The role of the bone biopsy in the diagnosis of renal osteodystrophy.

The bone and mineral complications associated with renal failure are numerous—hyperparathyroidism, adynamic bone disease, aluminum bone disease, acidosis, b2-microglobulin amyloidosis, gonadal deficiencyassociated osteopenia, and posttransplant osteoporosis. Renal osteodystrophy is the generic term generally used to describe the skeletal complications of renal failure. Renal osteodystrophy encompasses a wide spectrum of bone disorders and is often classified on the basis of the predominant histopathologic patterns. Several classification schemes have been used. Traditionally five major histopathologic patterns are described: osteitis fibrosa, mild lesion, osteomalacia, mixed uremic osteodystrophy, and adynamic bone disease. Others (1) proposed dividing the disorders into three major groups: predominant hyperparathyroid bone disease (including osteitis fibrosa and mild disease), low-turnover uremic osteodystrophy (including osteomalacia and adynamic bone disease), and mixed uremic osteodystrophy (mild to moderate hyperparathyroidism with defective mineralization). Osteitis fibrosa (predominant hyperparathyroid bone disease) is characterized by a marked increase in bone turnover as assessed by an elevated bone formation rate, increased remodeling (both formation and resorption), and peritrabecular fibrosis. It appears to be decreasing in frequency and has been reported in 5–50% of patients (1–5). The primary metabolic abnormality with this lesion is long-standing hyperparathyroidism. Although hyperparathyroidism is common early in the development of renal failure, osteitis fibrosa is relatively rare prior to the development of end-stage renal disease (ESRD). The mild lesion is characterized by a slight increase in the bone formation rate and remodeling, but is generally without significant peritrabecular fibrosis. It is the most common lesion seen prior to the development of ESRD (6) and has been increasing in frequency in dialysis patients, accounting for approximately 3–20% of patients (1–5). It is usually the result of mild or early secondary hyperparathyroidism or follows therapy for hyperparathyroidism. Osteomalacia is defined by a defect in mineralization with increased osteoid formation; however, bone formation is decreased, thus it is a low-turnover lesion. Aluminum intoxication, iron intoxication, severe vitamin D deficiency, plus other unidentified factors probably play a role in its pathogenesis. It is decreasing in frequency and is seen in approximately 4–8% of patients (1–5, 7). Features of osteomalacia with increased bone formation characterize the lesion of mixed uremic osteodystrophy. These features may coexist in varying degrees in different patients. Although there is no identifiable predominant cause, it appears to be secondary to hyperparathyroidism with a defect in mineralization. Aluminum or other unidentified factors may also be involved. This lesion may be found in 11–80% of patients (1–5). Adynamic bone disease (low turnover) represents the opposite end of the spectrum from osteitis fibrosa. It is characterized by a marked decrease in both remodeling and mineralization. There is a profound decrease in both osteoblasts and osteoclasts, and sites of active bone formation are rarely observed. The clinical significance of adynamic bone disease is controversial; however, it is associated with a propensity for hypercalcemia, extraskeletal calcifications, and a decreased ability of bone to buffer calcium (8, 9). Although there are identifiable risk factors associated with adynamic bone disease, the pathogenesis is poorly understood. The frequency has been increasing and is observed in 25–60% of patients (1–5, 7, 10). It is associated with relatively low levels of parathyroid hormone (after parathyroidectomy, overly aggressive medical management), aluminum intoxication, diabetes, and peritoneal dialysis (1, 2, 5, 10, 11). The current therapeutic approach to renal bone disease is to normalize the defect in bone remodeling. Thus it may be useful to classify renal osteodystrophy on the basis of being either a highor low-turnover lesion (Table 1). The high-turnover lesions include predominant hyperparathyroid bone disease (osteitis fibrosa), the mild lesion, and the subset of those with mixed uremic osteodystrophy with increased bone formation. The lowturnover lesions include the adynamic (both aluminumand non-aluminum-associated) and osteomalacia (both aluminumand non-aluminum-associated). It needs to be appreciated that in any patient, transformation from one lesion to another may occur. Therapy has predominantly focused on treating and or preventing the high-turnover lesion, which results from hyperparathyroidism. Thus parathyroid hormone (PTH) levels have become the surrogate measure of bone disease. In patients with markedly elevated PTH levels (>600–800 pg/ml), the diagnosis is rather obvious and therapy focuses on reducing PTH levels. In the rare patients who have had significant exposure to aluminum, aggressive therapy, especially parathyroidectomy, may Address correspondence to: Stuart M. Sprague, DO, Division of Nephrology, Department of Medicine, Evanston Northwestern Healthcare, 2650 North Ridge Ave., Evanston, IL 60201. E-mail: [email protected]. Seminars in Dialysis—Vol 13, No 3 (May–June) 2000 pp. 152–155