Bisphosphonates In Women Research Articles

Fracture risk after deprescription of bisphosphonates: Application of real-world data in primary care

PurposeTo compare the effect of discontinuing bisphosphonate treatment on fracture risk in postmenopausal women at high versus low risk of fracture. DesignRetrospective, longitudinal and population-based cohort study. SettingBarcelona City Primary Care. Catalan Health Institute. ParticipantsAll women attended by primary care teams who in January 2014 had received bisphosphonate treatment for at least five years were included and followed for another five years. InterventionPatients were classified according to their risk of new fractures, defined as those who had a history of osteoporotic fracture and/or who received treatment with an aromatase inhibitor, and the continuity or deprescription of the bisphosphonate treatment was analyzed over fiver year follow-up. Main measurementsThe cumulative incidence of fractures and the incidence density were calculated and analyzed using logistic regression and Cox models. ResultsWe included 3680 women. There were no significant differences in fracture risk in high-risk women who discontinued versus continued bisphosphonate treatment (hazard ratio [HR] 1.17, 95% confidence interval [CI] 0.87–1.58 for total osteoporotic fractures). However, discontinuers at low risk had a lower incidence of fracture than continuers. This difference was significant for vertebral fractures (HR 0.64, 95% CI 0.47–0.88) and total fractures (HR 0.77, 95% CI 0.64–0.92). ConclusionOur results suggest that deprescribing bisphosphonates in women who have already received five years of treatment does not increase fracture risk. In low-risk women, continuing this treatment might could even favor the appearance of new osteoporotic fractures.

Effects of Bisphosphonates Treatments in Osteopenic Older Women: A Systematic Review and Meta-Analysis

Aims: To review the effects of bisphosphonates on bone density, fractures, and bone markers in osteopenic older women. Methods: Relevant articles published before February 2022 were searched in PubMed, EMBASE, and the Cochrane Library. All randomized controlled trials that reported incident fractures, bone mineral density (BMD), bone markers, or adverse events with bisphosphonates in osteopenic older women were included. The quality of included studies was assessed using the Cochrane Risk of Bias tool. The risk ratios (RRs) for fractures, net percent change in bone mineral density and differences in bone markers were calculated using a meta-analysis. Results: A total of 11 studies were included in our meta-analysis. Bisphosphonates significantly increased the percent changes in the lumbar spine BMD (WMD, 5.60; 95% CI, 4.16–7.03; I 2 = 93.6%), hip BMD (WMD, 4.80; 95% CI, 2.93 to 6.66; I 2 = 97.1%), total body BMD (WMD, 3.24; 95% CI, 2.12–4.35; I 2 = 90.9%), femoral neck BMD (WMD, 4.02; 95% CI, 1.70–6.35; I 2 = 91.8%) and trochanter BMD (WMD, 5.22; 95% CI, 3.51–6.93; I 2 = 83.6%) when compared to placebo. Zoledronate was associated with a great treatment effect on fragility fracture (RR, 0.63; 95% CI, 0.50–0.79), clinical vertebral fracture (RR, 0.41; 95% CI, 0.22–0.76), and radiographic vertebral fracture (RR, 0.60; 95% CI, 0.27–1.35) compared to placebo. Meanwhile, alendronate was also associated with beneficial effects on fragility fracture (RR, 0.40; 95% CI, 0.15–1.07), clinical vertebral fracture (RR, 0.46; 95% CI, 0.17–1.24), and radiographic vertebral fracture (RR, 0.64; 95% CI, 0.38–1.09). In addition, the use of bisphosphonates reduced the concentration of procollagen type I N-terminal propeptide (PINP) and C-terminal telopeptide of type I collagen (CTX) over placebo by 15.79 (95% CI, −18.92 to −12.66; I 2 = 28.4%), −0.23 (95% CI, −0.35 to −0.10; I 2 = 91.3%), respectively. Although there was insufficient evidence to determine their safety, these bisphosphonates may have an effect on cancer, cardiac events, and mortality in osteopenic older women. Conclusion: All bisphosphonates examined were associated with beneficial effects on fractures, BMD, and bone markers in women with osteopenia. Further randomized controlled trials are necessary to clarify the safety of bisphosphonates in women with osteopenia.

