Comprehensive Associations between Acidosis and the Skeleton in Patients with Kidney Disease

Background: Renal osteodystrophy is a state of impaired bone quality and strength. Metabolic acidosis (MA) is associated with alterations in bone quality including remodeling, microarchitecture, and mineral-ization. No studies in patients with CKD have provided a comprehensive multimodal skeletal phenotype of MA. We aim to describe the structure and makeup of bone in patients with MA in the setting of CKD using biochemistry, noninvasive imaging, and histomorphometry.Methods: The retrospective cross-sectional analyses included 180 patients with CKD. MA was defined as bicarbonate #22 mEq/L. We evaluated circulating bone turnover markers and skeletal imaging with dual energy x-ray absorptiometry and high-resolution peripheral computed tomography. A subset of 54 par-ticipants had follow-up. We assessed associations between baseline and change in bicarbonate with change in bone outcomes. Histomorphometry, microCT, and quantitative backscatter electron micros-copy assessed bone biopsy outcomes in 22 participants.Results: The mean age was 68610 years, 54% of participants were male, and 55% were White. At baseline, acidotic subjects had higher markers of bone turnover, lower areal bone mineral density at the radius by dual energy x-ray absorptiometry, and lower cortical and trabecular volumetric bone mineral density and impaired trabecular microarchitecture. Over time, acidosis was associated with opposing cortical and trabecular effects: cortical expansion but trabecular deterioration. Bone-tissue analyses showed reduced tissue mineral density with increased heterogeneity of calcium distribution in acidotic participants.Conclusions: MA is associated with multiple impairments in bone quality. Future work should examine whether correction of acidosis improves bone quality and strength in patients with CKD.