Comparison of DXA, QCT and trabecular structure in beta-thalassaemia

Osteopathy, as a major feature of homozygous beta-thalassaemia, is a multifactorial disorder, not fully understood. We studied the lumbar vertebrae of 48 patients using Dual-Energy X-ray Absorptiometry (DXA) and Quantitative Computed Tomography (QCT), and we focused on structural properties, assessed by High Resolution Computed Tomography (HRCT). Bone Mineral Density (BMD) values were expressed as Z-scores and the results were correlated. The effect of age, sex, and type of thalassaemia and hormonal factors on BMD was assessed. We estimated, with HRCT, the cortex integrity and the number and thickness of trabeculae; the latter were classified to a three-grade scale. Our results showed the overall prevalence of osteoporosis to be 44% with DXA and 6% with QCT. Both techniques revealed an inverse correlation between age and BMD, whereas hormonal factors demonstrated associations with QCT and DXA measurements. The correlation coefficient between DXA's BMD and QCT's trabecular BMD was 0.545 (P < 0.001) whereas the corresponding value for Z-scores was r = 0.491 (P < 0.001). The classification of the patients into normal, osteopenic and osteoporotic categories, using QCT's Z, was in better agreement with the assignment based on trabecular number (K = 0.209, P = 0.053) than the classification using DXA's Z (K = 0.145, P = 0.120). Cortex evaluation by HRCT showed discontinuity in 15 patients. Both methods indicate a progression of osteoporosis with age. Hormonal deficiency is associated with thalassaemic osteoporosis whereas the visual estimation of cortex indicates that Thalassaemia Intermedia (TI) patients could be more affected than Thalassaemia Major (TM). Using the trabecular number as an indicator of osteoporosis, it seems that QCT may evaluate osteopathy better than DXA. Since the former has the ability to measure trabecular and cortical BMD separately, it could give early indication of which changes more rapidly and to what degree.     

Postmenopausal Canarian women receiving oral glucocorticoids have an increased prevalence of vertebral fractures and low values of bone mineral density measured by quantitative computer tomography and dual X-ray absorptiometry, without significant changes in parathyroid hormone

BACKGROUND: Daily doses higher than 7.5 mg/daily of prednisone or equivalents confer a great risk of vertebral and hip fractures with a clear dose dependence of fracture risk. Information regarding the utility in assessing trabecular bone mineral density by quantitative computer tomography (QCT) in these patients, either in the Canaries or in Spain, is lacking. Moreover, in this setting, the importance of secondary hyperparathyroidism is still controversial. DESIGN, PATIENTS AND METHODS: Cross-sectional observational study performed on 1177 consecutive Canary postmenopausal women who attended our Bone Metabolic Unit. The Patient Group was composed of 88 postmenopausal women who were taking oral corticosteroids in dose higher than 7.5 mg/day of prednisone or equivalent for more than 6 months (OG group). The Control Group included 838 postmenopausal women who did not take steroids. A complete validated questionnaire for osteoporosis risk assessment and a complete physical examination were performed. A lateral X-ray of the spine was performed on every woman. Bone mineral density (BMD) was measured at the lumbar spine (LS) by dual X-ray Absorptiometry (DXA) and QCT and at the femoral neck by DXA. Fasting serum and 24 hour urine was collected and biochemical markers of bone remodelling were studied. RESULTS: Both groups were comparable in general characteristics and calcium intake. The OG group showed lower values of BMD estimated both by DXA and QCT (p<0.05). LS BMD was closely correlated by using both methods (r=0.636, p<0.001). The OG group showed lower values of osteocalcin (p=0.023) and TRAP (p=0.026) without significant differences in PTH. Patients in OG group had a higher prevalence of vertebral fractures than controls (13.3% vs 8.6%; crude values: p=0.049, OR: 1.63 (0.99-2.67); age adjusted: p=0.003, OR 2.29 (1.33-9.93)). CONCLUSIONS: In postmenopausal Canarian women, chronic glucocorticoid therapy is associated with low bone mineral density, measured either by DXA or QCT, with evidence of low turnover and high prevalence of fractures without significant changes in PTH. DXA and QCT provide similar information in the assessment of this high risk population.     

