Effect of L-000845704, an alphaVbeta3 integrin antagonist, on markers of bone turnover and bone mineral density in postmenopausal osteoporotic women

The alphaVbeta3 integrin (vitronectin receptor) plays a pivotal role in bone resorption. We hypothesized that L-000845704, an alphaVbeta3 integrin antagonist, would potently inhibit bone resorption, thereby increasing bone mass as assessed by bone mineral density (BMD) in women with postmenopausal osteoporosis. In a multicenter, randomized, double-blind, placebo-controlled, 12-month study, 227 women (average 63 yr) with low lumbar spine or femoral neck BMD were randomly assigned to receive 100 or 400 mg L-000845704 once daily (qd), 200 mg L-000845704 twice daily (bid), or placebo. L-000845704 increased lumbar spine BMD (2.1, 3.1, and 3.5% for the 100-mg-qd, 400-mg-qd, and 200-mg-bid treatment groups, respectively, vs. -0.1% for placebo; P < 0.01 all treatments vs. placebo). Only 200 mg L-000845704 bid significantly increased BMD at the hip (1.7 vs. 0.3% for placebo; P < 0.03) and femoral neck (2.4 vs. 0.7% for placebo; P < 0.05). No L-000845704 group increased total body BMD. All doses of L-000845704 resulted in a similar approximately 42% decrease from baseline of N-telopeptide cross-links (P < 0.001 vs. placebo). L-000845704 was generally well tolerated; adverse events resulting in discontinuation from the study were relatively infrequent. In conclusion, the antiresorptive effect of the alphaVbeta3 integrin antagonist L-000845704 translated into significant increases in lumbar spine BMD. Furthermore, 200 mg L-000845704 bid provided efficacy at the hip sites. These data suggest that the alphaVbeta3 integrin antagonist L-000845704 could be developed as an effective therapeutic agent for osteoporosis.     

Comparison of the effects of alendronate and risedronate on bone mineral density and bone turnover markers in postmenopausal osteoporosis

The aim of the study was to compare the effects of once-weekly alendronate sodium and daily risedronate sodium treatment on bone mineral density (BMD) and bone turnover markers in postmenopausal osteoporotic subjects. For this purpose, 50 patients were included in this study and randomly classified into two groups. Group I (n=25) received risedronate (5 mg/day) and group II (n=25) received alendronate Na (70 mg/week). The study duration was limited to 12 months. The efficacy of the treatment was evaluated by BMD measurements at spine and hip at 6th and 12th months of the treatment, as well as by the measurement of bone turnover markers such as serum osteocalcin (OC), bone-specific alkaline phosphatase (BASP), urine deoxypyridinoline (DPD) and calcium/creatine ratio in 24-h urine at 1st, 3rd, 6th and 12th months. The evaluation of the changes in BMD in all regions revealed a significant increase in BMD in both groups compared to baseline values except for spine (L2–L4) in alendronate group at 6th and 12th month and femoral neck in risedronate group at 6th month. However, the difference in percentage increase in BMD measurements was not statistically significant between the two groups at 6th and 12th months. In both groups, serum OC, BSAP and urine DPD were found to be significantly attenuated at 1st month of the treatment period, and continued to be lowered throughout the 3rd, 6th and 12th months (P<0.05). However, there was no statistically-significant difference between both groups of patients (P>0.05). In conclusion, our results suggest that both treatment protocols provide treatment options of similar efficiencyfor postmenopausal osteoporosis, and have almost-similar effects in enhancing the BMD and in slowing the bone turnover. Risedronate seems to havea more potent effect in the spinal region than that of alendronate, although this potency was not statistically significant.     

Short-term changes in bone turnover markers and bone mineral density response to parathyroid hormone in postmenopausal women with osteoporosis

