Chronic Kidney disease (CKD) patients have an increased risk of fractures. In elderly patients, hip fractures are twice as common in those with stage 3 CKD as in those with normal renal function. Dialysis patients have four times as many hip fractures as expected for their age. Thus, the problem is clear, but the solution is not.1 Patients with the mineral and bone disorder seen with CKD (CKD-MBD) have complex abnormalities in bone physiology.2
Osteoporosis is a disease of reduced bone mass and reduced bone strength. There is some overlap between “ordinary” osteoporosis and CKD-MBD, but they are different diseases—just as hemolytic anemia and iron-deficiency anemia have similar manifestations but different physiology (Table 1).
Although there have been studies involving thousands of patients with osteoporosis, very few of these have included any patients with CKD-MBD. In fact, for the major new osteoporosis medications, the studies were designed to exclude those with renal disease. Nevertheless, because serum creatinine was used as an exclusion criterion and the patients were elderly, many subjects had stage 3 CKD.3-5 They had normal serum parathyroid hormone (PTH), alkaline phosphatase, calcium, and phosphate and thus did not have the biochemical abnormalities that herald the advanced mineral and bone disorders associated with CKD-MBD. These patients respond to osteoporosis medications and can be treated the same as other elderly persons with osteoporosis.
Published studies of osteoporosis therapies in patients with stage 4 or 5 CKD are very limited. For the Kidney Disease: Improving Global Outcomes (KDIGO) report, a literature review with pre-specification of 50 patients and six months’ duration found only one paper about raloxifene,6 and none using bisphosphonates. Since then, one trial of alendronate that enrolled 50 subjects was published.7 Unfortunately, there are no ongoing studies listed at ClinicalTrials.gov using osteoporosis medications in patients with stage 4 or 5 CKD.
Predicting fracture rate in CKD
Bone density in patients with stage 5 CKD is only weakly predictive of fractures.8 This is different from studies in patients with postmenopausal osteoporosis, in whom a standard-deviation decrease in bone density by dual-energy x-ray absorptiometry is associated with a doubling of the risk of a fragility fracture. There are several possible reasons for the poor performance of these tests in the kidney patients. Bone density tends to be worse in cortical sites and normal or even increased in cancellous sites, whereas in ordinary osteoporosis, bone is lost in both locations. CKD patients also may have poor-quality bone, so they can suffer fractures even without severe loss of bone mass. Low bone density is seen in patients with osteomalacia, even when their bone volume is normal. Many CKD patients have been treated with glucocorticosteroids, which also can cause fractures despite a deceivingly normal bone density.
Although nontraumatic fractures may still occur in patients with normal bone density, low bone density is always worrisome. Patients with fragility fractures with or without low bone density present a challenge. Since there is not enough evidence to decide on therapies, the only choice is to follow physiologic principles and to take care to do no harm.