Comparison of the cost-effectiveness of sequential treatment with abaloparatide in US men and women at very high risk of fractures.

BACKGROUND: Osteoporotic-related fractures represent an increasing burden to patients, health care systems and society. AIMS: This study estimated cost-effectiveness of sequential treatment with abaloparatide (ABL) followed by alendronate (ALN) compared to relevant alternative strategies in US men and women aged 50 to 80 years at very high fracture risk (bone mineral density T-score ≤ - 2.5 and a recent fracture). METHODS: A lifetime Markov-based microsimulation model was used to estimate healthcare costs and quality-adjusted life years (QALYs). Comparators were sequential treatment with unbranded teriparatide (TPTD)/ALN, generic ALN monotherapy, and no treatment. Analyses were conducted based on initial fracture site (hip, vertebral, or any fracture) and treatment efficacy data (derived from clinical trials or a recent network meta-analysis). RESULTS: From all analyses completed, sequential ABL/ALN demonstrated more QALYs for lower healthcare costs versus unbranded TPTD/ALN. No treatment was dominated (higher costs for less QALYs) versus ALN monotherapy. Sequential ABL/ALN resulted in favorable cost-effectiveness (at US threshold of $150,000/QALY) versus generic ALN monotherapy in men aged ≥ 50 years with any fracture type, women aged ≥ 65 years with any fracture type, and women aged ≥ 55 years having a hip or vertebral fracture. DISCUSSION: Similar cost-effectiveness of sequential ABL/ALN versus unbranded TPTD/ALN, ALN monotherapy, and no treatment was observed in both US men and women at very high fracture risk, with a moderate improvement in cost-effectiveness in men versus women and in patients with a hip or vertebral fracture. CONCLUSIONS: Sequential therapy with ABL/ALN was cost-effective in US men and women at very high risk of fractures.

Cost-Effectiveness of Sequential Abaloparatide/Alendronate in Men at High Risk of Fractures in the United States.

BACKGROUND AND OBJECTIVES: Abaloparatide (ABL) significantly increases bone mineral density in men with osteoporosis similar to what was reported in postmenopausal women with osteoporosis. The cost effectiveness of sequential treatment with ABL followed by alendronate (ALN) in men at high fracture risk was compared to relevant alternative treatments. METHODS: A Markov-based microsimulation model based on a lifetime US healthcare decision maker perspective was developed to evaluate the cost (expressed in US$2021) per quality-adjusted life-years (QALYs) gained of sequential ABL/ALN. Comparators were sequential treatment unbranded teriparatide (TPTD)/ALN, generic ALN monotherapy, and no treatment. Discount rates of 3% were used. Consistent with practice guidelines, patients received 18 months of ABL or TPTD followed by ALN for 5 years, or 5 years of ALN monotherapy. Analyses were conducted in high-risk men aged over 50 years defined as having a bone mineral density T-score ≤-2.5 and a recent fracture. Time-specific risk of subsequent fracture after a recent fracture, incremental costs up to 5 years following fractures, real-world medication adherence, and mostly US men-specific data were included in the model. One-way and probabilistic sensitivity analyses were conducted to assess the robustness of results. RESULTS: Over the full age range, sequential ABL/ALN led to more QALYs for lower costs than sequential unbranded TPTD/ALN, while no treatment was dominated (more QALYs, lower costs) by ALN monotherapy. The costs per QALY gained of sequential ABL/ALN were lower than the US threshold of US$150,000 versus generic ALN monotherapy. The probabilities that sequential ABL/ALN was cost effective compared to ALN monotherapy were estimated at 51% in men aged 50 years and between 88 and 90% in those aged ≥ 60 years. CONCLUSIONS: Sequential therapy using ABL/ALN may be cost effective compared with generic ALN monotherapy in US men aged ≥ 50 years at high fracture risk, especially in those aged ≥ 60 years. Unbranded TPTD/ALN and no treatment were dominated interventions (less QALY, more costs) compared with ABL/ALN or ALN monotherapy.

An Evaluation of Treatment Patterns for Osteoporosis and Outcomes After a Fragility Fracture in a Real-World Setting.

