Cost-effectiveness of weekly gastro-resistant risedronate 35 mg, compared with weekly alendronate 70 mg tablets, in the treatment of postmenopausal osteoporosis in Spain.

Aim: To estimate the cost-effectiveness of treating postmenopausal osteoporosis (PMO) with weekly gastro-resistant risedronate 35 mg gastro-resistant tablets (RIS-GR), compared with weekly alendronate 70 mg tablets (ALN) in Spain. Methods: A probabilistic analysis (second-order Monte Carlo simulation) was performed with a time horizon of 5 years, from the perspective of the Spanish National Health System. The bone fracture probabilities were obtained from a cohort study of 3614 women from USA with PMO treated with RIS-GR (1807) or ALN (1807) (Thomasius, 2022). The pharmacological cost and the cost of fractures were obtained from Spanish sources (€ 2022). The utilities of patients with and without fracture (quality-adjusted life years [QALYs]) were obtained from the medical literature. Results: Compared with ALN, treatment with RIS-GR can avoid 79 fractures (between 75 and 82) every 1000 patients treated, and 0.0119 QALYs would be gained (between 0.0098 and 0.0140) per patient. Additionally, GR-RIS would generate a cost saving per patient of €1994 (€1437-2904) with a probability of 99.7%. The scenario analyses confirmed the stability of the base case results. Conclusion: According to this study, RIS-GR would be the dominant treatment (lower costs with QALY gain) compared with ALN.

Fracture rates and economic outcomes in patients with osteoporosis prescribed risedronate gastro-resistant versus other oral bisphosphonates: a claims data analysis.

Patients with osteoporosis prescribed risedronate gastro-resistant had a lower incidence of fractures versus those prescribed other oral bisphosphonates. Administration of risedronate gastric-resistant does not require fasting, and this more convenient dosing administration may explain its improved efficacy. PURPOSE: Up to half of patients do not follow complex dosing instructions of immediate-release bisphosphonates used for the prevention of osteoporotic fractures, which can result in suboptimal effectiveness. Risedronate gastro-resistant (GR) offers a more convenient dosing option by eliminating the need for fasting. This study compares fracture rates and outcomes between osteoporosis women treated with risedronate GR (GR cohort) versus other oral bisphosphonates (other cohort). METHODS: Claims from women with osteoporosis in the USA were analyzed. Patients were classified into the two cohorts based on the first oral bisphosphonate observed (index date) and matched 1:1 based on patient characteristics. Patients were observed for ≥ 2 years following the index date. Fracture rates, health care resource utilization and costs, and treatment persistence were compared. RESULTS: In total, 2,726 patients were selected in each cohort (median age: 60.0 years). The incidence of fractures was lower in the GR versus the other cohort for any fracture sites (incidence rate ratio, 95% CI: 0.83, 0.70-0.97) and spine fractures (0.71, 0.54-0.95), although the respective rate of medication discontinuation at 2 years was 80.5% and 74.4%. Time to first fracture was delayed for the GR cohort, reaching statistical significance after 36 months. The GR cohort incurred fewer hospitalizations (incidence rate per 1,000 patient-years: GR = 106.74; other = 124.20, p < 0.05) translating into lower hospitalization costs per patient per year (GR = $3,611; other = $4,603, p < 0.05). CONCLUSIONS: Patients prescribed risedronate GR versus other bisphosphonates had a lower incidence of fractures, which may be explained by the fact that the GR formulation is absorbed even when taken with food.

Bridging the osteoporosis treatment gap: performance and cost-effectiveness of a fracture liaison service.