Bisphosphonate Use and Hospitalization for Hip Fractures in Women: An Observational Population-Based Study in France.

Bisphosphonates are widely used in the treatment of women at risk of osteoporotic hip fracture; however, the overall effectiveness of bisphosphonates in the prevention of osteoporotic fractures has not been studied in real life. To investigate whether the use of bisphosphonates in women aged 50 years and over is associated with a decrease in hospitalization for osteoporotic hip fractures, a historical prospective cohort study was conducted between 2009 and 2016 from a permanent representative sample consisting of 1/97 of the French health insurance beneficiaries. Bisphosphonate use was defined according to medication persistence and adherence regarding bisphosphonate dispensations. The primary outcome was the hospitalization rate for osteoporotic hip fracture. Among the 81,268 women included, 2005 were exposed to bisphosphonates. The median time of bisphosphonate exposure was 12 (IQR, 3–29) and 17 (IQR, 5–42) months for the persistence and adherence definitions, respectively. Exposure to bisphosphonates was not associated with a decrease in hospitalization for hip fracture: weighted HRadherence = 0.66 (95% CI, 0.33 to 1.33); HRpersistance = 0.77 (95% CI, 0.38 to 1.57). In real life, bisphosphonate use does not appear to reduce hospitalization for hip fractures, as to date, it is probably prescribed as primary prevention and for a duration too short to be effective.

Efficacy of Denosumab Therapy Following Treatment with Bisphosphonates in Women with Osteoporosis: A Cohort Study.

Denosumab is a human monoclonal antibody that neutralizes RANKL, a cytokine able to interact with the RANK receptor on preosteoclasts and osteoclasts, decreasing their recruitment and differentiation, leading to a decreased bone resorption. The aim of this observational real-life study was to analyze adherence to denosumab therapy and assess its efficacy in increasing bone mineral density (BMD) and modulating biochemical skeletal markers following previous treatments with bisphosphonates in a group of post-menopausal women with osteoporosis. Women were recruited in the specialized center from March 2012 to September 2019. Biochemical markers were recorded at baseline and every six months prior to subsequent drug injection. Dual X-ray absorptiometry was requested at baseline and after 18/24 months. Comparing BMD at baseline and after denosumab therapy in naive patients and in those previously treated with bisphosphonates, a positive therapeutic effect was observed in both groups. The results of our real-life study demonstrate, as expected, that BMD values significantly increased upon denosumab treatment. Interestingly, denosumab showed an increased efficacy in patients previously treated with bisphosphonates. Moreover, biochemical markers data indicate that osteoporotic patients, without other concomitant unstable health conditions, could be evaluated once a year, decreasing the number of specialistic center access.

A broader strategy for osteoporosis interventions.

Approximately 50% of women experience at least one bone fracture postmenopause. Current screening approaches target anti-fracture interventions to women aged >60 years who satisfy clinical risk and bone mineral density criteria for osteoporosis. Intervention is only recommended in 7-25% of those women screened currently, well short of the 50% who experience fractures. Large screening trials have not shown clinically significant decreases in the total fracture numbers. By contrast, six large clinical trials of anti-resorptive therapies (for example, bisphosphonates) have demonstrated substantial decreases in the number of fractures in women not identified as being at high risk of fracture. This finding suggests that broader use of generic bisphosphonates in women selected by age or fracture risk would result in a reduction in total fracture numbers, a strategy likely to be cost-effective. The utility of the current bone density definition of osteoporosis, which neither corresponds with who suffers fractures nor defines who should be treated, requires reappraisal.

