Pathophysiology of bone disease in chronic kidney disease: from basics to renal osteodystrophy and osteoporosis

Abstract

Chronic kidney disease (CKD) is a highly prevalent disease that has become a public health problem. Progression of CKD is associated with serious complications, including the systemic CKD-mineral and bone disorder (CKD-MBD). Laboratory, bone and vascular abnormalities define this condition, and all have been independently related to cardiovascular disease and high mortality rates. The “old” cross-talk between kidney and bone (classically known as “renal osteodystrophies”) has been recently expanded to the cardiovascular system, emphasizing the importance of the bone component of CKD-MBD. Moreover, a recently recognized higher susceptibility of patients with CKD to falls and bone fractures led to important paradigm changes in the new CKD-MBD guidelines. Evaluation of bone mineral density and the diagnosis of “osteoporosis” emerges in nephrology as a new possibility “if results will impact clinical decisions”. Obviously, it is still reasonable to perform a bone biopsy if knowledge of the type of renal osteodystrophy will be clinically useful (low versus high turnover-bone disease). However, it is now considered that the inability to perform a bone biopsy may not justify withholding antiresorptive therapies to patients with high risk of fracture. This view adds to the effects of parathyroid hormone in CKD patients and the classical treatment of secondary hyperparathyroidism. The availability of new antiosteoporotic treatments bring the opportunity to come back to the basics, and the knowledge of new pathophysiological pathways [OPG/RANKL (LGR4); Wnt-ß-catenin pathway], also affected in CKD, offers great opportunities to further unravel the complex physiopathology of CKD-MBD and to improve outcomes.

The relationship between weight-adjusted-waist index and total bone mineral density in adults aged 20-59

“…Previous research has demonstrated that osteoporosis prevalence is much higher in sufferers of CKD than in age-matched controls, with a loss in BMD launching at an early stage and CKD as a separate risk factor for osteoporosis (42)(43)(44). The complex and varied mechanisms that underlie this phenomenon are typically attributed to abnormalities in the metabolism of calcium and phosphorus, secondary hyperparathyroidism, abnormalities in bone conversion, deficiencies in 1,a-hydroxylase and vitamin D, metabolic acidosis, uremic toxins, microinflammatory states, among others (45)(46)(47). It might seem contrary to what we discovered.…”

Assessment of bone marrow fat by 3-Tesla magnetic resonance spectroscopy in patients with chronic kidney disease

“…Bone abnormalities affect almost all patients with CKD requiring dialysis and the majority of patients with CKD stages 3–5 ( 27 , 38 ). So, we hypothesized an increased marrow fat in patients with late stages of chronic renal insufficiency.…”

“…Sustained high PTH levels in CKD cause a high turnover state in bone, where bone resorption and, in a lesser degree, bone formation are stimulated. The disturbed osteoblast activity results in disorganized bone formation, with an excessive amount of non-mineralized component of bone, leading to skeletal fragility and subsequent increased fracture risk, particularly at the peripheral skeleton ( 27 ).…”

Practical Approaches to the Management of Cardiorenal Disease Beyond Congestion

“…Chronic kidney disease-mineral and bone disorder (CKD-MBD) is the term used to define the changes (laboratory abnormalities, bone abnormalities, and extra-skeletal calcifications) secondary to CKD. Secondary hyperparathyroidism (SHPT) results from CKD-MBD dysregulation and consists of hyperphosphatemia, [66].…”