Real-World Osteoporosis Treatment Gap and Costs in Spain: Data from Women with a First Fragility Fracture or Diagnosis of Postmenopausal Osteoporosis

Kanis J.A., Johansson H., McCloskey E.V., Liu E., Åkesson K.E., Anderson F.A., Azagra R., Bager C.L., Beaudart C., Bischoff-Ferrari H.A., Biver E., Bruyère O., Cauley J.A., Center J.R., Chapurlat R., et. al.

A large international meta-analysis using primary data from 64 cohorts has quantified the increased risk of fracture associated with a previous history of fracture for future use in FRAX. The aim of this study was to quantify the fracture risk associated with a prior fracture on an international basis and to explore the relationship of this risk with age, sex, time since baseline and bone mineral density (BMD). We studied 665,971 men and 1,438,535 women from 64 cohorts in 32 countries followed for a total of 19.5 million person-years. The effect of a prior history of fracture on the risk of any clinical fracture, any osteoporotic fracture, major osteoporotic fracture, and hip fracture alone was examined using an extended Poisson model in each cohort. Covariates examined were age, sex, BMD, and duration of follow-up. The results of the different studies were merged by using the weighted β-coefficients. A previous fracture history, compared with individuals without a prior fracture, was associated with a significantly increased risk of any clinical fracture (hazard ratio, HR = 1.88; 95% CI = 1.72–2.07). The risk ratio was similar for the outcome of osteoporotic fracture (HR = 1.87; 95% CI = 1.69–2.07), major osteoporotic fracture (HR = 1.83; 95% CI = 1.63–2.06), or for hip fracture (HR = 1.82; 95% CI = 1.62–2.06). There was no significant difference in risk ratio between men and women. Subsequent fracture risk was marginally downward adjusted when account was taken of BMD. Low BMD explained a minority of the risk for any clinical fracture (14%), osteoporotic fracture (17%), and for hip fracture (33%). The risk ratio for all fracture outcomes related to prior fracture decreased significantly with adjustment for age and time since baseline examination. A previous history of fracture confers an increased risk of fracture of substantial importance beyond that explained by BMD. The effect is similar in men and women. Its quantitation on an international basis permits the more accurate use of this risk factor in case finding strategies.

Pedersen A.B., Risbo N., Kafatos G., Neasham D., O’Kelly J., Ehrenstein V.

Abstract Summary Persistence with initial treatment was highest after 1 year, decreasing afterwards. Persistence was highest for denosumab followed by alendronate. We identified several factors associated with treatment persistence, some of which were the same irrespective of OTx agent, which could help target subgroups of patients in terms of social and healthcare support. Purpose To describe patient characteristics, persistence, and factors associated with the persistence of new users of the bisphosphonates (alendronate, risedronate, and ibandronate) and the RANKL inhibitor denosumab in Denmark. Methods A population-based cohort study using health registries (2010–2018). We included alendronate (n = 128,590), risedronate (n = 892), ibandronate (n = 5,855), and denosumab (n = 16,469) users, aged ≥ 50 years. Results The 1-year persistence was 68.2% in the alendronate cohort; 39.3% in the risedronate cohort; 56.3% in the ibandronate cohort; and 84.0% in the denosumab cohort. The 2-year persistence was 58.7% in the alendronate cohort; 28.0% in the risedronate cohort; 42.9% in the ibandronate cohort; and 71.9% in the denosumab cohort. The 4-year persistence was 46.3%, 15.4%, 29.6%, and 56.9%, respectively. Later years of treatment initiation were associated with lower persistence for alendronate (adjusted odds ratio (OR) with 95% CI was 0.86 (0.81–0.91) in 2016 compared to 2010), but not for risedronate (OR was 1.56 (0.60–4.06), ibandronate (OR was 0.92 (0.71–1.19) or denosumab (OR was 1.11 (0.87–1.43). Older age was associated with higher persistence for all medications and the same goes for the female sex except for ibandronate. Dementia was associated with higher persistence for alendronate but not denosumab, whereas prior osteoporosis treatment (OT) was the opposite. Several comorbidities were associated with lower persistence for alendronate, but not denosumab. Conclusion Persistence was highest for denosumab followed by alendronate. We identified several factors associated with treatment persistence, some of which were the same irrespective of OTx agent, which could help target subgroups of patients in terms of social and healthcare support.

