The development of chronic kidney disease (CKD) is associated with hormonal and biochemical changes that increase bone fragility and fracture risk, the development of vascular calcifications and cardiovascular events, and heighten mortality. Together, these inter-related features are known as ‘CKD-mineral and bone disorder’ (CKD-MBD). Fracture incidence increases in parallel with the deterioration of kidney function, and compared with the general community, fracture risk can increase 40-fold in young patients with kidney failure and 5-fold in older patients, with much higher post-fracture mortality than in the general community. A large patient cohort within any tertiary hospital has CKD-MBD. In the Western Sydney Local Health District, over 1000 patients are on dialysis, 50% of whom have diabetes as the cause of kidney failure. Many more community patients have CKD-MBD with moderate to severe kidney impairment.
While the concept of CKD-MBD has been valuable in focussing attention on physiological pathways linking the kidneys, vascular tissues, bone and the microbiota to fracture and cardiovascular outcomes, it could also be argued that the terminology has inhibited the development of effective interventions to reduce fracture risk. Patients with CKD-MBD have been systematically excluded from osteoporosis trials, so drugs that are effective for reducing fragility fracture have not been tested in this patient group, and generally are not advised or prescribed when eGFR values fall below 30 ml/min/1.73 m2. Similarly, patients with CKD-MBD are excluded from fracture liaison services due to their ‘complex bone pathology’. Nevertheless, these patients generally have significant risks for osteoporosis in addition to bone phenotypes related to kidney disease. Typically, they fall into the gap between nephrologists who are not expert in bone, and endocrinologists who are not expert in kidney disease.
A recent Kidney Disease Improving Global Outcomes (KDIGO) controversy conference and some guidelines have attempted to change this trajectory. If terms such as ‘CKD-related bone fragility’ or ‘CKD-related osteoporosis’ were accepted into the medical lexicon, the result may be a re-examination of management options, and carefully targeted trials of osteoporosis drugs. Such trials would require further evaluation of surrogate endpoints for fracture in this patient group. BMD by DXA is the obvious candidate, but until recently, DXA was not suggested for the evaluation of fracture risk in patients with kidney failure, and the value of DXA following kidney transplantation has been poorly evaluated.
The aim of this discussion will be to explore these concepts, suggest means to improve the evaluation and management of bone disease in CKD-MBD, and generate debate, whilst attempting to ‘mind the gap’.