Bone Phenotype in Autosomal Dominant Polycystic Kidney Disease

Autosomal dominant polycystic kidney disease (ADPKD) is a systemic ciliary disorder, yet the impact on bone health remains insufficiently defined. Given the expression of polycystins in osteocytes, osteoclasts and extracellular matrix, a disease-specific bone phenotype has been hypothesized. This study aimed to comprehensively characterize the bone phenotype in ADPKD across stages of chronic kidney disease (CKD) and Mayo Imaging Classification (MIC). In this cross-sectional study, 81 patients with ADPKD, 15 with CKD of other etiologies, and 21 healthy individuals were included. Bone phenotype was assessed across four domains: bone metabolism biomarkers, bone turnover biomarkers, bone mass/microarchitecture (dual-energy X-ray absorptiometry with trabecular scoring (TBS)) and bone material strength (microindentation, BMSi). Z-score-based heat-maps were used to visualize stage-specific alterations, and multivariable regression analysis was applied to estimate model parameters. ADPKD patients consistently showed lower bone turnover, particularly PINP and in CKD G1-2 also BALP, while BMSi, BMD and TBS did not differ from healthy individuals. Across CKD stages, mineral abnormalities reflected the effect of declining eGFR, whereas stratification by MIC revealed less distinct patterns, indicating that the bone phenotype may be more closely linked to CKD progression than cystic burden in later CKD stages. This first comprehensive analysis of the ADPKD bone phenotype reveals mineral disturbances, reduced bone turnover, and preserved bone mass and microarchitecture in early ADPKD. Bone alterations followed kidney function rather than MIC stage. Impact microindentation, BMSi, did not reveal any distinctive pattern in ADPKD.