Intravenous ibandronate injections given every three months: a new treatment option to prevent bone loss in postmenopausal women

OBJECTIVE: To investigate the efficacy, safety, and dose response of three doses of ibandronate, given intermittently by intravenous (IV) injection every three months, in preventing postmenopausal osteoporosis. PATIENTS AND METHODS: 629 postmenopausal women, categorised according to time since menopause and baseline lumbar spine (L1-4) bone mineral density (BMD), were enrolled into a multicentre, double blind, placebo controlled trial. They were randomly allocated to receive IV ibandronate 0.5 mg, 1 mg or 2 mg, or placebo every three months. All women received daily calcium supplementation. RESULTS: One year's treatment with intermittent IV ibandronate injections produced a dose dependent gain in mean (SD) lumbar spine BMD from baseline of 2.5 (2.5)%, 1.8 (2.6)%, and 1.0 (2.8)% in the groups receiving 2 mg, 1 mg, and 0.5 mg ibandronate, respectively, compared with a loss of BMD of 0.4 (2.4)% in the women in the placebo group; p=0.0001 for each ibandronate dose v placebo. Highest BMD gains occurred in women with osteopenia receiving 2 mg ibandronate. Similarly, at the hip, all three doses of ibandronate produced significantly better gains in BMD than placebo (p<0.05), with the greatest gains in the women with osteopenia receiving the 2 mg dose. Ibandronate concomitantly and dose dependently suppressed markers of bone turnover in comparison with placebo, and injections were well tolerated. CONCLUSION: IV ibandronate injections, given every three months, may be an effective alternative to oral bisphosphonates and hormonal therapy in the prevention of bone loss in postmenopausal women.     

Benefits of 2 years of intense exercise on bone density, physical fitness, and blood lipids in early postmenopausal osteopenic women: results of the Erlangen Fitness Osteoporosis Prevention Study (EFOPS)

BACKGROUND: Growing evidence indicates that physical exercise can prevent at least some of the negative effects on health associated with early menopause. Here we determine the effects of intense exercise on physical fitness, bone mineral density (BMD), back pain, and blood lipids in early postmenopausal women. METHODS: The study population comprised 50 fully compliant women, with no medication or illness affecting bone metabolism, who exercised over 26 months (exercise group [EG]), and 33 women who served as a nontraining control group (CG). Two group training sessions per week and 2 home training sessions per week were performed in the EG. Both groups were individually supplemented with calcium and cholecalciferol. Physical fitness was determined by maximum strength and cardiovascular performance. Bone mineral density was measured at the lumbar spine (dual-energy x-ray absorptiometry [DXA] and quantitative computed tomography [QCT]), the proximal femur (DXA), and the forearm (DXA). In serum samples taken from a subset of the study participants, we determined bone formation (serum osteocalcin) and resorption (serum cross-links) markers as well as blood lipid levels. Vasomotor symptoms related to menopause and pain were also assessed. RESULTS: After 26 months, significant exercise effects determined as percentage changes compared with baseline were observed for physical fitness (isometric strength: trunk extensors [EG +36.5% vs CG +1.7%], trunk flexors [EG +39.3% vs CG -0.4%], and maximum oxygen consumption [EG +12.4% vs CG -2.3%]); BMD (lumbar spine [DXA L1-L4, EG +0.7% vs CG -2.3%], QCT L1-L3 trabecular region of interest [EG +0.4% vs CG -6.6%], QCT L1-L3 cortical region of interest [EG +3.1% vs CG -1.7%], and total hip [DXA, EG -0.3% vs CG -1.7%]); serum levels (total cholesterol [EG -5.0% vs CG +4.1%] and triglycerides [EG -14.2% vs CG +23.2%]); and pain indexes at the spine. CONCLUSION: General purpose exercise programs with special emphasis on bone density can significantly improve strength and endurance and reduce bone loss, back pain, and lipid levels in osteopenic women in their critical early postmenopausal years.     

定量CT测量髋关节骨密度的重复性与DXA测量的一致性

目的 探讨定量CT（QCT）髋关节骨密度（BMD）测量重复性及与双能X线骨密度测定仪（DXA）测量的一致性.方法 随机抽取28名（男10例,女18例）老年受试者（男性＞60岁,女性＞50岁）,并分别采用QCT与DXA测量髋关节骨密度.收集左侧髋关节QCT扫描CT原始数据,分别由3名操作者各测量1次,其中1名操作者在不同时间重复测量3次,用于评价QCT髋关节骨密度结果的重复性.比较QCT和DXA测量左侧髋关节骨密度结果.结果 3名不同操作者或同一操作者不同时间采用QCT测量28名受试者左侧髋关节的骨密度值之间具有很好的相关性（ICC：0.93～0.98,P＜0.01）,全髋骨密度值之间差异无统计学意义.DXA与QCT测量的股骨颈和全髋骨密度结果之间具有显著相关性（r=0.88,0.89,P＜0.01）,DXA测量的骨密度值较QCT相对应骨密度值大10.5%和9.7%（t=7.53,9.68,P＜0.01）.上述骨密度值系统误差可被校正.结论采用QCT测量髋关节BMD具有较好的重复性,其BMD值与DXA所测BMD结果具有相关性.QCT髋关节（CTXA）骨密度测量可用于骨质疏松症的诊断和疗效随访,具有临床应用前景.     