CONTEXT: Treatment of osteoporotic women with PTH increases biochemical markers of bone turnover, increases axial bone mineral density (BMD), and reduces fracture risk. OBJECTIVE: Our objective was to determine the relationship between levels of baseline turnover before PTH therapy and short-term changes in turnover during PTH therapy and subsequent changes in areal and volumetric BMD. DESIGN AND SETTING: We conducted a randomized, placebo-controlled trial at four academic centers. PATIENTS: Patients included 238 postmenopausal women with low hip or spine BMD. INTERVENTION: Subjects were randomized to sc PTH (1-84), 100 mug/d (119 women), for 1 yr. MAIN OUTCOME MEASURE: Bone turnover markers were measured in fasting blood samples collected before therapy and after 1 and 3 months. Areal and volumetric BMD at the spine and hip were assessed by dual-energy x-ray absorptiometry and quantitative computed tomography (QCT) after 1 yr of therapy. RESULTS: Among women treated with PTH alone, the relationships between baseline turnover and 1-yr changes in dual-energy x-ray absorptiometry and QCT BMD were inconsistent. Greater 1- and 3-month increases in turnover, particularly the formation marker N-propeptide of type I collagen, were associated with greater increases in areal BMD. When volumetric hip and spine BMD were assessed by QCT, greater short-term increases in turnover were even more positively associated with 1-yr increases in BMD. Each sd increase in the 3-month change of N-propeptide of type I collagen was associated with an a 21% greater increase in QCT spine trabecular BMD. CONCLUSIONS: Greater short-term changes in turnover with PTH therapy are associated with greater 1-yr increases in spine and hip BMD among postmenopausal osteoporotic women.     

Effect of whole-body vibration exercise on lumbar bone mineral density, bone turnover, and chronic back pain in post-menopausal osteoporotic women treated with alendronate

BACKGROUND AND AIMS: Exercise may enhance the effect of alendronate on bone mineral density (BMD) and reduce chronic back pain in elderly women with osteoporosis. The aim of this study was to determine whether whole-body vibration exercise would enhance the effect of alendronate on lumbar BMD and bone turnover, and reduce chronic back pain in postmenopausal women with osteoporosis. METHODS: Fifty post-menopausal women with osteoporosis, 55-88 years of age, were randomly divided into two groups of 25 patients each: one taking alendronate (5 mg daily, ALN) and one taking alendronate plus exercise (ALN+EX). Exercise consisted of whole-body vibration using a Galileo machine (Novotec, Pforzheim, Germany), at an intensity of 20 Hz, frequency once a week, and duration of exercise 4 minutes. The study lasted 12 months. Lumbar BMD was measured by dual energy X-ray absorptiometry (Hologic QDR 1500W). Urinary cross-linked N-terminal telopeptides of type I collagen (NTX) and serum alkaline phosphatase (ALP) levels were measured by enzyme-linked immunosorbent assay and standard laboratory techniques, respectively. Chronic back pain was evaluated by face scale score at baseline and every 6 months. RESULTS: There were no significant differences in baseline characteristics, including age, body mass index, years since menopause, lumbar BMD, urinary NTX and serum ALP levels, or face scale score between the two groups. The increase in lumbar BMD and the reduction in urinary NTX and serum ALP levels were similar in the ALN and ALN+EX groups. However, the reduction in chronic back pain was greater in the ALN+EX group than in the ALN group. CONCLUSIONS: The results of this study suggest that whole-body vibration exercise using a Galileo machine appears to be useful in reducing chronic back pain, probably by relaxing the back muscles in post-menopausal osteoporotic women treated with alendronate.     

阿伦膦酸钠对绝经后骨质疏松症患者骨密度、细胞因子及骨代谢指标的影响

目的观察阿伦膦酸钠治疗绝经后骨质疏松症（PMO）患者,其骨密度（BMD）、IL-6、TNFα、胰岛素样生长因子-Ⅰ（IGF-Ⅰ）及骨代谢指标的变化。方法选择年龄55—60岁的PMO患者共185例,随机分为：阿伦膦酸钠组69例,替勃龙组66例,钙剂组50例和年龄相匹配的正常妇女20例作为对照组。各组均于用药前和用药后24、48周测定BMD（采用DEXA骨密度仪）、雌二醇（E2）、碱性磷酸酶（ALP,放免法）、骨钙素（BGP）、Ⅰ型胶原N末端肽（NTX）、IL-6、TNFα、IGF-Ⅰ（ELISA）。结果阿伦膦酸钠组和替勃龙组BMD较治疗前均有不同程度的提高,腰椎BMD增幅分别为2．53％、3．65％（P〈0．05）,非优势侧股骨近端增幅分别为7．17％、3．01％（P〈0．001）。替勃龙组E2水平明显上升（P〈0．01）,IL-6、TNFα、NTX下降（P〈0．01）;阿伦膦酸钠组E2水平无变化（P〉0．05）,ALP、BGP水平上升（P〈0．05）,NTX水平下降（P〈0．05）,IGF-Ⅰ、IL-6、TNFα水平无明显变化（P〉0．05）;钙剂组和对照组各部位BMD、E2、IGF-Ⅰ、ALP、BGP继续下降（P〈0．05）,而IL-6、TNFα、NTX升高（P〈0．05）。结论阿伦膦酸钠组治疗PMO疗效显著,与替勃龙相仿。单纯服用钙剂不能治疗PMO．且继续骨量丢失。     

