Effects of morning vs. evening teriparatide injection on bone mineral density and bone turnover markers in postmenopausal osteoporosis

Summary

A 12-month morning teriparatide (TPTD) administration resulted in a larger increase in the lumbar spine bone mineral density (BMD) than the evening application. The results indicate that the response of bone cells to teriparatide treatment depends on dosing time.

Introduction

The aim of this study was to assess the long-term effects of the morning vs. the evening teriparatide administration on BMD and bone turnover markers (BTMs) in postmenopausal osteoporosis.

Methods

Fifty women with established postmenopausal osteoporosis were randomized to 12-month treatment with 20?μg of TPTD, administered daily in the morning or in the evening. The BMD and serum concentrations of C-terminal telopeptide of type I collagen, N-terminal propeptide of type I procollagen (PINP), and tartrate-resistant acid phosphatase isoform 5b (TRAP 5b) were measured at baseline, after 6 and 12?months. General linear model-repeated measurements were used to analyze the data.

Results

After 12?months, the lumbar spine BMD grew markedly (p?<?0.001) with a significantly greater increase in the morning arm compared to the evening arm (9.1% vs. 4.8%, respectively, p?<?0.05). The BMD at the distal radius significantly decreased (p?<?0.001), with no differences between the arms. The BMD at proximal femur did not change significantly. After 6 months, the BTMs were significantly increased compared with baseline (p?<?0.001). The increases in the evening arm vs. the morning arm, however, were more pronounced in PINP (+358% vs. +215%, respectively) and in TRAP 5b (+70% vs. +37%, respectively) (both p?<?0.05).

Conclusion

12-month morning administration of TPTD resulted in a larger increase in the lumbar spine BMD than the evening application. The timing of TPTD administration may be important for its efficacy.     

Effect of teriparatide on bone mineral density and biochemical markers in Japanese women with postmenopausal osteoporosis: a 6-month dose-response study

The dose-response efficacy and safety with three doses of teriparatide and placebo was assessed, using oncedaily subcutaneous injections for 24 weeks, in Japanese postmenopausal women with osteoporosis at high risk of fracture for reasons of preexisting fracture(s), advanced age, and/or low bone mineral density (BMD). In this multicenter, randomized, placebo-controlled study, 159 subjects were randomized and 154 subjects were included for analysis. Teriparatide (10-μg, 20-μg, and 40-μg doses) showed a statistically significant increase with increasing treatment dose as assessed by the percent change of lumbar spine BMD from baseline to endpoint using Williams’ test when compared with placebo (P < 0.001). The mean (±SD) percent change in lumbar spine, femoral neck, and total hip BMD with the 20-μg dose from baseline to endpoint was 6.40% ± 4.76%, 1.83% ± 7.13%, and 1.91% ± 3.60%, respectively. Rapid and sustained increases in bone formation markers [type I procollagen N-terminal propeptide (PINP), type I procollagen C-terminal propeptide (PICP), and bone-specific alkaline phosphatase (BAP)], followed by late increases in a bone resorption marker [type I collagen cross-linked C-telopeptide (CTX)], were observed for the teriparatide treatment groups (20-μg, 40-μg), suggesting a persistent, positive, balanced anabolic effect of teriparatide. Optimal adherence was achieved by this daily self-injection treatment. Regarding safety, most of the adverse events were mild to moderate in severity. No study drug-or study procedure-related serious adverse events were reported during the treatment period. These results observed in Japanese patients may support the observation that teriparatide stimulates bone formation in patients with osteoporosis at a high risk of fracture.     

