Once-monthly oral ibandronate in postmenopausal osteoporosis: Translation and updated review

Background: As a result of the reported efficacy of oral Bisphosphonates in reducing fractures, increasing bone mineral density (BMD), and reducing bone turnover, these agents are the recommended first line of treatment of postmenopausal osteoporosis. However, in clinical practice, patients might not be diagnosed or prescribed appropriate treatment. Even when bisphosphonates are prescribed, their therapeutic benefit may be compromised by poor treatment compliance and/or failure to persist with the treatment prescribed. New drugs or treatment regimens that reduce the risk for osteoporotic fractures and make the treatment of osteoporosis more convenient and suitable for patients are needed.Objectives: The aims of the present review were to discuss the efficacy of monthly ibandronate in the treatment of postmenopausal osteoporosis and to determine treatment adherence with this drug.Methods: A search of MEDLINE (key terms: ibandronate and ibandronic acid; publication dates: 1996–December 2008) was used to identify studies of the efficacy and adherence of ibandronate in the treatment of postmenopausal osteoporosis. Additional searches were conducted to identify publications pertinent to compliance using the terms bisphosphonate and compliance.Results: A total of 15 articles were included in the present review. An analysis of data from 2 US data-bases reported that once-monthly ibandronate was associated with significantly improved treatment persistence relative to weekly bisphosphonates at 1 year. In BONE (Oral Ibandronate Osteoporosis Vertebral Fracture Trial in North America and Europe), the risk for new vertebral fractures was reduced by 62% with oral ibandronate 2.5 mg/d versus placebo (P < 0.001) at 3 years. In the 2-year MOBILE (Monthly Oral Ibandronate in Ladies) study, oral ibandronate 150 mg once monthly was associated with significantly increased lumbar spine BMD (P < 0.001), and bone turnover markers were numerically decreased compared with the daily regimen. A meta-analysis reported a 38% lower risk for nonvertebral fractures with combined high doses of ibandronate (including oral iban-dronate 150 mg monthly and ibandronate 3 mg IV every 3 months) compared with oral ibandronate 2.5 mg/d (change in annual cumulative exposure, from ≥10.8 to 5.5 mg).Conclusions: Based on the findings from the studies included in the present review, treatment with oral ibandronate 150 mg once monthly was reported to be at least as effective as the daily regimen and was associated with increased adherence. Monthly iban-dronate might provide an option for the treatment of postmenopausal osteoporosis.     

Once-monthly ibandronate for postmenopausal osteoporosis: review of a new dosing regimen

BACKGROUND: Ibandronate, a nitrogen-containing bisphosphonate, was approved by the US Food and Drug Administration (FDA) in May 2003 as a daily oral regimen for the treatment and prevention of post-menopausal osteoporosis. In March 2005, the FDA approved once-monthly dosing with ibandronate for the same indications. OBJECTIVE: The purpose of this article was to review the efficacy and tolerability of ibandronate 150 mg once monthly in the treatment and prevention of post-menopausal osteoporosis. METHODS: A search of MEDLINE (1966-September 2005) and International Pharmaceutical Abstracts (1971-September 2005) for articles relating to the efficacy and tolerability of once-monthly ibandronate in the treatment of postmenopausal osteoporosis was conducted using the terms ibandronate and ibandronic acid. Additional searches were conducted to identify publications relevant to compliance and pharmacoeconomic considerations using the terms bispbospbonate, compliance, cost, and pharmacoeconomics. The reference lists of identified articles and presentations from recent scientific meetings also were reviewed. Selected safety information from the manufacturer was incorporated. RESULTS: Ibandronate 2.5 mg/d and intermittent ibandronate (20 mg QOD for 12 doses every 3 months) have been shown to effectively reduce the incidence of vertebral fractures; after 3 years of therapy in a placebo-controlled clinical trial, the relative risk reductions for new vertebral fractures with daily and intermittent ibandronate were 62% and 50%, respectively (both, P<0.001 vs placebo). Once-monthly ibandronate has been evaluated in 2 clinical trials: a Phase I dose-ranging trial in 144 healthy postmenopausal women and a Phase III noninferiority trial in 1609 women with postmenopausal osteoporosis who were randomized to receive ibandronate 2.5 mg/d or 1 of 3 monthly ibandronate regimens: 50/50 mg (50 mg given on 2 consecutive days) once monthly; 100 mg once monthly; and 150 mg once monthly. The primary end point of the Phase III trial was the change from baseline in lumbar spine bone mineral density (BMD). After 1 year of therapy, patients who received ibandronate 150 mg once monthly had a significantly greater increase from baseline in lumbar spine BMD compared with those who received ibandronate 2.5 mg/d (4.9% vs 3.9%, respectively; P=0.002). The overall adverse-event profile was similar between the daily and monthly regimens. Drug-related adverse events were reported in 32.4% of patients receiving ibandronate 2.5 mg/d and 36.9% of patients receiving ibandronate 150 mg monthly. Upper gastrointestinal adverse events occurred in a respective 22.8% and 22.5% of the 2 groups. After 1 year of therapy, patients receiving ibandronate 150 mg monthly reported more flulike symptoms (8.3%) compared with those receiving ibandronate 2.5 mg/d (2.8%). In a crossover study comparing preference for and convenience of monthly ibandronate and weekly alendronate in 342 ambulatory women with postmenopausal osteoporosis, significantly more patients preferred the monthly ibandronate regimen to the weekly alendronate regimen (71.4% vs 28.5%, respectively; P<0.001). CONCLUSION: Once-monthly ibandronate is an effective and well-tolerated treatment option for postmenopausal osteoporosis.     

