Atherosclerosis

2020

DOI: 10.1016/j.atherosclerosis.2020.03.021

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Association between the cumulative exposure to bisphosphonates and hospitalization for atherosclerotic cardiovascular events: A population-based study

¹

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Elena Olmastroni

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,

Federica Galimberti

³

et al.

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Bisphosphonate Use Mortality and Vascular Calcification1

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Cited by 13 publications

(9 citation statements)

References 56 publications

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“…However, while some studies indicate that there is no beneficial effect on cardiovascular outcomes [59], others report a reduction in cardiovascular mortality and all-cause mortality [3]. A recent prospective cohort study involving nearly 83,000 bisphosphonate users indicates that higher treatment adherence is associated with better cardiovascular outcomes, with those in the strictest adherence displaying a hazard ratio of 0.75 [0.71-0.81] [60]. These studies provide evidence of a potential mechanism between arterial calcification and BMD, which requires further exploration.…”

Section: Bisphosphonate Use Mortality and Vascular Calcificationmentioning

confidence: 99%

The Treatment Gap in Osteoporosis

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et al. 2021

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Worldwide, there are millions of people who have been diagnosed with osteoporosis, a bone disease that increases the risk of fracture due to low bone mineral density and deterioration of bone architecture. In the US alone, there are approximately ten million men and women diagnosed with osteoporosis and this number is still growing. Diagnosis is made by measuring bone mineral density. Medications used for the treatment of osteoporosis are bisphosphonates, denosumab, raloxifene, and teriparatide. Recently, romosozumab has been added as well. In recent years, a number of advances have been made in the field of diagnostic methods and the diverse treatment options for osteoporosis. Despite these advances and a growing incidence of osteoporosis, there is a large group being left undertreated or even untreated. This group of the under/untreated has been called the treatment gap. Concerns regarding rare side effects of the medications, such as osteonecrosis of the jaw, have been reported to be one of the many causes for the treatment gap. Also, this group seems not to be sufficiently informed of the major benefits of the treatment and the diversity in treatment options. Knowledge of these could be very helpful in improving compliance and hopefully reducing the gap. In this paper, we summarize recent evidence regarding the efficacy of the various treatment options, potential side effects, and the overall benefit of treatment.

“…However, while some studies indicate that there is no beneficial effect on cardiovascular outcomes [59], others report a reduction in cardiovascular mortality and all-cause mortality [3]. A recent prospective cohort study involving nearly 83,000 bisphosphonate users indicates that higher treatment adherence is associated with better cardiovascular outcomes, with those in the strictest adherence displaying a hazard ratio of 0.75 [0.71-0.81] [60]. These studies provide evidence of a potential mechanism between arterial calcification and BMD, which requires further exploration.…”

Section: Bisphosphonate Use Mortality and Vascular Calcificationmentioning

confidence: 99%

The Treatment Gap in Osteoporosis

¹

,

²

,

³

et al. 2021

View full text Add to dashboard Cite

Worldwide, there are millions of people who have been diagnosed with osteoporosis, a bone disease that increases the risk of fracture due to low bone mineral density and deterioration of bone architecture. In the US alone, there are approximately ten million men and women diagnosed with osteoporosis and this number is still growing. Diagnosis is made by measuring bone mineral density. Medications used for the treatment of osteoporosis are bisphosphonates, denosumab, raloxifene, and teriparatide. Recently, romosozumab has been added as well. In recent years, a number of advances have been made in the field of diagnostic methods and the diverse treatment options for osteoporosis. Despite these advances and a growing incidence of osteoporosis, there is a large group being left undertreated or even untreated. This group of the under/untreated has been called the treatment gap. Concerns regarding rare side effects of the medications, such as osteonecrosis of the jaw, have been reported to be one of the many causes for the treatment gap. Also, this group seems not to be sufficiently informed of the major benefits of the treatment and the diversity in treatment options. Knowledge of these could be very helpful in improving compliance and hopefully reducing the gap. In this paper, we summarize recent evidence regarding the efficacy of the various treatment options, potential side effects, and the overall benefit of treatment.

