Improving Compliance and Persistence with Bisphosphonate Therapy for Osteoporosis

doi:10.1016/j.amjmed.2005.12.019

The American Journal of Medicine

Volume 119, Issue 4, Supplement 1, April 2006, Pages S18-S24

https://doi.org/10.1016/j.amjmed.2005.12.019 Get rights and content

Abstract

The successful treatment of patients at increased risk for fracture requires proper diagnosis and the development of a treatment plan that permits the patient to take medications in accordance with dosing guidelines and on the correct schedule. Data indicate that patients with osteoporosis who have good long-term medication compliance experience substantially lower risk of fracture. Persistence with therapy also correlates with better bone mineral density and improved suppression of bone turnover markers. Although bisphosphonates are the most potent currently approved antiresorptive agents, they have special dosing issues that can have a negative impact on long-term persistence. The inconvenience and complexity of some dosing requirements; the potential for adverse effects, especially when dosing recommendations are not followed; and very low absorption rates—even under ideal conditions—all contribute to poor outcomes. Extension of the dosing interval from a once-daily to a once-weekly regimen is associated with comparable efficacy, theoretically may improve gastrointestinal safety, and is associated with substantial improvement in persistence with therapy. However, compliance with weekly regimens remains suboptimal. Monthly dosing of ibandronate, a bisphosphonate, was recently approved by the US Food and Drug Administration (FDA). Although extending the dosing interval may improve compliance and persistence with bisphosphonate therapy, it is important to recognize that missed doses or improper dosing may have greater consequences with extended dosing intervals. This article highlights the importance of educating patients about their diagnosis and long-term treatment plan, including the importance of persistence with therapy and compliance with dosing recommendations.

Section snippets

Current state of diagnosis and treatment of osteoporosis

A retrospective study conducted by Gehlbach and colleagues¹ illustrates the failure to recognize and treat patients with fracture (Figure 1A). In this study, vertebral fractures in the thoracic region were retrospectively identified by radiologists and compared with diagnoses made at the time of hospitalization. Moderate or severe vertebral fractures were found in 132 (14.1%) women aged ≥60 years who were hospitalized for any reason. In these patients, only 50% of radiology reports and 17% of

Current state of compliance and persistence with osteoporosis therapy

The data summarized above clearly indicate a large gap between the need and the initial prescription for osteoporosis treatment. A second hurdle that must be overcome in the treatment of osteoporosis is ensuring that patients who receive therapy take their medications on schedule and remain on therapy as long as needed. Good compliance and persistence are essential to ensure the best long-term pharmacotherapy results.

Accurate real-world data about compliance and persistence with medications—for

Impact of compliance and persistence on osteoporosis treatment outcomes

A 2-year study conducted using healthcare database information on 11,249 women with osteoporosis found that those who took ≥80% of their prescribed medication doses had a 16% lower risk of fracture compared with less long-term compliant patients.¹³ Another recent study showed that patients who took ≥80% of their osteoporosis medications had 26% reduction in fractures compared with other patients with lower long-term compliance.¹⁴

Moreover, persistence with bisphosphonate therapy has been

Influences on long-term persistence with osteoporosis therapy

Many issues may impact long-term persistence with osteoporosis medication, including cost and availability, real or perceived adverse effects, dosing frequency and convenience, the number of concomitant diseases and medications, and patients’ understanding of their test results and need for therapy.

Cost and ready availability of medication are critical factors in ensuring compliance. As a direct result of cost, patients frequently do not have their prescriptions dispensed, take a lower dose of

Compliance and persistence with bisphosphonates: Key issues

Although bisphosphonates are the most potent antiresorptive agents currently available, they have special requirements that may negatively impact long-term persistence. Bisphosphonates must be taken according to strict treatment guidelines to achieve optimum absorption and minimize the risk of adverse gastrointestinal events. Patients must avoid food or drink for ≥30 to 60 minutes before taking the medication and the dose must be accompanied by water. Patients are then required to remain

Summary

The relatively low rate of patient compliance and persistence with osteoporosis therapy means that only a small percentage of patients are receiving adequate therapy. The ready availability of tools to assess BMD permits the identification of women with osteoporosis well before they experience the consequences of this disease. Implementing osteoporosis prevention strategies—lifestyle modification, dietary changes, and pharmacologic treatment—should reduce fracture-related morbidity and

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Siris E, Rosen CJ, Harris ST, Abbott TA III, Barr CE, Silverman SL. Adherence to bisphosphonate therapy: relationship...

