Intravenous Pamidronate is Associated with Reduced Mortality in Patients with Chronic Critical Illness

Schulman, Rifka; Moshier, Erin; Rho, Lisa; Casey, Martin F.; Godbold, James; Zaidi, Mone; Mechanick, Jeffrey I.

doi:10.4158/ep151050.or

Cited by 16 publications

(2 citation statements)

References 39 publications

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“…They have been studied in small trials in critically ill adults and children and showed promising results [ 30 – 32 ]. Two recent retrospective observational studies suggested that preadmission bisphosphonate use in critically ill patients may even be associated with increased survival [ 33 , 34 ].…”

Section: Discussionmentioning

confidence: 99%

Effect of vitamin D3 on bone turnover markers in critical illness: post hoc analysis from the VITdAL-ICU study

et al. 2017

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Summary In this post hoc analysis of the VITdAL-ICU study, an RCT in critically ill adults with 25-hydroxyvitamin D levels ≤20 ng/ml, vitamin D3 did not have a significant effect on β-Crosslaps and osteocalcin. Introduction Observational studies have shown accelerated bone loss in ICU survivors. A reversible contributor is vitamin D deficiency. In a post hoc analysis of the VITdAL-ICU study, we evaluated the effect of high-dose vitamin D3 on the bone turnover markers (BTM) β-Crosslaps (CTX) and osteocalcin (OC). Methods The VITdAL-ICU study was a randomized, double-blind, placebo-controlled trial in critically ill adults with 25-hydroxyvitamin D levels ≤20 ng/ml who received placebo or high-dose vitamin D3 (a loading dose of 540,000 IU and starting 1 month after the loading dose five monthly maintenance doses of 90,000 IU). In this analysis on 289 survivors (209 telephone, 80 personal follow-up visits), BTM were analyzed on days 0, 3, 7, 28, and 180; self-reported falls and fractures were assessed. Bone mineral density (BMD) was measured after 6 months. Results At baseline, CTX was elevated; OC was low in both groups-after 6 months, both had returned to normal. There were no differences between groups concerning BTM, BMD, falls, or fractures. In linear mixed effects models, CTX and OC showed a significant change over time (p < 0.001, respectively), but there was no difference between the vitamin D and placebo group (p = 0.688 and p = 0.972, respectively). Conclusions Vitamin D supplementation did not have a significant effect on BTM. Further studies should assess the effectiveness of vitamin D on musculoskeletal outcomes in ICU survivors.

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Section: Discussionmentioning

confidence: 99%

Effect of vitamin D3 on bone turnover markers in critical illness: post hoc analysis from the VITdAL-ICU study

et al. 2017

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“…Similar findings were reported in the post hoc analysis of a randomised controlled trial of ZOL in women over the age of 65 years ( Reid et al, 2021 ). Pneumonia is the most frequent cause of admission to ICU, and a study of long-term patients in respiratory ICU revealed a significant reduction in mortality in people treated with the N-BP pamidronate compared to those without treatment ( Schulman et al, 2016 ). Furthermore, in a retrospective cohort study of ICU subjects, we showed a 59% reduction in mortality in patients treated with bisphosphonate prior to hospitalisation ( Lee et al, 2016 ).…”

Section: Introductionmentioning

confidence: 99%

Bisphosphonate drugs have actions in the lung and inhibit the mevalonate pathway in alveolar macrophages

Munoz

Fletcher

Skinner

et al. 2021

eLife

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Bisphosphonates drugs target the skeleton and are used globally for the treatment of common bone disorders. Nitrogen-containing bisphosphonates act by inhibiting the mevalonate pathway in bone-resorbing osteoclasts but, surprisingly, also appear to reduce the risk of death from pneumonia. We overturn the long-held belief that these drugs act only in the skeleton and show that a fluorescently labelled bisphosphonate is internalised by alveolar macrophages and large peritoneal macrophages in vivo. Furthermore, a single dose of a nitrogen-containing bisphosphonate (zoledronic acid) in mice was sufficient to inhibit the mevalonate pathway in tissue-resident macrophages, causing the build-up of a mevalonate metabolite and preventing protein prenylation. Importantly, one dose of bisphosphonate enhanced the immune response to bacterial endotoxin in the lung and increased the level of cytokines and chemokines in bronchoalveolar fluid. These studies suggest that bisphosphonates, as well as preventing bone loss, may boost immune responses to infection in the lung and provide a mechanistic basis to fully examine the potential of bisphosphonates to help combat respiratory infections that cause pneumonia.

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Skeletal Complications

Via¹,

Iofin²,

Liu³

et al. 2022

Holland‐Frei Cancer Medicine

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Overview The skeletal complications of cancer are highly prevalent. Bone metastases are present in approximately 70% of patients with cancer‐related deaths. Skeletal complications can present clinically as pain associated with bone metastases, pathologic fractures, or hypercalcemia. Additionally, several therapies for cancers may have deleterious effect on bone health such as aromatase inhibition in patients with breast cancer. The presence of skeletal metastases often indicates that cure from cancer unlikely. Goals of therapy may shift to palliation and to systemic control with possible prolonged survival. Surgical treatments, medical therapies, including antiresorptive agents, and/or radiation therapy should each be considered to achieve optimal care in patients with skeletal complications of cancer.

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Intravenous Pamidronate is Associated with Reduced Mortality in Patients with Chronic Critical Illness

Cited by 16 publications

References 39 publications

Effect of vitamin D3 on bone turnover markers in critical illness: post hoc analysis from the VITdAL-ICU study

Effect of vitamin D3 on bone turnover markers in critical illness: post hoc analysis from the VITdAL-ICU study

Bisphosphonate drugs have actions in the lung and inhibit the mevalonate pathway in alveolar macrophages

Skeletal Complications

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