Explore the vast range of titles available.

Persistent use of glucocorticoid drugs is associated with bone loss and increased fracture risk. Concurrent oral bisphosphonates increase bone mineral density and reduce frequency of vertebral fractures, but are associated with poor compliance and adherence. We aimed to assess whether one intravenous infusion of zoledronic acid was non-inferior to daily oral risedronate for prevention and treatment of glucocorticoid-induced osteoporosis. This 1-year randomised, double-blind, double-dummy, non-inferiority study of 54 centres in 12 European countries, Australia, Hong Kong, Israel, and the USA, tested the effectiveness of 5 mg intravenous infusion of zoledronic acid versus 5 mg oral risedronate for prevention and treatment of glucocorticoid-induced osteoporosis. 833 patients were randomised 1:1 to receive zoledronic acid (n=416) or risedronate (n=417). Patients were stratified by sex, and allocated to prevention or treatment subgroups dependent on duration of glucocorticoid use immediately preceding the study. The treatment subgroup consisted of those treated for more than 3 months (272 patients on zoledronic acid and 273 on risedronate), and the prevention subgroup of those treated for less than 3 months (144 patients on each drug). 62 patients did not complete the study because of adverse events, withdrawal of consent, loss to follow-up, death, misrandomisation, or protocol deviation. The primary endpoint was percentage change from baseline in lumbar spine bone mineral density. Drug efficacy was assessed on a modified intention-to-treat basis and safety was assessed on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT00100620. Zoledronic acid was non-inferior and superior to risedronate for increase of lumbar spine bone mineral density in both the treatment (least-squares mean 4·06% [SE 0·28] vs 2·71% [SE 0·28], mean difference 1·36% [95% CI 0·67–2·05], p=0·0001) and prevention (2·60% [0·45] vs 0·64% [0·46], 1·96% [1·04–2·88], p<0·0001) subgroups at 12 months. Adverse events were more frequent in patients given zoledronic acid than in those on risedronate, largely as a result of transient symptoms during the first 3 days after infusion. Serious adverse events were worsening rheumatoid arthritis for the treatment subgroup and pyrexia for the prevention subgroup. A single 5 mg intravenous infusion of zoledronic acid is non-inferior, possibly more effective, and more acceptable to patients than is 5 mg of oral risedronate daily for prevention and treatment of bone loss that is associated with glucocorticoid use. Novartis Pharma.

Bone metastases are a major burden in men with advanced prostate cancer. We compared denosumab, a human monoclonal antibody against RANKL, with zoledronic acid for prevention of skeletal-related events in men with bone metastases from castration-resistant prostate cancer. In this phase 3 study, men with castration-resistant prostate cancer and no previous exposure to intravenous bisphosphonate were enrolled from 342 centres in 39 countries. An interactive voice response system was used to assign patients (1:1 ratio), according to a computer-generated randomisation sequence, to receive 120 mg subcutaneous denosumab plus intravenous placebo, or 4 mg intravenous zoledronic acid plus subcutaneous placebo, every 4 weeks until the primary analysis cutoff date. Randomisation was stratified by previous skeletal-related event, prostate-specific antigen concentration, and chemotherapy for prostate cancer within 6 weeks before randomisation. Supplemental calcium and vitamin D were strongly recommended. Patients, study staff, and investigators were masked to treatment assignment. The primary endpoint was time to first on-study skeletal-related event (pathological fracture, radiation therapy, surgery to bone, or spinal cord compression), and was assessed for non-inferiority. The same outcome was further assessed for superiority as a secondary endpoint. Efficacy analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00321620, and has been completed. 1904 patients were randomised, of whom 950 assigned to denosumab and 951 assigned to receive zoledronic acid were eligible for the efficacy analysis. Median duration on study at primary analysis cutoff date was 12·2 months (IQR 5·9–18·5) for patients on denosumab and 11·2 months (IQR 5·6–17·4) for those on zoledronic acid. Median time to first on-study skeletal-related event was 20·7 months (95% CI 18·8–24·9) with denosumab compared with 17·1 months (15·0–19·4) with zoledronic acid (hazard ratio 0·82, 95% CI 0·71–0·95; p=0·0002 for non-inferiority; p=0·008 for superiority). Adverse events were recorded in 916 patients (97%) on denosumab and 918 patients (97%) on zoledronic acid, and serious adverse events were recorded in 594 patients (63%) on denosumab and 568 patients (60%) on zoledronic acid. More events of hypocalcaemia occurred in the denosumab group (121 [13%]) than in the zoledronic acid group (55 [6%]; p<0·0001). Osteonecrosis of the jaw occurred infrequently (22 [2%] vs 12 [1%]; p=0·09). Denosumab was better than zoledronic acid for prevention of skeletal-related events, and potentially represents a novel treatment option in men with bone metastases from castration-resistant prostate cancer. Amgen.