Effect of raloxifene on bone mineral density and biochemical markers of bone turnover in Japanese postmenopausal women with osteoporosis: results from a randomized placebo-controlled trial

The safety and efficacy of raloxifene, a selective estrogen receptor modulator (SERM), has been studied extensively in large, global clinical trials. However, the effect of raloxifene on bone mineral density (BMD) and on biochemical markers of bone turnover in Japanese postmenopausal women with osteoporosis has not been rigorously evaluated. This study was designed to assess the safety and efficacy of raloxifene in Japanese postmenopausal women with osteoporosis following 1 year of therapy. Participants in this multicenter trial were randomly assigned to receive placebo, raloxifene 60 mg/day (RLX60), or raloxifene 120 mg/day (RLX120). Lumbar spine BMD was measured at baseline, 24, 40, and 52 weeks, and biochemical markers of bone turnover were assessed at baseline, 12, 24, and 52 weeks. Serum lipids were assessed at baseline, 12, 24, 40, and 52 weeks, and breast examinations and transvaginal ultrasound of the endometrium were performed at enrollment and 52 weeks. Compared with baseline, women taking RLX60 had significant increases in lumbar spine (L2-L4) BMD at 24 weeks (+3.3%, p<0.001) through 52 weeks (+3.5%, p<0.001) of therapy, and similar results were observed in the RLX120 group. Markers of bone turnover and total cholesterol and LDL-C were significantly reduced, and no significant treatment-group difference was observed for patients reporting at least one adverse event following randomization. In addition, there were no reported venous thromboembolic events (VTE) in any treatment group. The results of this study demonstrate that raloxifene is associated with early increases in lumbar spine BMD, has favorable effects on biochemical markers of bone turnover and lipid profile, and is well tolerated in postmenopausal Japanese women.The named authors wrote this article on behalf of the Japan Clinical Trial Research Group.     

骨转换指标和骨密度监测治疗骨质疏松及其与骨折的关系

骨转换指标和骨密度(BMD)对监测治疗骨质疏松及预测骨折的风险具有重要的临床意义。本文扼要综述了骨转换指标和BMD在治疗骨质疏松中的监测频率和最小显著变化(LSC),以及两者与骨折风险的关系,它对于指导临床监测治疗骨质疏松具有重要价值。     

Three-month changes in bone turnover markers and bone mineral density response to raloxifene in Japanese postmenopausal women with osteoporosis

It has been well established that raloxifene (RLX) improves bone turnover, increases bone mineral density (BMD), and reduces the risk of fractures. However, it remains obscure how to monitor the therapeutic effects of RLX, while numerous clinical trials for other antiresorptive agents have suggested that greater short-term reductions of bone turnover markers (BTMs) can predict greater increases in BMD and greater reduction in risk of future fractures. The purpose of this study was to investigate associations between short-term reductions of BTMs and subsequent changes of BMD after 1-year treatment with RLX. Seventy-three Japanese postmenopausal women with untreated osteoporosis were selected for this study. Reductions in BTMs [bone-specific alkaline phosphatase (BAP) or serum N-terminal telopeptide of type I collagen (NTx)] after 3 months did not correlate with increases of BMD at any major sites (lumbar spine, femoral neck, total neck, and distal 1/3 radius) either after 6 months or after 12 months. Our results suggest that short-term reductions or 3-month reductions of BTMs with RLX treatment cannot be used to predict increases of BMD. However, this does not directly mean that short-term reductions or 3-month reductions of BTMs with RLX treatment cannot be used to predict risk reduction of future fractures or the ultimate effects of RLX on bone. Further studies with fracture endpoints in longer observation and larger number of patients are warranted to establish how to monitor the therapeutic effects of RLX or early identification of responders or nonresponders to RLX treatment.     

