A pilot feasibility randomised controlled trial of bone antiresorptive agents on bone turnover markers in critically ill women
Abstract Critical illness is associated with increased bone turnover, loss of bone density, and increased risk of fragility fractures. The impact of bone antiresorptive agents in this population is not established. This trial examined the efficacy, feasibility, and safety of antiresorptive agents ad...
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2024-01-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-024-52607-1 |
| _version_ | 1797276594854690816 |
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| author | Neil R. Orford Allison Bone Mark A. Kotowicz Michael Bailey Julie A. Pasco Matthew Maiden Nima Kakho Claire Cattigan Martina Nichonghaile Claire Jones Carol Hodgson Priya Nair Jacqueline Center Rinaldo Bellomo |
| author_facet | Neil R. Orford Allison Bone Mark A. Kotowicz Michael Bailey Julie A. Pasco Matthew Maiden Nima Kakho Claire Cattigan Martina Nichonghaile Claire Jones Carol Hodgson Priya Nair Jacqueline Center Rinaldo Bellomo |
| author_sort | Neil R. Orford |
| collection | DOAJ |
| description | Abstract Critical illness is associated with increased bone turnover, loss of bone density, and increased risk of fragility fractures. The impact of bone antiresorptive agents in this population is not established. This trial examined the efficacy, feasibility, and safety of antiresorptive agents administered to critically ill women aged fifty years or greater. Women aged 50 years or greater admitted to an intensive care unit for at least 24 h were randomised to receive an antiresorptive agent (zoledronic acid or denosumab) or placebo, during critical illness and six months later (denosumab only). Bone turnover markers and bone mineral density (BMD) were monitored for 1 year. We studied 18 patients over 35 months before stopping the study due to the COVID-19 pandemic. Antiresorptive medications decreased the bone turnover marker type 1 cross-linked c-telopeptide (CTX) from day 0 to 28 by 43% (± 40%), compared to an increase of 26% (± 55%) observed with placebo (absolute difference − 69%, 95% CI − 127% to − 11%), p = 0.03). Mixed linear modelling revealed differences in the month after trial drug administration between the groups in serum CTX, alkaline phosphatase, parathyroid hormone, and phosphate. Change in BMD between antiresorptive and placebo groups was not statistically analysed due to small numbers. No serious adverse events were recorded. In critically ill women aged 50-years and over, antiresorptive agents suppressed bone resorption markers without serious adverse events. However, recruitment was slow. Further phase 2 trials examining the efficacy of these agents are warranted and should address barriers to enrolment. Trial registration: ACTRN12617000545369, registered 18th April 2017. |
| first_indexed | 2024-03-07T15:30:26Z |
| format | Article |
| id | doaj.art-294467ca53514911a837053623a31530 |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-03-07T15:30:26Z |
| publishDate | 2024-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-294467ca53514911a837053623a315302024-03-05T16:27:19ZengNature PortfolioScientific Reports2045-23222024-01-0114111010.1038/s41598-024-52607-1A pilot feasibility randomised controlled trial of bone antiresorptive agents on bone turnover markers in critically ill womenNeil R. Orford0Allison Bone1Mark A. Kotowicz2Michael Bailey3Julie A. Pasco4Matthew Maiden5Nima Kakho6Claire Cattigan7Martina Nichonghaile8Claire Jones9Carol Hodgson10Priya Nair11Jacqueline Center12Rinaldo Bellomo13Intensive Care Unit, University Hospital Geelong, Barwon HealthIntensive Care Unit, University Hospital Geelong, Barwon HealthIMPACT-Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin UniversityAustralian and New Zealand Intensive Care Research Centre (ANZIC-RC), School of Public Health and Preventive Medicine (SPPHPM), Monash UniversityIMPACT-Institute for Mental and Physical Health and Clinical Translation, School of Medicine, Deakin UniversityIntensive Care Unit, University Hospital Geelong, Barwon HealthIntensive Care Unit, University Hospital Geelong, Barwon HealthIntensive Care Unit, University Hospital Geelong, Barwon HealthIntensive Care Unit, University Hospital Geelong, Barwon HealthIntensive Care Unit, University Hospital Geelong, Barwon HealthAustralian and New Zealand Intensive Care Research Centre (ANZIC-RC), School of Public Health and Preventive Medicine (SPPHPM), Monash UniversityIntensive Care Unit, St Vincent’s Hospital SydneyIntensive Care Unit, St Vincent’s Hospital SydneyAustralian and New Zealand Intensive Care Research Centre (ANZIC-RC), School of Public Health and Preventive Medicine (SPPHPM), Monash UniversityAbstract Critical illness is associated with increased bone turnover, loss of bone density, and increased risk of fragility fractures. The impact of bone antiresorptive agents in this population is not established. This trial examined the efficacy, feasibility, and safety of antiresorptive agents administered to critically ill women aged fifty years or greater. Women aged 50 years or greater admitted to an intensive care unit for at least 24 h were randomised to receive an antiresorptive agent (zoledronic acid or denosumab) or placebo, during critical illness and six months later (denosumab only). Bone turnover markers and bone mineral density (BMD) were monitored for 1 year. We studied 18 patients over 35 months before stopping the study due to the COVID-19 pandemic. Antiresorptive medications decreased the bone turnover marker type 1 cross-linked c-telopeptide (CTX) from day 0 to 28 by 43% (± 40%), compared to an increase of 26% (± 55%) observed with placebo (absolute difference − 69%, 95% CI − 127% to − 11%), p = 0.03). Mixed linear modelling revealed differences in the month after trial drug administration between the groups in serum CTX, alkaline phosphatase, parathyroid hormone, and phosphate. Change in BMD between antiresorptive and placebo groups was not statistically analysed due to small numbers. No serious adverse events were recorded. In critically ill women aged 50-years and over, antiresorptive agents suppressed bone resorption markers without serious adverse events. However, recruitment was slow. Further phase 2 trials examining the efficacy of these agents are warranted and should address barriers to enrolment. Trial registration: ACTRN12617000545369, registered 18th April 2017.https://doi.org/10.1038/s41598-024-52607-1 |
| spellingShingle | Neil R. Orford Allison Bone Mark A. Kotowicz Michael Bailey Julie A. Pasco Matthew Maiden Nima Kakho Claire Cattigan Martina Nichonghaile Claire Jones Carol Hodgson Priya Nair Jacqueline Center Rinaldo Bellomo A pilot feasibility randomised controlled trial of bone antiresorptive agents on bone turnover markers in critically ill women Scientific Reports |
| title | A pilot feasibility randomised controlled trial of bone antiresorptive agents on bone turnover markers in critically ill women |
| title_full | A pilot feasibility randomised controlled trial of bone antiresorptive agents on bone turnover markers in critically ill women |
| title_fullStr | A pilot feasibility randomised controlled trial of bone antiresorptive agents on bone turnover markers in critically ill women |
| title_full_unstemmed | A pilot feasibility randomised controlled trial of bone antiresorptive agents on bone turnover markers in critically ill women |
| title_short | A pilot feasibility randomised controlled trial of bone antiresorptive agents on bone turnover markers in critically ill women |
| title_sort | pilot feasibility randomised controlled trial of bone antiresorptive agents on bone turnover markers in critically ill women |
| url | https://doi.org/10.1038/s41598-024-52607-1 |
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