Individuals who sustain fragility fractures are at high risk of refracture. However, osteoporosis treatment rates remain low for these patients. Therefore, we aimed to assess the performance and cost-effectiveness of introducing a fracture liaison service (FLS) into a tertiary hospital. In "nonhospitalized" ambulatory patients who had sustained fragility fractures, we assessed baseline osteoporosis investigation and treatment rates, and subsequently, the impact of introducing an orthopedic osteoporosis policy and an FLS. Outcomes measured were uptake of osteoporosis intervention, patient satisfaction, and quality-adjusted life years (QALYs) gained. QALYs were calculated over 5 years using predicted fracture risks without intervention and estimated fracture risk reduction with intervention. At baseline (n = 49), 2% of ambulatory patients who had sustained fragility fractures underwent dual-energy X-ray absorptiometry (DXA) and 6% received osteoporosis-specific medication. After introduction of an osteoporosis policy (n = 58), 28% were investigated with DXA (p < 0.0001). However, treatment rates were unchanged. An FLS was introduced, reviewing 203 new patients over the inaugural 2 years (mean age [standard deviation], 67 (11) years; 77% female). All underwent DXA, and criteria for osteoporosis and osteopenia were identified in 44% and 40%, respectively. Osteoporosis medications were prescribed to 61% patients (risedronate: 22%, alendronate: 16%, strontium ranelate: 13%, zoledronic acid: 8%, other: 2%). Eighty-five of 90 questionnaire respondents were very satisfied or satisfied with the FLS. With the treatment prescribed over 5 years, we conservatively estimated that this FLS would reduce nonvertebral refractures from 59 to 50, improving QALYs by 0.054 and costing $1716 per patient (incremental cost-effectiveness ratio: $31749). This FLS model improves uptake of osteoporosis intervention guidelines, is popular among patients, and improves cost-effectiveness. Thus, it has the capacity to substantially improve health in a cost-effective way.

Substantial under-treatment among women diagnosed with osteoporosis in a US managed-care population: a retrospective analysis.

BACKGROUND: Multiple therapies are approved for the treatment of osteoporosis (OP), but many patients with osteoporosis may not initiate treatment upon osteoporosis diagnosis. OBJECTIVE: To characterize initiation of pharmacologic OP treatment among women within 1 year of OP diagnosis in a US managed care population. RESEARCH DESIGN AND METHODS: The retrospective cohort study included women aged ≥55 years with a claims-documented diagnosis of OP who were naïve to OP medications prior to OP diagnosis (index date) during 2001-2010. Continuous enrollment for 12 months before (baseline) and after (follow-up) the index date was required. Patients who received OP medications but did not have an OP diagnosis were excluded. Differences in baseline characteristics between the treated and untreated cohorts were compared using Wilcoxon rank-sum (continuous variables) and chi-square tests (categorical variables). MAIN OUTCOMES MEASURES: During the follow-up period, the percentages of patients treated with bisphosphonates (alendronate, ibandronate, risedronate, zoledronic acid) and non-bisphosphonates (calcitonin, raloxifene, teriparatide) were determined. RESULTS: A total of 65,344 patients, mean age 65.7 years, met study inclusion exclusion criteria. During the follow-up period, 42,033 patients (64.3%) received no OP medication and 23,311 patients (35.7%) received OP treatment. A total of 20,200 patients (30.9% of total study population) received bisphosphonates and 3111 (4.8% of total) patients received non-bisphosphonates as their index medication. At baseline, untreated patients were slightly older and had higher rates of hypertension, chronic inflammatory joint disease, diabetes mellitus, and gastrointestinal events (p ≤ 0.01) compared with treated patients. CONCLUSIONS: Among women aged ≥55 years in a US managed-care population, 64.3% received no pharmacologic treatment within 1 year after being diagnosed with OP. The authors were not able to determine if untreated patients did not receive or did not fill a prescription. Further research is needed to understand the barriers to OP treatment and reasons for non-treatment.

Cost effectiveness of denosumab versus oral bisphosphonates for postmenopausal osteoporosis in the US.

BACKGROUND: In the US, 26 % of women aged ≥65 years, and over 50 % of women aged ≥85 years are affected with postmenopausal osteoporosis (PMO). Each year, the total direct health care costs are estimated to be $US12-18 billion. OBJECTIVE: The cost effectiveness of denosumab versus oral bisphosphonates in postmenopausal osteoporotic women from a US third-party payer perspective was evaluated. METHODS: A lifetime cohort Markov model was developed with seven health states: 'well', hip fracture, vertebral fracture, 'other' osteoporotic fracture, post-hip fracture, post-vertebral fracture, and dead. During each cycle, patients could have a fracture, remain healthy, remain in a post-fracture state or die. Relative fracture risk reductions, background fracture risks, mortality rates, treatment-specific persistence rate, utilities, and medical and drug costs were derived using published sources. Expected costs and quality-adjusted life years (QALYs) were estimated for generic alendronate, denosumab, branded risedronate, and branded ibandronate in the overall PMO population and high-risk subgroups: (a) ≥2 of the following risks: >70 years of age, bone mineral density (BMD) T score less than or equal to -3.0, and prevalent vertebral fracture; and (b) ≥75 years of age. Costs and QALYs were discounted at 3 % annually, and all costs were inflated to 2012 US dollars. Sensitivity analyses were conducted by varying parameters e.g., efficacies of interventions, costs, utilities, and the medication persistence ratio. RESULTS: In the overall PMO population, total lifetime costs for alendronate, denosumab, risedronate, and ibandronate were $US64,400, $US67,400, $US67,600 and $US69,200, respectively. Total QALYs were 8.2804, 8.3155, 8.2735 and 8.2691, respectively. The incremental cost-effectiveness ratio (ICER) for denosumab versus generic alendronate was $US85,100/QALY. Risedronate and ibandronate were dominated by denosumab. In the high-risk subgroup (a), total costs for alendronate, denosumab, risedronate and ibandronate were $US70,400, $US70,800, $US74,000 and $US76,900, respectively. Total QALYs were 7.2006, 7.2497, 7.1969 and 7.1841, respectively. Denosumab had an ICER of $US7,900/QALY versus generic alendronate and dominated all other strategies. Denosumab dominated all strategies in women aged ≥75 years. Base-case results between denosumab and generic alendronate were most sensitive to the relative risk of hip fracture for both drugs and the cost of denosumab. CONCLUSION: In each PMO population examined, denosumab represented good value for money compared with branded bisphosphonates. Furthermore, denosumab was either cost effective or dominant compared with generic alendronate in the high-risk subgroups.