A comparison of the effect of alendronate and risedronate on bone mineral density in postmenopausal women with osteoporosis: 24-month results from FACTS-International

Objectives: To compare alendronate 70 mg once weekly (OW) with risedronate 35 mg OW with respect to change in bone mineral density (BMD), biochemical markers and upper gastrointestinal (UGI) tolerability over 24 months. Methods: This was a 12‐month extension to the Fosamax^® Actonel^® Comparison Trial international study (FACTS). Postmenopausal women with osteoporosis randomly assigned to either alendronate 70 mg OW or risedronate 35 mg OW for the 12‐month base study continued taking the same double‐blind study medication. Efficacy measurements were BMD at the hip trochanter, lumbar spine, total hip, and femoral neck and levels of four bone turnover markers at 24 months. The primary hypothesis was that alendronate would produce a greater mean per cent increase from baseline in hip trochanter BMD at 24 months. Results: Trochanter BMD increased significantly from baseline to month 24 in both groups, with a significantly larger increase with alendronate: adjusted mean treatment difference of 1.50% (95% confidence interval: 0.74%, 2.26%; p < 0.001). Similar results were seen at all BMD sites. Significant geometric mean per cent decreases (p < 0.001) from baseline were seen for all four bone turnover markers in both groups, with significantly larger decreases (p < 0.001) with alendronate: adjusted mean treatment differences ranged from 8.9% to 25.3%. No significant differences were seen in incidence of UGI or other adverse events. Conclusions: Alendronate 70 mg OW yielded significantly greater BMD gains and larger decreases in bone turnover marker levels than risedronate 35 mg OW over 24 months, with no difference in UGI tolerability.     

Efficacy and tolerability of alendronate once weekly in Asian postmenopausal osteoporotic women

BACKGROUND: Osteoporosis has become a major health problem worldwide, and the incidence is rising in Asian countries. The aminobisphosphonates are potent inhibitors of bone resorption and are currently the mainstay of treatment for postmenopausal osteoporosis. Dosing frequency will likely affect tolerability and adherence to treatment. OBJECTIVE: To assess the tolerability and efficacy of a once-weekly aminobisphosphonate preparation in improving bone mineral density (BMD) and bone turnover markers in osteoporotic Asian women. METHODS: Chinese postmenopausal women with osteoporosis were randomized to receive either alendronate 70 mg once weekly plus calcium carbonate 500 mg daily (n = 29) or calcium carbonate 500 mg daily (n = 29) for one year. BMD was measured by dual energy X-ray absorptiometry. Markers of bone formation and bone resorption included plasma total alkaline phosphatase and urine N-telopeptides. RESULTS: Treatment with alendronate 70 mg once weekly for one year resulted in significant BMD improvement of 6.1% at the spine, 5.6% at the femoral neck, and 3.5% at the total hip. There was no significant change in the BMD values in the calcium group (spine 1.4%, femoral neck -0.2%, total hip 0%). The BMD response in the alendronate group was significantly different from that in the calcium group at all time points, and the difference was detectable as early as after 3 months of treatment (ANOVA p < 0.001). The changes remained significant after adjusting for age, age at menarche, and years since menopause (p < 0.001). Similarly, the reductions in bone markers at 12 months were significantly different between the 2 treatment groups (plasma total alkaline phosphatase: alendronate 27.9%, calcium 5.4%; urine N-telopeptide: alendronate 55.6%, calcium 11.2%; both p < 0.001). The alendronate regimen was well tolerated, without significant adverse events. CONCLUSIONS: The results confirmed that once-weekly alendronate was efficacious in increasing BMD and reducing bone turnover and was well tolerated in Asian women.     