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Resistance circuit training combined with hypoxia stimulates bone system of older adults: A randomized trial
2022, Experimental Gerontology
Citation Excerpt :
Moreover, it might achieve adaptations with less physical stress, which could be interesting to an aging population with pathologies or risk of injury (Pramsohler et al., 2017). Compared to the current anti-resorptive pharmacological treatments, the present intervention allows the reduction of resorption, but not its formation, while avoiding the side effects of these drugs (Emkey and Ettinger, 2006; Romero Barco et al., 2012). In addition, the poor adherence to the drugs is a real problem in osteoporotic patients (Varenna and Sinigaglia, 2009) that has been directly and significantly correlated with increases in BMD and reductions in the metabolic markers of bone resorption (Clowes et al., 2004; Yood et al., 2003).
Aging leads to gradual irreversible decline in bone mass. As adherence to pharmacological treatment is poor, hypoxia combined with strength training has been suggested for therapeutic benefit for clinical populations. The present study investigated the effects of normobaric cyclic hypoxic exposure combined with resistance circuit training on bone of older adults.
Healthy older adults (n = 50) were randomly assigned to a (1) control group (CON; n = 20), who were instructed to continue with their normal daily activities, (2) a group that performed resistance training in normoxia (RTN; n = 17) and (3) a group that performed resistance training in hypoxia (RTH; n = 13). During 24 weeks, RTH group performed resistance training with elastic bands under normobaric hypoxic conditions (16.1 % FiO2). A session of both exercise groups included nine exercises of several body areas with a structure of 3 sets × 12–15 repetitions per exercise, with a 1-minute rest between sets. Bone mineral density (g·cm-2) was measured using dual-energy X-ray absorptiometry. Bone turnover markers of formation (N-terminal propeptide of type I procollagen; PINP) and resorption (C-terminal telopeptide of type I collagen; bCTX) were analysed with enzyme-linked immunosorbent assay (ELISA) microplate reader.
Values of bCTX and bCTX/PINP significant decreased in RTN (bCTX: 47.79 %; p = 0.002; bCTX/PINP: 61.43 %; p = 0.007) and RTH (bCTX: 59.09 %; p = 0.001; bCTX/PINP: 62.61 %; p = 0.003) groups compared with CON group. Change in bone mineral density was not significantly different between groups. Based on clinically significant change, 23 % of the participants in the RTH group reached this value for femoral neck and trochanter bone mineral density (vs 0 % and 6 % of the RTN group, respectively).
24-Weeks of normobaric cyclic hypoxic exposure combined with resistance circuit training has potential to generate positive effects on bone in older adults.
Trial registration number: NCT04281264 (date of registration: February 24, 2020).
Bisphosphonates pharmacology and use in the treatment of osteoporosis
2020, Marcus and Feldman’s Osteoporosis
Bisphosphonates that have been widely used in the treatment of osteoporosis are popular and effective agents with robust evidence for fracture risk reduction. Bisphosphonates bind avidly to bone and reduce osteoclastic bone resorption. These agents are generally safe and well-tolerated, although concerns about long-term use have emerged. For most patients with osteoporosis, the benefits of treatment outweigh the risks. Because these agents accumulate in bone with some persistent antifracture efficacy after therapy is stopped, it is reasonable to consider a bisphosphonate “holiday.” The duration of treatment and the length of the holiday should be based on individual assessments of risk and benefit.
Reduced food interaction and enhanced gastrointestinal tolerability of a new system based on risedronate complexed with Eudragit E100: Mechanistic approaches from in vitro and in vivo studies
2016, European Journal of Pharmaceutics and Biopharmaceutics
Citation Excerpt :
Similarly, another investigation showed that the oral absorption of sodium alendronate (AlNa) in fasted rats was 4–5 times higher than after concomitant administration with food [3]. The most common reasons for patients to discontinue oral treatment with aminobisphosphonates are gastrointestinal side effects such as erosions or bleeding ulcers, which are more frequent in the stomach than in the intestine [8–10]. To ensure an effective treatment that can minimize both the risk of gastrointestinal damage and interactions with food, rigorous guidelines have been proposed for the oral administration of aminobisphosphonates, such as taking the drug with a full glass of water (180–250 mL) 30 min before the first food or drink of the day, with the patient in a standing position [9].
Novel complexes consisting of Eudragit E100-risedronate are presented. The oral bioavailability of risedronate in rats was determined through its percentage excreted in urine after administration of complexed or free risedronate in fed and fasted conditions. The evaluation of the risedronate gastro-duodenal irritation potential was carried out by macroscopic and histological analyses in an experimental rat model. The degree of counterionic condensation between Eudragit E100 and risedronate was assessed by dialysis with, mechanistic information about the interaction with calcium and the release of risedronate from the complexes being obtained using physiological solution and simulated gastric fluid without pepsin. Non-significant differences were observed in the urinary excretion of risedronate when the complex or free risedronate was administered to fasted rats. However, the urinary excretion of risedronate in the complex group was 4-times higher than in the free risedronate group when animals were concomitantly administered with food. This behavior was related to the high degree of counterionic condensation in the complex (86.5%), which led to a reduction in the calcium induced rate and magnitude of risedronate precipitation and resulted in a decrease in the gastroduodenal damage from the complex, as evidenced by a lower frequency of gastric mucosae hemorrhage. A sustained release of risedronate from the complex was observed toward water, simulated gastric fluid or physiological solution, through an ionic-exchange mechanism. In conclusion, complexation with Eudragit E100 could be a useful strategy to overcome the unfavorable properties of risedronate.