Riancho J.A., Peris P., González-Macías J., Pérez-Castrillón J.L.

Esta versión actualizada de las guías de osteoporosis de la Sociedad Española de Investigación en Osteoporosis y Metabolismo Mineral (SEIOMM) incorpora la información más relevante publicada en los últimos 7 años, desde las guías de 2015, con estudios de imagen, como la valoración de la fractura vertebral y el análisis del índice trabecular óseo. Además, los avances terapéuticos incluyen los nuevos fármacos anabólicos, los estudios comparativos de la eficacia de los fármacos y la terapia secuencial y combinada. Por ello se actualizan también las recomendaciones de los tratamientos. This updated version of the Spanish Society for Research in Osteoporosis and Mineral Metabolism (SEIOMM) osteoporosis guides incorporate the most relevant information published in the last 7 years, since the 2015 guides, with imaging studies, such as vertebral fracture assessment and bone trabecular score analysis. In addition, therapeutic advances include new anabolic agents, comparative studies of drug efficacy, and sequential and combined therapy. Therefore, therapeutic algorithms are also updated.

Martínez-Laguna D., Carbonell C., Bastida J., González M., Micó-Pérez R.M., Vargas F., Balcells-Oliver M., Canals L.

In Spanish primary care (PC), the prevalence of fragility fractures (FF) in subjects ≥ 70 years old is high, especially in women. One-third of subjects with an FF lacked osteoporosis (OP) diagnosis and >50% were not currently receiving OP medication. An improvement of the FF management in this population is needed. In Spanish PC, the prevalence of FF is high, especially in women. One-third of subjects with a FF lacked an OP diagnosis and more than half were not currently receiving OP medication. Several studies reported underdiagnosis/undertreatment of OP in PC among elderly subjects with FF. To date, no such data exist for Spain. The purpose is to estimate the prevalence of FF in the elderly population (≥ 70 years old) and to describe the characteristics, risk factors, comorbidities, and OP diagnosis and treatment rates of subjects with FF in Spanish PC centers. This is an observational, retrospective study in Spain consisting of two phases. Phase A included all subjects ≥ 70 years old listed in the center’s medical records from November 2018 to March 2020. Phase B included subjects with FF and prior consultation at the center for any reason. Subjects were excluded only if they had previously participated in another study. Primary outcomes were prevalence of FF (phase A) and characteristics of subjects with at least one FF (phase B). The overall prevalence of FF was 17.7% among subjects visiting medical centers for any reason (24.1% women vs. 8.0% men) (30 PC centers from 14 Spanish regions). Vertebral (5.1%) was the most prevalent fracture. Of 665 subjects in phase B, most (87%) were women and ≥ 80 years old (57%), suffered mainly major OP fracture (68%), and had multiple comorbidities (≥ 2, 89.2%). While two-thirds had OP diagnosis and 61.1% received OP medication anytime in the past, 56.8% were not currently receiving OP medication. Diagnosis and treatment rates were lower among men (43% and 38% vs. 70% and 65%, respectively). Prevalence of FF was high, especially in women. One-third of subjects lacked OP diagnosis and ≥ 50% were not receiving OP treatment; diagnosis and treatment gaps were larger among men. This reinforces the need to improve the management of FF in the elderly population. However, as PC centers participating in this study had high OP experience that have the potential to do better in terms of diagnosis and treatment, caution in the generalization of these data should be taken.

