Routine serum biomarkers, but not dual-energy X-ray absorptiometry, correlate with cortical bone mineral density in children and young adults with chronic kidney disease

Abstract

Background Biomarkers and dual-energy X-ray absorptiometry (DXA) are thought to be poor predictors of bone mineral density (BMD). The Kidney Disease: Improving Global Outcomes guidelines suggest using DXA if the results will affect patient management, but this has not been studied in children or young adults in whom bone mineral accretion continues to 30 years of age. We studied the clinical utility of DXA and serum biomarkers against tibial cortical BMD (CortBMD) measured by peripheral quantitative computed tomography, expressed as Z-score CortBMD, which predicts fracture risk. Methods This was a cross-sectional multicentre study in 26 patients with CKD4 and 5 and 77 on dialysis. Results Significant bone pain that hindered activities of daily living was present in 58%, and 10% had at least one low-trauma fracture. CortBMD and cortical mineral content Z-scores were lower in dialysis compared with CKD patients (P = 0.004 and P = 0.02). DXA BMD hip and lumbar spine Z-scores did not correlate with CortBMD or biomarkers. CortBMD was negatively associated with parathyroid hormone (PTH; r = −0.44, P < 0.0001) and alkaline phosphatase (ALP; r = −0.22, P = 0.03) and positively with calcium (Ca; r = 0.33, P = 0.001). At PTH <3 times upper limit of normal, none of the patients had a CortBMD below −2 SD (odds ratio 95% confidence interval 7.331 to infinity). On multivariable linear regression PTH (β = −0.43 , P < 0.0001), ALP (β = −0.36, P < 0.0001) and Ca (β = 0.21, P = 0.005) together predicted 57% of variability in CortBMD. DXA measures did not improve this model. Conclusions Taken together, routinely used biomarkers, PTH, ALP and Ca, but not DXA, are moderate predictors of cortical BMD. DXA is not clinically useful and should not be routinely performed in children and young adults with CKD 4–5D.

The burden of subclinical cardiovascular disease in children and young adults with chronic kidney disease and on dialysis

“…As skeletal mineralization can continue until 30 years of age, when peak bone mass is reached, we have included young adults up to 30 years of age [ 8 ]. Cross-sectional data on bone health of this cohort have been published previously [ 10 ]. We excluded patients with a functioning kidney transplant and those who would not have tolerated the scanning procedures.…”

“…Details on anthropometric measurements and serum biomarker collection have been published previously [ 10 ] and are described in detail in the Supplementary Materials . Manual blood pressure (BP) was recorded at routine clinic visits or before a midweek haemodialysis session by a single investigator (A.D.L.)…”

Hemodiafiltration Is Associated With Reduced Inflammation and Increased Bone Formation Compared With Conventional Hemodialysis in Children: The HDF, Hearts and Heights (3H) Study

“…Histomorphometric analysis of bone biopsies is the gold standard for diagnosis of renal bone disease 8 , but is invasive and not suited for screening and longitudinal monitoring. On the other hand, radiological bone assessment such as conventional x-rays or dual-energy X-ray absorptiometry (DXA), although non-invasive and widely available, has limited sensitivity and specificity in predicting changes in bone turnover and mineralization 9,10 .…”

Naturally occurring stable calcium isotope ratios are a novel biomarker of bone calcium balance in chronic kidney disease

“…Bone biomarkers reflect either the bone formation or the bone resorption process but not the net state of bone turnover, nor the bone calcium balance (BCaB). 7 Radiological changes may take months to years to manifest changes in BMD. 7 Dual-energy X-ray absorptiometry (DXA), although widely used, is not a reliable predictor of fracture risk, and is not recommended as a screening tool in patients with CKD.…”

“…7 Radiological changes may take months to years to manifest changes in BMD. 7 Dual-energy X-ray absorptiometry (DXA), although widely used, is not a reliable predictor of fracture risk, and is not recommended as a screening tool in patients with CKD. 8 Traditional Ca balance studies administering oral and i.v.…”