasts resulting in increased bone loss. Numerous agents used for the prevention and treatment of osteoporosis slow bone loss by decreasing both bone resorption and formation. These include bisphosphonates, hormone replacement therapy, selective oestrogen receptor modulators and calcitonins. All reduce vertebral fracture risk and some reduce non-vertebral fracture risk, but none routinely increases bone mass and strength or restores lost bone architecture. In many respects, antiresorptive therapies halt the progression of osteoporosis. However, for patients who have osteoporosis, particularly those who have sustained their first fracture and are at high risk for subsequent fractures, there is a need to develop agents that stimulate bone formation and, thus, reverse osteoporosis. Teriparatide is the recombinant human 1-34 amino acid sequence of parathyroid hormone recently approved in the US for the treatment of men and postmenopausal women at high risk for osteoporotic fracture and in Europe for the treatment of postmenopausal women with osteoporosis. When given by once-daily injection, teriparatide increases bone mass by stimulating formation of new bone, resulting in the restoration of bone architecture.     

Comparing therapies for postmenopausal osteoporosis prevention and treatment

OBJECTIVE: To review the literature concerning the efficacy of calcium, hormone replacement therapy (HRT), bisphosphonates, selective estrogen receptor modulators, and calcitonin in the prevention and treatment of postmenopausal osteoporosis. DATA SOURCES: Articles were identified through searches of the MEDLINE (1966-July 2002), EMBASE (1980-July 2002), and International Pharmaceutical Abstracts (1970-July 2002) databases using the key words osteoporosis, postmenopausal, fracture, calcium, vitamin D, hormone replacement therapy, bisphosphonates, alendronate, risedronate, raloxifene, and calcitonin. Additional references were located through review of the bibliographies of the articles cited. Searches were not limited by time restriction, language, or human subject. STUDY SELECTION AND DATA EXTRACTION: Experimental and observational studies of the use of calcium and antiresorptive therapies for the prevention and treatment of postmenopausal osteoporosis were selected. Articles evaluating bone mineral density (BMD) or fracture efficacy were included in this review. DATA SYNTHESIS: HRT, bisphosphonates, raloxifene, and calcitonin have demonstrated stabilization of and improvement in BMD. Randomized clinical trials have shown fracture risk reduction with bisphosphonates, raloxifene, HRT, calcium, and calcitonin. The largest risk reductions have been reported with use of bisphosphonates in several trials. CONCLUSIONS: Several therapeutic options with well-documented improvements in BMD and reductions in fracture risk are available to women for the prevention and treatment of postmenopausal osteoporosis.