Bone density, microarchitecture and estimated strength in stone formers: a cross-sectional HR-pQCT study

Abstract

Background Low areal bone mineral density (BMD), increased fracture risk, and altered bone remodelling have been described among stone formers (SF), but the magnitude of these findings differs by age, sex, menopausal status, and urinary calcium (uCa). This study aimed to investigate volumetric (v) BMD, bone microarchitecture and biomechanical properties by high-resolution peripheral quantitative computed tomography (HR-pQCT) and finite element analysis (FEA) in young SF, irrespective of calciuria, further distinguishing trabecular from cortical compartments. Methods HR-pQCT/FEA was performed at distal tibia (DT) and radius (DR) in 106 SF (57 males/49 premenopausal females; median age, 37 years) and compared with 106 non-SF (NSF) retrieved from an existing database, matched for age, sex, and body mass index (BMI). Biochemical/hormonal serum and urinary parameters were obtained from SF. Results SF exhibited significantly lower trabecular number (Tb.N), higher trabecular separation (Tb.Sp) than NSF at both anatomical sites and lower cortical porosity in DR. In a subgroup analysis separated by sex, female SF presented significantly lower Tb.vBMD, relative bone volume fraction (BV/TV) and Tb.N, and higher Tb.Sp than NSF at both sites, while male SF showed significantly lower stiffness and failure load. A multivariate analysis showed Tb.N to be independently associated with sex and BMI at both sites and with uCa at DR. Conclusions The present findings suggest that bone disease represents an early event among SF, associated at least in part with calcium excretion, and mainly characterized by trabecular bone microarchitecture impairment, especially among women, but with reduced bone strength parameters in men.

Urinary Calcium Is Associated with Serum Sclerostin among Stone Formers

“…Despite the well-known association of low BMD with hypercalciuria, as suggested by most studies [6,10,29], it still remains a controversial matter as many investigators have reported low BMD among normocalciuric individuals as well [12], which is in agreement with the present findings of a lack of differences in BMD according to the levels of calciuria. In a very recent cross-sectional study of our group employing HRpQCT in SFs, Esper et al [11] observed a reduced trabecular number (Tb.N) and volumetric BMD, indicating trabecular bone microarchitecture impairment, especially among women, as well as reduced bone strength parameters in men. Interestingly, they observed through a multivariate analysis an independent association of Tb.N with urinary calcium only at the distal radius, although BMI was a strong predictor of Tb.N at both radius and tibia.…”

“…Stone formers (SFs) exhibit reduced bone mineral density (BMD) [6,7], and previous histomorphometric studies have evidenced low bone formation and increased bone resorption [8,9]. Although bone demineralization occurs mostly in SFs with idiopathic hypercalciuria [8][9][10], it may be detected in normocalciuric SFs as well [11,12].…”

Vascular Calcification Is Associated with Fetuin-A and Cortical Bone Porosity in Stone Formers

“…Nephrolithiasis was systematically associated with low bone mineral density [ 12 , 13 ] and increased fracture risk [ 67 ], and previous histomorphometric analysis by our group showed high bone resorption and a mineralization defect [ 16 , 17 ]. More recently, we detected trabecular bone impairment and reduced bone strength by HR-pQCT in SF when compared to healthy controls [ 21 ]. Here, the subgroup of patients with higher VC (AAC > 5.8%) also exhibited significantly higher tibial cortical porosity, which may be consequent to bone resorption.…”

“…This study is a post hoc analysis of a prospective cohort that evaluated bone microarchitecture parameters by high-resolution peripheral quantitative computed tomography (HR-pQCT) in young SF [ 21 ]. The initial sample underwent nonenhanced computed tomography (CT) scans and full metabolic evaluation as a routine care at the nephrolithiasis outpatient clinic of the Nephrology Division of Universidade Federal de São Paulo (UNIFESP).…”

“…It is well established that stone formers (SF) exhibit a reduction of bone mineral density (BMD) [ 12 , 13 ], which may be exacerbated under low calcium intake [ 14 ], and histomorphometric studies have reported low bone formation and increased bone resorption [ 15 , 16 , 17 ]. Bone demineralization occurs mostly in SF with idiopathic hypercalciuria [ 16 , 17 , 18 ], but unexpectedly in patients with normal urinary calcium levels as well [ 19 , 20 , 21 , 22 ].…”