Association between refill compliance to oral bisphosphonate treatment, incident fractures, and health care costs--an analysis using national health databases.

SUMMARY: The study estimates the cost of poor and suboptimal refill compliance by estimating fracture costs and assessing the association between refill compliance with oral bisphosphonates and incident fractures using Danish health registers. Patients with poor and suboptimal refill compliance had more major osteoporotic fractures, and the direct costs related to hospital care, primary care, and pharmaceutical treatment for these excess fractures reached almost 14 M DKK (2.5 M USD) for the study population which compares to a national annual excess cost of around 17 M DKK (3.1 M USD) using 2011 prescription prevalence. INTRODUCTION: Adherence to oral anti-osteoporosis treatment has been shown in several studies to be relatively low and the potential impact on fracture burden is high. The aim of the study was to assess the association between refill compliance and all-cause health care costs. METHODS: A national dataset was extracted with all treatment-naive patients who began oral bisphosphonate (BP) treatment for osteoporosis in Denmark between 1997 and 2006 (N = 54,876, 87 % women). Patients who survived for at least 2 years (N = 47,176) were divided into groups based on Medication Possession Ratio (MPR). Logistic regressions were used to derive difference in the probability of incident fractures between the three MPR groups. Fracture costs (related to medication use, primary care practice, specialists, and hospitals) were derived by comparing cost 12 months before and after fracture. RESULTS: For alendronate, the adjusted risk of major osteoporotic fractures was significantly reduced (OR 0.768; 0.686-0.859), including fractures of the hip (0.718; 0.609-0.846) and humerus (0.54; 0.431-0.677) with MPR ≥ 0.8. The risk reduction was lower with etidronate. Over 2 years, a total of 171 hip fractures and 53 other major osteoporotic fractures were attributed to suboptimal or poor refill compliance, with an excess cost of 13.7 M DKK (2.5 M USD). CONCLUSIONS: Poor refill compliance is not unusual in patients on oral bisphosphonates, and we demonstrate that this is accompanied by excess major osteoporotic fractures and health care costs at the societal level.

Intervention thresholds for denosumab in the UK using a FRAX®-based cost-effectiveness analysis.

UNLABELLED: The objective was to undertake a health economic analysis of denosumab for the treatment of osteoporosis in women from the UK, using the FRAX® tool. Denosumab was cost-effective in women with a risk of major osteoporotic fracture meeting or exceeding approximately 20% who are unable to take, comply with or tolerate generic alendronate. INTRODUCTION: Denosumab is a novel biologic agent developed for the treatment of osteoporosis, which has been shown to reduce the risk of fractures in a phase-III trial. The objective of the present study was to undertake a health economic analysis of denosumab in women from the UK. Ten-year probabilities of a major osteoporotic fracture at which denosumab is a cost-effective alternative to no treatment, generic alendronate, risedronate and strontium ranelate were estimated. METHODS: A previously published Markov model was adapted to incorporate fracture and mortality risk assessments based on absolute fracture probability, as estimated by FRAX®. The model included treatment persistence and residual effect after discontinuation. RESULTS: At a willingness-to-pay (WTP) of £30,000 per quality-adjusted life year and a 10-year fracture probability equivalent to a woman with a prior fragility fracture, denosumab was cost-effective compared to no treatment from the age of 70 years. At the same WTP, denosumab was-irrespective of age-cost-effective compared to no treatment at a major osteoporotic fracture probability of approximately 20%. Denosumab was estimated to cost-effectively replace strontium, risedronate and generic alendronate at 10-year probabilities exceeding 11, 19 and 32%, respectively. CONCLUSION: FRAX® facilitates the estimation of cost-effectiveness-based intervention thresholds applicable to patients with different combinations of clinical risk factors, which more closely matches the situation in clinical practice. Denosumab is cost-effective in patients with major osteoporotic fracture probabilities meeting or exceeding approximately 20% who are unable to take, comply with or tolerate generic alendronate.