Adherence to and gastrointestinal tolerability of monthly oral or quarterly intravenous ibandronate therapy in women with previous intolerance to oral bisphosphonates: a 12-month, open-label, prospective evaluation

BACKGROUND: Gastrointestinal (GI) symptoms and high dosing frequency have been cited as reasons for inadequate adherence to daily or weekly oral bisphosphonate therapy. Inadequate adherence may lead to poor therapeutic outcomes. OBJECTIVE: The PRIOR study evaluated adherence to and GI tolerability of monthly therapy with oral and quarterly intravenous ibandronate in postmenopausal women with osteoporosis or osteopenia. METHODS: This 12-month, multicenter, prospective, nonrandomized, open-label, noninferiority study included postmenopausal women with osteoporosis or osteopenia who had discontinued previous daily or weekly oral bisphosphonate therapy because of GI intolerance. Participants chose to receive either monthly oral ibandronate 150 mg or quarterly intravenous ibandronate 3 mg and were permitted to switch formulations once during the study. For oral treatment, adherence was assessed based on doses taken, as recorded on the case-report form; for intravenous treatment, adherence was assessed based on doses administered, as recorded by study site personnel. Participants who took >or=75% of protocol-specified doses were considered adherent. The rate of adherence to oral ibandronate was protocol defined as noninferior to that of intravenous ibandronate if the upper limit of the 2-sided 90% CI for the adjusted difference in adherence rates was >20%. At screening, participants assessed the tolerability of their previous bisphosphonate therapy using the GI Experience Survey; using the same instrument, they assessed the tolerability of ibandronate 1 month from baseline and at months 4, 7, and 10. RESULTS: Of 543 participants in the intent-to-treat population, 147 (27.1%) chose to receive oral treatment and 396 (72.9%) chose to receive intravenous treatment. The mean age of participants was approximately 66 years in both groups, and >90% of participants were white. A significantly greater proportion of participants who selected intravenous versus oral treatment had a primary diagnosis of osteoporosis (72.2% vs 57.1%, respectively; P<0.001) and a history of fracture as an adult (35.6% vs 22.4%; P >or= 0.004); significantly fewer recipients of intravenous versus oral ibandronate were currently working (29.0% vs 39.5%; P >or= 0.021). Overall, 82.9% of participants had previously received alendronate and 44.9% had previously received risedronate. Eleven participants switched from oral to intravenous therapy and 16 switched from intravenous to oral therapy during the study. In the perprotocol population, 69.7% of participants in the oral group (101/145) and 82.9% of participants in the intravenous group (325/392) were adherent to their originally selected therapy. Adherence to oral therapy fell within the prespecified boundary for noninferiority to intravenous therapy (adjusted difference: 12.4%; 90% CI, 5.1-19.7). Mean GI tolerance scores were significantly improved from screening at all subsequent assessment times in both treatment groups (P < 0.001); >75% of participants had a >or=10% increase in GI tolerability scores from screening. Both dosing regimens were generally well tolerated. CONCLUSION: Self-selected monthly oral or quarterly intravenous ibandronate therapy was associated with high adherence rates among these postmenopausal women with osteoporosis or osteopenia who had previously discontinued oral bisphosphonate treatment because of GI intolerance.     

Ibandronate (Boniva): a new oral bisphosphonate

In a 3-year study with 2.5 mg of ibandronate daily in postmenopausal women with at least 1 pre-existing vertebral fracture, the drug reduced new vertebral fractures by 50%, but had no effect on non-vertebral fractures. The 150-mg once-monthly formulation of ibandronate was as effective as the daily one in increasing bone mineral density and decreasing bone turnover markers. It appears to be similar to alendronate and risedronate in efficacy and tolerability, but head-to-head comparisons are lacking.     

