Fracture rates in patients discontinuing alendronate treatment in real life: a population-based cohort study

Sølling, Anne Sophie; Christensen, Diana Hedevang; Darvalics, Bianka; Harsløf, Torben; Thomsen, Reimar Wernich; Langdahl, Bente

doi:10.1007/s00198-020-05745-x

Cited by 10 publications

(18 citation statements)

References 46 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…A nationwide population‐based cohort from Denmark reported similar fracture rates in patients undertaking a 5‐year drug holiday or persisting with treatment after at least 5 years of alendronate use. ( 45 ) Importantly, both men and postmenopausal women were included in this study, factors impacting treatment decisions were adjusted using Cox proportional hazards regression analysis and high adherence rates while on treatment were reported, likely protective against holiday fractures.…”

Section: Perspectives From Real World Studiesmentioning

confidence: 99%

“…Studies circumvented the issue of confounding by adjusting for clinical risk factors that could impact on drug holiday decisions in these studies, propensity score matching for control cohorts, and use of multivariate models. (43)(44)(45) Postmenopausal women with low BMD were the predominant group examined in these studies. Nine studies included men who represented 10% to 20% of the cohort, and premenopausal women were examined in one study.…”

Section: Perspectives From Real World Studiesmentioning

confidence: 99%

“…Although shorter drug holidays led to significant declines in lumbar spine BMD, (42) changes were confounded by degenerative artifact in holidays beyond 2 years and lumbar BMD was no longer an accurate marker of long-term fracture risk. (45,46,49,54) Drug holidays led to a more rapid decline in bone density and increases in bone turnover in subjects previously prescribed risedronate versus alendronate. (49,53) In a study examining different durations of alendronate use in postmenopausal women, drug holidays did not lead to significant changes in bone density.…”

Section: Bmd and Btmsmentioning

confidence: 99%

“…Predominantly, postmenopausal women with a mean age of 69 to 75 years with adherence rates of >50% to 80%, prescribed any of a number of BPs including oral and intravenous formulations, were included. (44,45,50) A large retrospective study of a racially and socioeconomically diverse cohort from the United States identified adherence as the main determinant of sustained reductions in fractures during a drug holiday. (44) Subjects in the BP holiday group who had greater adherence to oral BPs (MPR > 50%) while on treatment had a 30% reduction compared to nonpersistent BP users, defined by MPR < 50% or no BP use for <12 months, in the 3-year-long drug holiday.…”

Section: Fractures During Bp Drug Holidaymentioning

confidence: 99%

“…( 42 ) In general, fracture events were sourced from electronic medical records, patient registries including healthcare databases, hospital admission, and emergency presentation codes. ( 43 , 44 , 45 ) Medication adherence, measured using medication possession ratios (MPRs) or proportion of days covered (PDC), were reported with the caveat that MPR may overestimate adherence when patients frequently refill prescriptions. Studies circumvented the issue of confounding by adjusting for clinical risk factors that could impact on drug holiday decisions in these studies, propensity score matching for control cohorts, and use of multivariate models.…”

Section: Perspectives From Real World Studiesmentioning

confidence: 99%

See 4 more Smart Citations

Bisphosphonate Drug Holidays: Evidence From Clinical Trials and Real‐World Studies

Wang

Girgis

2022

JBMR Plus

View full text Add to dashboard Cite

Bisphosphonates (BPs) are commonly used in the treatment of osteoporosis and are effective in the prevention of fragility fracture. Long‐term use has been associated with the development of atypical femur fractures (AFFs) and osteonecrosis of the jaw (ONJ). Drug holidays seek to reduce the risk of insufficiency fractures (AFFs) while maintaining durable effects of long‐term treatment in the prevention of fragility fracture. Guidelines suggest that BP drug holidays be considered after 3 to 5 years. However individual factors impacting this decision and outcomes are unclear. This review examines key factors in the planning of a safe BP drug holiday and surrogate markers of fracture risk in patients discontinuing treatment. Fifteen randomized control trials and 19 real‐world studies were included, including nationwide prospective studies from several countries. Increases in bone turnover markers (BTMs) and reductions in bone mineral density (BMD) were generally observed during BP drug holidays. Resurgent bone turnover was problematic in high‐risk patients in whom fractures recurred as early as 12 months following a drug holiday. Risk factors for holiday‐related fractures included older age, low hip BMD, underweight, low medication adherence, and prevalent/incident fractures. Zoledronic acid conferred the most durable reduction in fractures, particularly after six annual infusions. Five years of alendronate was insufficient in preventing vertebral fractures in high‐risk patients embarking on a drug holiday. Relatively faster offset of antiresorptive effect was seen in risedronate users with more frequent fractures than alendronate during a drug holiday. Studies directly counterbalancing effects of long‐term treatment on AFF risk versus drug holiday outcomes in the same population were lacking. In the absence of persistently high fracture risk and following a specific treatment duration dependent on the BP used, drug holidays are safe and mitigate the risk of AFF. However, anti‐resorptive effects diminish over time; ongoing monitoring and careful planning of BP resumption is necessary. © 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

show abstract

Section: Perspectives From Real World Studiesmentioning

confidence: 99%

Section: Perspectives From Real World Studiesmentioning

confidence: 99%

Section: Bmd and Btmsmentioning

confidence: 99%

Section: Fractures During Bp Drug Holidaymentioning

confidence: 99%

Section: Perspectives From Real World Studiesmentioning

confidence: 99%

See 3 more Smart Citations

Bisphosphonate Drug Holidays: Evidence From Clinical Trials and Real‐World Studies

Wang

Girgis

2022

JBMR Plus

View full text Add to dashboard Cite

show abstract

Utilization patterns and factors associated with persistence of new users of anti-osteoporosis treatment in Denmark: a population-based cohort study

et al. 2023

View full text Add to dashboard Cite

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.

show abstract

Bisphosphonate Drug Holiday and Fracture Risk: Reviewing the Evidence

Adams

Ryan

Lawless

et al. 2022

Curr Treat Options in Rheum

View full text Add to dashboard Cite

Fracture rates in patients discontinuing alendronate treatment in real life: a population-based cohort study

Cited by 10 publications

References 46 publications

Bisphosphonate Drug Holidays: Evidence From Clinical Trials and Real‐World Studies

Bisphosphonate Drug Holidays: Evidence From Clinical Trials and Real‐World Studies

Utilization patterns and factors associated with persistence of new users of anti-osteoporosis treatment in Denmark: a population-based cohort study

Bisphosphonate Drug Holiday and Fracture Risk: Reviewing the Evidence

Contact Info

Product

Resources

About