Pediatr Nephrol (2008) 23:195–207 lesion of renal osteodystrophy in children is one of high bone turnover, also termed “secondary hyperparathyroid- ism”. Long-term exposure to high serum PTH levels often leads to fibrous changes in bones; this lesion is termed “osteitis fibrosa cystica”. Since PTH activates the PTH/ parathyroid hormone-related protein (PTHrP) receptor on osteocytes and osteoblasts, increasing cellular activity of both osteoblasts and osteoclasts [21, 22], excessive levels of circulating PTH result in increased bone turnover [23]. Increased bone turnover (secondary hyperparathyroidism) is evident in patients with early and advanced stages of CKD and is nearly universal in untreated children at the initiation of dialysis [24]. This condition is marked by increased numbers of osteoblasts and osteoclasts. Due to excess osteoclastic activity, increased resorption of mineral and matrix along trabecular surfaces and haversian canals is evident. Osteitis fibrosa cystica, the advanced lesion of secondary hyperparathyroidism, is also associated with peritrabecular fibrosis [25]. A state of low-turnover bone disease (adynamic renal osteodystrophy) also occurs in children treated with maintenance dialysis, although it has not been demon- strated in adults or children with earlier stages of CKD [26]. Adynamic bone results from over-suppression of serum PTH, due to excess treatment with vitamin D and calcium salts and is characterized by normal osteoid volume, an absence of fibrosis, and a reduced bone formation rate, as indicated by reduced or absent double tetracycline label on bone histology [27, 28]. A paucity of osteoblasts and osteoclasts is present [23]. Adynamic bone has also been associated with low alkaline phosphatase levels, high serum calcium levels, and a propensity for increased vascular calcification [29, 30]. In addition to the increased risk of fractures that is observed in adults with adyamic bone, adynamic bone in children treated with dialysis is associated with an increased severity of growth retardation [31, 32]. Mineralization Alterations in skeletal mineralization are also prevalent in children with CKD [33]. Increases in unmineralized bone (osteoid), in conjunction with delayed rates of mineral deposition, are common [25, 33]. Defective mineralization that is associated with high-turnover bone disease is termed “mixed lesion”; when associated with low-to-normal bone turnover, it is referred to as “osteo- malacia” [1]. While the implications of defective mineral- ization remain to be established, increased fracture rates, bone deformities, and growth retardation are prevalent in patients with CKD and may be due, in part, to altered mineralization. 197 Volume Since PTH is an anabolic steroid at the level of trabecular bone, high levels of serum PTH are typically associated with increases in bone volume, trabecular volume, and trabecular width [20, 33–35]. Thus, children with CKD typically have normal or high bone volume as assessed by bone histomorphometry. Those treated with corticosteroids, however, may display loss of bone volume, termed “osteoporosis”. The impact of osteoporosis in childhood may not always be immediately apparent; however, sub- optimal peak bone mass accretion in adolescence is associated with an increased risk of osteoporosis, hip fractures, and mortality in adulthood [36]. Growth Growth retardation is the hallmark of CKD in children. Protein and calorie malnutrition, metabolic acidosis, end- organ growth hormone resistance, and renal bone disease are the factors most commonly implicated in growth failure [37]. Despite correction of acidosis and anemia, normali- zation of serum calcium and phosphorus levels, and vitamin D sterol therapy replacement, the majority of children with CKD continue to grow poorly. Growth failure worsens as renal function declines; the average height of children with even mild CKD [glomerular filtration rate (GFR) 50–70 ml/min per 1.73 m2 body surface area] is 1 standard deviation score (SDS) below the average for healthy children. Moderate CKD (GFR 25–49 ml/min per 1.73 m2) is associated with a height SDS of −1.5, and, at the time of initiation of dialysis, the mean height SDS is −1.8 [38]. Secondary hyperparathyroidism contributes to growth retardation, although optimal target values for PTH in chil- dren in all stages of CKD remain controversial. In children with moderate CKD, some data indicate that normal growth velocity is achieved when PTH levels are maintained within the normal range [39], while others have demonstrated a linear correlation between growth and PTH levels in the same patient population, those with the highest PTH values maintaining the highest rates of growth [40]. In children treated with maintenance dialysis, adynamic bone disease and growth failure have been associated with PTH levels around 100 pg/ml (1st generation assay), causing many experts to recommend target PTH levels 3–5 times the normal range in advanced CKD [32]. Data from the European community, however, have demonstrated that optimal growth velocity in this population may be associated with PTH levels of 2–3 times the normal range [41]. As a result, optimal PTH targets remain controversial, and recommendations vary between experts (Table 1).