Alendronate use and bone mineral density gains in women with moderate-severe (stages 3B–5) chronic kidney disease: an open cohort multivariable and propensity score analysis from Funen, Denmark

Abstract

Summary

Bisphosphonates are contraindicated in moderate-to-severe chronic kidney disease patients. However, they are used to prevent fragility fractures in patients with impaired kidney function, despite a lack of evidence on their effects on bone density in these patients. We demonstrated that Alendronate had a positive effect on bone in these patients.

Purpose

This study aimed to assess the association between alendronate use and bone mineral density (BMD) change in subjects with moderate-severe chronic kidney disease (CKD).

Methods

We created a cohort of CKD stage 3B–5 patients by linking all DXA-based measurements in the Funen area, Denmark, to biochemistry, national health registries and filled prescriptions. Exposure was dispensation of alendronate and the outcome was annualized percentage change in BMD at the femoral neck, total hip and lumbar spine. Individuals were followed from first BMD to the latest of subsequent DXA measurements. Alendronate non-users were identified using incidence density sampling and matched groups were created using propensity scores. Linear regression was used to estimate average differences in the annualized BMD.

Results

Use of alendronate was rare in this group of patients: propensity score matching (PSM) resulted in 71 alendronate users and 142 non-users with stage 3B–5 CKD (as in the 1 year before DXA). Whilst alendronate users gained an average 1.07% femoral neck BMD per year, non-users lost an average of 1.59% per annum. The PSM mean differences in annualized BMD were + 2.65% (1.32%, 3.99%), + 3.01% (1.74%, 4.28%) and + 2.12% (0.98%, 3.25%) at the femoral neck, total hip and spine BMD, respectively, all in favour of alendronate users.

Conclusion

In a real-world cohort of women with stage 3B–5 CKD, use of alendronate appears associated with a significant improvement of 2–3% per year in the femoral neck, total hip and spine BMD. More data are needed on the anti-fracture effectiveness and safety of bisphosphonate therapy in moderate-severe CKD.

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Funding

This project was funded by the NIHR HTA (project number or 14/36/02) and supported by the NIHR Biomedical Research Centre, Oxford.

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Correspondence to Daniel Prieto-Alhambra.

Ethics declarations

The study was approved by the Data Protection Agency (OUH 15/37999) and by Statistics Denmark (ref. 705079). All statistical analyses were done on de-identified patient data merged at Statistics Denmark.

Conflicts of interest

NK Arden reports personal fees from Flexion, Freshfields, Janssen, Merck and Regeneron. C Cooper reports lecture fees and honoraria from the Alliance for Better Bone Health Amgen, Eli Lilly, GSK, Medtronic, Merck, Novartis, Pfizer, Roche, Servier, Takeda and UCB. A Judge is a subpanel member of the NIHR PGfAR, has received consultancy fees from Freshfields Bruckhaus Deringer and has held advisory board positions (which involved receipt of fees) at Anthera Pharmaceuticals, INC. MK Javaid reports research support and speaker fees from Amgen. D Prieto-Alhambra reports research grants from UCB, Amgen and Les Laboratoires Servier and (not personal) speaker and consultancy fees from UCB and Amgen. D Prieto-Alhambra is a member of the NIHR HTA CET panel since November 2017. DE Robinson, MS Ali, KRubin, M Ernst, P Hermann, M Nybo, Y Ben-Shlomo and F Caskey have nothing to disclose. The views expressed are those of the authors and not necessarily those of the NHS, NIHR or Department of Health.

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Ali, M.S., Ernst, M., Robinson, D.E. et al. Alendronate use and bone mineral density gains in women with moderate-severe (stages 3B–5) chronic kidney disease: an open cohort multivariable and propensity score analysis from Funen, Denmark. Arch Osteoporos 15, 81 (2020). https://doi.org/10.1007/s11657-020-00746-z

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Keywords

  • Alendronate
  • Bone mineral density
  • Chronic kidney disease
  • Osteoporosis
  • Incidence density sampling
  • Propensity score