OBJECTIVES: Treatment initiation and persistence after a fragility fracture are critical to reduce the risk of subsequent fractures. The authors evaluated osteoporosis management and outcomes after index fracture. METHODS: This retrospective cohort study used real-world data for patients (≥50 years), including pharmacy claims linked to commercial and Medicare medical claims from Symphony Health Patient Source. Osteoporosis management was evaluated for at least 12 months after the first case-qualifying fracture during the identification period and continued until a second fracture or March 31, 2020 (depending on data availability). Secondary fracture incidence was evaluated overall and for subgroups at very high risk. RESULTS: Of 755,312 eligible patients, the proportion with a claim for bone mineral density testing at 12 months after index fracture was low [64,932 (8.6%)], and 75.3% of those tested were ≥65 years of age. Most patients (88.6%) remained untreated at any time after fracture. Among those treated, most (64.9%) were initially treated with bisphosphonates (oral, 93.7%; IV, 6.3%). Treatment duration and persistence were low for all treatments ranging from 6.5 months with 19.6% persistent for abaloparatide to 11.3 months with 45.0% persistent for denosumab. During follow-up, 13.6% of patients had a secondary fracture at any site, with higher incidence in subgroups considered to be at high risk for fracture than in the overall population. CONCLUSIONS: Low rates of osteoporosis testing and treatment initiation and high secondary fracture rates (particularly among patients at very high risk) highlight the need for better management of patients after a fracture. LEVEL OF EVIDENCE: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Cost Effectiveness Analyses of Interventions for Osteoporosis in Men: A Systematic Literature Review.

BACKGROUND: Osteoporosis is often considered to be a disease of women. Over the last few years, owing to the increasing clinical and economic burden, the awareness and imperative for identifying and managing osteoporosis in men have increased substantially. With the approval of agents to treat men with osteoporosis, more economic evaluations have been conducted to assess the potential economic benefits of these interventions. Despite this concern, there is no specific overview of cost-effectiveness analyses for the treatment of osteoporosis in men. OBJECTIVES: This study aims (1) to systematically review economic evaluations of interventions for osteoporosis in men; (2) to critically appraise the quality of included studies and the source of model input data; and (3) to investigate the comparability of results for studies including both men and women. METHODS: A literature search mainly using MEDLINE (via Ovid) and Embase databases was undertaken to identify original articles published between 1 January, 2000 and 30 June, 2022. Studies that assessed the cost effectiveness of interventions for osteoporosis in men were included. The Economic Aspects of Osteoporosis, Osteoarthritis and Musculoskeletal Diseases and the International Osteoporosis Foundation osteoporosis-specific guideline was used to assess the quality of design, conduct, and reporting of included studies. RESULTS: Of 2973 articles identified, 25 studies fulfilled the inclusion criteria, classified into economic evaluations of active drugs (n = 8) or nutritional supplements (n = 4), intervention thresholds (n = 5), screening strategies (n = 6), and post-fracture care programs (n = 2). Most studies were conducted in European countries (n = 15), followed by North America (n = 9). Bisphosphonates (namely alendronate) and nutritional supplements were shown to be generally cost effective compared with no treatment in men over 60 years of age with osteoporosis or prior fractures. Two other studies suggested that denosumab was cost effective in men aged 75 years and older with osteoporosis compared with bisphosphates and teriparatide. Intervention thresholds at which bisphosphonates were found to be cost effective varied among studies with a 10-year probability of a major osteoporotic fracture that ranged from 8.9 to 34.2% for different age categories. A few studies suggested cost effectiveness of screening strategies and post-fracture care programs in men. Similar findings regarding the cost effectiveness of drugs and intervention thresholds in women and men were captured, with slightly greater incremental cost-effectiveness ratios in men. The quality of the studies included had an average score of 18.8 out of 25 (range 13-23.5). Hip fracture incidence and mortality risk were mainly derived from studies in men, while fracture cost, treatment efficacy, and disutility were commonly derived from studies in women or studies combining both sexes. CONCLUSIONS: Anti-osteoporosis drugs and nutritional supplements are generally cost effective in men with osteoporosis. Screening strategies and post-fracture care programs also showed economic benefits for men. Cost-effectiveness and intervention thresholds were generally similar in studies conducted in both men and women, with slightly greater incremental cost-effectiveness ratios in men.

Closing the gap in osteoporosis management: the critical role of primary care in bone health.

OBJECTIVE: The World Health Organization issued a call to action for primary care to lead efforts in managing noncommunicable diseases, including osteoporosis. Although common, osteoporosis remains underdiagnosed and undertreated. Primary care practitioners (PCPs) are critical in identifying individuals at risk for osteoporosis and osteoporotic fractures; however, recent advances in assessment, diagnosis, and treatment of osteoporosis have not been incorporated into clinical practice in primary care due to numerous reasons including time constraints and insufficient knowledge. To close this gap in clinical practice, we believe PCPs need a practical strategy to facilitate osteoporosis assessment and management that is easy to implement. METHODS: In this article, we consolidate information from various global guidelines and highlight areas of agreement to create a streamlined osteoporosis management strategy for a global audience of PCPs. RESULTS: We present a systematic approach to facilitate osteoporosis assessment and management that includes four steps: (1) identifying patients at risk through proactive screening strategies, (2) investigating and diagnosing patients, (3) intervening with personalized treatment plans, and (4) implementing patient-centered strategies for long-term management and monitoring of patients. CONCLUSION: Primary care has a central role in ensuring the incorporation of key elements of holistic care as outlined by the World Health Organization in managing noncommunicable diseases including osteoporosis; namely, a people-centered approach, incorporation of specialist services, and multidisciplinary care. This approach is designed to strengthen the health system's response to the growing osteoporosis epidemic.

