The therapeutic approach to bone disease in CKD is based on its specific type. As such, this Guideline encompasses 3 parts: Guideline 13A deals with high-turnover and mixed bone disease; Guideline 13B with osteomalacia; and Guideline 13C with adynamic bone disease.
GUIDELINE 13B. OSTEOMALACIA
13B.1 Osteomalacia due to aluminum toxicity should be prevented in dialysis patients by maintaining aluminum concentration in dialysate fluid at <10 µg/L and avoiding the use of aluminum-containing compounds (including sucralfate). (OPINION)
13B.2 Aluminum overload leading to aluminum bone disease should be treated with deferoxamine (DFO). (See Guidelines 11 and 12.) (OPINION)
13B.3 Osteomalacia due to vitamin D2 or D3 deficiency or phosphate depletion, though uncommon, should be treated with vitamin D2 or D3 supplementation (see Guideline 7) and/or phosphate administration, respectively. (OPINION)
13B.3a If osteomalacia due to vitamin D deficiency fails to respond to ergocalciferol or cholecalciferol, particularly in patients with kidney failure (Stage 5), treatment with an active vitamin D sterol may be given. (OPINION) (See Guideline 8B.)
13B.3b Doses of phosphate supplementation should be adjusted upwards until normal serum levels of phosphorus are achieved. (OPINION)
As aluminum accumulates on bone surfaces, it impairs bone formation, leading to either osteomalacia or adynamic bone disease. Since this was recognized and aluminum exposure curtailed, osteomalacia has largely disappeared. However, patients may still be seen with this problem and its diagnosis and treatment need to be understood. If osteomalacia is found in the absence of aluminum, it is often related to pre-existing tubular defects of phosphate depletion or vitamin D2 or D3 deficiency.
In the late 1970s, it was documented that osteomalacic bone changes occur in patients with CKD Stage 5 secondary to aluminum intoxication. The clinical manifestations of such lesions are bone pain, fractures, and deranged mineral homeostasis. When marked aluminum loading occurs, brain abnormalities develop which, if untreated, are usually lethal. Treatment with a chelating agent, DFO, dramatically improves patients both clinically and histologically. The avoidance of aluminum has largely eliminated aluminum-related osteomalacia as a clinical problem in the dialysis population. Occasionally, dialysis patients may present with osteomalacia not associated with aluminum intoxication. This may be due to vitamin D deficiency, drugs (inducers of cytochrome P450 pathways), alcohol, calcium and/or phosphate deficiency, or other toxins.
There is compelling evidence of the role of aluminum in the development of osteomalacia. For detailed discussion, see the corresponding sections in Guidelines 11 and 12.
Due to the severe clinical outcome of osteomalacia and other complications resulting from aluminum toxicity, no placebo-controlled studies are possible.
A DFO challenge test (see Guidelines 11 and 12) can often identify aluminum overload, but is not specific for the presence of bone lesions. A firm diagnosis of bone aluminum accumulation and its associated histological derangements requires a bone biopsy (see Guideline 12). Treatment approaches to nonaluminum-related osteomalacia need to be tailored according the underlying causative agent (removal of the toxin or supplementation of the missing factors such as vitamin D and/or phosphate). Treatment should be continued until clinical indicators of osteomalacia, such as bone alkaline phosphatase activity in serum, normalize.
Aluminum accumulation in bone has become much less frequent with cessation of use of aluminum-containing phosphate binders. Unfortunately, the binders which have largely replaced aluminum have not proven completely satisfactory. Studies need to be conducted to determine whether there is a threshold of kidney function below which aluminum-based phosphate binders might be acceptable, and whether there are other substances besides citrate that increase intestinal aluminum absorption. Most importantly, studies evaluating the efficacy and safety of nonaluminum-containing and calcium-based binders are needed.