The first therapeutic steps in a patient with fractures or bone density in the “osteoporotic” range (hip T-score <-2.5) are to correct the known associated problems with the mineral and bone disorder seen in CKD-MBD. It is difficult but important to simultaneously treat abnormalities in serum calcium, phosphate, and PTH. The new KDIGO guidelines have extensively reviewed studies about medications that can help achieve this.1 Careful attention to these “standard” problems will help with the bones, and many patients with fractures have abnormalities that can be improved with greater attention to phosphate control using diet, dialysis, and medications. Hyperparathyroidism increases bone resorption, especially in the cortical bone of the forearm and the hip, and excessively high PTH levels can be controlled with vitamin D analogs or cinacalcet.

Lower vitamin D levels

Many dialysis patients are deficient in vitamin D. They are not eating dairy products, and the specific nephrology vitamins do not contain vitamin D. Patients often do not get adequate sunlight exposure. It had been thought that 25-hydroxyvitamin D—25(OH)D—levels were not important in patients who were taking calcitriol or vitamin D analogues because they had adequate amounts of the active hormone, and only the kidney (and possibly some granuloma cells) had 1-alpha-hydroxylase. However, it has been documented that many cells can convert 25(OH)D into 1,25(OH)2D intracellularly without secretion of the 1,25(OH)2D, so that serum levels did not reflect the actual activity. This is seen in skeletal muscle, T-cells, and parathyroid cells. The optimal serum level of 25(OH)D in dialysis patients has not been determined, particularly if the patients are receiving analogs, but until ongoing studies are completed, it makes sense to aim for a level of 20 to 50 ng/mL. This is the range associated with the lowest mortality in men and women from the general population.


Continue Reading

Bones respond to mechanical forces, and many patients with stage 4 or 5 CKD do not get much weight-bearing exercise. Walking, stair-climbing, and dancing, as well as back-extension exercises, should be encouraged in these patients. Exercise programs have not been shown to reduce fractures in large trials, but they make a lot of sense and can also improve cardiovascular and mental health.

Potential treatments

When deciding about potential pharmaceutical treatment, remember that renal osteodystrophy and postmenopausal osteoporosis have important differences. A substantial proportion of renal patients have adynamic bone disease with low bone resorption. In these patients it makes sense, on a physiologic basis, to treat with drugs that stimulate bone formation and not drugs that inhibit bone resorption. Even in patients with “ordinary” osteoporosis, the fracture rate is not decreased in those who begin bisphosphonate therapy with low bone formation. The beneficial effects of bisphosphonates are seen in patients with high bone resorption. Unfortunately, the only effective medicine that increases bone formation is teriparatide. Most patients with CKD-MBD already have abnormalities in the parathyroid gland and it is not clear if further increases in PTH analogs would have the same anabolic effect as in patients with normal or mildly reduced renal function. Consider teriparatide in patients who had bone fractures after total parathyroidectomy, but until there are more data, use of this drug otherwise cannot be recommended.