How rebates, copayments, and administration costs affect the cost-effectiveness of osteoporosis therapies.

PURPOSE: Because of rising drug expenditures, cost considerations have become essential, necessitating the requirement for cost-effectiveness analyses for managed care organizations (MCOs). The study objective is to examine the impact of various drug-cost components, in addition to wholesale acquisition cost (WAC), on the cost-effectiveness of osteoporosis therapies. DESIGN: A Markov model of osteoporosis was used to exemplify different drug cost scenarios. METHODOLOGY: We examined the effect of varying rebates for oral bisphosphonates--risedronate and ibandronate--as well as considering the impact of varying copayments and administration costs for intravenous zoledronate. The population modeled was 1,000 American women, > or = 50 years with osteoporosis. Patients were followed for 1 year to reflect an annual budget review of formularies by MCOs. The cost of therapy was based on an adjusted WAC, and is referred to as net drug cost. The total annual cost incurred by an MCO for each drug regimen was calculated using the net drug cost and fracture cost. We estimated cost on a quality adjusted life year (QALY) basis. PRINCIPAL FINDINGS: When considering different rebates, results for risedronate versus ibandronate vary from cost-savings (i.e., costs less and more effective) to approximately $70,000 per QALY. With no risedronate rebate, an ibandronate rebate of approximately 65% is required before cost per QALY surpasses $50,000. With rebates greater than 25% for risedronate, irrespective of ibandronate rebates, results become cost-saving. Results also showed the magnitude of cost savings to the MCO varied by as much as 65% when considering no administration cost and the highest coinsurance rate for zoledronate. CONCLUSION: Our study showed that cost-effectiveness varies considerably when factors in addition to the WAC are considered. This paper provides recommendations for pharmaceutical manufacturers and MCOs when developing and interpreting such analyses.

Cost-effectiveness of denosumab in the treatment of postmenopausal osteoporosis in Canada.

OBJECTIVE: Denosumab is a novel biologic agent approved in Canada for treatment of post-menopausal osteoporosis (PMO) in women at high risk for fracture or who have failed or are intolerant to other osteoporosis therapies. This study estimated cost-effectiveness of denosumab vs usual care from the perspective of the Ontario public payer. METHODS: A previously published PMO Markov cohort model was adapted for Canada to estimate cost-effectiveness of denosumab. The primary analysis included women with demographic characteristics similar to those from the pivotal phase III denosumab PMO trial (FREEDOM; age 72 years, femoral neck BMD T-score -2.16 SD, vertebral fracture prevalence 23.6%). Three additional scenario sub-groups were examined including women: (1) at high fracture risk, defined in FREEDOM as having at least two of three risk factors (age 70+; T-score ≤ -3.0 SD at lumbar spine, total hip, or femoral neck; prevalent vertebral fracture); (2) age 75+; and (3) intolerant or contraindicated to oral bisphosphonates (BPs). Analyses were conducted over a lifetime horizon comparing denosumab to usual care ('no therapy', alendronate, risedronate, or raloxifene [sub-group 3 only]). The analysis considered treatment-specific persistence and post-discontinuation residual efficacy, as well as treatment-specific adverse events. Both deterministic and probabilistic sensitivity analyses were conducted. RESULTS: The multi-therapy comparisons resulted in incremental cost-effectiveness ratios for denosumab vs alendronate of $60,266 (2010 CDN$) (primary analysis) and $27,287 per quality-adjusted life year gained for scenario sub-group 1. Denosumab dominated all therapies in the remaining scenarios. LIMITATIONS: Key limitations include a lack of long-term, real-world, Canadian data on persistence with denosumab as well as an absence of head-to-head clinical data, leaving one to rely on meta-analyses based on trials comparing treatment to placebo. CONCLUSIONS: Denosumab may be cost-effective compared to oral PMO treatments for women at high risk of fractures and those who are intolerant and/or contraindicated to oral BPs.