Effects of alendronate on bone mineral density and bone metabolic markers in postmenopausal asthmatic women treated with inhaled corticosteroids

We have recently shown that long-term use of inhaled corticosteroids decreases bone mineral density (BMD) of the lumbar spine in postmenopausal asthmatic women. The present study aimed to evaluate the efficacy of alendronate in comparison with that of alfacalcidol (1-alpha-hydroxyvitamin D(3)) for the treatment of BMD reduction in postmenopausal asthmatic patients who had inhaled corticosteroid therapy without regular use of systemic corticosteroids. Twenty-eight postmenopausal asthmatic patients with BMD T score of -1.0 or less were randomized to receive alendronate (5 mg/d) or alfacalcidol (1 microg/d). Bone mineral density was determined at baseline and 12 months after the treatment, and biochemical markers of bone metabolism were measured at baseline and after 6 and 12 months of treatment. The mean (+/-SD) BMD values at the lumbar spine, the total hip, and the Ward's triangle significantly increased by 4.9 +/- 4.5% (P = .0005), 2.4 +/- 2.2% (P = .0005), and 3.6 +/- 5.2% (P = .02) at 12 months in the alendronate group, whereas the corresponding values did not significantly change in the alfacalcidol group. In the alendronate group, urinary N-telopeptide (NTx), serum osteocalcin, and serum alkaline phosphatase concentrations significantly decreased, and serum intact parathyroid (PTH) level significantly increased, from baseline at both 6 and 12 months. In the alfacalcidol group, urinary NTx showed modest but significant decrease, although the extent of the change was smaller than that in the alendronate group. We concluded that alendronate was effective to improve reduced BMD in postmenopausal asthmatic patients on inhaled corticosteroid therapy through the mechanism of inhibiting bone resorption.     

Effects of denosumab on bone mineral density and bone turnover in postmenopausal women

CONTEXT: Denosumab is an investigational fully human monoclonal antibody against receptor activator of nuclear factor-kappaB ligand, a mediator of osteoclastogenesis and osteoclast survival. OBJECTIVE: This study evaluated the ability of denosumab to increase bone mineral density (BMD) and decrease bone turnover markers (BTMs) in early and later postmenopausal women with low BMD. DESIGN AND SETTING: This 2-yr randomized, double-blind, placebo-controlled study was conducted in North America. PARTICIPANTS: Subjects included 332 postmenopausal women with lumbar spine BMD T-scores between -1.0 and -2.5. Interventions: SUBJECTS were randomly assigned to receive denosumab sc, 60 mg every 6 months, or placebo. Randomization was stratified by time since onset of menopause (< or =5 yr or > 5 yr). MAIN OUTCOME MEASURES: The primary end point was the percent change in lumbar spine BMD by dual-energy x-ray absorptiometry at 24 months. Additional end points were percent change in volumetric BMD of the distal radius by quantitative computed tomography; percent change in BMD by dual-energy x-ray absorptiometry for the total hip, one-third radius, and total body; hip structural analysis; percent change in BTMs; and safety. RESULTS: Denosumab significantly increased lumbar spine BMD, compared with placebo at 24 months (6.5 vs. -0.6%; P<0.0001) with similar results for both strata. Denosumab also produced significant increases in BMD at the total hip, one-third radius, and total body (P < 0.0001 vs. placebo); increased distal radius volumetric BMD (P < 0.01); improved hip structural analysis parameters; and significantly suppressed serum C-telopeptide, tartrate-resistant acid phosphatase-5b, and intact N-terminal propeptide of type 1 procollagen. The overall incidence of adverse events was similar between both study groups. CONCLUSIONS: Twice-yearly denosumab increased BMD and decreased BTMs in early and later postmenopausal women.     