Willers C., Norton N., Harvey N.C., Jacobson T., Johansson H., Lorentzon M., McCloskey E.V., Borgström F., Kanis J.A.

This report describes epidemiology, burden, and treatment of osteoporosis in each of the 27 countries of the European Union plus Switzerland and the UK (EU 27+2). The aim of this report was to characterize the burden of osteoporosis in each of the countries of the European Union plus Switzerland and the UK in 2019 and beyond. The data on fracture incidence and costs of fractures in the EU27+2 was taken from a concurrent publication in this journal (SCOPE 2021: a new scorecard for osteoporosis in Europe) and country-specific information extracted. The information extracted covered four domains: burden of osteoporosis and fractures; policy framework; service provision; and service uptake. The clinical and economic burden of osteoporotic fractures in 2019 is given for each of the 27 countries of the EU plus Switzerland and the UK. Each domain was ranked and the country performance set against the scorecard for all nations studied. Data were also compared with the first SCOPE undertaken in 2010. Fifteen of the 16 score card metrics on healthcare provision were used in the two surveys. Scores had improved or markedly improved in 15 countries, remained constant in 8 countries and worsened in 3 countries. The average treatment gap increased from 55% in 2010 to 71% in 2019. Overall, 10.6 million women who were eligible for treatment were untreated in 2010. In 2019, this number had risen to 14.0 million. In spite of the high cost of osteoporosis, a substantial treatment gap and projected increase of the economic burden driven by aging populations, the use of pharmacological prevention of osteoporosis has decreased in recent years, suggesting that a change in healthcare policy concerning the disease is warranted.

Sicras-Mainar A., Sicras-Navarro A., Palacios B., Varela L., Delgado J.F.

Describir la epidemiología y el tratamiento administrado recientemente a una amplia cohorte de pacientes con insuficiencia cardiaca (IC).

Kanis J.A., Norton N., Harvey N.C., Jacobson T., Johansson H., Lorentzon M., McCloskey E.V., Willers C., Borgström F.

This scorecard summarises key indicators of the burden of osteoporosis and its management in the 27 member states of the European Union, as well as the UK and Switzerland. The resulting scorecard elements, assembled on a single sheet, provide a unique overview of osteoporosis in Europe. The scorecard for osteoporosis in Europe (SCOPE) is a project of the International Osteoporosis Foundation (IOF) that seeks to raise awareness of osteoporosis care in Europe. The aim of this project was to develop a scorecard and background documents to draw attention to gaps and inequalities in the provision of primary and secondary prevention of fractures due to osteoporosis. The SCOPE panel reviewed the information available on osteoporosis and the resulting fractures for each of the 27 countries of the European Union plus the UK and Switzerland (termed EU27+2). The information obtained covered four domains: background information (e.g. the burden of osteoporosis and fractures), policy framework, service provision and service uptake, e.g. the proportion of men and women at high risk that do not receive treatment (the treatment gap). There was a marked difference in fracture risk among the EU27+2 countries. Of concern was the marked heterogeneity in the policy framework, service provision and service uptake for osteoporotic fracture that bore little relation to the fracture burden. For example, despite the wide availability of treatments to prevent fractures, in the majority of the EU27+2, only a minority of patients at high risk receive treatment even after their first fracture. The elements of each domain in each country were scored and coded using a traffic light system (red, orange, green) and used to synthesise a scorecard. The resulting scorecard elements, assembled on a single sheet, provide a unique overview of osteoporosis in Europe. The scorecard enables healthcare professionals and policy makers to assess their country’s general approach to the disease and provide indicators to inform the future provision of healthcare.

Åkesson K.E., McGuigan F.E.