Clinical Vignettes: Using Non-BMD Measurements in Clinical Practice

Dual-energy X-ray absorptiometry (DXA) is a well-established clinical tool for measuring bone mineral density (BMD) in the assessment of patients at risk of fracture. DXA is commonly used to diagnose osteoporosis, assess fracture risk, and assess the skeletal effects of treatment. Non-BMD DXA measurements, such as vertebral fracture assessment, hip access length, and trabecular score, have clinical applications that can guide patient treatment decisions. Quantitative computed tomography (QCT) measures three-dimensional volumetric BMD that is correlated with fracture risk. QCT measurements of the hip can also be used to generate a two-dimensional DXA-equivalent areal BMD and T-score that can be used for diagnosis of osteoporosis and the assessment of fracture risk in the FRAX algorithm. Opportunistic measurements of BMD obtained with CT scans evaluating non-skeletal conditions have potential clinical utility in identifying patients at high risk of fracture. This is a collection of clinical vignettes that illustrate potential applications of non-BMD DXA measurements and CT scanning in the management of patients at risk of fracture.     

Quantitative computed tomography of the lumbar spine,not dual x-ray absorptiometry,is an independent predictor of prevalent vertebral fractures in postmenopausal women with osteopenia receiving long-term glucocorticoid and hormone-replacement therapy

OBJECTIVE: To determine which measurement of bone mineral density (BMD) predicts vertebral fractures in a cohort of postmenopausal women with glucocorticoid-induced osteoporosis. METHODS: We recruited 114 subjects into the study. All had osteopenia of the lumbar spine or hip, as demonstrated by dual x-ray absorptiometry (DXA), and were receiving long-term glucocorticoids and hormone replacement therapy (HRT). Measurements of BMD by DXA of the lumbar spine, hip (and subregions), and forearm (and subregions), quantitative computed tomography (QCT) of the spine and hip (n = 59), and radiographs of the thoracolumbar spine were performed on all subjects to assess prevalent vertebral fractures. Vertebral fracture prevalence, as determined by morphometry, required a >or=20% (or >or=4-mm) loss of vertebral body height. Demographic information was obtained by questionnaire. Multiple regression and classification and regression trees (CART) analyses were used to assess predictors of vertebral fracture. RESULTS: Twenty-six percent of the study subjects had prevalent fractures. BMD of the lumbar spine, total hip and hip subregions, as measured by QCT, but only the lumbar spine and total hip, as measured by DXA, were significantly associated with prevalent vertebral fractures. However, only lumbar spine BMD as measured by QCT was a significant predictor of vertebral fractures. CART analysis showed that a BMD value <0.065 gm/cm(3) was associated with a 7-fold higher risk of fracture than a BMD value >or=0.065 gm/cm(3).CONCLUSION: In postmenopausal women with osteoporosis induced by long-term glucocorticoid treatment who are also receiving HRT, BMD of the lumbar spine as measured by QCT, but not DXA, is an independent predictor of vertebral fractures.     

Restoration of the coupling process and normalization of bone mass following successful treatment of endogenous Cushing's syndrome: a prospective, long-term study