Comparison of the effect of alendronate on lumbar bone mineral density and bone turnover in men and postmenopausal women with osteoporosis

The purpose of the present study was to compare the effect of alendronate treatment on lumbar bone mineral density (BMD) and bone turnover in men and postmenopausal women with osteoporosis. Sixty men with primary or secondary osteoporosis and 318 women with postmenopausal osteoporosis were treated with alendronate. The primary end points were lumbar BMD and urinary cross-linked N-terminal telopeptides of type I collagen (NTX) and serum alkaline phosphatase (ALP) levels. The secondary end point was the incidence of vertebral and nonvertebral fractures. Forty-seven (78.3%) men and 254 (79.9%) women who could complete the 12-month trial were analyzed. The mean ages of men and postmenopausal women were 69.1 and 70.4 years, respectively. Both men and postmenopausal women showed higher levels of urinary NTX as compared with normal range of premenopausal women. Alendronate treatment decreased urinary NTX level by 39.2% in men and 45.4% in postmenopausal women at 3 months and serum ALP level by 17.8 and 21.0%, respectively, at 12 months. Following reduction in bone turnover markers, lumbar BMD increased 5.8 and 7.6% in men and postmenopausal women, respectively, at 12 months. Reduction in urinary NTX level and increase in lumbar BMD were smaller in men than in postmenopausal women. The incidence of vertebral and nonvertebral fractures was 10.6 and 8.5%, respectively, in men and 8.3 and 7.5%, respectively, in postmenopausal women, with no significant difference in these incidences between them. These results suggested that alendronate treatment effectively increased lumbar BMD from baseline in men with primary or secondary osteoporosis following reduction in bone turnover, although its efficacy did not appear to be greater than in postmenopausal women with osteoporosis. We have no funding sources; we have no conflict of interest.     

The study of bone mineral density and bone turnover markers in postmenopausal women with active rheumatoid arthritis

The aim of this study was to investigate determinants of reduced bone mineral density (BMD) in postmenopausal women with active rheumatoid arthritis (RA) and to evaluate whether there are common markers of bone loss. We evaluated BMD of the femoral neck using dual-energy X-ray absorptiometry, and the measured biochemical markers included serum bone-specific alkaline phosphatase (BALP), serum osteocalcin (OC), and serum cross-linked N-telopeptidases of type I collagen (NTx). Serum BALP and NTx concentrations were measured by enzyme-linked immunsorbent assay, and OC was measured using an immunoradiometric assay. One hundred and forty postmenopausal Japanese women who had not received treatment with bisphosphonates or hormone replacement therapy were entered into the study. Thirty-four patients (41.0%) had femoral osteopenia (T score −1 to −2.5) and 23 patients (27.7%) had osteoporosis (T < −2.5). The body mass index of patients with normal BMD (T score ≥ −1.0) was significantly higher (P < 0.01) than in patients with osteoporosis at the femoral neck. The T score exhibited a significant negative correlation with age and the duration of RA disease. Serum BALP and serum OC, markers of osteoblast function, were negatively related to erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and matrix metalloproteinase-3 (MMP-3). However, serum NTx, a marker of resorptive function, exhibited a positive correlation with ESR, CRP, and MMP-3. From these results, this study suggests that generalized bone loss occurs in active RA and is characterized by evidence of bone resorption that is correlated with the high levels of inflammation. Body mass index, disease duration, and high serum NTx level were common risk factors in osteoporosis of postmenopausal women with RA.     

The study of bone mineral density and bone turnover markers in postmenopausal women with active rheumatoid arthritis

Abstract

The aim of this study was to investigate determinants of reduced bone mineral density (BMD) in postmenopausal women with active rheumatoid arthritis (RA) and to evaluate whether there are common markers of bone loss. We evaluated BMD of the femoral neck using dual-energy X-ray absorptiometry, and the measured biochemical markers included serum bone-specific alkaline phosphatase (BALP), serum osteocalcin (OC), and serum cross-linked N-telopeptidases of type I collagen (NTx). Serum BALP and NTx concentrations were measured by enzyme-linked immunsorbent assay, and OC was measured using an immunoradiometric assay. One hundred and forty postmenopausal Japanese women who had not received treatment with bisphosphonates or hormone replacement therapy were entered into the study. Thirty-four patients (41.0%) had femoral osteopenia (T score ?1 to ?2.5) and 23 patients (27.7%) had osteoporosis (T < ?2.5). The body mass index of patients with normal BMD (T score ≥ ?1.0) was significantly higher (P < 0.01) than in patients with osteoporosis at the femoral neck. The T score exhibited a significant negative correlation with age and the duration of RA disease. Serum BALP and serum OC, markers of osteoblast function, were negatively related to erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and matrix metalloproteinase-3 (MMP-3). However, serum NTx, a marker of resorptive function, exhibited a positive correlation with ESR, CRP, and MMP-3. From these results, this study suggests that generalized bone loss occurs in active RA and is characterized by evidence of bone resorption that is correlated with the high levels of inflammation. Body mass index, disease duration, and high serum NTx level were common risk factors in osteoporosis of postmenopausal women with RA.     