This review outlines the scope of the problem in osteoporosis care and secondary fracture prevention and describes fracture prevention strategies, with a focus on the frail elderly. Despite heightened awareness among patients and clinicians alike and the availability of efficacious anti-osteoporosis medications, osteoporosis is still underdiagnosed and undertreated. However, the introduction of systematic risk assessment and secondary fracture prevention programmes has gained momentum, and evidence of success is accumulating. We possess today the knowledge required to close the osteoporosis care gap. The basic components in a secondary prevention model are similar in all health care settings, number one being a dedicated fracture coordinator, with anti-osteoporosis medications and multifaceted falls prevention as cornerstones, particularly in the frailest, both in the near and long-term. Initiation of structured care pathways including the key elements – identification, investigation, intervention and follow-up of adherence – demonstrably reduces re-fracture rates and is cost-effective.

McCloskey E., Rathi J., Heijmans S., Blagden M., Cortet B., Czerwinski E., Hadji P., Payer J., Palmer K., Stad R., O’Kelly J., Papapoulos S.

This study in 8 countries across Europe found that about 75% of elderly women seen in primary care who were at high risk of osteoporosis-related fractures were not receiving appropriate medication. Lack of osteoporosis diagnosis appeared to be an important contributing factor. Treatment rates in osteoporosis are documented to be low. We wished to assess the osteoporosis treatment gap in women ≥ 70 years in routine primary care across Europe. This cross-sectional observational study in 8 European countries collected data from women 70 years or older visiting their general practitioner. The primary outcome was treatment gap: the proportion who were not receiving any osteoporosis medication among those at increased risk of fragility fracture (using history of fracture, 10-year probability of fracture above country-specific Fracture Risk Assessment Tool [FRAX] thresholds, T-score ≤ − 2.5). Median 10-year probability of fracture (without bone mineral density [BMD]) for the 3798 enrolled patients was 7.2% (hip) and 16.6% (major osteoporotic). Overall, 2077 women (55%) met one or more definitions for increased risk of fragility fracture: 1200 had a prior fracture, 1814 exceeded the FRAX threshold, and 318 had a T-score ≤ − 2.5 (only 944 received a dual-energy x-ray absorptiometry [DXA] scan). In those at increased fracture risk, the median 10-year probability of hip and major osteoporotic fracture was 11.2% and 22.8%, vs 4.1% and 11.5% in those deemed not at risk. An osteoporosis diagnosis was recorded in 804 patients (21.2%); most (79.7%) of these were at increased fracture risk. The treatment gap was 74.6%, varying from 53% in Ireland to 91% in Germany. Patients with an osteoporosis diagnosis were found to have a lower treatment gap than those without a diagnosis, with an absolute reduction of 63%. There is a large treatment gap in women aged ≥ 70 years at increased risk of fragility fracture in routine primary care across Europe. The gap appears to be related to a low rate of osteoporosis diagnosis.

Koller G., Goetz V., Vandermeer B., Homik J., McAlister F.A., Kendler D., Ye C.

Osteoporosis is a chronic disease of low bone mass and fragility. Treatment is frequently compromised by suboptimal medication compliance causing increased morbidity. This review investigates adherence and persistence to parenteral osteoporosis therapies. Findings reveal parenteral medications requiring reduced dosing frequency have higher compliance than oral therapies. This systematic review examines real-world adherence to parenteral osteoporosis therapies. We searched PubMed, Medline, and EMBASE databases for English language observational studies that examined patient adherence and/or persistence to parenteral osteoporosis treatments (teriparatide sc, ibandronate iv, zoledronic acid iv, and denosumab sc) in adults with osteoporosis published up to September 2018. Studies with only self-reported adherence or persistence data and those with less than 20 patients were excluded. Quality assessment of included studies was completed using the Newcastle-Ottawa quality assessment scale (NOS). We identified 40 eligible studies. Teriparatide was examined in 29 studies, with persistence rates of 10–87% (median 55%) at 1 year and 10–69% (median 29.5%) at 2 years, and adherence rates of 21–89% (median 53%) at 1 year and 37–68% (median 40%) at 2 years. Ten studies of zoledronic acid reported persistence rates of 34–73% (median 42%) for second dose and 20–54% (median 35.8%) for third dose. Ten studies of ibandronate adherence reported and 2-year persistence rates of 31–58% (median 47.5%) in 1 year and 13–35% (median 25%) at 2 years, and adherence rates of 21–72% (median 47.3%) and 15–58% (median 36.5%) respectively. Denosumab was reported in 19 studies, with second (1 year) and fourth (2 year) dose persistence rates of 61–100% (median 81%) and 36–99% (median 45.5%). There is substantial heterogeneity in reports of persistence and adherence rates with parenteral osteoporosis therapies. Most of the published data are from short-term studies and evaluations of long-term adherence and persistence with parenteral therapies for osteoporosis are needed.