Treatment persistence with once-monthly ibandronate and patient support vs. once-weekly alendronate: results from the PERSIST study

Osteoporosis is a common and debilitating condition associated with significant morbidity and mortality. The efficacy and safety of oral bisphosphonates for the treatment of osteoporosis are well established. However, patient adherence and persistence on treatment are suboptimal. This randomised open-label multi-centre study of 6-months' duration compared persistence on treatment in postmenopausal women with osteoporosis receiving either once-monthly ibandronate plus a patient support programme (PSP), or once-weekly alendronate. To avoid falsely elevated persistence rates often associated with clinical trials, the study was designed to reflect everyday clinical practice in the UK and follow-up visits were limited to be consistent with the primary care setting. Analysis of the primary endpoint showed that persistence was significantly higher in the ibandronate/PSP group compared with the alendronate group (p < 0.0001). The estimated proportion of patients persisting with treatment at 6 months was 56.6% (306/541) and 38.6% (198/513) in the ibandronate/PSP and alendronate groups, respectively. Therefore, compared with alendronate, there was a 47% relative improvement in the proportion of patients persisting with treatment in the ibandronate/PSP group. Secondary endpoint measurements of adherence (e.g. proportion of patients remaining on treatment at study end; proportion of patients discontinuing from the study) were also significantly different in favour of ibandronate plus patient support. In summary, the PERSIST study demonstrated that persistence on treatment was increased in patients receiving once-monthly ibandronate plus patient support compared with once-weekly alendronate. Increased persistence on bisphosphonate treatment is expected to improve patient outcomes and decrease the social and economic burden of osteoporosis.     

Testing an Intervention for Preventing Osteoporosis in Postmenopausal Breast Cancer Survivors

Purpose: To test a 12-month multicomponent intervention for preventing or treating osteoporosis in 21 postmenopausal women who had completed treatment (except Tamoxifen) for breast cancer, and for whom hormone replacement therapy (HRT) was contraindicated.
Design: Pilot intervention study.
Methods: The intervention consisted of home-based strength and weight training exercises, 5 or 10 mg alendronate per day, 1500 mg calcium per day, 400 IU vitamin D per day, education on osteoporosis, and facilitative strategies to promote adherence to the intervention. Outcome measures were: adherence to the intervention, dynamic balance, muscle strength, and bone mineral density (BMD) of the hip, spine, and forearm.
Findings and Conclusions: Adherence to calcium, vitamin D, and alendronate therapy was above 95%, and adherence to strength training exercises was above 85%. Over the 12 months, the 21 participants had significant improvements in dynamic balance, muscle strength for hip flexion, hip extension, and knee flexion, and BMD of the spine and hip. Participants had a significant decrease in BMD of the forearm. Three of the 21 women who had measurable bone loss at baseline had normal BMD after 12 months of the intervention.     

Comparison of testosterone, alendronate, and a combination of both therapies in men with low bone mineral density.

BACKGROUND: Both bisphosphonates and testosterone are known to improve bone mineral density (BMD) in men with low bone mass, but whether combination therapy is superior to these agents used alone is not clear. We compared the changes in lumbar spine BMD when men with low bone mass were treated with each agent alone or as combination therapy. METHODS: In a retrospective study, we analyzed serum and BMD data from 149 men who had been evaluated in the Endocrinology Clinic at the Dallas Veterans Affairs Medical Center, Dallas, Texas. The subjects were divided into three cohorts: 59 men receiving testosterone therapy alone, 68 men receiving alendronate therapy alone, and 22 receiving combination therapy. RESULTS: Compared with the baseline values, the lumbar spine and BMD increased significantly in each of the testosterone, alendronate, and combination therapy cohorts (median annualized rate of change: 2.1% [p < .001], 2.6% [p < .001], and 2.5% [p = .04], respectively). The combination therapy group did not demonstrate any additional increase in BMD at the lumbar spine or total hip compared with either agent alone. The results did not change after adjusting for differences in baseline weight, age, BMD, or baseline testosterone level. CONCLUSION: The results suggest that the combination of testosterone and alendronate does not appear to be superior to single-drug therapy in our patient population.     