Long-term treatment of osteoporosis in postmenopausal women: a review from the European Society for Clinical and Economic Aspects of Osteoporosis and Osteoarthritis (ESCEO) and the International Osteoporosis Foundation (IOF).

INTRODUCTION: Postmenopausal osteoporosis is a chronic disease requiring treatment that balances long-term fracture efficacy against risk. METHODS: We reviewed the efficacy and safety of calcium and vitamin D, the selective estrogen receptor modulators (SERMs), the bisphosphonates, denosumab, and strontium ranelate in studies of 3 years or longer. RESULTS: Six trials lasted for 5 years, and seven went beyond that. The evidence beyond 5 years is generally weak, mainly due to methodological issues (open-label design, small samples, or absence of placebo control). Although calcium and vitamin D appear to be beneficial, the data are insufficient to evaluate benefits and risk beyond 3 years. The fracture efficacy of SERMs beyond 5 years is not known, though increases in bone mineral density (BMD) appear to be maintained. The SERMs have good long-term safety, including protective effects against breast cancer. The bisphosphonates have established fracture efficacy to 3 years, and 4 or 5 years with alendronate and risedronate. The evidence beyond 5 years indicates sustained increases in BMD. The safety of the bisphosphonates does not appear to be modified with time, with the possible exceptions of atypical subtrochanteric fracture and other events of unknown frequency. Denosumab has been tested up to 5 years, with continued increased in BMD and no reported safety issues. There is evidence for fracture efficacy of strontium ranelate, and sustained increases in BMD over 10 years. Strontium ranelate has good long-term safety. CONCLUSION: Robust long-term studies are relatively rare for the osteoporosis treatments, and generally show maintenance of BMD and, for some agents, an additional reduction in fracture incidence.

Evidence to inform decision makers in Thailand: a cost-effectiveness analysis of screening and treatment strategies for postmenopausal osteoporosis.

OBJECTIVES: To assess value for money of providing systematic screening for osteoporosis among postmenopausal women and medical treatments for those diagnosed with osteoporosis as evidence-based decision making for the revision of the National List of Essential Medicines. METHODS: Decision analytic models were constructed, using a societal perspective, to assess the cost per quality-adjusted life-years (QALYs) gained from systematic screening using the Osteoporosis Self-Assessment Tool and dual-energy X-ray absorptiometry or dual-energy X-ray absorptiometry alone compared with no screening. Alendronate, risedronate, raloxifene, and nasal calcitonin were economically evaluated to determine a treatment of choice for the prevention of osteoporosis-related fractures. Most input parameters were obtained from literature reviews, and systematic reviews and meta-analyses, if available. The service costs and related household expenses were based on the Thai setting. Probabilistic and one-way sensitivity analyses were used to incorporate the impact of parameter uncertainty. RESULTS: The Osteoporosis Self-Assessment Tool and sequential dual-energy X-ray absorptiometry provided better value for money for osteoporosis screening among young age groups (<60 years old). Although there was no significant difference in cost per QALY for older age groups, alendronate provided the lowest incremental cost-effectiveness ratio while nasal calcitonin presented the highest incremental cost-effectiveness ratio. It was shown that providing medication for a secondary prevention yielded a much higher cost per QALY gained compared with providing medication for a primary prevention. CONCLUSIONS: Given the benchmark set at 100,000 Thai baht per QALY gained, providing systematic screening and treatment for osteoporosis was cost-ineffective in the Thai setting.

The assessment of regional skeletal metabolism: studies of osteoporosis treatments using quantitative radionuclide imaging.

Studies of bone remodeling using bone biopsy and biochemical markers of bone turnover play an important role in research studies to investigate the effect of new osteoporosis treatments on bone quality. Quantitative radionuclide imaging using either positron emission tomography with fluorine-18 sodium fluoride or gamma camera studies with technetium-99m methylene diphosphonate provides a novel tool for studying bone metabolism that complements conventional methods, such as bone turnover markers (BTMs). Unlike BTMs, which measure the integrated response to treatment across the whole skeleton, radionuclide imaging can distinguish the changes occurring at sites of particular clinical interest, such as the spine or proximal femur. Radionuclide imaging can be used to measure either bone uptake or (if done in conjunction with blood sampling) bone plasma clearance. Although the latter is more complicated to perform, unlike bone uptake, it provides a measurement that is specific to the bone metabolic activity at the measurement site. Treatment with risedronate was found to cause a decrease in bone plasma clearance, whereas treatment with the bone anabolic agent teriparatide caused an increase. Studies of teriparatide are of particular interest because the treatment has different effects at different sites in the skeleton, with a substantially greater response in the flat bone of the skull and cortical bone in the femur compared with the lumbar spine. Future studies should include investigations of osteonecrosis of the jaw and atypical fractures of the femur to examine the associated regional changes in bone metabolism and to throw light on the underlying pathologies.