中老年女性骨转换指标与骨密度和骨质疏松风险的关系

目的了解中老年女性骨转换指标变化对骨密度(BMD)和骨质疏松患病风险的影响。方法 632名健康中老年女性(年龄40~89岁),测定空腹血清骨特异性碱性磷酸酶(BAP)、骨钙素(OC)、骨I型胶原C-末端肽(s CTX)和N-末端肽(s NTX),以及腰椎和近端股骨骨密度(BMD),并分析这些骨转换指标与BMD和骨质疏松患病风险的关系。结果本研究检测的各种骨转换指标与腰椎、股骨颈和髋部BMD呈显著负相关(r=-0.238~-0.528,P均=0.000)。调整年龄、身高、体重和体重指数后,血清BAP、OC和s CTX与腰椎和股骨颈BMD的偏相关系数仍然有显著性意义。多元线性回归分析显示,这些骨转换指标对腰椎BMD是一个有意义的负性决定因素,大约可以解释腰椎BMD 7.6%~27.9%的变异性。各种骨转换指标水平最高的四分位组(Q4)与最低的组(Q1)比较,腰椎、股骨颈和髋部的骨质疏松患病风险,分别显著增加4.6~15倍(OR=4.6~15,95%CI:2.6~30),3.2~13倍(OR=3.2~13,95%CI:1.5~36)和3.0~13倍(OR=3.0~13,95%CI:1.3~44)。结论本研究揭示了中老年女性骨转换指标与BMD和骨质疏松患病风险的关系,提示骨转换指标水平变化是中老年女性BMD的重要决定因素,骨形成指标和/或骨吸收指标水平增加者骨质疏松患病率和患病风险大大增加。     

Positive effect of alendronate on bone mineral density and markers of bone turnover in patients with rheumatoid arthritis on chronic treatment with low-dose prednisone: a randomized, double-blind, placebo-controlled trial

Introduction Alendronate has been described to have a bone-sparing effect in patients treated with moderate and high dosages of prednisone for heterogeneous diseases, however no data are available on groups of patients with the same underlying diseases who receive chronic low-dose prednisone treatment. The objective of the investigation reported here was, therefore, to study the effect of alendronate on bone mineral density (BMD) of the lumbar spine and hips in patients with rheumatoid arthritis (RA) who are on chronic low-dose prednisone treatment. Methods A total of 163 patients with RA, according to the ACR-criteria, were enrolled in a double-blind, placebo-controlled trial. The patients were treated with low-dose prednisone (≤10 mg/day) for at least 3 months. The patients were randomized to receive daily doses of alendronate or placebo: men and premenopausal women received 5 mg alendronate (or placebo) daily; postmenopausal women received 10 mg alendronate (or placebo) daily. All patients received daily calcium (500 mg, or 1000 mg, depending on baseline dietary calcium intake) and vitamin D₃ (400 IU) supplementation. BMD of the lumbar spine (L1–L4) and the (total) hip was measured at baseline and after 6 and 12 months. The primary endpoint was change in BMD of the lumbar spine after 12 months (ITT). At baseline and after 3 and 12 months, serum bone-specific alkaline phosphatase (BAP) and urinary excretion of N-telopeptide (NTX) were measured. Radiographs of the thoracic and lumbar spine were made at baseline and after 12 months and subsequently scored for vertebral deformities. Results The groups were comparable at baseline in age, gender, daily dosage of prednisone, BMD at the spine and the hip and markers of bone turnover, while the number of patients with prevalent vertebral deformities was slightly higher in the alendronate-treated patients (54% versus 39%, not significant). After 12 months, BMD at the lumbar spine had increased by 3.7% in the alendronate-treated patients and decreased by –1.0% in the placebo-treated patients (p<0.0001); at the hip, the changes were +1.0% and –0.1%, respectively (not significant). After 3 months, serum BAP had decreased by 16.9% in the alendronate group versus 3.3% in the placebo group (p=0.0005), while urinary NTX had decreased by 46.4% in the alendronate group versus 12.1% in the placebo group (p<0.0001). After 12 months, no statistically significant difference was found between the groups with respect to number of patients with incident vertebral or non-vertebral fractures. Adverse effects were relatively common in these patients with severe RA: adverse effects were observed in 68% of the alendronate-treated patients and in 73% of the placebo patients (not significant), while serious adverse events were observed in 13% and 17%, respectively (not significant). Conclusion We observed a favourable effect of alendronate on the BMD of the lumbar spine and on the markers of bone turnover in patients with RA treated with low-dose prednisone. These data support the conclusion that the prescribing of alendronate is not only beneficial in patients treated with high-dose prednisone but also in RA patients chronically treated with low-dose prednisone. This trial was financially supported by a grant from MSD, The Netherlands     

