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Abstract: TH-OR37

Bone Quality in Uremic Patients: Interactions Between Parathyroid Hormone (PTH) and Propionic Acid

Session Information

Category: Bone and Mineral Metabolism

  • 502 Bone and Mineral Metabolism: Clinical

Authors

  • Kermgard, Elizabeth Mary, Children's Hospital Los Angeles, Los Angeles, California, United States
  • Wesseling-Perry, Katherine, Phoenix Children's Hospital, Phoenix, Arizona, United States
  • Nickolas, Thomas, Columbia University Irving Medical Center, New York, New York, United States
Background

Chronic kidney disease (CKD) associated hyperparathyroidism (HPT) results in impaired bone quality and strength. While calcitriol deficiency partially drives elevations in parathyroid hormone (PTH), skeletal resistance to PTH also contributes to progressive HPT. In mice with normal kidney function, short-chain fatty acids (SCFAs) produced by the gut microbiome, were shown to moderate PTH effects on bone. Interactions between SCFAs and PTH on bone quality in humans with CKD are unknown. We hypothesized that SCFAs moderate the skeletal effects of PTH in CKD.

Methods

In a cross-sectional study of 60 CKD patients with double label transiliac crest bone biopsies, we measured parameters of dynamic histomorphometry, PTH and 24 SCFA metabolites (Metabolon, Inc). Ages were 29-88 yrs, 13% were on dialysis and 40% were male. High resolution peripheral quantitative computed tomography (HRpQCT; resolution 60 μm3) imaging of the radius and tibia for cortical (Ct) and trabecular (Tb) geometry, density and microarchitecture was performed in a subset of 45 patients. SCFAs were dichotomized at the median. Generalized linear regression models were used to evaluate relationships between bone outcomes, PTH, SCFA, SCFA-PTH and SCFA-sex interactions.

Results

We found that the SCFA, propionic acid (PA), modified relationships between PTH and bone outcomes. In contrast to low levels of PA, high levels of PA and PTH were associated with thicker osteoid (β=3.32, SE 1.58, p=0.041) on histomorphometry, thicker cortices at the radius (β=12.50, SE 3.43, p=0.001) and tibia (β=24.46, SE 8.34, p=0.006) and greater Tb volumetric density (β=26.59, SE 11.28, p=0.024) at the radius by HRpQCT.

Conclusion

In conclusion, in a cohort of CKD patients with bone biopsy and HRpQCT imaging, we observed that PA modified the skeletal response to PTH. When PA levels were elevated, higher PTH was associated with better bone quality. In contrast, when PA levels were low, higher PTH levels were associated with catabolic effects on bone quality. Prospective studies are needed to investigate whether PA has a therapeutic role in the management of renal osteodystrophy.

Funding

  • NIDDK Support