Uremia and parathyroid hormone have distinct effects on bone protein and gene expression
Abstract
INTRODUCTION: Chronic kidney disease (CKD)-associated osteoporosis is highly prevalent and increases the risk of fractures. Current therapy aims to preserve normal bone turnover, by maintaining parathyroid hormone (PTH) at relatively adequate levels. However, these patients continue to experience fractures.
METHODS: To assess potential adverse effects of PTH on bone, we examined bone histology and osteocytic gene and protein expression in 76 patients receiving hemodialysis compared to that of 33 control individuals.
RESULTS: Using bulk bone tissue RNAseq, we observed that CKD is associated with enhanced inflammatory signaling, increased cell death, impaired osteoblastic differentiation, and reduced bone mass, consistent with low osteocyte count and increased apoptosis. Patients with elevated PTH levels showed an attenuation of these alterations, but exhibited increased expression of genes related to fibrosis, matrix apposition, and bone remodeling, leading to increased cortical porosity.
CONCLUSIONS: CKD induces inflammation and cell death in bone. However, elevated PTH levels exhibited dual effects that were both protective and detrimental to bone tissue quality and strength. Our findings suggest that combining anabolic agents with relatively low PTH levels may be a potential approach to improve bone quality in CKD. This hypothesis warrants further investigation in future studies.
How strong is the evidence?
Evidence Hub reads this as a case-control, done in people. Its evidence level is 4 of 5 (Low · observational). Observational designs can show an association but not prove cause. Reported size: 76 participants or records.
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