Reproductive safety of bisphosphonates in women of childbearing age

Bisphosphonates (BPs) are bone resorption inhibitors, which are increasingly used in the treatment of bone metabolic diseases in women of childbearing age. It is unclear whether the use of BPs in women of childbearing age will affect the health of their offspring. This article retrieved 66 reports in the past 40 years by searching on the databases of Pubmed, Embase, Ovid, Medline and so on. A number of reports found that BPs may be responsible for shortening gestational age, increasing spontaneous abortion, and decreasing neonatal birth weight. Three women′s offsprings were found to have abnormal blood calcium after birth. Cases of skeletal malformations include two bilateral talipes equinus, one Apert′s syndrome and one rickets. However, there have been many reports of no reproductive abnormalities or abnormal blood calcium level. Occasionally, children breast-fed by women who had received BPs have had a transient hypocalcemia. There is currently insufficient evidence to confirm that BPs can cause significant reproductive malformations during pregnancy or pre-pregnancy. However, due to the long-term presence of BPs in the bones, women of childbearing age who have a need for pregnancy should choose to use these drugs with caution. Key words: Bisphosphonate; Women of childbearing age; Reproductive safety; Breast-feeding; Pregnancy; Fetus

A five-year prospective study of spinal radiographic progression and its predictors in men and women with ankylosing spondylitis

BackgroundKnowledge about predictors of new spinal bone formation in patients with ankylosing spondylitis (AS) is limited. AS-related spinal alterations are more common in men; however, knowledge of whether predictors differ between sexes is lacking. Our objectives were to study spinal radiographic progression in patients with AS and investigate predictors of progression overall and by sex.MethodsSwedish patients with AS, age (mean ± SD) 50 ± 13 years, were included in a longitudinal study. At baseline and at 5-year follow up, spinal radiographs were graded according to the modified Stoke Ankylosing Spondylitis Spine Score (mSASSS). Predictors were assessed by questionnaires, spinal mobility tests and blood samples.ResultsOf 204 patients included, 166 (81%) were re-examined and 54% were men. Men had significantly higher mean mSASSS at baseline and higher mean increase in mSASSS than women (1.9 ± 2.8 vs. 1.2 ± 3.3; p = 0.005) More men than women developed new syndesmophytes (30% vs. 12%; p = 0.007). Multivariate logistic regression analyses with progression ≥ 2 mSASSS units over 5 years or development of new syndesmophytes as the dependent variable showed that presence of baseline AS-related spinal radiographic alterations and obesity (OR 3.78, 95% CI 1.3 to 11.2) were independent predictors of spinal radiographic progression in both sexes. High C-reactive protein (CRP) was a significant predictor in men, with only a trend seen in women. Smoking predicted progression in men whereas high Bath Ankylosing Spondylitis Metrology Index (BASMI) and exposure to bisphosphonates during follow up (OR 4.78, 95% CI 1.1 to 20.1) predicted progression in women.ConclusionThis first report on sex-specific predictors of spinal radiographic progression shows that predictors may partly differ between the sexes. New predictors identified were obesity in both sexes and exposure to bisphosphonates in women. Among previously known predictors, baseline AS-related spinal radiographic alterations predicted radiographic progression in both sexes, high CRP was a predictor in men (with a trend in women) and smoking was a predictor only in men.Trial registrationClinicalTrials.gov, NCT00858819. Registered on 9 March 2009. Last updated 28 May 2015.

What are the effects of bisphosphonates in women with early breast cancer?

What are the effects of bisphosphonates in women with early breast cancer?

The effect of denosumab or bisphosphonates in women with severe postmenopausal osteoporosis after completion of teriparatide treatment

The effect of denosumab or bisphosphonates in women with severe postmenopausal osteoporosis after completion of teriparatide treatment

Age-related differences in persistence with bisphosphonates in women with metastatic breast cancer