OBJECTIVE: Endogenous Cushing's syndrome (CS) is associated with bone loss and an increased risk of fractures. However, the long-term outcome of treatment on bone health has not been adequately clarified. DESIGN: We followed 33 patients with active CS prospectively before and twice after treatment (mean follow-up 33 (n = 25) and 71 months (n = 18), respectively). The patients were compared to age-, sex- and body mass index (BMI)-matched controls, also followed longitudinally. METHODS: Bone mineral indices (bone mineral density (BMD), bone mineral content (BMC) and bone area) were evaluated in the lumbar spine (LS), femoral neck (FN), and total body (TB) by dual-energy X-ray absorptiometry (DXA). Biochemical markers of bone turnover were assessed by serum levels of osteocalcin and C-terminal telopeptides of Type-1 collagen (CTX-1). RESULTS: Mann-Whitney rank sum tests showed that BMD of the LS, FN and TB was reduced by 14.8% (P < 0.001), 15.7% (P < 0.001), and 9.2% (P < 0.001) in CS vs. controls at baseline, with markedly reduced serum osteocalcin (P = 0.014) and increased CTX-1 (P = 0.012) levels, but no correlation between markers. At first follow-up, BMD was increased in LS (7.9%, P < 0.001) and FN (3.5%, P = 0.003) compared to baseline. The time-dependent rise in BMD (LS (r = 0.59; P = 0.002) and FN (r = 0.52; P = 0.007); Spearman's rank correlation), in CS was paralleled by increased osteocalcin (275%, P < 0.001) and correlation between biochemical markers (r = 0.92, P < 0.001; Pearson's correlation). TB BMD did not increase significantly before the second follow-up, when BMD Z-scores were normalized in all three compartments. CONCLUSION: Our observations demonstrate restoration of coupled bone remodeling and normalization of bone mineral density in all measured skeletal compartments of treated CS patients after prolonged recovery, first significant in predominantly trabecular bone (i.e. lumbar spine).     

Efficacy and tolerability of intravenous ibandronate injections in postmenopausal osteoporosis: 2-year results from the DIVA study

OBJECTIVE: An effective and well tolerated intravenous (IV) bisphosphonate could provide a new treatment method for patients with osteoporosis. The Dosing IntraVenous Administration (DIVA) study was designed to identify the optimal ibandronate IV injection schedule for the treatment of postmenopausal osteoporosis by comparing the efficacy and tolerability of 2- and 3-monthly injections with the previously evaluated daily oral ibandronate regimen. We report the effects on lumbar spine and proximal femur bone mineral density (BMD) and bone resorption markers over 2 years. METHODS: This randomized, double-blind, double-dummy, noninferiority study recruited 1395 women (aged 55-80 yrs; > or = 5 yrs since menopause) with osteoporosis [mean lumbar spine (L2-L4) BMD T-score < -2.5 and > or = -5.0]. Patients received IV ibandronate (2 mg every 2 mo or 3 mg every 3 mo) plus daily oral placebo, or 2.5 mg daily oral ibandronate plus 2- or 3-monthly IV placebo. Supplemental vitamin D (400 IU) and calcium (500 mg) were provided throughout the 2-year study. RESULTS: At 2 years, the 2- and 3-monthly IV regimens achieved statistically noninferior and also superior increases in lumbar spine BMD compared with the daily regimen (6.4% and 6.3% vs 4.8%, respectively; p < 0.001). Greater increases were also obtained with IV ibandronate versus daily in proximal femur BMD. Serum concentrations of the biochemical marker of bone resorption C-telopeptide of the alpha-chain of type I collagen were reduced to a similar extent in all treatment arms (53.4%-59.9%). The tolerability profile of the IV regimens was similar to that observed with daily oral therapy. CONCLUSION: Ibandronate IV injections are an effective and well tolerated treatment for postmenopausal osteoporosis and provide a useful alternative to oral dosing.     

Monthly oral ibandronate is well tolerated and efficacious in postmenopausal women: results from the monthly oral pilot study

CONTEXT: Ibandronate, a potent, nitrogen-containing bisphosphonate developed for intermittent administration in postmenopausal osteoporosis, aims to overcome current adherence issues with daily and weekly oral bisphosphonates through once-monthly oral dosing. OBJECTIVE: The purpose of this study was to investigate the safety, pharmacodynamics, and pharmacokinetics of once-monthly oral ibandronate. DESIGN: A randomized, 3-month, double-blind, placebo-controlled, phase I study (Monthly Oral Pilot Study) was conducted. SETTING: The study was conducted at five clinical trial centers in the United Kingdom and Belgium. PATIENTS OR OTHER PARTICIPANTS: Subjects were postmenopausal women (age, 55-80 yr; > or =3 yr post menopause; n = 144). INTERVENTION(S): Once-monthly oral ibandronate 50, 100, or 150 mg or placebo was used. After the first cycle, the 50-mg arm was split, with participants continuing on either 50 or 100 mg. MAIN OUTCOME MEASURE(S): Primary outcome measures were safety, serum and urinary C-telopeptide (CTX), and serum ibandronate AUC0-infinity. RESULTS: Once-monthly oral ibandronate was well tolerated, with a similar overall and upper gastrointestinal safety profile to placebo. Once-monthly ibandronate was also highly effective in decreasing bone turnover; substantial reductions from baseline in serum CTX (-56.7% and -40.7% in the 150- and 100-mg arms, respectively; P < 0.001 vs. placebo) and urinary CTX (-54.1% and -34.6%, respectively; P < 0.001 vs. placebo) were observed at d 91 (30 d after the final dose). Analysis of the area under the effect curve (d 1-91) for change from baseline (percent x days) in serum CTX and urinary CTX indicated a dose-response relationship. The AUC0-infinity for ibandronate increased with dose but not in a dose-proportional manner. CONCLUSIONS: These findings indicate a potential role for once-monthly oral ibandronate in the treatment of postmenopausal osteoporosis.     