The efficacy and tolerability of risedronate on bone mineral density and bone turnover markers in osteoporotic Chinese women: a randomized placebo-controlled study

Osteoporosis has become an important health problem in postmenopausal Asian populations as the prevalence of hip and vertebral fractures in some Asian countries has risen to approach that of Caucasian populations. Risedronate, a pyridinyl-bisphosphonate agent, is a potent inhibitor of bone resorption. Risedronate increases bone mineral density (BMD), reduces markers of bone turnover, and reduces the risk of fractures in Caucasian postmenopausal women. To determine the efficacy and tolerability of risedronate in Chinese, a multicenter, randomized, double blind, placebo controlled study was performed in Hong Kong. Sixty-five (65) postmenopausal osteoporotic Southern Chinese women, aged 67+/-6 years, were randomly assigned to receive either risedronate 5 mg daily (n=31) or placebo (n=34) for 12 months. All women received calcium carbonate 500 mg daily and vitamin D 400 IU daily. Mean baseline BMD T-score at the spine and total hip was -3.4 and -2.6, respectively. A significant increase in spine BMD was already evident at month 3 of risedronate treatment (P<0.001). Risedronate significantly increased BMD and reduced bone turnover markers as compared with placebo. The risedronate group had significant increase in BMD at 12 months at both the spine and hip when compared with the placebo group (L1-4 6.6% vs. 0.4%, P<0.001; total hip 2.7% vs. 0.3, P<0.0001; femoral neck 1.8% vs. 1.1%, P<0.02; trochanter 4% vs. 1.1%, P<0.0001, respectively). Significant changes in urine N-telopeptide (NTx) and serum osteocalcin were evident as early as 1 and 3 months, respectively, with risedronate treatment. No significant changes were seen in both BMD and bone markers in the placebo group. Risedronate was well tolerated without major adverse effects. We conclude that risedronate is an effective and well-tolerated agent for the treatment of postmenopausal osteoporosis in Asian population.     

Improving clinical decisions for women at risk of osteoporosis: dual-femur bone mineral density testing

CONTEXT: In bone mineral density (BMD) testing, unilateral hip analysis and lumbar spine measurement have been the clinical standard for diagnosis and treatment classification for postmenopausal women at risk of osteoporosis. OBJECTIVE: To determine if analysis of the bilateral hip in BMD testing has a clinical effect on diagnosis of osteoporosis and treatment classification of patients. METHODS: Dual-femur BMD test results from 313 postmenopausal women (mean age 61.2 years, range 32-90 years) were evaluated using standard BMD reference values for diagnosis and treatment classification. The author compared T scores for right and left femurs at three sites: femoral neck, trochanter, and total femur. Results: When the bilateral hip was considered in BMD testing and compared with unilateral hip results, a clinical change in diagnosis from normal to osteopenia occurred in 5.7% of subjects. In addition, a clinical change in diagnosis from osteopenia to osteoporosis occurred in 3.3% of subjects. A clinical change in treatment classification from "no treatment required" to "treatment required if one or more risk factors are present" occurred in 3% of subjects. A change in treatment classification from "treatment required if one or more risk factors are present" to "treatment required independent of risk factors" happened in 2.4% of subjects. CONCLUSION: When compared with BMD testing of the unilateral hip, inclusion of the bilateral hip in BMD testing resulted in a change in classification to a more severe diagnosis in a total of 9% of subjects, and to a more aggressive treatment category in a total of 5.4% of subjects. Dual-femur BMD testing may improve diagnosis and treatment classification for postmenopausal women at risk of osteoporosis.     