Borgström F., Karlsson L., Ortsäter G., Norton N., Halbout P., Cooper C., Lorentzon M., McCloskey E.V., Harvey N.C., Javaid M.K., Kanis J.A.

This report provides an overview and a comparison of the burden and management of fragility fractures in the largest five countries of the European Union plus Sweden (EU6). In 2017, new fragility fractures in the EU6 are estimated at 2.7 million with an associated annual cost of €37.5 billion and a loss of 1.0 million quality-adjusted life years. Osteoporosis is characterized by reduced bone mass and strength, which increases the risk of fragility fractures, which in turn, represent the main consequence of the disease. This report provides an overview and a comparison of the burden and management of fragility fractures in the largest five EU countries and Sweden (designated the EU6). A series of metrics describing the burden and management of fragility fractures were defined by a scientific steering committee. A working group performed the data collection and analysis. Data were collected from current literature, available retrospective data and public sources. Different methods were applied (e.g. standard statistics and health economic modelling), where appropriate, to perform the analysis for each metric. Total fragility fractures in the EU6 are estimated to increase from 2.7 million in 2017 to 3.3 million in 2030; a 23% increase. The resulting annual fracture-related costs (€37.5 billion in 2017) are expected to increase by 27%. An estimated 1.0 million quality-adjusted life years (QALYs) were lost in 2017 due to fragility fractures. The current disability-adjusted life years (DALYs) per 1000 individuals age 50 years or more were estimated at 21 years, which is higher than the estimates for stroke or chronic obstructive pulmonary disease. The treatment gap (percentage of eligible individuals not receiving treatment with osteoporosis drugs) in the EU6 is estimated to be 73% for women and 63% for men; an increase of 17% since 2010. If all patients who fracture in the EU6 were enrolled into fracture liaison services, at least 19,000 fractures every year might be avoided. Fracture-related burden is expected to increase over the coming decades. Given the substantial treatment gap and proven cost-effectiveness of fracture prevention schemes such as fracture liaison services, urgent action is needed to ensure that all individuals at high risk of fragility fracture are appropriately assessed and treated.

Morley J., Moayyeri A., Ali L., Taylor A., Feudjo-Tepie M., Hamilton L., Bayly J.

Gaining full benefits from osteoporosis medications requires long-term treatment. Investigating the real-world persistence of women receiving osteoporosis medications in the UK, we found that most patients stop treatment within a year. To prevent osteoporotic fragility fractures, long-term treatment persistence must be improved. Persistence with osteoporosis therapies has historically been poor. To treat this chronic and progressive disease, it is essential that patients receive the full benefit of these medications. We estimated persistence and compliance with osteoporosis therapies in a large sample of postmenopausal women in the UK. Data were obtained from the Clinical Practice Research Datalink for all women aged 50 years and over or women with early menopause, who received at least one prescription in primary care for any licensed osteoporosis therapy between January 1, 2010 and December 31, 2015. Persistence and compliance at 24 months (primary objective) and at 5 years (exploratory objective) were estimated in three patient cohorts: “All Patients,” “Naïve Patients,” and “Drug-Specific.” The All Patients cohort included 72,256 women. Persistence with any therapy was 56.1%, 43.6%, 36.4%, and 31.0% at 6, 12, 18, and 24 months, respectively, and 23.2% and 13.1% at 3 years and 5 years, respectively. Patients were generally more persistent and compliant if evaluated from their first exposure to osteoporosis therapy (Naïve Patients cohort). In the drug-specific analysis, 64% of patients receiving denosumab (administered subcutaneously every 6 months) were persistent at 24 months compared with 28% and 23% of those taking oral bisphosphonates and intravenous bisphosphonates, respectively. Only about one in three patients who received osteoporosis therapy continued to be on treatment after 2 years. There is a need to improve persistence with osteoporosis therapy, especially for high-risk patients