“…These results may indicate a critical timing in respect of BiP usage. Recent clinical studies indicate a negative correlation between the cumulative BiP dosage (an indication of portion of day covered) to hazard ratio of hospitalization due to atherosclerotic cardiovascular events [35]. Female patients indicated higher hazard ratio (0.958) compared to associated male patients (0.897) [35], an effect that may explain the sex-dependent observation in our week 10 group.…”

Section: Discussionmentioning

confidence: 81%

“…Recent clinical studies indicate a negative correlation between the cumulative BiP dosage (an indication of portion of day covered) to hazard ratio of hospitalization due to atherosclerotic cardiovascular events [35]. Female patients indicated higher hazard ratio (0.958) compared to associated male patients (0.897) [35], an effect that may explain the sex-dependent observation in our week 10 group. Furthermore, these clinical outcomes support our data that the longer BiP usage duration may lead to larger minerals with a narrow size distribution, which in silico studies suggest associate with stable plaque and lower rupture risk [8, 36].…”

Section: Discussionmentioning

confidence: 81%

Time-dependent Role of Bisphosphonates on Atherosclerotic Plaque Calcification

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²

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³

et al. 2022

Preprint

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Atherosclerotic plaque calcification directly contributes to the leading cause of morbidity and mortality by affecting the plaque vulnerability and rupture risk. Small microcalcifications can increase plaque stress and promote rupture, whereas large calcifications can stabilize plaques. Drugs that target bone mineralization may lead to unintended consequences on ectopic plaque calcification and cardiovascular outcomes. Bisphosphonates, common anti-osteoporotic agents, elicited unexpected cardiovascular events in clinical trials. Here, we investigated the role of bisphosphonates treatment and timing on the disruption or promotion of vascular calcification and bone mineral in a mouse model of atherosclerosis. We started the bisphosphonate treatment either before plaque formation, at early plaque formation times associated with the onset of calcification, or at late stages of plaque development. Our data indicate that long term bisphosphonate treatment (beginning prior to plaque development) leads to higher levels of plaque calcification, with a narrower mineral size distribution. When given later in plaque development, we measured a wider distribution of mineral size. These morphological alterations may associate with higher risk of plaque rupture by creating stress foci. Yet, bone mineral density positively correlated with the duration of bisphosphonate treatment.

“…These results might indicate a critical timing in respect of BiP usage. Recent clinical studies indicated a negative correlation between the cumulative BiP dosage (an indication of portion of day covered) to hazard ratio of hospitalization due to atherosclerotic cardiovascular events [ 37 ]. Female patients indicated higher hazard ratio (0.958) compared to associated male patients (0.897) [ 37 ], an effect that might explain the sex-dependent observation in our week 10 group.…”

Section: Discussionmentioning

confidence: 99%

The Time-Dependent Role of Bisphosphonates on Atherosclerotic Plaque Calcification

¹

,

²

,

³

et al. 2022

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Atherosclerotic plaque calcification directly contributes to the leading cause of morbidity and mortality by affecting plaque vulnerability and rupture risk. Small microcalcifications can increase plaque stress and promote rupture, whereas large calcifications can stabilize plaques. Drugs that target bone mineralization may lead to unintended consequences on ectopic plaque calcification and cardiovascular outcomes. Bisphosphonates, common anti-osteoporotic agents, have elicited unexpected cardiovascular events in clinical trials. Here, we investigated the role of bisphosphonate treatment and timing on the disruption or promotion of vascular calcification and bone minerals in a mouse model of atherosclerosis. We started the bisphosphonate treatment either before plaque formation, at early plaque formation times associated with the onset of calcification, or at late stages of plaque development. Our data indicated that long-term bisphosphonate treatment (beginning prior to plaque development) leads to higher levels of plaque calcification, with a narrower mineral size distribution. When given later in plaque development, we measured a wider distribution of mineral size. These morphological alterations might be associated with a higher risk of plaque rupture by creating stress foci. Yet, bone mineral density positively correlated with the duration of the bisphosphonate treatment.

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