Effect of daily and intermittent use of ibandronate on bone mass and bone turnover in postmenopausal osteoporosis: a review of three phase II studies

BACKGROUND: Oral bisphosphonates are well established for the treatment and prevention of postmenopausal osteoporosis; however, they are poorly absorbed from the gastrointestinal (GI) tract and have been associated with GI adverse events. Thus, current dosing guidelines recommend that the patient not eat or lie down for at least 30 minutes after taking oral bisphosphonates, a requirement that is inconvenient and may be associated with reduced compliance. The drawbacks of these dosing requirements may be overcome either by reducing dosing frequency or by using alternative routes of administration. OBJECTIVE: Ibandronate is a potent nitrogen-containing bisphosphonate that can be given orally or IV, daily or intermittently, with a between-dose interval of up to 3 months. This article presents the results of published Phase II trials of the efficacy and safety profile of oral and IV ibandronate administered daily or intermittently to postmenopausal women with low bone mass. METHODS: MEDLINE was searched through January 2002 to identify all published Phase II clinical studies of oral and IV ibandronate in the treatment of post-menopausal osteoporosis. RESULTS: In the 3 Phase II studies identified, marked reductions in biochemical markers of bone resorption (50%-70%) and bone formation (40%-50%) were seen to a similar and statistically significant extent with oral ibandronate 2.5 mg/d (P<0.001), oral ibandronate 20 mg QOD given for 12 doses at the start of each 3-monthly period (P<0.001), and injections of ibandronate 2 mg IV given every 3 months (P<0.01). All treatment regimens produced comparable significant increases in bone mineral density at the lumbar spine (P<0.01) and hip (P<0.05). Ibandronate was well tolerated when administered both orally and as an IV injection. CONCLUSIONS: In these Phase II studies, oral or IV ibandronate, administered continuously or intermittently, reduced markers of bone turnover, significantly increased bone mineral density, and was well tolerated in the treatment of osteoporosis in postmenopausal women. The data from these studies provided the rationale for further investigation of ibandronate in larger longer-term Phase III studies evaluating its potential as an efficacious and flexible alternative to existing bisphosphonate regimens.     

Importance of Time Point–Specific Indirect Treatment Comparisons of Osteoporosis Treatments: A Systematic Literature Review and Network Meta-Analyses

PurposeThe efficacy comparison of osteoporosis treatments can be hindered by the absence of head-to-head trials; instead, network meta-analyses (NMAs) have been used to determine comparative effectiveness. This study was the first to investigate the impact of time point–specific NMAs of osteoporosis treatments on variability in treatments’ onset of action caused by their different mechanisms of actions and trial designs.MethodsA systematic literature review was conducted to identify randomized controlled trials (RCTs) of treatments for postmenopausal women with osteoporosis, including romosozumab (ROMO), teriparatide (TPTD), abaloparatide (ABL), alendronate (ALN), risedronate (RIS), ibandronate (IB), zoledronic acid/zoledronate (ZOL), denosumab (DEN), and raloxifene (RLX), on at least 1 fracture or bone mineral density (BMD) outcome. Of 100 RCTs identified in 5 databases, 27 RCTs were included for NMAs of new vertebral, nonvertebral, and hip fracture outcomes at 12, 24, and 36 months, and 47 RCTs were included for NMAs of BMD outcomes at lumbar spine, total hip, and femoral neck to compare the relative efficacy of osteoporosis treatments. Quality of included studies was assessed using the Cochrane Risk of Bias tool.FindingsFor vertebral fractures, TPTD (83.63%), ABL (69.11%), and ROMO/ALN (78.70%) had the highest probability to be the most effective treatment at 12, 24, and 36 months, respectively. ROMO/ALN had the highest probability (54.4%, 64.69%, and 90.29%, respectively) to be the most effective treatment for nonvertebral fractures at 12, 24, and 36 months. For hip fractures, ROMO/ALN (46.31%), ABL (61.1%), and DEN (55.21%) had the highest probability to be the most effective treatment at 12, 24, and 36 months, respectively. ROMO had the highest probability (76.06%, 44.19%, and 51.78%, respectively) to be the most effective treatment for BMD outcomes at lumbar spine, total hip, and femoral neck.ImplicationsThe importance of indirectly comparing available osteoporosis treatments using time point–specific NMAs was confirmed because indirect comparison results differed substantially across time points.     