AimsTo investigate age-related persistence with bisphosphonates (BIS) in women with breast cancer (BC) and bone metastases. MethodsWe included a dataset of 1541 patients diagnosed with BC and bone metastases and initially treated with BIS between 1994 and 2013. The primary outcome measure was the age-related rate of BIS discontinuation within 12 months after treatment initiation. Therapy discontinuation was defined as a period of at least 90 days without treatment. A multivariate Cox regression model was created to determine the influence of age on the risk of discontinuation. Health insurance coverage (private/statutory), type of care (gynecological/general), region (West/East Germany), depression, chemotherapy, hormone therapy, pain medication, antidepressants, and the number of co-medications were included as covariates. ResultsThe mean ages in the group of women <70 and that of women ≥70 years of age were 55.7 (SD: 9.8) and 76.7 (SD: 5.1) years respectively. Within 12 months after treatment initiation, 44.3% of women <70 and 34.8% of women ≥70 had terminated treatment (p-value<0.001). Patients aged ≥70 were at a lower risk of treatment discontinuation than patients <70 (HR=0.78, 95% CI: 0.67–0.91). Furthermore, treatment in gynecological practices, chemotherapy, hormone therapy, pain medication, and number of co-medications decreased the risk of discontinuation. By contrast, residing in West Germany and private health insurance coverage increased discontinuation risk. ConclusionsWomen with metastatic BC aged ≥70 are at a lower risk of BIS treatment discontinuation than younger women.

Risk of atypical femoral fracture during and after bisphosphonate use

Background and purpose — Use of bisphosphonates in women is associated with higher risk of atypical femoral fractures. The risk in terms of timing of use and type of bisphosphonate, and in men, remains unclear. Patients and methods — We reviewed radiographs of 5,342 Swedish women and men aged 55 years or more who had had a fracture of the femoral shaft in the 3-year period 2008–2010 (97% of those eligible), and found 172 patients with atypical fractures (93% of them women). We obtained data on medication and comorbidity. The risk of atypical fracture associated with bisphosphonate use was estimated in a nationwide cohort analysis. In addition, we performed a case-control analysis with comparison to 952 patients with ordinary shaft fractures. A short report of the findings has recently been presented (Schilcher et al. 2014a). Here we provide full details. Results — The age-adjusted relative risk (RR) of atypical fracture associated with bisphosphonate use was 55 (95% CI: 39–79) in women and 54 (CI: 15–192) in men. In bisphosphonate users, women had a 3-fold higher risk than men (RR = 3.1, CI: 1.1–8.4). Alendronate users had higher risk than risedronate users (RR = 1.9, CI: 1.1–3.3). The RR after 4 years or more of use reached 126 (CI: 55–288), with a corresponding absolute risk of 11 (CI: 7–14) fractures per 10,000 person-years of use. The risk decreased by 70% per year since last use. Interpretation — Women have a higher risk of atypical femoral fracture than men. The type of bisphosphonate used may affect risk estimates and the risk decreases rapidly after cessation.

Effect of oral bisphosphonates for osteoporosis on development of skeletal metastases in women with breast cancer: results from a pharmaco-epidemiological study.

Treatment with bisphosphonates in women with breast cancer and established bone metastasis delays further skeletal-related events. Evidence is emerging that bisphosphonates are beneficial for secondary prevention of bone metastasis. The study aimed to estimate the effect of oral bisphosphonates for treatment or prevention of osteoporosis on development of bone metastasis in a population of women with breast cancer. A historical cohort of 21664 women diagnosed with breast cancer was created from health administrative data in Quebec, Canada. The primary outcome was time to develop bone metastasis; exposure was bisphosphonate use prediagnosis, postdiagnosis, both, or neither and a cumulative index of drug exposure. The sample was stratified according to stage (0-II or III) at time of diagnosis. Cox proportional hazards tested the effect of bisphosphonate use on time to develop bone metastases. Taking bisphosphonates postdiagnosis of breast cancer only or continuing bisphosphonates started prior to diagnosis after diagnosis was associated with a reduction in risk of bone metastasis from 45% to 28% in women with local disease at diagnosis. In women with regional disease, postdiagnosis bisphosphonate use, with or without prediagnosis use, reduced risk by almost 50%. A statistically significant dose-response trend was observed relating increased use to lower risk (slope = 0.94, 95% confidence interval = 0.90 to 0.99). Bisphosphonates were also associated with a decreased risk of all-cause mortality similar to that of the development of bone metastasis. Low-dose oral bisphosphonates administered for prevention or treatment of postmenopausal osteoporosis were associated with lower risk of skeletal metastasis in patients with early- or more advanced-stage breast cancer.