Longitudinal changes of bone mineral density and bone turnover in postmenopausal women on thyroxine

OBJECTIVE The skeletal risks of subclinical hyperthyroidism in postmenopausal women on replacement thyroxine remain controversial. The aims of this study were to determine (1) the relationship between bone turnover and TSH levels and (2) whether reduction of thyroxine (T4) dose in postmenopausal women who have suppressed TSH levels is beneficial to bone mineral density (BMD) and bone turnover. DESIGN A prospective study over 2 years of postmenopausal women treated with T4 with an age- and sex-matched healthy control group. PATIENTS AND MEASUREMENTS Sixty-four postmenopausal women, ages 47 to 74 (61 ±9, mean ± SD), on T4 for between 2 and 14 years. Patients were divided into three groups: group 1 (n =23) with normal serum TSH levels, group 2 (n = 18) with suppressed serum TSH levels and group 3 (n =23) with a history of thyroidectomy and suppressed TSH levels (patients with thyroid cancer). Thirty-six age-matched healthy postmenopausal women were recruited as a control group. Bone mineral density (BMD), measured by dual-energy X-ray absorptiometry and bone turnover, were evaluated at baseline and over 2 years in the four groups. Serum TSH levels were measured every 6 to 12 months. In group 2, the dose of T4 was reduced after the baseline measurement and serum TSH levels were remeasured 1 to 4 months later. Serum TSH levels returned to the reference range after the reduction of T4 dose in group 2. RESULTS The serum TSH level, after log transformation, was negatively correlated with serum levels of osteocalcin (BGP), bone alkaline phosphatase (BAP) and urinary cross-linked N-telopeptides pyridinoline of type I collagen (NTx) (linear correlation, r = ?0.41 P < 0.001, r = ?0.29 P =0.01 and r = ?0.26 P = 0.033), respectively. There was no significant difference in BMD and bone turnover between the four groups at either baseline or follow-up (ANOVA, P >0.05). The levels of serum BGP, BAP and urinary NTx decreased whereas lumbar spine and femoral neck BMD increased significantly in group 2 over 2 years (one sample t-test, P =0.0021, 0.034, 0.0017, 0.011 and >0.001, respectively). In group 2, the rates of change of lumbar spine and femoral BMD were increased significantly and the rates of change of serum BGP and urinary NTx were decreased significantly compared with other groups (Scheffe test, P <0.05). CONCLUSIONS In postmenopausal women on T4, bone turnover is related to the serum TSH level and a reduction of T4 dose in those with suppressed serum TSH levels can result in a decrease in bone turnover and an increase in bone mineral density.     

Oral alendronate increases bone mineral density in postmenopausal women with primary hyperparathyroidism

The effect of biphosphonate therapy on bone mineral density (BMD) in patients with primary hyperparathyroidism (PHP) is unknown. Forty postmenopausal women (mean age, 70 yr) with PHP were randomized to receive alendronate 10 mg/d or placebo for 48 wk, followed by treatment withdrawal for 24 wk. The mean (+/-SD) changes in BMD at femoral neck (+4.17 +/- 6.01% vs. -0.25 +/- 3.3%; P = 0.011) and lumbar spine (+3.79 +/- 4.04% vs. 0.19 +/- 2.80%; P = 0.016) were significantly higher with alendronate at 48 wk. Serum calcium was reduced with alendronate but not placebo (-0.09 vs. +0.01 mmol/liter; P = 0.018). Serum bone-specific alkaline phosphatase activity was lower with alendronate from 12 wk onward and increased 24 wk after treatment withdrawal (21.1 +/- 12.8 to 7.3 +/- 4.9 IU/liter at 48 wk, and 15.0 +/- 14.8 IU/liter 24 wk after withdrawal; P = 0.002 for trend). Osteocalcin concentration decreased at 48 wk and increased 24 wk after alendronate withdrawal (P = 0.019 for trend of change over time) but not with placebo. Urinary N-telopeptide/creatinine ratio decreased with alendronate at 48 wk and increased 24 wk after treatment withdrawal (P = 0.008 for trend). N-telopeptide/creatinine ratio did not change with placebo. Alendronate improves BMD and reduces bone turnover markers in postmenopausal women with PHP.     

