Therapies for Treatment of Osteoporosis in US Women: Cost-effectiveness and Budget Impact Considerations

Objective: To evaluate the cost-effectiveness of osteoporosis treatments for women at high fracture risk and estimate the population-level impact of providing bisphosphonate therapy to all eligible high-risk US women.

Study Design: Fractures, healthcare costs, and quality-adjusted life-years (QALYs) were estimated over 10 years using a Markov model.

Methods: No therapy, risedronate, alendronate, ibandronate, and teriperatide (PTH) were compared among 4 risk groups. Sensitivity analyses examined the robustness of model results for 65-year-old women with low bone density and previous vertebral fracture.

Results: Women treated with a bisphosphonate experienced fewer fractures and more QALYs compared with no therapy or PTH. Total costs were lowest for the untreated cohort, followed by risedronate, alendronate, ibandronate, and PTH in all risk groups except women aged 75 years with previous fracture. The incremental cost-effectiveness of risedronate compared with no therapy ranged from cost saving for the base case to $66,722 per QALY for women aged 65 years with no previous fracture. Ibandronate and PTH were dominated in all risk groups. (A dominated treatment has a higher cost and poorer outcome.) Treating all eligible women with a bisphosphonate would cost an estimated additional $5563 million (21% total increase) and would result in 390,049 fewer fractures (35% decrease). In the highest risk group, the additional cost of therapy was offset by other healthcare cost savings.

Conclusions: Osteoporosis treatment of high-risk women is cost-effective, with bisphosphonates providing the most benefit at lowest cost. For highest risk women, costs are offset by savings from fracture prevention.

(Am J Manag Care. 2008;14(9):605-615)

Osteoporosis has been defined as a skeletal disorder characterized by compromised bone strength predisposing a person to an increased risk of fracture.¹ The National Health and Nutrition Examination Survey (NHANES) III estimated that 13% to 18% of women in the United States have osteoporosis.² The prevalence of postmenopausal osteoporosis (PMO) increases with age from approximately 6% at age 50 years to more than 50% above age 80 years.² The high osteoporosis prevalence coupled with its significant health consequences makes effective prevention and treatment leading public health concerns.^3,4

Current treatment options include bisphosphonates (eg, alendronate, risedronate, ibandronate), calcitonins, parathyroid hormone (PTH), and selective estrogen receptor modulators.

Cost-effectiveness analysis provides important information about the value of alternative therapies that may assist decision makers who seek to equitably allocate constrained resources to achieve maximum healthcare benefits on a population level. Although several articles have addressed the economic value of specific agents,^5-7 the cost-effectiveness of all currently available bone-specific agents approved for treatment of PMO in the United States has not been reported. Another point of differentiation is that our study includes a population-based budget impact analysis to evaluate a policy to extend treatment to all eligible patients within defined risk groups. Budget impact analysis estimates the cost of treatment on an annual basis for budgeting purposes.

The objective of this study was to evaluate (from the healthcare system perspective) the cost-effectiveness of risedronate therapy compared with alendronate, ibandronate, and PTH for the treatment of women with PMO at high fracture risk. A secondary objective was to estimate the population-level impact of a decision to provide bisphosphonate treatment to all eligible US women not currently treated.

STUDY DESIGNModel Overview

Patient Population

For all model parameters, published data sources were used wherever possible and consisted primarily of clinical trials, economic studies, observational studies, and epidemiologic databases. Details are provided below and summarized in Table 1. With respect to treatment, the base-case estimates for therapy duration, offset, and discontinuation were derived from advice from clinical experts.

Fracture IncidenceOur analysis focuses on treatment of postmenopausal women at high risk for fractures; therefore, fracture rates in the age-matched general population were adjusted to reflect the increased risk of new fractures in patients with low BMD and a previous vertebral fracture using the relative risk values noted in Table 1.¹⁷ This adjustment has been described fully elsewhere.⁵

Age-specific hip fracture incidence rates for the total US female population aged 65 to 100 years (all races) were obtained from a retrospective study on the Nationwide Inpatient Sample 2001 hospital discharge database. The analysis included only closed fractures that did not result from severe trauma, and were defined as inpatient hospital cases with 1 of the following International Classification of Diseases, Ninth Revision codes as the primary diagnosis: 820.0x (transcervical), 820.2x (pertrochanteric), 820.8x (neck of femur).¹⁰

Age-specific incidence rates for clinically ascertained vertebral fracture were taken from an analysis of the Rochester Epidemiological Project database, which captured patients treated on both an inpatient and outpatient basis (only 24% of fracture patients are hospitalized).