Osteoporosis is a chronic condition associated with aging in which bones become "porous" and weak, and are more likely to break (i.e., fracture) even with minimal trauma such as tripping or falling from a standing height. A broken bone is a serious condition that not only affects daily activities, but can also lead to reduced quality of life, need for caregiver support, work loss, hospital and rehabilitation costs, nursing home costs, and increased mortality. Although osteoporosis is common, it is often undiagnosed or untreated, leaving many people at risk for experiencing broken bones. A broken bone increases the risk of more broken bones. Given the growing size of the aging global population, osteoporosis and the risk of broken bones represent an urgent problem and growing burden. We need ways to make it easier for primary care practitioners (PCPs), such as family physicians, internists, physician assistants, nurse practitioners, and nurses, to include osteoporosis care as part of routine clinical visits. In this article, we discuss the critical role of PCPs in early detection, diagnosis, and treatment of osteoporosis as they are often the first point of contact for at-risk patients. We present a simple, four-step approach to help PCPs and patients navigate the journey from osteoporosis diagnosis to a treatment plan. The four steps are to: (1) identify at-risk patients by screening for weak bones or osteoporosis, (2) perform necessary tests to diagnose patients, (3) develop a personalized treatment plan, and (4) determine long-term strategies for managing and monitoring bone health.

Multidisciplinary Management of Menopause: Symposium Proceedings.

This proceeding summarizes a symposium on multidisciplinary management of menopause held on July 30, 2021 as part of the Health of Women 2021 conference. The workshop featured presentations by national experts who provided insights into multidisciplinary approaches to the management of menopause, vasomotor symptoms and genitourinary syndrome of menopause, bone health (including osteoporosis, muscular strength, and mobility), as well as sexual and psychological health during menopause. In this study, we highlight the major points of each presentation and the resultant discussion.

Healthcare Policy Changes in Osteoporosis Can Improve Outcomes and Reduce Costs in the United States.

In the United States, osteoporosis affects over 10 million adults, has high societal costs ($22 billion in 2008), and is currently being underdiagnosed and undertreated. Given an aging population, this burden is expected to rise. We projected the fracture burden in US women by modeling the expected demographic shift as well as potential policy changes. With the anticipated population aging and growth, annual fractures are projected to increase from 1.9 million to 3.2 million (68%), from 2018 to 2040, with related costs rising from $57 billion to over $95 billion. Policy-driven expansion of case finding and treatment of at-risk women could lower this burden, preventing 6.1 million fractures over the next 22 years while reducing payer costs by $29 billion and societal costs by $55 billion. Increasing use of osteoporosis-related interventions can reduce fractures and result in substantial cost-savings, a rare and fortunate combination given the current landscape in healthcare policy. © 2019 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.

Fracture and Bone Mineral Density Response by Baseline Risk in Patients Treated With Abaloparatide Followed by Alendronate: Results From the Phase 3 ACTIVExtend Trial.

In the randomized, placebo-controlled, double-blind phase 3 ACTIVE study (NCT01343004), 18 months of abaloparatide 80 µg daily (subcutaneous injection) in postmenopausal women at risk of osteoporotic fracture significantly reduced the risk of vertebral, nonvertebral, clinical, and major osteoporotic fractures and significantly increased bone mineral density (BMD) versus placebo regardless of baseline risk factors. Women from the abaloparatide and placebo groups who completed ACTIVE were eligible for ACTIVExtend (NCT01657162), in which all enrollees received sequential, open-label monotherapy with alendronate 70 mg once weekly for up to 24 months. This prespecified analysis evaluated whether fracture risk reductions and bone mineral density (BMD) gains associated with abaloparatide during ACTIVE persisted through the full 43-month ACTIVE-ACTIVExtend study period in nine prespecified baseline risk subgroups. Baseline risk subgroups included BMD T-score at the lumbar spine, total hip, and femoral neck (≤ - 2.5 versus > - 2.5 and ≤ -3.0 versus > - 3.0), history of nonvertebral fracture (yes/no), prevalent vertebral fracture (yes/no), and age (<65 versus 65 to <75 versus ≥75 years). Forest plots display treatment effect. Treatment-by-subgroup interactions were tested using the Breslow-Day test, Cox proportional hazards model, and ANCOVA model. After the combined ACTIVE-ACTIVExtend study period, reductions in relative risk for new vertebral, nonvertebral, clinical, and major osteoporotic fractures were greater among patients in the abaloparatide/alendronate group than among those in the placebo/alendronate group across all nine baseline risk subgroups. BMD gains at the lumbar spine, total hip, and femoral neck were greater in the abaloparatide/alendronate group versus the placebo/alendronate group. No clinically meaningful interaction between treatment assignment and any baseline risk variable was observed. The sequence of abaloparatide for 18 months followed by alendronate for up to 24 months appears to be an effective treatment option for a wide range of postmenopausal women at risk for osteoporotic fractures. © 2019 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals, Inc.