Bone turnover markers and bone mineral density response with risedronate therapy: Relationship with fracture risk and patient adherence

Surrogate markers of fracture risk—bone turnover markers (BTMs) and bone mineral density (BMD)—can be used to monitor treatment response. We assessed whether changes in these markers greater than the least significant change (LSC) were associated with fracture risk reduction and greater adherence. This secondary analysis of the Improving Measurements of Persistence on ACtonel Treatment (IMPACT) study—a multinational prospective, open‐label, cluster‐randomized study of postmenopausal women on oral risedronate 5 mg/d for 52 weeks—assessed adherence by electronic monitors. Urinary N‐terminal cross‐linked telopeptide of type 1 collagen (uNTX) and serum C‐terminal cross‐linked telopeptide of type 1 collagen (sCTX) levels were assessed at baseline and weeks 10 and 22, and BMD at baseline and week 52. Fractures were recorded as adverse events. In 2302 women, responses beyond LSC in BTMs (uNTX and sCTX) and BMD (spine only) were associated with a reduced risk of nonvertebral fractures (NVFs) and all fractures. NVF incidence was about 50% lower in patients with 30% or more of uNTX reduction at week 22 (1.6%) than in those with less than 30% reduction (3.2%, p = .015). NVFs also were reduced in patients with more than 3% spine BMD increase at 52 weeks than those with 3% or less. Responses greater than LSC in BTMs and BMD were associated with greater adherence, but there was no association between adherence and fracture outcomes at 52 weeks. Changes greater than the LSC in BTMs and BMD reflect better treatment adherence, were associated with fracture risk reduction, and identify differences in individual responsiveness to risedronate. © 2011 American Society for Bone and Mineral Research.     

Predictors of bone mineral density testing in patients at high risk of osteoporosis: secondary analyses from the OSTEOPHARM randomized trial

In a randomized trial, we demonstrated that a community pharmacist osteoporosis screening intervention doubled the rates of bone mineral density (BMD) testing in high-risk patients. The purpose of this secondary analysis was to evaluate the potentially modifiable factors associated with BMD testing. From 2005 to 2007, 15 pharmacies randomized 262 patients to intervention (education, pamphlets, point-of-care quantitative heel ultrasound [QUS]) or usual care. The main outcome was BMD testing within 4mo. Multivariate regression was used to determine independent correlates of BMD testing. The median age of the cohort was 62yr, 65% were women, and 49% (n=129) were randomized to intervention. Compared with patients who were not tested, those with BMD were more likely to be women (p=0.007) and have excellent or very good health (p<0.001). Postrandomization correlates of BMD test were intervention (p=0.017), greater osteoporosis knowledge (p=0.004), and osteoporosis-specific physician visits (p<0.001). In adjusted analyses, only female sex (adjusted odds ratio [aOR]: 3.0; 95% confidence interval [CI]: 1.3-7.4) and osteoporosis-specific visits (aOR: 3.2; 95% CI: 1.4-7.8) were independently associated with BMD testing. In analyses restricted to intervention patients, abnormal QUS (aOR: 3.7, 95% CI: 1.4-9.1) was the only independent predictor of BMD test. Future interventions should incorporate the finding that osteoporosis-specific visits and abnormal QUS results were strongly associated with getting a BMD testing and should give greater attention to men.     

The effect of 1-year transdermal estrogen replacement therapy on bone mineral density and biochemical markers of bone turnover in osteopenic postmenopausal systemic lupus erythematosus patients: a randomized,double-blind,placebo-controlled trial

