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. 2024 Apr 1;19(4):483-493.
doi: 10.2215/CJN.0000000000000368. Epub 2023 Nov 29.

Associations of Changes in Bone Turnover Markers with Change in Bone Mineral Density in Kidney Transplant Patients

Hanne Skou Jørgensen  1   2 , Kathleen Claes  1   3 , Dieter Smout  1   3 , Maarten Naesens  1   3 , Dirk Kuypers  1   3 , Patrick D'Haese  4 , Etienne Cavalier  5 , Pieter Evenepoel  1   3
Affiliations

Associations of Changes in Bone Turnover Markers with Change in Bone Mineral Density in Kidney Transplant Patients

Hanne Skou Jørgensen et al. Clin J Am Soc Nephrol. .

Abstract

Background: Bone loss after kidney transplantation is highly variable. We investigated whether changes in bone turnover markers associate with bone loss during the first post-transplant year.

Methods: Bone mineral density (BMD) was measured at 0 and 12 months, with biointact parathyroid hormone, bone-specific alkaline phosphatase (BALP), intact procollagen type I N -terminal propeptide (PINP), and tartrate-resistant acid phosphatase isoform 5b (TRAP5b) measured at 0, 3, and 12 months post-transplant ( N =209). Paired transiliac bone biopsies were available in a subset ( n =49). Between-group differences were evaluated by Student's t test, Wilcoxon signed-rank test, or Pearson's chi-squared test.

Results: Changes in BMD varied from -22% to +17%/yr. Compared with patients with no change (±2.5%/yr), patients who gained BMD had higher levels of parathyroid hormone (236 versus 136 pg/ml), BALP (31.7 versus 18.8 μ g/L), and Intact PINP (121.9 versus 70.4 μ g/L) at time of transplantation; a greater decrease in BALP (-40% versus -21%) and Intact PINP (-43% versus -13%) by 3 months; and lower levels of Intact PINP (36.3 versus 60.0 μ g/L) at 12 months post-transplant. Patients who lost BMD had a less marked decrease, or even increase, in Intact PINP (+22% versus -13%) and TRAP5b (-27% versus -43%) at 3 months and higher Intact PINP (83.7 versus 60.0 μ g/L) and TRAP5b (3.89 versus 3.16 U/L) at 12 months compared with patients with no change. If none of the biomarkers decreased by the least significant change at 3 months, an almost two-fold (69% versus 36%) higher occurrence of bone loss was seen at 12 months post-transplant.

Conclusions: Bone loss after kidney transplantation was highly variable. Resolution of high bone turnover, as reflected by decreasing bone turnover markers, associated with BMD gain, while increasing bone turnover markers associated with bone loss.

Trial registration: ClinicalTrials.gov NCT00547040 NCT01886950.

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Conflict of interest statement

E. Cavalier reports consultancy for bioMerieux, DiaSorin, Fujirebio, IDS, Nittobo, Orifarm, Snibe, and Werfen. K. Claes reports consultancy for Astellas, Fresenius Kabi, GSK, and Sanofi; support from Alexion, Astellas, and AstraZeneca; advisory or leadership role for Alexion, Astellas, and Fresenius Kabi; and speaker's fee from AstraZeneca and Vifor Pharma. P. Evenepoel reports consultancy for Vifor CSL; research funding from Amgen, Sanofi, and Vifor CSL; and honoraria from Vifor CSL. H.S. Jørgensen reports other interests or relationships as a Steering Committee member of the European Renal Osteodystrophy initiative, under the CKD-MBD working group of the European Renal Association (ERA). D. Kuypers reports consultancy for Astellas Company, AZ, GSK, Hansa, Sangamo-Tx, and Takeda; honoraria from Astellas, AZ, GSK, Hansa, and Takeda; speakers bureau for Astellas and HIKMA; and advisory or leadership role as an Associate Editor for Transplantation and as an Editorial Board member of Current Clinical Pharmacology, Therapeutic Drug Monitoring, and Transplantation Reviews. M. Naesens reports consultancy for Agomab, Aiosyn, Argenx, and Hansa; research funding from CareDx; and honoraria from Argenx and Hansa. M. Naesens is inventor of two patents related to the FWO-SBO application: EP19152365.3: mRNA-based biomarkers for antibody-mediated transplant rejection. This biomarker was licensed in September 2020 to CareDx, a precision medicine solutions company focused on solutions for transplant patients; PCT/EP2018/097044: Biomarkers for typing allograft recipients (patent application submitted December 2018). All remaining authors have nothing to disclose.

Figures

None
Graphical abstract
Figure 1
Figure 1
Prevalence of osteoporosis, defined as a DXA T-score <−2.5 at time of transplantation and at 12 months post-transplant. DXA, dual-energy x-ray absorptiometry.
Figure 2
Figure 2
Changes in BMD from time of transplantation to 12 months post-transplant; number of patients and mean change in percentage from baseline given for each skeletal site. *P < 0.05. BMD, bone mineral density.
Figure 3
Figure 3
Trajectories of PTH in times upper normal limit and bone turnover markers in patients who lost, remained stable, or gained BMD at the lumbar spine in the first post-transplant year. Medians with IQR, *P < 0.05, ‡P < 0.01, and †P < 0.001 compared with stable group. BALP, bone-specific alkaline phosphatase; IQR, interquartile range; PINP, procollagen type I N-terminal propeptide; PTH, parathyroid hormone; TRAP5b, tartrate-resistant acid phosphatase isoform 5b.
Figure 4
Figure 4
Risk of lumbar spine and total hip BMD loss at 12 months by whether biomarkers decreased by the least significant change at 3 months post-transplant (D+: descender, non-D; nondescender). *P < 0.05, ‡P < 0.01, and †P < 0.001 by Pearson's chi-squared test.
See this image and copyright information in PMC

References

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