Lack of Evidence Linking Calcium With or Without Vitamin D Supplementation to Cardiovascular Disease in Generally Healthy Adults: A Clinical Guideline From the National Osteoporosis Foundation and the American Society for Preventive Cardiology.

DESCRIPTION: Calcium is the dominant mineral present in bone and a shortfall nutrient in the American diet. Supplements have been recommended for persons who do not consume adequate calcium from their diet as a standard strategy for the prevention of osteoporosis and related fractures. Whether calcium with or without vitamin D supplementation is beneficial or detrimental to vascular health is not known. METHODS: The National Osteoporosis Foundation and American Society for Preventive Cardiology convened an expert panel to evaluate the effects of dietary and supplemental calcium on cardiovascular disease based on the existing peer-reviewed scientific literature. The panel considered the findings of the accompanying updated evidence report provided by an independent evidence review team at Tufts University. RECOMMENDATION: The National Osteoporosis Foundation and American Society for Preventive Cardiology adopt the position that there is moderate-quality evidence (B level) that calcium with or without vitamin D intake from food or supplements has no relationship (beneficial or harmful) to the risk for cardiovascular and cerebrovascular disease, mortality, or all-cause mortality in generally healthy adults at this time. In light of the evidence available to date, calcium intake from food and supplements that does not exceed the tolerable upper level of intake (defined by the National Academy of Medicine as 2000 to 2500 mg/d) should be considered safe from a cardiovascular standpoint.

The National Osteoporosis Foundation's methods and processes for developing position statements.

The methods and processes described in this manuscript have been approved and adopted by the NOF Board of Trustees on November 11, 2015. This manuscript has been peer-reviewed by the NOF Research Committee and Osteoporosis International. The National Osteoporosis Foundation frequently publishes position statements for the benefit of educating healthcare professionals and the general public on a particular issue and/or concern related to preventing osteoporosis and/or promoting strong bones throughout the lifespan. This manuscript represents the official methods and processes adopted by the NOF Board of Trustees for the purpose developing future position statements in a transparent and unbiased manner.

Osteoporosis management: translating research into optimal fracture protection II.

BACKGROUND: Osteoporosis is a prevalent disease with substantial individual and socioeconomic consequences. The challenges faced by physicians include identifying individuals at high risk of fracture, selecting the optimal treatment plan for each patient, and educating patients regarding their role in the effectiveness of therapy. SCOPE: This article discusses screening and patient selection for osteoporosis treatment, as well as available bisphosphonate therapies. Data on patient adherence and cost-effectiveness are also reviewed. The aim is to raise awareness among clinicians of the importance of osteoporosis assessment and of the differences in clinical outcomes between therapies. FINDINGS: Reviewed data indicates that risk-factor assessment is invaluable in diagnosing osteoporosis and guidelines are available which should be consulted to help determine which patients need treatment. When selecting a treatment plan, the differences between therapies in terms of vertebral and nonvertebral efficacy, timing of onset of action, and tolerability should be considered. Furthermore, patient adherence to a particular therapy will affect its effectiveness and can be improved through active patient education. Finally, given the large number of affected individuals, cost-effectiveness of therapies should be considered. CONCLUSION: The appropriate therapy should match individual patient needs in terms of efficacy, early onset of action, tolerability, and likelihood of patient adherence to treatment.

Osteoporosis management: impact of fracture type on cost and quality of life in patients at risk for fracture I.

BACKGROUND: Osteoporosis is a major and costly global public health problem. It is a chronic disease in which fracture is the main outcome, and the impact of these fractures can vary depending on the age of the individual and the severity of the fracture. SCOPE: Using literature review, this paper discusses and summarizes the information available regarding the individual and socio-economic consequences associated with the several types of osteoporotic fractures. FINDINGS: Different types of osteoporotic fractures are generally associated with different age groups. The health-economic impact of vertebral and hip fractures has been extensively explored and it is well known that these fractures are associated with morbidity/disability and increased mortality; they also account for a substantial portion of the direct fracture costs. However, to accurately estimate the individual and socio-economic burden of the disease, further research is needed on the morbidity/disability, mortality, and costs associated with non-hip, nonvertebral fractures, which account for more than half of the total fractures. More data are also required on the indirect costs associated with all fracture types. CONCLUSIONS: Understanding the socio-economic consequences of each fracture type will be important to fully estimate the burden of osteoporosis and may help clinicians tailor management plans for individual patients.