Randomized trial of once-weekly parathyroid hormone (1-84) on bone mineral density and remodeling

CONTEXT: Daily PTH administration increases bone mineral density (BMD) and reduces fracture risk. However, cost and compliance significantly limit clinical use. OBJECTIVE: Our objective was to determine whether less frequent PTH administration increases lumbar spine BMD. PARTICIPANTS, DESIGN, AND SETTING: Fifty postmenopausal women ages 45-70 yr with femoral neck BMD T-score between -1.0 and -2.0 participated in a double-blind, randomized, placebo-controlled trial at St. Joseph Hospital, Bangor, ME. INTERVENTION: Subjects received sc injections of daily PTH(1-84) (100 mug) or placebo for 1 month, followed by weekly injections (PTH or placebo) for 11 months. OUTCOMES: Change in lumbar spine dual-energy x-ray absorptiometry areal BMD (primary) was assessed. Secondary outcomes included volumetric BMD at spine and hip by quantitative computed tomography, trabecular bone microarchitecture by magnetic resonance imaging of distal radius, and biochemical bone turnover markers. RESULTS: At 12 months, lumbar spine areal BMD increased 2.1% in PTH-treated women compared with placebo (P = 0.03). Vertebral trabecular volumetric BMD increased 3.8% in PTH-treated women compared with placebo group (P = 0.08). PTH-treated women also had higher distal radial trabecular bone volume, number, and thickness compared with placebo-treated women (P < 0.04). After 1 month of daily PTH, N-terminal propeptide of type I collagen (P1NP) was markedly increased compared with placebo (P < 0 .0001), and a difference persisted, although lessened, throughout the study. Bone resorption indices were unchanged in PTH-treated women and were reduced in the placebo group. CONCLUSION: Once-weekly PTH after 1 month of daily treatment increases spine BMD, radial trabecular bone, and bone formation markers in postmenopausal women. These results suggest that less frequent alternatives to daily PTH dosing for 2 yr could be effective. Additional studies are required to define the optimal frequency of PTH administration.     

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.     

Bone Mineral Density and Serum Biochemical Predictors of Bone Loss in Patients with CKD on Dialysis

Background

and objectives Use of bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA) is controversial for diagnosing bone loss in CKD patients on dialysis. The alternative quantitative computed tomography (QCT) is expensive and requires high radiation exposure. This study compared the two techniques and evaluated serum biochemical parameters for prediction of bone loss.

Design, setting, participants, & measurements

This prospective study enrolled patients from dialysis centers throughout Kentucky. BMD of the spine and hip was measured at baseline and after 1 year by DXA and QCT. Customary and novel serum biochemical parameters were obtained at the same times, including calcium, phosphorus, whole and intact parathyroid hormone, bone-specific alkaline phosphatase, procollagen type 1 N-terminal propeptide, tartrate-resistant acid phosphatase-5b, Dickkopf-1, fibroblast growth factor, and sclerostin. Rates of detection of osteoporosis by DXA and QCT were compared. Correlations were calculated between baseline biochemical parameters and BMD at baseline and changes over 1 year. Multivariable regression was performed to adjust for age, sex, body mass index, and race.

Results

Eighty-one patients completed the study (mean age=52.6±12.3 years, 56% men, 53% African American, and median dialysis vintage=41 months). At baseline, QCT and DXA of the spine identified similar rates of osteoporosis (13.6% and 13.6%), but at the hip, DXA identified more osteoporosis (22.2% versus 13.6%). At any site and by either method, 33.3% of the patients were osteoporotic. Baseline BMD correlated with sclerostin, intact parathyroid hormone, bone-specific alkaline phosphatase, tartrate-resistant acid phosphatase-5b, and fibroblast growth factor. At 1 year, hip QCT identified a higher number of patients experiencing bone loss (51.3%) than DXA (38.5%). After multivariable adjustment, baseline sclerostin and tartrate-resistant acid phosphatase-5b predicted bone loss measured by QCT of the hip; procollagen type 1 N-terminal propeptide predicted cortical spine bone gain by QCT.