Effect of zoledronic acid on markers of bone turnover and mineral density in osteoporotic patients with beta-thalassaemia

Osteoporosis has emerged as an important cause of morbidity in patients with thalassemia major. Studies regarding the efficacy of bisphosphonates in thalassemia-induced osteoporosis have yielded conflicting results. We performed this prospective study to evaluate the efficacy of zoledronic acid in osteoporotic patients with thalassemia major. Patients, 29, were given 1 mg zoledronic acid intravenously every 3 months for a total of four doses. Twenty age- and sex-matched healthy blood donors served as controls. Before each infusion and 3 months after the last infusion, we determined serum levels of osteoprotegerin (OPG), N-terminal cross-linking telopeptide of type I collagen (NTX), osteocalcin (OC) and insulin-like growth factor 1 (IGF-1). Bone mineral density (BMD) of the lumbar spine was measured at baseline and after the treatment’s completion. At baseline, OPG did not differ significantly between patients and controls (p=0.2), NTX were higher in patients although not significantly (p=0.139), whereas, OC levels were significantly higher and IGF-1 levels significantly lower in patients than in controls (p<0.001 and p<0.006, respectively). Zoledronic acid administration resulted in a significant decrease in NTX, OC and IGF-1 (p<0.05, p<0.001 and p<0.05, respectively) and in a significant increase in OPG and BMD (p<0.05 for both comparisons). The change in NTX, osteocalcin and IGF-1 became significant as early as 3 months after the first administration of zoledronic acid, while the change in OPG reached significance only after three infusions. Our study supports the effectiveness of bisphosphonates in the treatment of thalassemia-induced osteoporosis.     

Comparative effects of antiresorptive agents on bone mineral density and bone turnover in postmenopausal women

Postmenopausal osteoporosis is a common clinical entity; its complications represent a significant burden to society. In recent years the choice of therapies available for the treatment of postmenopausal osteoporosis has increased dramatically. There are a number of antiresorptive agents currently available including hormone replacement therapy (HRT), selective estrogen receptor modulators (SERMs), bisphosphonates, and dual action bone agents. It is difficult to truly compare these therapies given the lack of direct head-to head studies. The efficacy of antiresorptive therapies can be assessed in a number of ways including measurement of bone mineral density (BMD), assessment of bone turnover markers, and fracture reduction. Other important factors include ease of administration and consequent patient compliance. This article reviews the currently available antiresorptive agents and their effects on the above outcome measures.     

Effect of combined risedronate and hormone replacement therapies on bone mineral density in postmenopausal women

Both hormone replacement therapy (HRT) and bisphosphonates are efficacious in the prevention and treatment of postmenopausal osteoporosis. Combined therapy with bisphosphonate and HRT is likely to be used in clinical practice, and limited data are available regarding its efficacy and safety. This was a 1-yr, double blind, placebo-controlled study in which 524 postmenopausal women received daily treatment with conjugated equine estrogens (0.625 mg) alone or in combination with risedronate (5 mg). Women who had not undergone hysterectomy received medroxyprogesterone acetate (up to 5 mg, daily or cyclically) at the discretion of the investigator. The primary efficacy end point was the percent change from baseline in mean lumbar spine bone mineral density (BMD) at 1 yr. Changes in BMD at the proximal femur and forearm, bone turnover markers, and histology and histomorphometry were also assessed. At 12 months, significant (P < 0.05) increases from baseline in lumbar spine BMD were observed in both treatment groups (HRT-only, 4.6%; combined risedronate-HRT, 5.2%); the difference between the two groups was not statistically significant. Both therapies led to significant increases in BMD at 12 months at the femoral neck (1.8% and 2.7%, respectively), femoral trochanter (3.2% and 3.7%), distal radius (1.7% and 1.6%), and midshaft radius (0.4% and 0.7%). The differences between groups were statistically significant (P < 0.05) at the femoral neck and midshaft radius. Both combined risedronate-HRT and HRT-only produced significant decreases in the biochemical markers of bone turnover, with somewhat greater decreases in the combined treatment group. Bone biopsy data showed normal bone structure and normal mineralization with either treatment. Expected decreases in bone turnover were observed and were greater in the combined treatment group (68-79% reduction relative to baseline values, P < 0.005). Overall, combined treatment had a safety profile similar to that of HRT-only, including bone and gastrointestinal safety profiles. In conclusion, the combined treatment with risedronate and HRT had a favorable effect on BMD similar to that of HRT alone at the lumbar spine and slightly, but significantly, greater than that of HRT alone at the femoral neck and midshaft radius. The combined treatment was well tolerated, and there were no adverse effects on the skeleton.     