Comparison of the effects of elcatonin and risedronate on back and knee pain by electroalgometry using fall of skin impedance and quality of life assessment using SF-36.

Back and knee pain is a widespread health problem and a serious threat to the quality of life (QOL) in middle-aged and older adults, as it frequently accompanies osteoporosis and osteoarthritis. In order to compare the effects of elcatonin and risedronate on such pain, 20 units of elcatonin was intramuscularly injected to 18 patients, and 5 mg of risedronate was orally administered daily to 20 others with similar backgrounds. Exercise-induced pain was analyzed by measuring the fall of skin impedance by electroalgometry (EAM), and subjective pain was recorded by a visual rating system (VRS) on a scale of 0 (no pain) to 100 (unbearable pain). In patients treated with elcatonin, the mean EAM-estimated pain was significantly reduced after 4, 5 and 6 months of treatment, and the VRS score after 3, 5 and 6 months, indicating a significant analgesic effect. In the risedronate group, however, improvement was less remarkable. Two-way analysis of variance using pain as a dependent variable and treatment group and time as independent variables revealed a significantly greater effect of elcatonin over risedronate on both the EAM and VRS scores, and the influence of treatment time on pain was indistinguishable between the two treatment groups. Effect of exercise load on pain was less on knee load than knee and spine load and spine load, but indistinguishable between the two groups. Changes in QOL were evaluated by the SF-36 system. Norm-based scoring showed significant improvements in 3 of 4 categories for elcatonin and in 2 of 4 for risedronate, suggesting comparable effects on the physical aspects of QOL, whereas responses to emotionally and socially directed questions indicated significant improvements in all 4 categories for risedronate, but none for elcatonin, suggesting a more physical than emotional component in elcatonin effects compared to risedronate.

Cost-effectiveness of Denosumab for the treatment of postmenopausal osteoporosis.

UNLABELLED: Denosumab is an injectable drug that reduces the risk of fractures. The objective was to estimate the cost-effectiveness of denosumab in a Swedish setting, also accounting for poor adherence to treatment. Denosumab is cost-effective, particularly for patients at high risk of fracture and low adherence to oral treatments. INTRODUCTION: Denosumab is a novel biologic agent developed for the treatment of osteoporosis and osteoporotic fractures that has been shown to reduce the risk of fractures in a phase III trial. The objective of this study was to estimate the cost-effectiveness of denosumab from a societal perspective compared with generic alendronate, branded risedronate, strontium ranelate, and no treatment in a Swedish setting. METHODS: A Markov cohort model was used to estimate the cost-effectiveness of denosumab given for up to 5 years to a typical Swedish patient population (women aged 71 years, T-score ≤ -2.5 SD and a prevalence of morphometric vertebral fractures of 34%). The model included treatment persistence and residual effect after discontinuation assumed to be equal to the time on treatment. Persistence with the comparator treatments and with denosumab was derived from prescription data and a persistence study, respectively. RESULTS: The base-case incremental cost-effectiveness ratios were estimated at €27,000, €12,000, €5,000, and €14,000, for denosumab compared with generic alendronate, risedronate, strontium ranelate, and no treatment, respectively. Sub-optimal persistence had the greatest impact in the comparison with generic alendronate, where the difference in drug cost was large. CONCLUSION: Improving persistence with osteoporosis treatment impacts positively on cost-effectiveness with a larger number of fractures avoided in the population targeted for treatment. Denosumab is a cost-effective alternative to oral osteoporosis treatments, particularly for patients at high risk of fracture and low expected adherence to oral treatments.

Assessment of the relationship between age and the effect of risedronate treatment in women with postmenopausal osteoporosis: a pooled analysis of four studies.