Conclusions

QCT identified prospectively more bone loss at the hip than DXA. The baseline serum biochemical parameters sclerostin and tartrate-resistant acid phosphatase-5b were noninvasive independent predictors of bone loss in CKD patients on dialysis.     

Comparison of alendronate and intranasal calcitonin for treatment of osteoporosis in postmenopausal women

This study compared the effects of oral alendronate and intranasal calcitonin for treatment of osteoporosis in postmenopausal women. Women at least 5 yr postmenopause (n = 299) were randomized to either 10 mg alendronate, matching alendronate placebo, or open-label intranasal calcitonin 200 IU daily for 12 months. Hip and spine bone mineral density (BMD) and markers of bone turnover were measured, and safety and tolerability were assessed. Alendronate produced greater increases in BMD than calcitonin at 12 months at the lumbar spine (5.16% vs. 1.18%; P < 0.001), trochanter (4.73% vs. 0.47%; P < 0.001), and femoral neck (2.78% vs. 0.58%; P < 0.001). Changes in BMD with calcitonin were greater than with placebo at the femoral neck, but were not different from placebo at either the trochanter or lumbar spine. Greater decreases in bone turnover were seen with alendronate than with calcitonin (serum bone-specific alkaline phosphatase, 43% vs. 9%, P < 0.001; urinary N-telopeptide, 62% vs. 11%, P < 0.001). Similar percentages of patients in each group reported an adverse experience during the study. We conclude that, in postmenopausal women with osteoporosis, 12 months of therapy with alendronate produced significantly greater increases in BMD of the hip and spine and greater decreases in bone turnover than intranasal calcitonin.     

Alendronate produces greater effects than raloxifene on bone density and bone turnover in postmenopausal women with low bone density: results of EFFECT (Efficacy of FOSAMAX versus EVISTA Comparison Trial) International

OBJECTIVES: Alendronate and raloxifene are antiresorptive agents with different mechanisms of action, each used to treat osteoporosis in postmenopausal women. This study was undertaken to compare the efficacy and tolerability of alendronate to raloxifene in postmenopausal women with low-bone density. DESIGN: Randomized, double-masked, double-dummy multicentre international study. SETTING: Clinical trial centres in Europe, South America and Asia-Pacific. SUBJECTS: A total of 487 postmenopausal women with low bone density, based on bone mineral density (BMD) of the lumbar spine or hip (T-score < or =-2.0). Interventions. Patients received either alendronate 70 mg once weekly and daily placebo identical to raloxifene or raloxifene 60 mg daily and weekly placebo identical to alendronate for 12 months. MAIN OUTCOME MEASURES: Evaluations included BMD of the lumbar spine and hip and markers of bone turnover at 6 and 12 months and adverse event reporting. RESULTS: Alendronate demonstrated substantially greater increases in BMD than raloxifene at both lumbar spine and hip sites at 12 months. Lumbar spine BMD increased 4.8% with alendronate vs. 2.2% with raloxifene (P < 0.001). The increase in total hip BMD was 2.3% with alendronate vs. 0.8% with raloxifene (P < 0.001). Reductions in bone turnover were significantly larger with alendronate than raloxifene. Overall tolerability was similar, however, the proportion of patients reporting vasomotor events was significantly higher with raloxifene (9.5%) than with alendronate (3.7%, P = 0.010). The proportion of patients reporting gastrointestinal events was similar between groups. CONCLUSION: In postmenopausal women with low bone density, improvements in BMD and markers of bone turnover were substantially greater during treatment with alendronate compared to raloxifene.     