We studied the effect of 1-year transdermal estrogen replacement therapy (ERT) on bone mineral density (BMD) and biochemical markers of bone turnover in osteopenic postmenopausal systemic lupus erythematosus (SLE) patients in a randomized, double-blind, placebo-controlled trial. SLE patients were randomly allocated to treatment (estradiol; 50 g transdermal 17-estradiol; n=15) or placebo (n=17) group. Both groups received 5 mg continuous oral medroxyprogesterone acetate, 500 mg calcium and 400 IU vitamin D₃. L₁–L₄ spine (LS), left femur and total hip BMD were measured at baseline and at 6 and 12 months. Serum osteocalcin (OC) and degradation products of C-terminal telopeptides of type-I collagen (CTx) levels were measured at baseline and 3, 6, 9, and 12 months. There was a significant difference in the percentage change of LS BMD at 6 months between the two groups (103.24±3.74% (estradiol group) vs 98.99±3.11% (placebo group); P<0.005). There was a significant decrease within the estradiol group in the CTx levels between baseline and all subsequent visits (P<0.05). There was no significant difference in SLE disease activity index, Systemic Lupus International Collaborating Clinics/American College of Rheumatology (ACR) damage index and corticosteroid dose during the study period. Transdermal estradiol may prevent bone loss in postmenopausal SLE women at the lumbar spine and femur, with no increase in disease activity among postmenopausal SLE women receiving transdermal ERT. The high dropout rate (8/15) leads us to the conclusion that efficacy of HRT in a high-risk group such as SLE women can be attained only in a small number of patients, provided all inclusion/exclusion criteria are strictly adhered to.     

Effects of bazedoxifene on bone mineral density,bone turnover,and safety in postmenopausal japanese women with osteoporosis

This randomized, double‐blind, placebo‐controlled, dose‐response late phase 2 study evaluated the efficacy and safety of bazedoxifene in postmenopausal Japanese women 85 years of age or younger with osteoporosis. Eligible subjects received daily treatment with oral doses of bazedoxifene 20 or 40 mg or placebo for 2 years. Efficacy assessments included bone mineral density (BMD) at the lumbar spine and other skeletal sites, bone turnover marker levels, lipid parameters, and incidence of new fractures. Of 429 randomized subjects, 387 were evaluable for efficacy, and 423 were included in the safety analyses (mean age, 64 years). At 2 years, the mean percent changes from baseline in lumbar spine BMD were significantly greater with bazedoxifene 20 and 40 mg (2.43% and 2.74%, respectively) than with placebo (?0.65%, p < .001 for both). Both bazedoxifene doses significantly improved BMD at the total hip, femoral neck, and greater trochanter compared with placebo (p < .001 for all). Decreases in bone turnover markers were observed with bazedoxifene 20 and 40 mg as early as 12 weeks (p < .05 for all) and were sustained throughout the study. Total and low‐density lipoprotein cholesterol levels were significantly decreased from baseline with both bazedoxifene doses compared with placebo (p < .05 for all). Incidences of new vertebral and nonvertebral fractures were similar among the bazedoxifene and placebo groups. Overall, the incidence of adverse events with bazedoxifene 20 and 40 mg was similar to that with placebo. Bazedoxifene significantly improved BMD, reduced bone turnover, and was well tolerated in postmenopausal Japanese women with osteoporosis. © 2011 American Society for Bone and Mineral Research.     

The effect of weight training on bone mineral density and bone turnover in postmenopausal breast cancer survivors with bone loss: a 24-month randomized controlled trial

Summary  

This study examined whether 24 months of weight training exercises enhanced the effectiveness of risedronate, calcium, and vitamin D in maintaining or improving bone mineral density (BMD) in 223 postmenopausal breast cancer survivors. Subjects who were ≥50% adherent to exercise had no improvement in BMD but were less likely to lose BMD.     

