Pathogenesis of osteomalacia in chronic renal failure and its relationship to vitamin D

Abstract

Considerable confusion arises in defining osteomalacia in the presence of renal disease. There are no radiographic or biochemical features which satisfactorily identify all patients with osteomalacia. Histological definitions need to distinguish increased amounts of osteoid due to defective mineralisation from that due to increased bone turnover, both of which may coexist in chronic renal failure. The pathogenesis of osteomalacia in renal failure is multifactorial and not always due to defective metabolism of vitamin D. Deficient production of 25-hydroxyvitamin D may occur because of nutritional privation or urinary losses in the nephrotic syndrome, but these are rare causes of osteomalacia in patients on haemodialysis treatment. It is not clear to what extent defective production of calcitriol, characteristic of end-stage chronic renal failure is causally related to osteomalacia, in part due to uncertainties as to whether vitamin D acts directly on bone to promote mineralisation or whether its effects are mediated indirectly by modulating calcium and phosphate transport at other sites. Following the institution of renal replacement therapy, the incidence of osteomalacia varies markedly between renal units due to the skeletal retention of aluminium caused by the contamination of dialysis fluid or by the chronic ingestion of aluminium-containing phosphate binding agents. This form of osteomalacia is associated with a high risk of fracture, probably more related to depressed bone formation than to the presence of osteomalacia. Rarer causes of osteomalacia include parathyroidectomy and calcium and phosphate deficiency.