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

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

Cyclosporine induces high bone turnover and may contribute to bone loss after heart transplantation

Cardiac transplantation has become a successful therapy for end-stage heart disease. However, increased bone loss has been observed in heart transplant recipients, sometimes being responsible for osteoporotic fractures. Glucocorticoids cause dose-related bone loss, particularly in the first 6–12 months of use, but cyclosporine might play a role as well. The evolution of bone mineral density (BMD) and biochemical parameters was prospectively assessed in 24 patients (mean age 52 years) from cardiac transplantation. All patients received cyclosporin A (CsA) and prednisone, the latter at decreasing dosage. The mean current daily dose of CsA was 321 mg and serum levels of CsA were constant. All patients received calcium (500 mg day⁻¹) and vitamin D (1000 U day⁻¹) for prevention of bone loss. BMD (g cm⁻²) was measured in 17 patients at the lumbar spine, femoral neck and total hip with dual energy X-ray absorptiometry every 6 months. Spinal BMD as well as neck and total hip BMD decreased at 6 and 12 months after transplantation, being statistically significant at the three sites: −5.6 and −3.4% for the lumbar spine, −9.3 and−8.5% for the femoral neck, −4.8% and −6.0% for the total hip respectively. Parathyroid hormone (PTH) and osteocalcin (BGP) increased by 90% and 800% respectively between pretransplantation values and 18 months after transplantation. BGP levels measured every 2 months from transplantation increased continuously from 8.7 μg L⁻¹ (mean ± SEM) before transplantation to 31.3 ± 10.1 (P<0.05) at 4 months, to 59.1 ± 8.8 (P<0.01) at 6 months and to 72.2 ± 9.9 (P<0.01) at 18 months (Kruskal–Wallis analysis: P<0.0001). PTH showed a biphasic pattern with an initial decrease from 39.3 ± 4.1 ng L⁻¹ at baseline to 22.0 ± 2.8 ng L⁻¹ at 2 months, but increasing thereafter to 45.9 ± 5.7 at 6 months and 74.2 ± 8.9 at 18 months (Kruskal–Wallis analysis: P<0.001). These variations represent a biochemical profile remarkably different from that of glucocorticoid-induced osteoporosis. In summary, cardiac transplant patients lose bone immediately after transplantation at the spine and the hip. Later on, the loss in BMD discontinues at all sites of the skeleton, but predominantly at the spine, and a few patients still lose bone at the hip. This is probably a result of the high bone turnover either due to secondary hyperparathyroidism or induced by cyclosporin A.     

Comparison of biochemical markers of bone remodelling in the assessment of the effects of alendronate on bone in postmenopausal osteoporosis.

The effects of alendronate treatment on biochemical markers of bone remodelling and bone mineral density (BMD) were studied in 30 Caucasian women (postmenopausal for at least 3 years, age 42-76 years, with BMD of the lumbar spine at least 2 S.D. below the mean for mature, premenopausal women). The patients were randomly assigned to receive alendronate (10 mg/day) or placebo for 12 months (double blind). The study was subsequently extended to a second year of open alendronate treatment. The treatment with alendronate resulted in a significant and progressive increase in BMD of the lumbar spine and femoral neck. Under the treatment, the maximal decrease of biochemical markers of bone remodelling (osteocalcin in plasma, bone-specific alkaline phosphatase, N-terminal propeptide of type I procollagen and C-terminal telopeptide of type I collagen in serum, and cross-linked amino-terminal N-telopeptide and total hydroxyproline in urine) was observed at 6 months with no further change during the 2-year period. There were no significant differences in discriminating between patients treated for 1 year with alendronate or placebo using either the percentage change in spine BMD at month 12, or a single measurement of the marker at month 6, or log (percent of baseline at month 6 of value of the marker). In this respect, the power of all the biochemical markers were comparable. The markers are a valuable adjunct to the measurements of BMD, especially in the patients not showing an increase of 3% or more at the lumbar spine BMD after 1 year of treatment.     

Age-related changes of serum bone alkaline phosphatase and cross-linked C-telopeptides of type I collagen and the relationship with bone mineral density in Chinese women

