Can bone turnover markers help to define the suitability and duration of bisphosphonate drug holidays?

Statham, Louise; Abdy, Sharon; Aspray, Terry

doi:10.7573/dic.2020-1-3

Cited by 8 publications

(5 citation statements)

References 16 publications

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“… 80 Particularly, Statham et al identify a subset of BP users with a suboptimal suppression of cross-linked C-telopeptide of type I collage (CTX) in which the drug holiday should be avoided. 81 …”

Section: Affs: Prevention and Early Diagnosismentioning

confidence: 99%

The role of the fracture liaison service in the prevention of atypical femoral fractures

Toro,

Braile,

Liguori

et al. 2023

Therapeutic Advances in Musculoskeletal

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Osteoporosis and fragility fractures (FFs) are considered critical health problems by the World Health Organization (WHO) because of high morbidity, mortality, and healthcare costs. The occurrence of a FF raises the risk of a subsequent fracture (refracture). The hip is the most common site of fragility refracture, and its onset is associated with a further increase in patient’s morbidity, mortality, and socioeconomic burden. Therefore, the prevention of refracture is essential. In this context, fracture liaison service (FLS) demonstrated to be able to reduce FF risk and also improve patients’ adherence to anti-osteoporotic treatments, particularly for bisphosphonates (BPs). However, long-term and high adherence to BPs may lead to atypical femoral fractures (AFFs). These latter are tensile side stress fractures of the femur, with high rates of complications, including delayed and non-healing. An effective FLS should be able to prevent both FF and AFF. A comprehensive and interdisciplinary approach, through the involvement and education of a dedicated team of healthcare professionals (i.e. orthopedic, geriatrician, primary care physician, rehabilitation team, and bone nurse) for evaluating both FF and AFF risks might be useful to improve the standard of care.

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Section: Affs: Prevention and Early Diagnosismentioning

confidence: 99%

The role of the fracture liaison service in the prevention of atypical femoral fractures

Toro,

Braile,

Liguori

et al. 2023

Therapeutic Advances in Musculoskeletal

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“…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%

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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“…On the other hand, procollagen type II C-propeptide (CPII) and CTX-I increase as a response to exercise and bone turnover in foals [90]. In humans, BPs may reduce serum bone markers over time [91][92][93]. In horses, conflicting reports exist regarding the effect of BPs on CTX-I [40,56,76,94].…”

Section: The Use Of Bisphosphonates In Young/exercising Animalsmentioning

confidence: 99%

Is the Use of Bisphosphonates Putting Horses at Risk? An Osteoclast Perspective

Vergara-Hernandez

Nielsen

Colbath

2022

Animals

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Osteoclasts are unique and vital bone cells involved in bone turnover. These cells are active throughout the individual’s life and play an intricate role in growth and remodeling. However, extra-label bisphosphonate use may impair osteoclast function, which could result in skeletal microdamage and impaired healing without commonly associated pain, affecting bone remodeling, fracture healing, and growth. These effects could be heightened when administered to growing and exercising animals. Bisphosphonates (BPs) are unevenly distributed in the skeleton; blood supply and bone turnover rate determine BPs uptake in bone. Currently, there is a critical gap in scientific knowledge surrounding the biological impacts of BP use in exercising animals under two years old. This may have significant welfare ramifications for growing and exercising equids. Therefore, future research should investigate the effects of these drugs on skeletally immature horses.

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Can bone turnover markers help to define the suitability and duration of bisphosphonate drug holidays?

Cited by 8 publications

References 16 publications

The role of the fracture liaison service in the prevention of atypical femoral fractures

The role of the fracture liaison service in the prevention of atypical femoral fractures

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

Is the Use of Bisphosphonates Putting Horses at Risk? An Osteoclast Perspective

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