Effectiveness of resistance training or jumping-exercise to increase bone mineral density in men with low bone mass: A 12-month randomized,clinical trial

PurposeTo examine the effects of 12 mo of resistance training (RT, 2 ×/wk, N = 19) or jump training (JUMP, 3 ×/wk, N = 19) on bone mineral density (BMD) and bone turnover markers (BTM) in physically active (≥ 4 h/wk) men (mean age: 44 ± 2 y; median: 44 y) with osteopenia of the hip or spine.MethodsParticipants rated pain and fatigue following each RT or JUMP session. All participants received supplemental calcium (1200 mg/d) and vitamin D (10 μg/d). BMD was measured at 0, 6, and 12 mo using DXA scans of the whole body (WB), total hip (TH) and lumbar spine (LS). BTM and 25 OHD were measured by ELISA. The effects of RT or JUMP on BMD and BTM were evaluated using 3x2 repeated measures ANOVA (time, group). This study was conducted in accordance with the Declaration of Helsinki and was approved by the University of Missouri IRB.ResultsAt baseline, 36 of 38 participants were vitamin D sufficient (25OHD > 50 nmol/L); at 12 mo, all participants were 25OHD sufficient. 25OHD did not differ between groups. WB and LS BMD significantly increased after 6 months of RT or JUMP and this increase was maintained at 12 mo; TH BMD increased only in RT. Osteocalcin increased significantly after 12 mo of RT or JUMP; CTx decreased significantly after 6 mo and returned to baseline concentrations at 12 mo in both RT and JUMP. Pain and fatigue ratings after RT or JUMP sessions were very low at 0, 6, and 12 mo.ConclusionRT or JUMP, which appeared safe and feasible, increased BMD of the whole body and lumbar spine, while RT also increased hip BMD, in moderately active, osteopenic men.     

Relative contributions of bone density, bone turnover, and clinical risk factors to long-term fracture prediction.

Long-term fracture prediction using bone mineral density remains controversial, as does the additional contribution from assessing bone turnover or clinical risk factors. We measured bone mineral density at various sites, along with biochemical markers of bone turnover, sex steroid levels, and over 100 clinical variables, at baseline on an age-stratified sample of 304 Rochester, MN women in 1980. The 225 postmenopausal women were subsequently followed for 3146 person-years (median, 16.2 years per subject), wherein they experienced 302 new fractures: 81% resulted from minimal or moderate trauma and 60% of these involved the proximal femur, thoracic or lumbar vertebrae, or distal forearm. Accounting for multiple fractures per subject, these osteoporotic fractures together were best predicted by baseline femoral neck bone mineral density (age-adjusted hazard ratio [HR] per SD decrease, 1.37; 95% CI, 1.10-1.70); 19 moderate trauma forearm fractures were best predicted by distal radius bone mineral content, whereas 28 hip fractures and 100 vertebral fractures were best predicted by femoral neck bone mineral density. Femoral neck bone mineral density performed comparably in predicting osteoporotic fracture risk within the first decade of follow-up (HR, 1.38; 95% CI, 1.10-1.74) as well as more than 10 years after baseline (HR, 1.39; 95% CI, 1.05-1.84). The older biochemical markers were not associated with fractures, but serum "free" estradiol index was independently predictive of short- and long-term fracture risk. Consistent clinical risk factors were not identified, but statistical power was limited. Identifying patients at increased long-term risk of fracture is challenging, but it is reassuring that femoral neck bone mineral density can predict osteoporotic fractures up to 20 years later.     

骨矿含量与骨折相关性及其骨折危险阈值研究

本文测量了８２例骨折病人和１７１例正常人的桡骨骨矿含量，结果表明：骨折病人的骨矿含量显著低于正常人；用ｌｏｇｉｓｔｉｃ回归来分析骨矿含量与骨折危险性之间的关系，结果表明骨矿含量与骨折危险性呈负相关，骨矿含量每下降０．１ｇ／ｃｍ２，骨折危险性增加１倍。以骨折危险性高于２０％为骨折高危人群，则男性骨折危险阈值为０．５８ｇ／ｃｍ２，女性骨折危险阈值为０．５４ｇ／ｃｍ２。     