BACKGROUND: Previous studies have shown that bone turnover rate changes with age. At the same time, there is no definitive research regarding age-related changes of bone turnover level and its association with bone mineral density (BMD) in Chinese mainland women. METHODS: In a cohort of 663 Chinese mainland women aged 20-70 years, serum bone alkaline phosphatase (BAP) and serum cross-linked C-telopeptides of type I collagen (sCTX) were measured to evaluate the state of bone formation and resorption, respectively. BMD was measured in the posteroanterior spine, supine lateral spine, hip and forearm using a dual-energy X-ray absorptiometry. RESULTS: The cubic polynomial regression model best fit age-related changes in serum BAP (R2=0.398, p<0.001) and sCTX concentrations (R2=0.148, p<0.001) with largest R2 from comparison 8 different regression models. Their values reached a minimal level in the 30-39 years age group, and increased dramatically in the 40-59 years groups. There was a decreasing trend of BAP in women >60 years. The levels of BAP and sCTX were inversely correlated to BMD in various skeletal regions over the entire population (r=-0.096 to -0.357, p<0.05). sCTX was a significant predictor of a T-score< or =-2.5 of BMD in postmenopausal women with sCTX levels above mean+2 SD of women aged 30-39 years compared with other postmenopausal women, which indicated by odds ratios 1.9-3.7 (p<0.05) for various skeletal regions, especially for the lateral lumbar spine (2.2, p<0.01), Ward's triangle (3.7, p<0.01), and ultradistal end of radius + ulna (2.8, p<0.001). CONCLUSIONS: Age-dependent serum BAP and sCTX were inversely correlated to BMD, and sCTX was a useful parameter for the prediction of a low T-score of BMD at skeletal sites with abundant cancellous bone in postmenopausal women.     

Significance of a decline in bone mineral density while receiving oral bisphosphonate treatment

BACKGROUND: Oral bisphosphonates are routinely prescribed for the treatment of postmenopausal osteoporosis. In clinical trials, oral bisphosphonates have been found to increase bone mineral density (BMD) and decrease fracture risk in the majority of the treated population. However, in both clinical trials and clinical practice, not all patients experience significant increases in BMD. In clinical trials, nonresponse is often defined as a BMD change of 相似文献   

The safety and efficacy of early-stage bi-weekly alendronate to improve bone mineral density and bone turnover in chinese post-menopausal women at risk of osteoporosis

The efficacy and safety of early, low frequency antiresorptive drug intervention for osteopaenia on bone mineral density (BMD) and bone turnover in Chinese post-menopausal women at risk of developing osteoporosis were investigated. A total of 180 women aged 40 - 70 years were enrolled and equally randomized to receive either 70 mg alendronate once every 2 weeks plus 0.5 μg alfacalcidol daily (treatment group) or alfacalcidol 0.5 μg daily alone (control group) for 12 months. In the treatment group, lumbar spine and total hip BMD at 12 months had increased significantly from baseline and compared with the control group. There were also significant reductions in serum levels of the bone turnover biomarkers, bone-specific alkaline phosphatase and C-terminal telopeptide of type I collagen, compared with the control. No serious adverse events were observed in either group and safety profiles were similar. It was concluded that early intervention with 70 mg alendronate once every 2 weeks was safe, well tolerated and more effective than alfacalcidol alone (control) in increasing BMD and reducing bone turnover, and might prevent serious outcomes, such as fragility fractures, reduce rates of adverse effects and improve patient compliance.     

伊班膦酸钠对维持性血液透析骨质疏松患者骨密度的影响

目的 探讨伊班膦酸钠对维持性血液透析骨质疏松或骨量低下患者的治疗作用.方法 20例维持性血液透析骨质疏松或骨量低下患者随机分为两组(各10例).对照组血液透析3次/周,试验组在透析结束后加伊班膦酸钠静脉滴注,首次剂量1 mg,后续为2 mg/3个月,观察12个月.结果 治疗12个月后,对照组患者腰椎骨密度降低了16.6％(P＜0.01),试验组骨密度增加了2.9％,两组骨密度变化差异具有统计学意义(P＜0.01);两组髋部骨密度均有降低,但试验组变化幅度显著低于对照组(P＜0.01).对照组和试验组钙、磷水平比较差异无统计学意义(P＞0.05).不同时间点血磷水平差异有统计学意义(P＜0.05).结论 使用伊班膦酸钠可有效控制维持性血液透析患者骨量丢失,降低骨折风险.     