Mitchell P.J., Cooper C., Fujita M., Halbout P., Åkesson K., Costa M., Dreinhöfer K.E., Marsh D.R., Lee J., Chan D., Javaid M.K.

This review sought to describe quality improvement initiatives in fragility fracture care and prevention. A major care gap persists throughout the world in the secondary prevention of fragility fractures. Systematic reviews have confirmed that the Fracture Liaison Service (FLS) model of care is associated with significant improvements in rates of bone mineral density testing, initiation of osteoporosis treatment and adherence with treatment for individuals who sustain fragility fractures. Further, these improvements in the processes of care resulted in significant reductions in refracture risk and lower post-fracture mortality. The primary challenge facing health systems now is to ensure that best practice is delivered effectively in the local healthcare setting. Publication of clinical standards for FLS at the organisational and patient level in combination with the establishment of national registries has provided a mechanism for FLS to benchmark and improve their performance. Major efforts are ongoing at the global, regional and national level to improve the acute care, rehabilitation and secondary prevention for individuals who sustain fragility fractures. Active participation in these initiatives has the potential to eliminate current care gaps in the coming decade.

Sicras-Mainar A., Enriquez J.L., Hernández I., Sicras-Navarro A., Aymerich T., Leon M.

Fatoye F., Smith P., Gebrye T., Yeowell G.

ObjectivesThis study examined patient adherence and persistence to oral bisphosphonates for the treatment of osteoporosis in real-world settings.MethodsA systematic review was completed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Medical Literature Analysis and Retrieval System Online (MEDLINE), Cumulative Index to Nursing and Allied Health Literature (CINAHL), Allied and Complementary Medicine Database (AMED), Database of Abstracts of Reviews of Effects (DARE), Health Technology Assessment (HTA) and National Health Service Economic Evaluation Database NHS EED) databases were searched for studies published in English language up to April 2018. Prospective and retrospective observational studies that used prescription claim databases or hospital medical records to examine patient adherence and persistence to oral bisphosphonate treatment among adults with osteoporosis were included. The Newcastle–Ottawa quality assessment scale (NOS) was used to assess the quality of included studies.ResultsThe search yielded 540 published studies, of which 89 were deemed relevant and were included in this review. The mean age of patients included within the studies ranged between 53 to 80.8 years, and the follow-up varied from 3 months to 14 years. The mean persistence of oral bisphosphonates for 6 months, 1 year and 2 years ranged from 34.8% to 71.3%, 17.7% to 74.8% and 12.9% to 72.0%, respectively. The mean medication possession ratio ranged from 28.2% to 84.5%, 23% to 50%, 27.2% to 46% over 1 year, 2 years and 3 years, respectively. All studies included scored between 6 to 8 out of 9 on the NOS. The determinants of adherence and persistence to oral bisphosphonates included geographic residence, marital status, tobacco use, educational status, income, hospitalisation, medication type and dosing frequency.ConclusionsWhile a number of studies reported high levels of persistence and adherence, the findings of this review suggest that patient persistence and adherence with oral bisphosphonates medications was poor and reduced notably over time. Overall, adherence was suboptimal. To maximise adherence and persistence to oral bisphosphonates, it is important to consider possible determinants, including characteristics of the patients.