Renal osteodystrophy

Renal osteodystrophy is defined as an alteration of bone in patients with chronic kidney disease. It is one measure of the skeletal component of the systemic disorder of chronic kidney disease-mineral and bone disorder. The term "renal osteodystrophy" was coined in 1943, 60 years after an association was identified between bone disease and kidney failure.
The types of renal osteodystrophy have traditionally been defined on the basis of bone turnover and mineralization:
1) mild, slight increase in turnover and normal mineralization;
2) osteitis fibrosa, increased turnover and normal mineralization;
3) osteomalacia, decreased turnover and abnormal mineralization;
4) adynamic, decreased turnover and acellularity; and,
5) mixed, increased turnover with abnormal mineralization.
A Kidney Disease: Improving Global Outcomes report has suggested that bone biopsies in patients with CKD should be characterized by determining bone turnover, mineralization, and volume.
On the other hand, CKD-MBD is defined as a systemic disorder of mineral and bone metabolism due to CKD manifested by either one or a combination of:
1) abnormalities of calcium, phosphorus, PTH, or vitamin D metabolism;
2) abnormalities in bone turnover, mineralization, volume, linear growth, or strength vascular or other soft-tissue calcification.

Signs and symptoms

Renal osteodystrophy may exhibit no symptoms; if it does show symptoms, they can include:

Bone pain
Joint pain
Muscle pain
Itching
Bone deformation
Bone fracture
The broader concept of chronic kidney disease-mineral and bone disorder is not only associated with fractures but also with cardiovascular calcification, poor quality of life and increased morbidity and mortality in CKD patients. These clinical consequences are acquiring such an importance that scientific working groups or international initiatives are trying to promote research in the field including basic, translational and clinical research.

Pathogenesis

Renal osteodystrophy has been classically described as the result of hyperparathyroidism secondary to hyperphosphatemia combined with hypocalcemia, both of which are due to decreased excretion of phosphate by the damaged kidney.
Low activated vitamin D₃ levels are a result of the damaged kidneys' inability to convert vitamin D₃ into its active form, calcitriol, and result in further hypocalcemia. High levels of fibroblast growth factor 23 seem to be the most important cause of decreased calcitriol levels in CKD patients.
In CKD, the excessive production of parathyroid hormone increases the bone resorption rate and leads to histologic bone signs of secondary hyperparathyroidism. However, in other situations, the initial increase in parathyroid hormone and bone remodeling may be slowed excessively by a multitude of factors, including age, ethnic origin, sex, and treatments such as vitamin D, calcium salts, calcimimetics, steroids, and so forth, leading to low bone turnover or adynamic bone disease.
Both high and low bone turnover diseases are observed equally in CKD patients treated by dialysis, and all types of renal osteodystrophy are associated with an increased risk of skeletal fractures, reduced quality of life, and poor clinical outcomes.

Diagnosis

Renal osteodystrophy is usually diagnosed after treatment for end-stage kidney disease begins; however the CKD-MBD starts early in the course of CKD. In advanced stages, blood tests will indicate decreased calcium and calcitriol and increased phosphate, and parathyroid hormone levels. In earlier stages, serum calcium, phosphate levels are normal at the expense of high parathyroid hormone and fibroblast growth factor-23 levels. X-rays will also show bone features of renal osteodystrophy but may be difficult to differentiate from other conditions. Since the diagnosis of these bone abnormalities cannot be obtained correctly by clinical, biochemical, and imaging methods, bone biopsy has been, and still remains, the gold standard analysis for assessing the exact type of renal osteodystrophy.

Differential diagnosis

To confirm the diagnosis, renal osteodystrophy must be characterized by determining bone turnover, mineralization, and volume . All forms of renal osteodystrophy should also be distinguished from other bone diseases which may equally result in decreased bone density :

osteoporosis
osteopenia
osteomalacia
brown tumor should be considered as the top-line diagnosis if a mass-forming lesion is present.

Treatment

Treatment for renal osteodystrophy includes the following:

calcium and/or native vitamin D supplementation
restriction of dietary phosphate
phosphate binders such as calcium carbonate, calcium acetate, sevelamer hydrochloride or carbonate, lanthanum carbonate, sucroferric oxyhydroxide, ferric citrate among others
active forms of vitamin D
cinacalcet
renal transplantation
haemodialysis five times a week is thought to be of benefit
parathyroidectomy for symptomatic medication refractive end stage disease

Prognosis

Recovery from renal osteodystrophy has been observed following kidney transplantation. Renal osteodystrophy is a chronic condition with a conventional hemodialysis schedule. Nevertheless, it is important to consider that the broader concept of CKD-MBD, which includes renal osteodystrophy, is not only associated with bone disease and increased risk of fractures but also with cardiovascular calcification, poor quality of life and increased morbidity and mortality in CKD patients., bone may be considered a new endocrine organ at the heart of CKD-MBD.

Epidemiology

Renal osteodystrophy is a common disorder associated with chronic kidney disease, occurring in nearly all affected adults and children. CKD affects an estimated 752 million people globally.