Denosumab: A Review of its Use in Postmenopausal Women with Osteoporosis

Subcutaneous denosumab (Prolia(®) [USA, Europe]; Pralia(®) [Japan]) once every 6 months is indicated in several countries for the treatment of postmenopausal women with osteoporosis at increased or high risk for fractures (featured indication). In some countries, it is also indicated for use in postmenopausal women who have failed or are intolerant to other osteoporosis treatments. In several international, phase III trials (≤3 years' duration) involving more than 12,000 women with postmenopausal osteoporosis or low bone mineral density (BMD), including Asian studies, denosumab was an effective and generally well tolerated treatment. Relative to placebo, denosumab treatment significantly reduced the risk of vertebral, nonvertebral and hip fractures and increased BMD at all skeletal sites evaluated, including the lumbar spine and total hip. Furthermore, the benefits of denosumab treatment were generally evident after the first dose and were maintained during up to 8 years of treatment in an ongoing extension study. The tolerability profile of denosumab during this extension phase was consistent with that observed during the initial 3-year FREEDOM trial. At 12 months, denosumab treatment increased BMD at the total hip, lumbar spine and/or femoral neck and reduced markers of bone turnover to a significantly greater extent than oral bisphosphonates in women who were essentially bisphosphonate-naive and in those who had switched from alendronate to denosumab treatment. Further clinical experience, including an ongoing postmarketing safety study, will more fully define the long-term safety of denosumab. In the meantime, denosumab is an important option for the treatment of women with postmenopausal osteoporosis at increased or high-risk of fractures, including in women at increased risk of fracture who are unable to take other osteoporosis treatments.

Improving the Use of Intravenous Bisphosphonates in Women With Breast Cancer Metastatic to Bone

The City of Hope Comprehensive Cancer Center has a long commitment to the creation of and adherence to treatment guidelines. The NCCN Opportunities for Improvement project provided the institution with a report card for adherence to the NCCN Clinical Practice Guidelines in Oncology for Breast Cancer and the opportunity to determine reasons for nonconcurrence and improve concurrence rates. The institution focused on improving compliance with the use of intravenous bisphosphonates in women with metastatic bone disease.

A Review of Osteoporosis Management in Younger Premenopausal Women

The purpose of this review is to describe the available evidence for osteoporosis treatments in young and premenopausal women. A review of articles evaluating the treatment or prevention of osteoporosis in young (age less than 50 years) or premenopausal women was conducted. Several trials evaluating the treatment of anorexia nervosa and use of hormone therapy in those women, the use of bisphosphonates in women undergoing chemotherapy for breast cancer and the use of bisphosphonates, teriparatide and vitamin D in women with glucocorticoid-induced osteoporosis are described. Limited data were found to support the treatment of osteoporosis in women with idiopathic osteoporosis or cystic fibrosis, or after kidney transplant. The evidence for treatment of osteoporosis in premenopausal women is not nearly as robust as that for postmenopausal osteoporosis. Although fracture risk in the premenopausal population is low, women with secondary osteoporosis may benefit from treatment with various agents, depending upon the condition.

The non-interventional BonViva Intravenous Versus Alendronate (VIVA) study: real-world adherence and persistence to medication, efficacy, and safety, in patients with postmenopausal osteoporosis