This large trial tested the effect of adding zoledronic acid to adjuvant endocrine treatment (goserelin plus tamoxifen or anastrozole) in premenopausal women with early-stage breast cancer. The results show that adding zoledronic acid to adjuvant endocrine therapy prolongs disease-free survival in these patients without adding substantially to the burden of adverse events. These results show that adding zoledronic acid to adjuvant endocrine therapy prolongs disease-free survival in premenopausal women with early-stage breast cancer. The optimal management of endocrine-responsive early breast cancer in premenopausal women remains controversial. Although aromatase inhibitors have shown benefits beyond those of tamoxifen in postmenopausal women, 1 – 6 their benefits in premenopausal women, among whom endocrine-responsive disease accounts for 62% of early breast cancers, are unknown. 7 The combination of ovarian suppression with the use of gonadotropin-releasing hormone analogues and tamoxifen is a standard of care for premenopausal women because it is at least as effective as established cytotoxic chemotherapy regimens and is better tolerated than chemotherapy. 8 – 12 In a study involving premenopausal women with advanced breast cancer, ovarian suppression combined with . . .

This multicenter trial evaluated zoledronic acid versus placebo in men with osteoporosis for a primary end point of new morphometric vertebral fracture over 24 months. Zoledronic acid was associated with a significantly reduced risk of vertebral fracture. Osteoporosis is an important cause of morbidity and mortality among men. 1 , 2 Among persons older than 50 years of age, approximately 40% of all osteoporotic fractures worldwide occur in men. 3 Mortality after osteoporotic fracture is higher among men than among women. 2 , 4 Previous studies involving men with osteoporosis have focused on the surrogate outcomes of bone mineral density and bone-turnover markers, 5 – 9 but data from double-blind, randomized studies assessing antifracture efficacy are lacking. In addition, given the low awareness of the disease, 10 the development of guidelines for the detection and treatment of osteoporosis in men has been limited. 11 Hence, there . . .

