Bone-kidney-endocrine axis in nephrolithiasis and crystalluria

Background. Nephrolithiasis (NL) is a common polyetiological urological disease with multifactorial pathogenesis. In recent years, increasing attention has been paid to the association between NL and alterations in bone mineral density (BMD). Insufficient dietary intake of calcium-containing foods and renal tubular alterations are considered key mechanisms affecting bone metabolism, including activation of calcification markers such as osteopontin, osteocalcin, and endocrine regulator fibroblast growth factor 23 (FGF23). The purpose of the study was to evaluate bone mineral density, markers of bone metabolism and calcification (osteocalcin, osteopontin), FGF23, and salt transport parameters in patients with NL and crystalluria. Materials and methods. The study was conducted at the Department of Urology of the Bogomolets National Medical University and the Urology Department of the Kyiv Regional Clinical Hospital. All participants provided written informed consent. NL was diagnosed using renal ultrasonography and computed tomography when calculi were present. Assessment of BMD, bone markers and trabecular bone score (TBS) was carried out on the basis of the Ukrainian Osteoporosis Center of the State Institution “D.F. Chebotarеv Institute of Gerontology of NAMS” (Kyiv, Ukraine). Dual X-ray absorptiometry (DXA) was performed on the Hologic Discovery device. The following indices were evaluated: BMD (g/cm2) of the lumbar spine, right and left femoral necks, ultradistal radius. The degree of BMD impairment was assessed by the T-score, which is the deviation from the reference value of the peak bone mass of a healthy person. According to the IOF recommendations in postmenopausal women, the T-criterion from –1 to –2.5 SD is considered as osteopenia, a decreased T-score (< –2.5 SD) — as osteoporosis. The TBS iNsight method, developed by Medimaps (Bordeaux, France), was used to assess the bone tissue quality (TBS, units). This is bone microarchitecture visualization software for DXA. The analysis of this index is based on the variation of gray shades and the amplitude of the pixel density of the X-ray image. Salt transport parameters, osteopontin, and FGF23 were assessed in a certified laboratory (ML “DILA”). FGF23 was measured by enzyme-linked immunosorbent assay using the Human FGF23 kit, and osteopontin by Human Osteopontin (OPN) ELISA. Results. Patients with crystalluria demonstrated significantly lower BMD at the ultradistal radius and TBS, without significant changes in bone remodeling markers. Levels of calcification markers and endocrine regulator FGF23 were significantly higher in patients with NL and crystalluria and were independent of the degree of BMD reduction. Oxalaturia was predominant in patients with NL and crystalluria. No differences in salt transport parameters were observed across BMD-based groups. FGF23 levels were positively associated with serum phosphate concentrations, consistent with its biological mechanism of action. Conclusions. The obtained data suggest that disturbances in renal tubular metabolism (with endocrine regulator FGF23 serving as an early marker) in NL and crystalluria may affect bone quality, particularly at the ultradistal radius, which appears to be more sensitive to tubular dysfunction. Crystalluria may exert a more pronounced impact on changes in bone mineral density than NL, likely due to the more multifactorial pathogenesis of the latter.