OBJECTIVES: To quantify the effect of age on the incidence of osteoporosis-related fractures and of risedronate treatment on fracture risk in different age groups in women with postmenopausal osteoporosis. DESIGN: Data from four randomized, double-blind, placebo-controlled, Phase III studies were pooled and analyzed. PARTICIPANTS: The analysis population (N=3,229) consisted of postmenopausal women with osteoporosis as determined on the basis of prevalent vertebral fractures, low bone mineral density (BMD), or both. INTERVENTION: Patients had received risedronate 5 mg daily or placebo for 1 to 3 years. MEASUREMENTS: The endpoints of interest were the incidence of osteoporosis-related fractures, clinical fractures, nonvertebral fractures, and morphometric vertebral fractures. The effect of age on fracture risk and treatment benefit was examined using Cox regression models with age and treatment as explanatory variables. The 3-year fracture risk was estimated for patients in each treatment group at a given age. RESULTS: Irrespective of treatment, fracture risks were greater in older patients (P<.001). On average, for every 1-year increase in age, a patient's risk for osteoporosis-related fracture increased 3.6% (95% confidence interval=2.3-5.0%). Irrespective of age, risedronate treatment reduced fracture risk 42%. Risedronate-treated patients had fracture risks similar to those of placebo-treated patients 10 to 20 years younger. CONCLUSION: Patients treated with risedronate have a significantly lower fracture risk, similar to that of untreated patients 10 to 20 years younger.

Risedronate versus alendronate in older patients with osteoporosis at high risk of fracture: an Italian cost-effectiveness analysis.

BACKGROUND AND AIMS: This evaluation of the cost-effectiveness of risedronate vs generic alendronate is based on effectiveness data from a large real practice study. Applying a published cost-effectiveness model, we found that risedronate is cost-effective vs generic alendronate in an Italian population aged > or =65 years, and becomes dominant, saving costs and avoiding fractures, in patients aged > or =75 years. The aim of this work was to assess the cost-effectiveness and health utility of risedronate vs generic alendronate in clinical practice in Italy, using effectiveness data from the REAL study. METHODS: A pre-existing model of osteoporosis was used to predict numbers of fractures, quality-adjusted life-years (QALYs), and costs associated with risedronate or alendronate treatment in post-menopausal (PMO) women aged > or =65 years with a previous vertebral fracture, within the Italian National Health System (NHS). Duration of treatment with risedronate or alendronate was assumed to occur for one year and patients were followed for an additional five years to capture longterm costs and outcomes, with a discount rate of 3% for costs and outcomes. Comprehensive sensitivity analyses were run. RESULTS: The lower fracture rate among risedronate patients with respect to alendronate patients resulted in savings of euro 19,083, a reduction of 8.91 hip fractures and an associated benefit of 7.46 QALYs, in an Italian cohort of 1,000 patients. Sensitivity analyses confirmed the robustness of these results. CONCLUSIONS: This economic analysis showed that risedronate is a cost-effective treatment in a population of Italian women aged 65 years and older at high risk of PMO-related fractures. Risedronate becomes dominant over generic alendronate in patients of 75 years or older and its cost-effectiveness even appears improved in patients with BMD score < or = -3 or < or = -3.5, with/without maternal history of fractures. Risedronate should be considered as a cost-effective option vs generic alendronate, in the Italian NHS' perspective.

Morphological assessment of basic multicellular unit resorption parameters in dogs shows additional mechanisms of bisphosphonate effects on bone.

Bisphosphonates (BPs) slow bone loss by reducing initiation of new basic multicellular units (BMUs). Whether or not BPs simply prevent osteoclasts from initiating new BMUs that resorb bone or also reduce the amount of bone they resorb at the BMU level is not clear. The goal of this study was to determine the effects of BPs on three morphological parameters of individual BMUs, resorption depth (Rs.De), area (Rs.Ar), and width (Rs.Wi). After 1 year of treatment with vehicle (VEH), alendronate (ALN; 0.10, 0.20, or 1.00 mg/kg/day), or risedronate (RIS; 0.05, 0.10, or 0.50 mg/kg/day), resorption cavity morphology was assessed in vertebral trabecular bone of beagle dogs by histology. Animals treated with ALN or RIS at the doses representing those used to treat postmenopausal osteoporosis (0.20 and 0.10 mg/kg/day, respectively) had significantly lower Rs.Ar (-27%) and Rs.Wi (-17%), with no difference in Rs.De, compared to VEH-treated controls. Low doses of ALN and RIS did not affect any parameters, whereas higher doses resulted in similar changes to those of the clinical dose. There were no significant differences in the resorption cavity measures between RIS and ALN at any of the dose equivalents. These results highlight the importance of examining parameters beyond erosion depth for assessment of resorption parameters. Furthermore, these results suggest that in addition to the well-known effects of BPs on reducing the number of active BMUs, these drugs also reduce the activity of osteoclasts at the individual BMU level at doses at and above those used clinically for the treatment of postmenopausal osteoporosis.