Retraction Note: Comparison of the effect of alendronate on lumbar bone mineral density and bone turnover in men and postmenopausal women with osteoporosis

Clinical Rheumatology - A correction to this paper has been published: https://doi.org/10.1007/s10067-021-05788-3     

Effects of alendronate and hormone replacement therapy, alone and in combination, on bone mass and markers of bone turnover in elderly women with osteoporosis

The aim of the study was to compare alendronate, hormone replacement therapy (HRT), and their combination in treatment of osteoporosis in elderly postmenopausal women. Ninety patients, aged 65-80 yr (mean 71), with a T-score of bone mineral density (BMD) of 2.5 or less at either the lumbar spine or the femoral neck were randomized to receive daily 10 mg alendronate (n = 30), 2 mg estradiol plus 1 mg norethisterone acetate (n = 30) (HRT), or their combination (n = 30) for 2 yr. BMD of the lumbar spine and the upper femur was measured at baseline and after 1 and 2 yr of treatment. Urinary excretion of type I collagen aminoterminal telopeptide as related to creatinine and serum type I procollagen aminoterminal propeptide was assayed at baseline and at 6-month intervals thereafter. Increases of 9.1-11.2% in lumbar spine BMD at 2 yr were similar in the study groups. Only HRT increased femoral neck BMD statistically significantly (P < 0.0001 for a change from baseline) at both 1 (+4.9%; P =NS vs. the other groups) and 2 yr (+5.8%; P < 0.05 vs. the other groups). Total hip BMD increased similarly in all study groups. Percentage reductions in urinary type I collagen aminoterminal telopeptide in the HRT group (60.2-62.7%) were significantly smaller than those in the combination group (78.1-80.4%) (P < 0.0001-0.0069) and the alendronate-only group (72.4-76.1%) (P = 0.047 at 24 months). Serum type I procollagen aminoterminal propeptide decreased less in the HRT group (53.6-59.8%) than in the other groups [73.0-75.0% in the alendronate group (P < 0.001 at 12 months); 67.0-71.5% in the combination group (P < 0.0001 at 12 months, P = 0.013 at 24 months)]. We conclude that in elderly postmenopausal women with osteoporosis, the combination of HRT and alendronate did not offer an extra gain of bone mass over either treatment alone. In terms of BMD changes, the single treatments were equally effective, but the reductions in bone markers were less with HRT than with alendronate.     

替勃龙对绝经后骨质疏松症患者骨密度及骨代谢指标的影响

目的观察替勃龙(Livial)对绝经后女性骨质疏松症患者骨密度(BMD)和骨代谢指标的影响。方法对121名年龄51～62岁、自然绝经的女性进行骨密度测定,将89例骨质疏松女性患者随机分为替勃龙组(45例)和钙剂组(44例);32名绝经后骨密度正常的女性作为对照组。各组均于用药前、用药后12、24周采用酶联免疫吸附试验(ELISA)测定骨碱性磷酸酶(sBAP)、骨钙素(sOC)、Ⅰ型胶原交联C端肽(sCTx)和尿Ⅰ型胶原交联N端肽(uNTx),用双能X线吸收法(DEXA)测定腰椎正位,股骨颈,Ward’s三角和大粗隆的骨密度(BMD)。结果经治疗后,替勃龙组骨密度有所提高,而钙剂组和对照组骨密度均下降;替勃龙组的sBAP、sOC升高,sCTx、uNTx/Cr明显下降,钙剂组和对照组变化不明显。结论替勃龙治疗绝经后骨质疏松症疗效显著。单纯服用钙剂不能治疗绝经后骨质疏松症,且继续骨流失。