Analysis of the Austrian Breast and Colorectal Cancer Study Group trial-12 (ABCSG-12) at 48 months' follow-up showed that addition of zoledronic acid to adjuvant endocrine therapy significantly improved disease-free survival. We have now assessed long-term clinical efficacy including disease-free survival and disease outcomes in patients receiving anastrozole or tamoxifen with or without zoledronic acid. ABSCG-12 is a randomised, controlled, open-label, two-by-two factorial, multicentre trial in 1803 premenopausal women with endocrine-receptor-positive early-stage (stage I–II) breast cancer receiving goserelin (3·6 mg every 28 days), comparing the efficacy and safety of anastrozole (1 mg per day) or tamoxifen (20 mg per day) with or without zoledronic acid (4 mg every 6 months) for 3 years. Randomisation (1:1:1:1 ratio) was computerised and based on the Pocock and Simon minimisation method to balance the four treatment arms across eight prognostic variables (age, neoadjuvant chemotherapy, pathological tumour stage; lymph-node involvement, type of surgery or locoregional therapy, complete axillary dissection, intraoperative radiation therapy, and geographical region). Treatment allocation was not masked. The primary endpoint was disease-free survival (defined as disease recurrence or death) and analysis was by intention to treat. This trial is registered with ClinicalTrials.gov, number NCT00295646; follow-up is ongoing. At a median follow-up of 62 months (range 0–114·4 months), more than 2 years after treatment completion, 186 disease-free survival events had been reported (53 events in 450 patients on tamoxifen alone, 57 in 453 patients on anastrozole alone, 36 in 450 patients on tamoxifen plus zoledronic acid, and 40 in 450 patients on anastrozole plus zoledronic acid). Zoledronic acid reduced risk of disease-free survival events overall (HR 0·68, 95% CI 0·51–0·91; p=0·009), although the difference was not significant in the tamoxifen (HR 0·67, 95% CI 0·44–1·03; p=0·067) and anastrozole arms (HR 0·68, 95% CI 0·45–1·02; p=0·061) assessed separately. Zoledronic acid did not significantly affect risk of death (30 deaths with zoledronic acid vs 43 deaths without; HR 0·67, 95% CI 0·41–1·07; p=0·09). There was no difference in disease-free survival between patients on tamoxifen alone versus anastrozole alone (HR 1·08, 95% CI 0·81–1·44; p=0·591), but overall survival was worse with anastrozole than with tamoxifen (46 vs 27 deaths; HR 1·75, 95% CI 1·08–2·83; p=0·02). Treatments were generally well tolerated, with no reports of renal failure or osteonecrosis of the jaw. Bone pain was reported in 601 patients (33%; 349 patients on zoledronic acid vs 252 not on the drug), fatigue in 361 (20%; 192 vs 169), headache in 280 (16%; 147 vs 133), and arthralgia in 266 (15%; 145 vs 121). Addition of zoledronic acid improved disease-free survival in the patients taking anastrozole or tamoxifen. There was no difference in disease-free survival between patients receiving anastrozole and tamoxifen overall, but those on anastrozole alone had inferior overall survival. These data show persistent benefits with zoledronic acid and support its addition to adjuvant endocrine therapy in premenopausal patients with early-stage breast cancer. AstraZeneca; Novartis.

Mortality is increased in the year after a hip fracture, and strategies that improve the outcome are needed. This randomized, double-blind, placebo-controlled trial compared yearly intravenous zoledronic acid with placebo first administered within 90 days after surgical repair of a hip fracture in patients who were unable or unwilling to take oral bisphosphonates. Zoledronic acid was associated with a reduced relative risk of a new clinical fracture and a reduction in mortality from all causes. This trial compared yearly zoledronic acid with placebo after surgical repair of a hip fracture. Zoledronate was associated with a reduced relative risk of a new clinical fracture and a reduction in mortality from all causes. Hip fractures are associated with increased morbidity, functional decline, and death in older adults, as well as increased use of health care services. 1 , 2 Mortality is increased in the year after hip fracture, with reported rates of 15 to 25% and an estimated 9 excess deaths per 100 patients among women 70 years of age or older. 2 – 10 One source of the excess morbidity and cost incurred by patients with hip fractures is new osteoporotic fractures. Such fractures occur at a rate of 10.4 per 100 patients per year, which is 2.5 times as high as the rate in age-matched . . .

Osteoporosis Choice, an encounter decision aid, can engage patients and clinicians in shared decision making about osteoporosis treatment. Its effectiveness compared to the routine provision to clinicians of the patient's estimated risk of fracture using the FRAX calculator is unknown. Patient-level, randomized, three-arm trial enrolling women over 50 with osteopenia or osteoporosis eligible for treatment with bisphosphonates, where the use of Osteoporosis Choice was compared to FRAX only and to usual care to determine impact on patient knowledge, decisional conflict, involvement in the decision-making process, decision to start and adherence to bisphosphonates. We enrolled 79 women in the three arms. Because FRAX estimation alone and usual care produced similar results, we grouped them for analysis. Compared to these, use of Osteoporosis Choice increased patient knowledge (median score 6 vs. 4, p = .01), improved understanding of fracture risk and risk reduction with bisphosphonates (p = .01 and p<.0001, respectively), had no effect on decision conflict, and increased patient engagement in the decision making process (OPTION scores 57% vs. 43%, p = .001). Encounters with the decision aid were 0.8 minutes longer (range: 33 minutes shorter to 3.0 minutes longer). There were twice as many patients receiving and filling prescriptions in the decision aid arm (83% vs. 40%, p = .07); medication adherence at 6 months was no different across arms. Supporting both patients and clinicians during the clinical encounter with the Osteoporosis Choice decision aid efficiently improves treatment decision making when compared to usual care with or without clinical decision support with FRAX results. clinical trials.gov NCT00949611.

