Abstract
Mineral and bone disorder in chronic kidney disease (CKD-MBD) is a triad of biochemical imbalances of calcium, phosphate, parathyroid hormone and vitamin D, bone abnormalities and soft tissue calcification. Maintaining optimal bone health in children with CKD is important to prevent long-term complications, such as fractures, to optimise growth and possibly also to prevent extra-osseous calcification, especially vascular calcification. In this review, we discuss normal bone mineralisation, the pathophysiology of dysregulated homeostasis leading to mineralisation defects in CKD and its clinical consequences. Bone mineralisation is best assessed on bone histology and histomorphometry, but given the rarity with which this is performed, we present an overview of the tools available to clinicians to assess bone mineral density, including serum biomarkers and imaging such as dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. We discuss key studies that have used these techniques, their advantages and disadvantages in childhood CKD and their relationship to biomarkers and bone histomorphometry. Finally, we present recommendations from relevant guidelines—Kidney Disease Improving Global Outcomes and the International Society of Clinical Densitometry—on the use of imaging, biomarkers and bone biopsy in assessing bone mineral density. Given low-level evidence from most paediatric studies, bone imaging and histology remain largely research tools, and current clinical management is guided by serum calcium, phosphate, PTH, vitamin D and alkaline phosphatase levels only.
Highlights
There is a growing awareness that mineral dysregulation in chronic kidney disease (CKD) is closely linked to abnormal bone pathology, and that this in turn, may potentially lead to extra-skeletal calcification
A study comparing 156 children with CKD to 831 healthy participants using tibial Peripheral quantitative CT (pQCT) showed that iPTH levels above the Kidney Disease Outcomes Quality Initiative (KDOQI) recommended target was associated with increased trabecular bone mineral density (BMD) Z-scores (p < 0.01), but lower cortical BMD scores (p < 0.01)
Skeletal abnormalities are prevalent in children with CKD, affecting bone mineralisation from early CKD and manifesting as bone pains, deformities and fractures
Summary
There is a growing awareness that mineral dysregulation in chronic kidney disease (CKD) is closely linked to abnormal bone pathology, and that this in turn, may potentially lead to extra-skeletal calcification. The Saskatchewan Paediatric Bone Mineral Accrual Study followed 164 children aged 8–14 years into their early 30s with dietary information and whole body DXA scans [21, 22] They showed that peak height velocity (PHV) was reached by 11.8 and 13.5 years for females and males, respectively, but PBM (highest BMC by total body DXA) was attained 7 years later. Osteocytic markers: Phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX), dentin matrix protein-1 (DMP1), matrix extracellular phospho-glycoprotein (MEPE), sclerostin and FGF23 that can regulate both osteoblastic and osteoclastic activity [61] All these biomarkers have been researched, drawing correlations with bone histology, imaging and fracture outcomes, but only PTH and BSAP are considered useful adjuncts to calcium and phosphate measurements in clinical practice. Larger paediatric studies that correlate bone biomarkers with the gold standard of bone histomorphometry as well as patient-level outcomes such as fractures are required
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