Real-world effects of once vs greater daily inhaled corticosteroid dosing on medication adherence
2013, Annals of Allergy, Asthma and Immunology
Nonadherence to inhaled corticosteroids (ICSs) for asthma maintenance therapy is common and is associated with poor asthma outcomes. Simplifying dosing regimens for some chronic disease conditions has resulted in better adherence; however, little is known regarding the effect of ICS dosing on adherence for the treatment of asthma.
To determine whether once daily dosing is associated with higher adherence to ICS therapy when compared with 2 or more times daily dosing among patients with asthma.
Six years of pharmacy claims data were linked with prescription information to estimate ICS therapy adherence for patients with asthma 12 to 56 years of age who were members of a large health maintenance organization. Patient follow-up continued from the initial ICS fill until one of the following: the last ICS fill in the observation period, a switch of ICS dosing regimen, or the initiation of ICS and long-acting β-agonist combination therapy. Adherence was estimated by calculating a continuous multiple-interval measure of medication availability. Regression models were used to assess the relationship between adherence in patients treated with once daily vs 2 or more times daily ICS therapy.
Among the 1,302 patients who met the inclusion criteria, 17% were prescribed once daily therapy, and 83% were prescribed 2 or more times daily therapy. Models comparing ICS adherence among individuals following once daily and 2 or more times daily ICS regimens suggested that once daily dosing was associated with an approximately 20% increase in adherence. This significant difference persisted among subgroups defined by sex, race/ethnicity, age, and asthma severity.
Once daily dosing was associated with higher adherence to ICS therapy; this included clinically relevant subgroups.
Bisphosphonates: Pharmacology and Use in the Treatment of Osteoporosis
2013, Osteoporosis: Fourth Edition
Bisphosphonates, which have been widely used in the treatment of osteoporosis, are popular and effective agents with robust evidence for fracture risk reduction. Bisphosphonates bind avidly to bone and reduce osteoclastic bone resportion. These agents are generally safe and well-tolerated, although concerns about long-term use have emerged. For most patients with osteoporosis, the benefits of treatment outweigh the risks. Because these agents accumulate in bone with some persistent antifracture efficacy after therapy is stopped, it is reasonable to consider a “drug holiday.” The duration of treatment and the length of the holiday should be based on individual assessments of risk and benefit.
Practice guidelines of the use of bisphosphonates in solid tumours with bone metastases and in multiple myeloma
2011, Revue de Medecine Interne
Les bisphosphonates sont indiqués pour le traitement des lésions osseuses malignes des tumeurs solides et du myélome multiple. Les bisphosphonates ont montré leur intérêt en cancérologie osseuse car ils réduisent le nombre d’événements osseux (hypercalcémie, douleurs, fractures pathologiques, compression médullaire, chirurgie osseuse, radiothérapie à visée antalgique ou décompressive) et retardent leur apparition. Ces résultats ont conduit à l’élaboration de recommandations internationales sur l’utilisation des bisphosphonates pour le traitement des lésions osseuses malignes des tumeurs solides et du myélome multiple. Pour aider le clinicien à prescrire des bisphosphonates en cancérologie osseuse, il nous a semblé important d’établir un guide pratique de leur utilisation sous la forme d’arbres décisionnels et de tableaux comportant des informations sur le bilan pré-thérapeutique, les indications de traitement, la surveillance et les précautions d’emploi à prendre avec ces molécules. En 2007, un groupe de travail s’est mis en place dans le cadre du réseau régional de cancérologie Rhône-Alpes (GIP ONCORA) pour établir ce guide qui a été validé en réunion plénière en juillet 2009 à l’occasion des journées de travail pour la mise en commun des référentiels sur les soins de support qui ont réuni le réseau régional de cancérologie de la Lorraine et le réseau régional de cancérologie Rhône-Alpes (GIP ONCORA).
Bisphosphonates are indicated for the treatment of bone lesions in patients with solid tumours or multiple myeloma. Bisphosphonates have proven their effectiveness in reducing the number of bone complications (hypercalcemia, pain, disease-related fractures, spinal cord compression) and delaying their occurrence in patients with bone tumours; they have also been shown to reduce the need for bone surgery and palliative or pain-relieving radiotherapy in these patients. International recommendations for the treatment of bone lesions related to malignant solid tumours and multiple myeloma have been established. We have elaborated clinical practice guidelines on the use of bisphosphonates to assist treatment decision-making in bone oncology. The guide contains decision trees and tables with information to guide pre-treatment evaluation and patient follow-up, as well as indications and conditions of use of bisphosphonates. In 2007, the regional cancer network of Rhône-Alpes, ONCORA, formed a working group (GIP ONCORA) to elaborate the guideline. The final version was then discussed and adopted at a plenary session in July 2009, during a collaborative workshop on supportive care recommendations organized by ONCORA and the regional cancer network of Lorraine.