Summary We used bone turnover markers to identify women who responded to bisphosphonate treatment for osteoporosis. Response was more likely with alendronate and ibandronate than risedronate. There was a greater decrease in bone markers if baseline bone turnover markers were higher and if the patient took more than 80 % of her medication. Introduction Biochemical response to bisphosphonate therapy can be assessed using either a decrease in bone turnover marker beyond the least significant change (LSC) or a reduction to within a reference interval (RI). We compared the performance of these target responses and determined whether response was related to the type of bisphosphonate, compliance and baseline bone turnover markers. Methods Biochemical responses to three oral bisphosphonates were assessed in an open, controlled trial comprising 172 postmenopausal osteoporotic women (age 53–84 years), randomised to alendronate, ibandronate or risedronate, plus calcium and vitamin D supplementation for 2 years. The LSC for each marker was derived within the study population, whereas RIs were obtained from a control group of healthy premenopausal women (age 35–40 years). Results Over 70 % of women achieved a target response for serum CTX and PINP, irrespective of the approach used. The percentage decrease at 12 weeks was greater for women with baseline PINP above the RI −63 % (difference 13 %, 95 % CI 0 to 27.1, P  = 0.049) and good compliance −67 % (difference 15.9 %, 95 % CI 6.3 to 25.5, P  = 0.001). Responders had a greater increase in spine bone density compared to nonresponders; for example 6.2 vs. 2.3 % (difference 3.9 %, 95 % CI 1.6 to 6.3, P  = 0.0011) for PINP LSC. The magnitude of change in bone markers was greater with ibandronate and alendronate than risedronate. Conclusions Both approaches to response identified similar proportions of women as responders. Nonresponders had smaller increases in BMD, and we suggest that biochemical assessment of response is a useful tool for the management of women with postmenopausal osteoporosis.

A large, randomized trial has shown that the addition of zoledronic acid to adjuvant chemotherapy in patients with early-stage breast cancer does not influence rates of recurrence or survival. Metastasis is a complex process that is dependent on both the biologic features of the primary tumor and cellular interactions within host tissues. In the bone microenvironment, cancer cells stimulate osteoblasts to release receptor activator of nuclear factor κB ligand (RANKL), which binds to its receptor, RANK, on both precursor and mature osteoclasts. The resulting increase in osteoclastic bone resorption leads to the release of bone-derived growth factors that may provide a fertile environment for survival and growth of adjacent cancer cells. 1 Thus, targeting bone-cell function provides a potential additional approach to preventing bone metastases as a component of standard . . .

AbstractObjectiveTo estimate the effect of denosumab compared with oral bisphosphonates on reducing the risk of type 2 diabetes in adults with osteoporosis.DesignPopulation based study involving emulation of a randomized target trial using electronic health records.SettingIQVIA Medical Research Data primary care database in the United Kingdom, 1995-2021.ParticipantsAdults aged 45 years or older who used denosumab or an oral bisphosphonate for osteoporosis.Main outcome measuresThe primary outcome was incident type 2 diabetes, as defined by diagnostic codes. Cox proportional hazards models were used to estimate adjusted hazard ratios and 95% confidence intervals, comparing denosumab with oral bisphosphonates using an as treated approach.Results4301 new users of denosumab were matched on propensity score to 21 038 users of an oral bisphosphonate and followed for a mean of 2.2 years. The incidence rate of type 2 diabetes in denosumab users was 5.7 (95% confidence interval 4.3 to 7.3) per 1000 person years and in oral bisphosphonate users was 8.3 (7.4 to 9.2) per 1000 person years. Initiation of denosumab was associated with a reduced risk of type 2 diabetes (hazard ratio 0.68, 95% confidence interval 0.52 to 0.89). Participants with prediabetes appeared to benefit more from denosumab compared with an oral bisphosphonate (hazard ratio 0.54, 0.35 to 0.82), as did those with a body mass index ≥30 (0.65, 0.40 to 1.06).ConclusionsIn this population based study, denosumab use was associated with a lower risk of incident type 2 diabetes compared with oral bisphosphonate use in adults with osteoporosis. This study provides evidence at a population level that denosumab may have added benefits for glucose metabolism compared with oral bisphosphonates.