Comparison of the effects of once-monthly versus once-daily risedronate in postmenopausal osteoporosis: A phase II, 6-month,multicenter, randomized,double-blind,active-controlled,dose-ranging study

Background: Risedronate 5 mg/d is approved by the US Food and Drug Administration for the treatment and prevention of postmenopausal osteoporosis. Once-monthly dosing options might increase treatment compliance and persistence.Objective: The aim of this study was to compare the tolerability and efficacy of 3 once-monthly risedronate dosing regimens with those of risedronate 5 mg/d.Methods: This Phase II, 6-month, randomized, double-blind, active-controlled, dose-ranging study was conducted at 13 clinical research centers and hospitals in Croatia, Poland, Canada, and the United States between April 2004 and June 2005. Post-menopausal women aged 50 to 85 years with a lumbar spine T-score <-2.0 were randomly assigned to 1 of 4 treatment groups: risedronate 100, 150, or 200 mg/mo or 5 mg/d (active control), administered PO for 6 months. Evaluation of tolerability, the primary study objective, was based on adverse-event (AE) profiles and clinical laboratory values. Efficacy evaluation, a secondary objective, was a noninferiority comparison of the changes from baseline in bone mineral density (BMD) and bone turnover markers (BTMs).Results: Of 370 patients randomized (91, 88, 88, and 103 patients in the risedronate 100-, 150-, and 200-mg/mo and 5-mg/d groups, respectively), 57% were ≥65 years of age and 99% were white; 316 patients (85.4%) completed the study. Completion rates were not significantly different across treatment groups, nor were reasons for discontinuation. Between-group differences in the incidences of treatment-emergent AEs, serious AEs, and upper gastrointestinal (GI) AEs were nonsignificant. Overall, 6 (7%), 14 (16%), 6 (7%), and 9 patients (9%) withdrew because of AEs in the 100-, 150-, and 200-mg/mo and 5 mg/d groups, respectively. GI disorders were the AEs that most frequently led to study withdrawal (5 [5.5%], 7 [8.0%], 4 [4.5%], and 6 [5.8%]). No trends were observed in the nature or frequency of other AEs causing withdrawal. All serious AEs were considered unrelated to treatment, with the exception of erosive esophagitis in 1 patient (1%) who received the 5-mg/d dose. Mean percentage increases in BMD were 2.10%, 2.99%, and 3.38% with risedronate 100, 150, and 200 mg/mo, respectively, versus 3.05% with 5 mg/d. At the 2 higher monthly doses, the changes from baseline in BMD were not significantly different from those in the 5-mg/d group. Mean BTM values were decreased significantly from baseline in all 4 treatment groups, and the changes from baseline at 6 months at the 2 higher monthly doses were not significantly different from those at 5 mg/d.Conclusions: Overall, in this study, the safety profiles of risedronate 100, 150, and 200 mg/mo were not different from that of risedronate 5 mg/d. Changes in efficacy measures in the monthly treatment groups were considered dose related and were not significantly different between the 5-mg/d group and the 150- and 200-mg/mo groups; similarity was greatest with 150 mg/mo.     

Change in bone mineral density during adjuvant chemotherapy for early-stage breast cancer

Purpose

Adjuvant chemotherapy has been associated with loss of bone mineral density (BMD) either as a direct effect or due to glucocorticoids used as supportive care medication. A prospective cohort study was conducted to evaluate changes in BMD from baseline to right after completion of chemotherapy, i.e., 4 months.

Methods

Dual-imaging X-ray absorptiometry (DXA) was performed at baseline and after completing anthracycline- and taxane-based chemotherapy to measure BMD in the spine, hip, and forearm in early-stage breast cancer patients. High-dose prednisolone was used at three weekly intervals to reduce nausea and vomiting. Patients were advised a daily calcium/vitamin D supplement. Linear regression was used to assess mean percentage change in BMD and 95 % confidence intervals (95 % CI) according to doses of prednisolone, menopausal status, smoking, and BMI.

Results

Eight patients were excluded: seven because of initiation of bisphosphonate treatment due to osteoporosis at baseline, and one had non-interpretable DXA. The final cohort included 97 patients with a mean age of 53 years (range 34–72). Mean cumulative prednisolone dose was 1308 mg (95 % CI 1255; 1362). BMD increased 1.36 % (95 % CI 0.7; 2.0, p?<?0.001) in the spine and 1.27 % (95 % CI 0.9; 1.7, p?<?0.001) in the hip. Forearm BMD did not change. Postmenopausal women had increases in spine BMD of 2.35 % (95 % CI 1.1; 3.6, p?<?0.001) compared to premenopausal women. The spine BMD of current smokers decreased 1.67 % (95 % CI ?3.3; ?0.1, p?=?0.04) compared to never/former smokers.

Conclusions

Adjuvant chemotherapy supplemented with prednisolone was not associated with loss of BMD. Postmenopausal women gained bone mass, whereas current smokers lost bone mass.