Cost-effectiveness of strontium ranelate versus risedronate in the treatment of postmenopausal osteoporotic women aged over 75 years.

OBJECTIVE: To estimate the cost-effectiveness of strontium ranelate in the treatment of postmenopausal osteoporotic women aged over 75 years. MATERIALS AND METHODS: A validated Markov microsimulation model with a Belgian payer's perspective estimated the cost per quality-adjusted life-year (QALY) of a 3-year strontium ranelate treatment compared with no treatment and with the bisphosphonate risedronate. Data on the effect of both treatments on fracture risk were taken from the Cochrane Database of Systematic Reviews. Analyses were performed for postmenopausal women aged 75 and 80 years, either with a diagnosis of osteoporosis (i.e. bone mineral density T-score

The cost-effectiveness of risedronate in the UK for the management of osteoporosis using the FRAX.

SUMMARY: The study estimated the cost-effectiveness of risedronate compared to no treatment in UK women using the FRAX algorithm for fracture risk assessment. A Markov cohort model was used to estimate the cost-effectiveness. Risedronate was found cost-effective from the age of 65 years, assuming a willingness to pay for a QALY of 30,000 pounds. INTRODUCTION: The aim of this study was to assess the cost-effectiveness of risedronate for the prevention and treatment in a UK setting using the FRAX algorithm for fracture risk assessment. A further aim was to establish intervention thresholds with risedronate treatment. METHODS: The cost-effectiveness of risedronate was compared to no treatment in post-menopausal women with clinical risk factors for fracture using a Markov cohort model populated with data relevant for the UK. The model incorporated the features of FRAX (the WHO risk assessment tool). The analysis had a health care perspective and quality adjusted life years was used as the main outcome measure. RESULTS: Treatment was cost-effective from the age of 65 years, assuming a willingness to pay for a QALY of 30,000 pounds. Treatment was also cost-effective at all ages in women who had previously sustained a fragility fracture or in women with a parental history of hip fracture with a bone mineral density set at the threshold of osteoporosis. At the 30,000 pounds threshold value for a QALY, risedronate was on average found to cost-effective below the 10-year probability of a major osteoporotic fractures of 13.0%. CONCLUSIONS: Risedronate is a cost-effective agent for the treatment of established osteoporosis (osteoporosis and a prior fragility fracture) in women from the age of 50 years and older and above 65 years in women with osteoporosis alone. The results support the treatment recommendations in recent UK guidelines for osteoporosis.

Comparison of direct health care costs related to the pharmacological treatment of osteoporosis and to the management of osteoporotic fractures among compliant and noncompliant users of alendronate and risedronate: a population-based study.

UNLABELLED: This population-based study aimed to compare direct health care costs related to the pharmacological treatment of osteoporosis and to the management of osteoporotic fractures among compliant and noncompliant users of alendronate and risedronate. During a 2-year follow-up period, compared to those with medication possession ratio (MPR) > or = 80%, women with MPR < 80% incurred significantly higher physician care costs and hospital care costs. INTRODUCTION: This study aimed to compare direct health care costs related to the treatment of osteoporosis and osteoporotic fractures among compliant and noncompliant users of alendronate and risedronate. METHODS: A cohort of 15,027 women having initiated alendronate or risedronate was identified. MPR and direct health care costs (physician care, hospital care, drugs) were assessed during a 2-year period. Regression models were used to estimate mean predicted cost for compliant (MPR > or = 80%) and noncompliant (MPR < 80%) women. RESULTS: Mean predicted physician care cost (in Canadian dollars) was $51 among women with MPR < 80% and $34 among those with MPR > or = 80%: mean difference $17, 95% confidence interval (CI) $2-22. Mean predicted hospital care cost was $568 among women with MPR < 80% and $379 among those with MPR > or = 80%: mean difference $189, 95% CI $56-320. Mean predicted drug cost was $439 among women with MPR < 80% and $1,068 among those with MPR > or = 80%: mean difference $-639, 95% CI $-649 to -629. CONCLUSION: Compared to compliant women, noncompliant women incurred significantly higher physician care and hospital care costs. Due to lower drug costs, total direct health care costs were lower among noncompliant women.