Oral weekly ibandronate prevents bone loss in postmenopausal women

OBJECTIVES: To investigate the efficacy, safety, and dose-response of once-weekly oral ibandronate in the prevention of postmenopausal bone loss. DESIGN: This was a multi-centre, placebo-controlled, double-blind, randomized, 24-month phase II/III dose-finding study. SETTING: Primary care units in 14 osteoporosis centres. SUBJECTS: A total of 630 women were stratified into four strata according to time since menopause (TSM, 1-3 vs. >3 years) and baseline bone mineral density (BMD; normal: T-score > or =1 vs. osteopenic: -2.5 < or = T-score < or = 1) of the lumbar spine. INTERVENTIONS: Within each stratum women were further randomized to receive once-weekly ibandronate (5, 10, or 20 mg week-1) or placebo for 24 months. MAIN OUTCOME MEASURES: Efficacy parameters were the relative changes from baseline in spine (L1-4) and hip BMD, and biochemical markers of bone turnover (serum and urinary C-telopeptide of collagen type I (CTx), osteocalcin, and alkaline phosphatase) measured by dual energy X-ray absorptiometry and enzyme immunoassays, respectively. RESULTS: Once-weekly therapy with ibandronate induced dose-dependent increases in spine and hip BMD. At month 24, differences between the relative changes in spine and hip BMD induced by 20 mg ibandronate and placebo was 4.0 and 2.7%, respectively. Similar or more pronounced differences were seen in osteopenic women of TSM 1-3 years (5.3 and 3.5%) and of TSM >3 years (3.5 and 2.9%), respectively. A dose-dependent suppression of all biochemical markers of bone turnover was observed with significant decreases in the 20 mg dose groups of all strata at month 24. The overall safety results indicated that once-weekly oral ibandronate was well-tolerated at all three doses. CONCLUSION: Once-weekly oral therapy with 20 mg ibandronate provides an effective and safe therapy for the prevention of postmenopausal bone loss.     

Intravenous ibandronate injections in postmenopausal women with osteoporosis: one-year results from the dosing intravenous administration study

OBJECTIVE: Although oral bisphosphonates are effective treatments for postmenopausal women with osteoporosis, oral dosing may be unsuitable for some patients. An efficacious intravenously administered bisphosphonate could be beneficial for such patients. Ibandronate, a potent nitrogen-containing bisphosphonate, can be administered using extended dosing intervals, either orally or by rapid intravenous injection. The aim of this study was to identify the optimal intravenous dosing regimen for ibandronate in postmenopausal women with osteoporosis. METHODS: In a randomized, double-blind, double-dummy, phase III, noninferiority study, we compared 2 regimens of intermittent intravenous injections of ibandronate (2 mg every 2 months and 3 mg every 3 months) with a regimen of 2.5 mg of oral ibandronate daily, the latter of which has proven antifracture efficacy. The study group comprised 1,395 women (ages 55-80 years) who were at least 5 years postmenopausal. All patients had osteoporosis (lumbar spine [L2-L4] bone mineral density [BMD] T score less than -2.5). Participants also received daily calcium (500 mg) and vitamin D (400 IU). The primary end point was change from baseline in lumbar spine BMD at 1 year. Changes in hip BMD and in the level of serum C-telopeptide of type I collagen (CTX) were also measured, as were safety and tolerability. RESULTS: At 1 year, mean lumbar spine BMD increases were as follows: 5.1% among 353 patients receiving 2 mg of ibandronate every 2 months, 4.8% among 365 patients receiving 3 mg of ibandronate every 3 months, and 3.8% among 377 patients receiving 2.5 mg of oral ibandronate daily. Both of the intravenous regimens not only were noninferior, but also were superior (P < 0.001) to the oral regimen. Hip BMD increases (at all sites) were also greater in the groups receiving medication intravenously than in the group receiving ibandronate orally. Robust decreases in the serum CTX level were observed in all arms of the study. Both of the intravenous regimens were well tolerated and did not compromise renal function. CONCLUSION: As assessed by BMD, intravenous injections of ibandronate (2 mg every 2 months or 3 mg every 3 months) are at least as effective as the regimen of 2.5 mg orally daily, which has proven antifracture efficacy, and are well tolerated.     

Monthly oral ibandronate is effective and well tolerated after 3 years: the MOBILE long-term extension

Oral ibandronate is the first bisphosphonate licensed for once-monthly treatment of postmenopausal osteoporosis. The 2-year Monthly Oral iBandronate In LadiEs (MOBILE) registration study assessed bone mineral density (BMD) and markers of bone turnover and showed that monthly oral ibandronate was at least as effective and well tolerated as a 2.5-mg daily oral regimen. In this study, we report the first year of a long-term extension study to MOBILE and a post hoc analysis of patients receiving 3 years of continuous treatment with monthly ibandronate. Patients who completed MOBILE were eligible for the partially randomized, double-blind extension study and received 100 mg (n = 359) or 150 mg (n = 360) monthly oral ibandronate. A post hoc analysis included patients who received either 100 mg (n = 173) or 150 mg (n = 169) monthly ibandronate continuously throughout the original 2-year MOBILE study and during the first year of the extension study. After one additional year of treatment (total of 3 years), mean lumbar spine BMD increased a further 1.5 and 1.1% in the 150 and 100 mg arms, respectively, compared with 2-year data (original MOBILE study). Total hip BMD changed by 0.3 and -0.08%, respectively. In the post hoc analysis, 3-year increases in lumbar spine BMD were significant in patients receiving ibandronate 150 mg monthly (7.6%; p < 0.0001 vs. baseline) and 100 mg monthly (6.4%; p < 0.0001 vs. baseline). Both groups achieved significant increases in total hip BMD after 3 years compared with baseline (3.4%, 100 mg; 4.1%, 150 mg; p < 0.0001). Serum C-telopeptide of the alpha chain of type I collagen decreased significantly over 3 years' treatment (p < 0.001; all comparisons vs. baseline), remaining within the premenopausal range. Once-monthly oral ibandronate was well tolerated with a low incidence of clinical osteoporotic fractures and upper gastrointestinal events. In conclusion, 150-mg monthly oral ibandronate is an effective and well-tolerated long-term treatment for postmenopausal osteoporosis, with consistent improvement in BMD and bone turnover during 3 years' continuous treatment.     

