Bisphosphonate drug holidays: Risk of fractures and mortality in a prospective cohort study

Pfeilschifter, Johannes; Steinebach, I.; Trampisch, Hans–Joachim; Rudolf, Henrik

doi:10.1016/j.bone.2020.115431

Cited by 11 publications

(11 citation statements)

References 47 publications

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“…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%

“…(48) Prevalent fracture was a significant predictor of vertebral fracture during drug holidays (54) imparting a 3.53-fold increase in risk of major osteoporotic fracture in a German study, most pronounced in those with holidays >12 months. (50) In several studies, fractures were detected soon after the onset of a drug holiday, as early as 6 months. (46,48,59) In a large study of over 80,000 postmenopausal women >65 years, there was a trend for more holiday-related fractures in subjects discontinuing alendronate and risedronate versus zoledronic acid and ibandronate.…”

Section: Fractures During Bp Drug Holidaymentioning

confidence: 99%

“…Nine studies included men who represented 10% to 20% of the cohort, and premenopausal women were examined in one study. ( 42 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 ) The main BP used was alendronate, followed by risedronate, zoledronic acid, and ibandronate.…”

Section: Perspectives From Real World Studiesmentioning

confidence: 99%

“…Three population‐based studies from the United States and Europe with sample sizes as high as 50,000 subjects did not find significant increase in fractures in patients discontinuing BP after a period of use of more than 3 years and monitored for up to 5 years. ( 44 , 45 , 50 ) These included population‐based studies with fracture outcomes extracted from healthcare databases ( 44 , 45 ) and an interview‐based prospective observational study with fracture self‐reporting. ( 50 ) It is possible that a proportion of fractures were not accounted for in these real‐world studies.…”

Section: Perspectives From Real World Studiesmentioning

confidence: 99%

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

Wang

Girgis

2022

JBMR Plus

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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.

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Section: Fractures During Bp Drug Holidaymentioning

confidence: 99%

Section: Fractures During Bp Drug Holidaymentioning

confidence: 99%

Section: Perspectives From Real World Studiesmentioning

confidence: 99%

Section: Perspectives From Real World Studiesmentioning

confidence: 99%

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

Wang

Girgis

2022

JBMR Plus

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“…A substantial proportion of patients may discontinue anti-osteoporosis medication [ 9 , 10 ], including self-discontinuing and bisphosphonate drug holidays. Mortality risks among patients continuing to take bisphosphonate are similar to those of patients on bisphosphonate drug holidays [ 11 ]. However, the factors contributing to mortality risks in patients who self-discontinued anti-osteoporosis medication remain largely unknown.…”

Section: Introductionmentioning

confidence: 99%

Low Bone Mineral Density and Calcium Levels as Risks for Mortality in Patients with Self-Discontinuation of Anti-Osteoporosis Medication

Hsu

Chang

Cheng

et al. 2021

IJERPH

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Bone mass density (BMD) has been used universally in osteoporosis diagnosis and management. Adherence to anti-osteoporosis medication is related to mortality risk. This study aimed to investigate the relationship between mortality and low BMD of the femoral neck and vertebra among patients self-discontinuing anti-osteoporosis medication. Between June 2016 and June 2018, this single-center retrospective study recruited 596 participants who self-discontinued anti-osteoporosis medication. Patients were categorized into four groups by BMD of the right femoral neck and lumbar spine. Occurrence and causes of mortality were obtained from medical records. Independent risk factors and the five-year survival of various levels of BMD were analyzed by Cox regression and the Kaplan–Meier survival analysis. BMD value and serum calcium level were significantly lower in the mortality group (p < 0.001). Compared to the reference, the adjusted hazard ratio (HR) for all-cause mortality in patients with lower BMD of both the lumbar spine and femoral neck was 3.03. The five-year cumulative survival rate was also significantly lower (25.2%, p < 0.001). A low calcium level was also associated with mortality (HR: 0.87, 95% CI: 0.76–0.99, p = 0.033). In conclusion, lower BMD and calcium levels were associated with higher mortality risk in patients with poor adherence. Hence, patients self-discontinuing anti-osteoporosis medication should be managed accordingly.

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Bisphosphonate drug holidays in osteoporosis according to fracture risk profile

Salmoral,

Peris,

López Medina

et al. 2024

Osteoporos Int

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Bisphosphonate drug holidays: Risk of fractures and mortality in a prospective cohort study

Cited by 11 publications

References 47 publications

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

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

Low Bone Mineral Density and Calcium Levels as Risks for Mortality in Patients with Self-Discontinuation of Anti-Osteoporosis Medication

Bisphosphonate drug holidays in osteoporosis according to fracture risk profile

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