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Abstract: SA-PO179

Skeletal Responsiveness to Parathyroid Hormone in Hemodialysis Patients: International Variation and Association With Factors and Risk of Fractures in the DOPPS

Session Information

Category: Bone and Mineral Metabolism

  • 402 Bone and Mineral Metabolism: Clinical

Authors

  • Yamamoto, Suguru, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan
  • Zhao, Junhui, Arbor Research Collaborative for Health, Ann Arbor, Michigan, United States
  • Karaboyas, Angelo, Arbor Research Collaborative for Health, Ann Arbor, Michigan, United States
  • Komaba, Hirotaka, Tokai University School of Medicine, Isehara, Japan
  • Joergensen, Hanne Skou, Aarhus University Hospital, Aarhus, Netherlands
  • Vervloet, Marc G., Amsterdam University Medical Center, Amsterdam, Netherlands
  • Mazzaferro, Sandro, Sapienza University, Rome, Italy
  • Cavalier, Etienne, Centre Hospitalier Universitaire de Liege, Liege, Belgium
  • Bieber, Brian, Arbor Research Collaborative for Health, Ann Arbor, Michigan, United States
  • Robinson, Bruce M., Arbor Research Collaborative for Health, Ann Arbor, Michigan, United States
  • Evenepoel, Pieter, University Hospitals Leuven, Leuven, Belgium
  • Fukagawa, Masafumi, Tokai University School of Medicine, Isehara, Japan
Background

Bone response to parathyroid hormone (PTH) is impaired in chronic kidney disease (CKD) owing to multiple factors including phosphate loading, calcitriol deficiency, and accumulation of uremic toxins. Other factors may also affect PTH responsiveness including regional and/or ethnic differences, and pharmacological treatment. Using alkaline phosphatase (ALP)/PTH ratio as a proxy for skeletal responsiveness to PTH, we investigated (1) the differences in ALP/PTH by international region and race, (2) patient factors associated with ALP/PTH, and (3) association between ALP/PTH and incidence of fracture in hemodialysis (HD) patients.

Methods

The analysis includes 31,701 HD patients with dialysis vintage >120 days in 9 countries in DOPPS phase 3-7 (2005-2021). The primary exposure variable was ALP/PTH. ALP and PTH levels were both divided by the facility upper normal limit to normalize the values. Cox models were used to estimate hazard ratios (HR) of fracture across levels of ALP/PTH and also for normalized ALP alone. Logistic regression was used to model associations between low ALP/PTH (< 0.1) and clinical factors. All models were adjusted for potential confounders including country, case-mix, and laboratory values.

Results

Median ALP/PTH was 0.21, 0.33, 0.17, and 0.23 in Europe, Japan, US-Black, and US-Nonblack, respectively. ALP/PTH <0.1 was associated with male gender, Black race, higher body mass index, higher serum levels of albumin, phosphorus and calcium, and use of vitamin D analogues and cinacalcet. ALP/PTH was not associated with any fractures (p=0.81). In contrast, normalized ALP had a strong monotonic association with fracture rate; the HR (95% CI) compared to the reference group of 0.75-0.99 ranged from 0.77 (0.60,0.97) for ALP <0.50 to 1.35 (1.06,1.74) for ALP 1.50+.

Conclusion

In this large international cohort study, skeletal responsiveness to PTH in HD patients showed regional and ethnical differences and may be affected by pharmacological treatment and clinical factors. We did not observe a direct association between ALP/PTH and fracture, but higher ALP production reflecting bone responsiveness to PTH may increase fracture risk in HD patients.