Mortality in the year after hip fracture was modeled based on analysis of Medicare claims data from 1999 to 2000 with age-specific mortality rates per 10,000 estimated at 130.29 for age 65 to 69 years, 138.07 for age 70 to 74 years, 166.80 for age 75 to 79 years, 203.38 for age 80 to 84 years, 298.74 for age 85 to 89 years, and 298.74 for age 90 years and older. No excess mortality was modeled following vertebral fracture.

Treatment EfficacyThe bone-specific osteoporosis treatments evaluated in the model include risedronate, alendronate, ibandronate, and PTH. These reflect current practice patterns, capturing those treatments that are used most frequently. The model did not consider possible concomitant calcium or vitamin D treatment with these therapies, as the efficacy estimates for the comparator therapies were derived from comparisons with placebo patients who received clinically appropriate calcium and/or vitamin D supplementation. To estimate fracture rates in the treated cohort, therapy-specific efficacy rates were multiplied by adjusted age-specific fracture incidence. Therapy-specific efficacy values (percent risk reduction for hip and vertebral fracture) were obtained from randomized controlled trials with a patient population similar to the base-case risk group.^12-16 For PTH and ibandronate, where there was no evidence (statistically significant data from a randomized controlled trial) to support the effect of a treatment on the incidence of hip fracture, only the effect on the incidence of vertebral fracture was modeled. Although we modeled clinical vertebral fracture incidence, treatment effectiveness was estimated based on clinical trial data, which relies on radiographically evident vertebral fracture.

Direct Medical Costs

To calculate the QALYs, utility weights were applied to each health state. Utilities reflect how quality of life in a health state is valued on a scale from 0 (death) to 1 (perfect health). This analysis assumed an age-specific utility weight of 0.833 for women aged 65 to 69 years and 0.792 for women aged 75 to 79 years in the general population.28 Age-specific utilities were reduced following fracture based on published evidence (Table 1).^25,26

Cost-effectiveness Analysis

To test the robustness of model results, model parameters were varied in multiple 1-way sensitivity analyses for women aged 65 years with low BMD and a previous vertebral fracture. To characterize the impact of uncertainty on treatment efficacy in the cost-effectiveness analyses, analyses that utilized either upper or lower bounds of the 95% confidence intervals for treatment efficacy for each agent were undertaken. Analyses that varied the analytic time horizon from 3 years to lifetime (base case = 10 years) and modified the therapy offset to 5 years (base case = immediate offset) also were undertaken. Therapy offset, or percentage of maximum effect after cessation of therapy, was assumed to decline linearly over time at 90%, 70%, 50%, 30%, and 10% for years 1, 2, 3, 4, and 5, respectively.⁵ For alendronate, however, based on data from the Fracture Intervention Trial Long-term Extension (FLEX) study,^17,29 a 50% slower rate of efficacy decline was used (ie, 90%, 80%, 70%, 60%, 50%). The impact of health utilities on the base-case estimates was evaluated first by varying the utilities by ±25%, and then by limiting utility decrements due to fracture only to the year of the fracture.²⁵ Additional analyses that addressed therapy discontinuation and fracture costs also were completed based on results from the Persistence Study of Ibandronate versus Alendronate (PERSIST) trial.³⁰ We used a cumulative therapy discontinuation rate of 76%,⁵ except for ibandronate, for which persistence was assumed to be 50% better than it was for weekly bisphosphonate dosing.³⁰

Given that treatment efficacy is a key factor driving the results of the cost-effectiveness analysis, we explored a broad range of comparisons for this parameter value. The trials were not able to show any statistically significant difference in effects because they may have been underpowered for hip fractures; therefore, we explored a 1-way sensitivity analysis scenario where a 90% hip fracture efficacy rate was applied to PTH. We also undertook a probabilistic sensitivity analysis, applying triangular distributions to the efficacy variables and using upper and lower 95% confidence intervals as minimum and maximum values.

