The evaluation and treatment of osteoporosis in patients with renal insufficiency or requiring dialysis can be complex. Renal osteodystrophy refers to the bone disease and abnormal mineralization associated with chronic renal disease.
Hyperparathyroidism is common as renal insufficiency worsens due to numerous causes including, but not limited to, lower levels of 1,25 (OH)2 D and skeletal resistance to the calcemic actions of PTH. Secondary hyperparathyroidism results in high-turnover bone disease and loss of bone. A substantial number of patients on dialysis have adynamic bone disease. The PTH level is not increased, and bone resorption and formation rates are low. With better knowledge and more aggressive treatment, the number of patients with hyperparathyroidism and high turnover bone disease has decreased, but the number of patients with adynamic bone disease - the other end of the spectrum - has increased.
Osteomalacia can be seen in patients renal insufficiency and renal failure on dialysis. Osteomalacia is characterized by low rates of bone formation and resorption as well as an additional defect in mineralization. Contributing causes of osteomalacia specific to dialysis include aluminum toxicity, malnutrition, excess doses of vitamin D sterols, and calcium supplementation. The two latter modalities are used to help control hypophosphatemia.
The variability of bone disease in patients with renal insufficiency or renal failure can often be understood with the aid of a bone biopsy. In states of hyperparathyroidism, the finding is osteitis fibrosa. There is increased osteoblast and osteoclast activity. There are increased quantities of woven osteoid and haphazard arrangement of collagen fibers. The mineralization may be with amorphous calcium phosphate rather than hydroxapatite;, which may account for the finding of osteosclerosis in some uremic patients. In contrast, in patients with osteomalacia, there is reduced bone resorption and formation. This is the rationale in the concept of adynamic bone disease: the rate of mineralization is abnormal. Tetracycline labeling is helpful with this diagnosis.
Bone density testing may not give an understanding of bone health in patients with renal insufficiency. Bone density does not give any information about bone quality. If bone density is low, the information may be more helpful than if bone density is normal. As noted above, some patients with renal failure have osteosclerosis and would have a high density reading. This speaks nothing of bone quality or strength. The astute clinician would have to use the bone density reading in combination with a fracture history and various lab tests. Useful tests in this situation include parathyroid hormone, vitamin D levels, calcium, phosphorus, alkaline phosphatase, and perhaps a bone biopsy. Serum N-telopeptide may be useful in this population; there is not enough information yet.
A treatment plan in these patients must include an understanding of the specific bone health in a given patient. In general, calcium and phosphorus levels must be maintained in the normal range. Phosphorus levels can be controlled with a low-phosphorus diet and phosphate-binding antacids, such as calcium carbonate. Vitamin D supplementation, i.e. calcitriol, can help control secondary hyperparathyroidism. Parathyroidectomy may be indicated for severe secondary hyperparathyroidism. Exposure to toxic agents, such as aluminum, must be minimized. Chelation therapy can aide in treatment of aluminum intoxication.
In patients with osteoporosis, hormone replacement therapy may still have a role in both men and women. HRT and testosterone replacement can help maintain and improve bone density. Raloxifene may also be used in women. Bisphosphonate therapy can be problematic in patients with renal insufficiency. Bisphosphonates are not metabolized; the drug that is not bound to skeletal sites is excreted unchanged in the urine. Because of the renal route of metabolism, bisphosphonates should be given with caution to patients with renal insufficiency. Teriparatide would not be an appropriate choice in patients with renal insufficiency due to its mechanism of action. Given the small treatment armamentarium for treatment of osteoporosis in patient with renal insufficiency, a preventative approach is quite important.