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Improving Compliance and Persistence with Bisphosphonate Therapy for Osteoporosis

Abstract

Section snippets

Current state of diagnosis and treatment of osteoporosis

Current state of compliance and persistence with osteoporosis therapy

Impact of compliance and persistence on osteoporosis treatment outcomes

Influences on long-term persistence with osteoporosis therapy

Compliance and persistence with bisphosphonates: Key issues

Summary

Am J Geriatr Pharmacother

Clin Ther

Recognition of vertebral fracture in a clinical setting

Osteoporos Int

Hip fracture patients are not treated for osteoporosisa call to action

Arthritis Rheum

Low frequency of treatment of osteoporosis among postmenopausal women following a fracture

Arch Intern Med

Undertreatment of osteoporosis in men with hip fracture

Arch Intern Med

Follow-up treatment for osteoporosis after fracture

Osteoporos Int

Preventing osteoporotic fracturean overview

Am J Med

Adherence with statin therapy in elderly patients with and without acute coronary syndromes

JAMA

Nonadherence in asthmatic patientsis there a solution to the problem?

Ann Allergy Asthma Immunol

Young HIV-infected adults are at greater risk for medication nonadherence

MedGenMed

Compliance of osteoporotic patients with different treatment regimens

Isr Med Assoc J

Compliance with pharmacologic therapy for osteoporosis

Osteoporos Int

The impact of compliance with osteoporosis therapy on fracture rates in actual practice

Osteoporos Int