Adherence and persistence to oral bisphosphonates in women with postmenopausal osteoporosis is suboptimal. In this study, patients were treated with either oral or intravenous bisphosphonates. The increased adherence and persistence observed in patients receiving intravenous medication compared with those receiving oral medication may improve health outcomes. Poor adherence and persistence to oral medication are often observed in women with postmenopausal osteoporosis (PMO). The purpose of the non-interventional BonViva Intravenous Versus Alendronate (VIVA) study was to determine whether, in a real-world setting, (1) increased adherence and persistence to medication would be observed in women with PMO receiving intravenous (i.v.) ibandronate versus oral alendronate, (2) a correlation exists between adherence and persistence to medication and drug efficacy, and (3) any unexpected adverse events/serious adverse events (AEs/SAEs) may occur. The study was conducted in 632 centers in Germany. A total of 6,064 females with PMO were enrolled and recruited into one of two treatment arms: quarterly i.v. administration of 3 mg ibandronate or weekly oral medication of 70 mg alendronate, for 12 months. At the end of the study, adherence and persistence to medication, new osteoporotic fractures, mobility, use of analgesics, and AEs/SAEs were determined. Greater adherence and persistence to medication were observed in the ibandronate treatment arm compared with the alendronate treatment arm. Although there was no significant difference in the number of patients with new vertebral, hip, or forearm fractures between treatment arms, a significantly greater increase in mobility and decrease in the use of analgesics were reported in the ibandronate treatment arm. No unexpected AEs/SAEs occurred in either arm. Adherence and persistence to medication were greater in women with PMO receiving i.v. ibandronate compared with those receiving oral alendronate. This may have led to an increase in mobility and a decrease in pain in these patients.

Abstract P6-12-03: Effects of high dose of bisphosphonate therapy on bone microarchitecture of the peripheral skeleton in women with early stage breast cancer

Abstract Background: Randomized studies investigating adjuvant bisphosphonates in women with breast cancer are ongoing. While bisphosphonates would be expected to prevent the deterioration of bone microarchitecture that accompanies hormone or chemotherapy, complete suppression of osteoclast activity for prolonged periods of time can decrease repair of micro-cracks, and possibly lead to decreased bone strength. While bone strength is governed by the amount of bone present, trabecular and cortical components of bone microarchitecture also contribute independently to bone strength. We aimed to characterize the effects of long-term bisphosphonates on bone microarchitecture in women with breast cancer using high-resolution peripheral quantitative computed tomography (HR-pQCT) of the distal radius and tibia. Methods: We conducted a cross-sectional study involving early stage breast cancer patients treated with bisphosphonates on the S0307 clinical trial. Women were randomized to receive zoledronic acid, oral clodronate or oral ibandronate in doses far higher than those used in osteoporosis treatment as per protocol. After 18–36 months of bisphosphonate therapy, participates underwent a one-time evaluation of areal bone mineral density (aBMD) of the 1/3 radius, lumbar spine, and hip by dual energy x-ray absorptiometry (DXA), and cortical and trabecular volumetric BMD (vBMD) and trabecular microarchitecture of the radius and tibia by HR-pQCT. HR-pQCT measurements were compared to healthy young premenopausal women and age-matched Caucasian women. Results: Baseline characteristics of the 12 enrolled patients: median age of 53 (range 40–67); white/Hispanics 7/5; pre/postmenopausal 4/8; mean body mass index 28.7 kg/m2 (20.9–34.8); average time on bisphosphonates 20 months (18–30); zoledronic acid/clodronate/ibandronate 5/6/1. The median aBMD DXA T-score of the 1/3 radius, lumbar spine and total hip were normal at +0.3, +0.1, and +0.2, respectively. Mean total, cortical, and trabecular vBMD of the radius as measured by HR-pQCT were 330±71, 905±55, and 146±35 mg hydroxyapatite/cm3, respectively. Mean cortical thickness was 0.803±0.170 mm, and mean trabecular number was 1.9±0.2. Mean total, cortical, and trabecular vBMD of the tibia were 285±54, 880±54, and 150±38 mg hydroxyapatite/cm3, respectively. Mean cortical thickness was 1.135±0.264 mm, and mean trabecular number was 1.7±0.3. There were no statistically significant differences between study group and each control. However, results were more similar to healthy young premenopausal control than the age-matched control. Conclusion: Women on long-term bisphosphonate therapy for breast cancer had normal aBMD by DXA and normal cortical and trabecular vBMD, cortical thickness and trabecular number at the peripheral skeleton compared to healthy young women and age-matched women. This preliminary data is reassuring for cancer survivors if benefits from this therapy are established in the adjuvant setting. Citation Information: Cancer Res 2012;72(24 Suppl):Abstract nr P6-12-03.