北京深圳西藏三地人群骨折风险因子对骨密度的影响

目的 研究北京、深圳和西藏三地人群骨折风险因子对骨密度的影响.方法 使用桡骨、尺骨远段的Pdexa对男性1465例,女性931例进行测试,并填写相关骨折风险因子信息(年龄、性别、身高、体重和体重指数(kgm2),进行SPSS统计分析.结果 北京、深圳、西藏三地男女人群骨密度按照年龄分布基本一致,即地域差异对于中国入骨密度并不显著.按体重指数计算骨密度测量结果分布有一定差异,其中男性骨密度曲线分布一致性非常好,三地到达峰值骨量的男性人群之间,身高、体重和BMI基本没有显著差异(P＞0.05).女性则有一定差异.峰值骨量出现的年龄基本在34～35岁左右,三地之间没有明显差异(P＞0.05).结论 中国人群很少得到骨折风险因子方面的量化数据和研究,应进一步加强这方面的研究.     

Epimedium-derived phytoestrogen flavonoids exert beneficial effect on preventing bone loss in late postmenopausal women: a 24-month randomized, double-blind and placebo-controlled trial.

Epimedium brevicornum maxim, a nonleguminous medicinal plant, has been found to be rich in phytoestrogen flavonoids. Results from a 24-month randomized double-blind placebo-controlled clinical trial showed that Epimedium-derived phytoestrogen flavonoids were able to exert beneficial effects on preventing bone loss in late postmenopausal women, without resulting in a detectable hyperplasia effect on the endometrium. INTRODUCTION: We performed a 24-mo randomized double-blind placebo-controlled clinical trial for evaluating the effect of the Epimedium-derived phytoestrogen flavonoids (EPFs) on BMD, bone turnover biochemical markers, serum estradiol, and endometrial thickness in postmenopausal women. MATERIALS AND METHODS: One hundred healthy late postmenopausal women, with a natural menopausal history within 10 approximately 18 yr and with a BMD T-score at the lumbar spine between -2 and -2.5 SD, were randomized into EPF treatment group (n = 50; a daily dose of 60 mg Icariin, 15 mg Daidzein, and 3 mg Genistein) or placebo control group (n = 50). All participants received 300 mg element calcium daily. BMD, bone turnover biochemical markers, serum estradiol, and endometrial thickness were measured at baseline and 12 and 24 mo after intervention. RESULTS: Eighty-five participants completed the trial. The patterns of BMD changes were significantly different between the EPF treatment group and placebo control group by repeated-measures ANOVA (p = 0.045 for interaction between time and group at femoral neck; p = 0.006 for interaction between time and group at lumbar spine). BMD was found with a decreased tendency in the placebo control group at 12 (femoral neck: -1.4%, p = 0.104; lumbar spine: -1.7%, p = 0.019) and 24 mo (femoral neck: -1.8%, p = 0.048; lumbar spine: -2.4%, p = 0.002), whereas EPF treatment maintained BMD at 12 (femoral neck: 1.1%, p = 0.285; lumbar spine:1.0%, p = 0.158) and 24 mo (femoral neck: 1.6%, p = 0.148; lumbar spine: 1.3%, p = 0.091). The difference in lumbar spine between the two groups was significant at both 12 (p = 0.044) and 24 mo (p = 0.006), whereas the difference in the femoral neck was marginal at 12 mo (p = 0.061) and significant at 24 mo (p = 0.008). Levels of bone biochemical markers did not change in the placebo control group. In contrast, EPF intervention significantly decreased levels of deoxypyrdinoline at 12 (-43%, p = 0.000) and 24 mo (-39%, p = 0.000), except for osteocalcin at 12 (5.6%, p = 0.530) and 24 mo (10.7%, p = 0.267). A significant difference in deoxypyrdinoline between the two groups was found at both 12 (p = 0.000) and 24 mo (p = 0.001). Furthermore, neither serum estradiol nor endometrial thickness was found to be changed in either groups during the clinical trial. CONCLUSIONS: EPFs exert a beneficial effect on preventing bone loss in late postmenopausal women without resulting in a detectable hyperplasia effect on the endometrium.