Budget Impact Analysis

Over the 10-year period, women aged 65 years with a previous vertebral fracture who were treated with a bisphosphonate (risedronate, alendronate, or ibandronate) experienced fewer hip and vertebral fractures (a total of 441-464 fractures) compared with those receiving no therapy (550 fractures) or treatment with PTH (501 fractures) (Table 2). Likewise, those treated with a bisphosphonate (risedronate, alendronate, or ibandronate) had more QALYs (6.646, 6.647, and 6.624 QALYs, respectively) compared with those receiving no therapy (6.580 QALYs) or treatment with PTH (6.608 QALYs). The most hip fractures (n = 137) and vertebral fractures (n = 413) were experienced by those who received no therapy. Women treated with risedronate experienced the fewest hip fractures (n = 105), whereas patients treated with ibandronate experienced the fewest vertebral fractures (n = 327). Except for those who received no therapy, women treated with PTH experienced the most vertebral fractures (n = 364), whereas those treated with ibandronate or PTH experienced the most hip fractures (n = 137). A similar pattern was observed among treatments across each risk group.

Total cost was lowest for the untreated cohort, followed by risedronate, alendronate, ibandronate, and PTH in all risk groups except patients aged 75 years with previous fracture. In that group the total costs were lowest for the risedronate cohort, followed by alendronate, no therapy, ibandronate, and PTH.

Cost-effectiveness Analysis

The cost-effectiveness results changed qualitatively with changes in the assumptions about treatment efficacy and analytical time horizon (Table 3). That is, from the decision makers’ point of view, when $50,000 per QALY was considered to be a decision threshold, the decision to adopt a treatment strategy changed. When the low estimates for efficacy were modeled, the cost-effectiveness for risedronate compared with no therapy changed from $22,068 per QALY gained to $114,694 per QALY gained. When a 3-year time horizon was assumed, the cost-effectiveness estimates for risedronate compared with no therapy changed from $22,068 per QALY gained to $85,391 per QALY gained, and the cost-effectiveness estimates for alendronate compared with risedronate changed from $362,845 to $258,803 per QALY gained. Although the cost-effectiveness estimates for alendronate compared with risedronate changed substantially in the sensitivity analyses, all the values were much greater than $50,000 (ie, dominated), with the only exception being the 5-year therapy offset scenario, where alendronate’s cost per QALY gained was similar to risedronate’s, so this would not likely impact the adoption decision. A comparable pattern emerged for the results reported as cost per hip fracture averted. Both ibandronate and PTH were dominated in all of the sensitivity analyses measured as both cost per QALY gained and cost per hip fracture averted, except for the therapy discontinuation analysis, where ibandronate was on the cost-effectiveness frontier for cost per QALY gained.

Budget Impact Analysis Aggregating the 4 risk groups yielded an estimated 8.23 million women in the United States aged 65 to 84 years with low BMD. Currently, 27% of these women receive bisphosphonates and a further 2.9% receive PTH or calcitonin. The rest remain untreated. Based on our estimates of cost-effectiveness of the individual therapies over a 3-year time horizon, a decision to treat the approximately 5.7 million women not receiving active therapy with bisphosphonates would cost an additional $5563 million (21% increase in total cost) and would result in an additional 83,159 QALYs (0.45% increase) and 390,049 fewer fractures (35% decrease) (Table 4).

In the highest risk group (women aged 75 years with previous fracture), the additional cost of therapy was offset by the savings in inpatient, outpatient, and long-term care for a net savings of $18 million (0.2% decrease in total cost), accompanied by an additional 18,232 QALYs (0.5% increase) and 96,786 fewer fractures (28% decrease).

Currently 48.5% of women with previous fracture (aged 65-84 years with low BMD) are treated with bisphosphonates and an additional 5.1% receive PTH or calcitonin. A policy decision to treat with bisphosphonates the approximately 1.5 million untreated women in this group would result over a 3-year period in 32,558 QALYs gained (0.46% increase) and 155,038 fractures avoided (28% decrease), at an additional societal cost of $783 million (6.2% increase) (data not shown).

DISCUSSION

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