Influence of age at menarche on forearm bone microstructure in healthy young women

BACKGROUND: Shorter estrogen exposure from puberty onset to peak bone mass attainment may explain how late menarche is a risk factor for osteoporosis. The influence of menarcheal age (MENA) on peak bone mass, cortical, and trabecular microstructure was studied in 124 healthy women aged 20.4 +/- 0.6 (sd) yr. METHODS: At distal radius, areal bone mineral density (aBMD) was measured by dual-energy x-ray absorptiometry, and volumetric bone mineral density (BMD) and microstructure were measured by high-resolution peripheral computerized tomography, including: total, cortical, and trabecular volumetric BMD and fraction; trabecular number, thickness, and spacing; cortical thickness (CTh); and cross-sectional area (CSA). RESULTS: Median MENA was 12.9 yr. Mean aBMD T score of the whole cohort was slightly positive. aBMD was inversely correlated to MENA for total radius (R = -0.21; P = 0.018), diaphysis (R = -0.18; P = 0.043), and metaphysis (R = -0.19; P = 0.031). Subjects with MENA more than the median [LATER: 14.0 +/- 0.7 (+/-sd) yr] had lower aBMD than those with MENA less than the median (EARLIER: 12.1 +/- 0.7 yr) in total radius (P = 0.026), diaphysis (P = 0.042), and metaphysis (P = 0.046). LATER vs. EARLIER displayed lower total volumetric BMD (315 +/- 54 vs. 341 +/- 56 mg HA/cm(3); P = 0.010), cortical volumetric BMD (874 +/- 49 vs. 901 +/- 44 mg HA/cm(3); P = 0.003), and CTh (774 +/- 170 vs. 849 +/- 191 microm; P = 0.023). CTh was inversely related to CSA (R = -0.46; P < 0.001). In LATER reduced CTh was associated with 5% increased CSA. CONCLUSIONS: In healthy young adult women, a 1.9-yr difference in mean MENA was associated with lower radial aBMD T score, lower CTh without reduced CSA, a finding compatible with less endocortical accrual. It may explain how late menarche is a risk factor for forearm osteoporosis.     

Once-Monthly Ibandronate

Ibandronate is a nitrogen-containing bisphosphonate that has been approved for once-monthly administration in women with post-menopausal osteoporosis. Animal data suggest that the efficacy of the drug is determined by the cumulative dose rather than the frequency of administration. After treatment for 1 year in a large, randomized, double-blind, multicenter trial in women with postmenopausal osteoporosis, once-monthly ibandronate 150 mg was non-inferior to once-daily ibandronate 2.5 mg in terms of increases in mean lumbar spine (primary endpoint) and hip bone mineral density (BMD). In addition, once-monthly ibandronate 150 mg was significantly more effective than once-daily ibandronate for mean increase from baseline in lumbar spine BMD after 1 and 2 years. In another large, randomized, double-blind trial in women with osteoporosis, both once-daily and intermittent (>2-month between-dose interval [not approved]) ibandronate were significantly more effective than placebo in reducing the risk of new vertebral fractures, after treatment for 3 years. Once-daily and intermittent ibandronate also increased mean lumbar spine and hip BMD from baseline by significantly more than placebo. Oral once-monthly, once-daily, and intermittent ibandronate were generally well tolerated. Monthly ibandronate had a similar tolerability profile to once-daily ibandronate. The incidence of adverse events, including gastrointestinal events, with once-daily and intermittent ibandronate did not differ significantly from that with placebo. Significantly more women with osteoporosis preferred once-monthly ibandronate and found it more convenient than once-weekly alendronate, according to data from a 6-month, randomized, open-label, crossover study.