P4-16-08: Pilot Randomized Trial of De-Escalated (q12 Weekly) Versus Standard (q3-4 Weekly) Intravenous Bisphosphonates in Women with Low-Risk Bone Metastases from Breast Cancer.

Abstract Background: Bone-targeted agent such as bisphosphonates (BPs) can reduce skeletal complications from bone metastases but have no effect on either disease progression or survival. Despite substantial variability in the frequency and severity of skeletal complications, patients are empirically treated with BPs at the same dose and schedule irrespective of their individual risk. Materials and Methods: A pilot, randomized, non-inferiority trial was conducted. Patients with low-risk bone metastases (serum C-telopeptide [CTx] &amp;lt;600ng/L after at least 3 cycles of monthly IV BP) were assigned to pamidronate 90mg IV either every 3–4 weeks (control) or every 12 weeks (de-escalated). Data on serum CTx and bone alkaline phosphatase (BAP), pain scores (brief pain inventory [BPI] and functional assessment of cancer therapy-bone pain [FACT-BP]) were collected at 12 weekly intervals for 48 weeks. Results: Fifty-four patients were approached, 44 provided consent and 38 were eligible for randomization. Median age was 55 (range 29–77) and mean baseline CTx was 319ng/L (range 10–526). Thirty-five participants (92%) completed the trial, 2 withdrew consent and one participant died. Fourteen control group participants (73.7%) and 13 experimental group participants (68.4%) maintained CTx in the low risk range (test for two proportions p=0.64). All patients not maintaining CTx in the low risk range showed evidence of both visceral and bone progression. Compared to the control group, there was a trend towards increasing CTx with time in the experimental group (p=0.10). There was no significant difference in BAP (p=0.37), BPI (p=0.21) or FACT-BP scores (p=0.59) between the two groups. Over the 48 week follow-up, two skeletal events were observed in each group. Conclusions: Randomized trials of de-escalated BP therapy in women with low-risk bone metastases are feasible. Twelve-weekly pamidronate appears non-inferior to 3–4 weekly treatment. Larger trials are required to assess whether; 1) increasing CTx levels with de-escalated therapy will lead to higher rates of skeletal complications and 2) whether BP should be given every 3–4 weeks in patients with progressive visceral and bone disease. Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P4-16-08.

A Review of the Cost Effectiveness of Bisphosphonates in the Treatment of Post-Menopausal Osteoporosis in Switzerland

The economic burden associated with osteoporosis is considerable. As such, cost-effectiveness analyses are important contributors to the diagnostic and therapeutic decision-making process. The aim of this study was to review the cost effectiveness of treating post-menopausal osteoporosis with bisphosphonates and identify the key factors that influence the cost effectiveness of such treatment in the Swiss setting. A systematic search of databases (MEDLINE, EMBASE and the Cochrane Library) was conducted to identify published literature on the cost effectiveness of bisphosphonates in post-menopausal osteoporosis in the Swiss setting. Outcomes were compared with similar studies in Western European countries. Three cost-effectiveness studies of bisphosphonates in this patient population were identified; all were from a healthcare payer perspective. Outcomes showed that, relative to no treatment, treatment with oral bisphosphonates was predicted to be cost saving for most women aged ≥70 years with osteoporosis or at least one risk factor for fracture, and cost effective for women aged ≥75 years without prior fracture when used as a component of a population-based screen-and-treat programme. Results were most sensitive to changes in fracture risk, cost of fractures, cost of treatment, nursing home admissions and adherence with treatment. Swiss results were generally comparable to those in other European settings. Assuming similar clinical efficacy, lowering treatment cost (through the use of price-reduced brand-name or generic drugs) and/or improving adherence should both contribute to further improving the cost effectiveness of bisphosphonates in women with post-menopausal osteoporosis. Published evidence indicates that bisphosphonates are estimated to be similarly cost effective or cost saving in most treatment scenarios of post-menopausal osteoporosis in Switzerland and in neighbouring European countries.

Safety of bisphosphonates in women of child bearing age: authors’ reply

Safety of bisphosphonates in women of child bearing age: authors’ reply