Children with chronic kidney disease: a 3‐year prospective study of growth, bone mass and bone turnover

Swolin-Eide, Diana; Hansson, Sverker; Magnusson, Per

doi:10.1111/j.1651-2227.2008.01073.x

Cited by 13 publications

(8 citation statements)

References 28 publications

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“…Consistent with our findings, other studies have also reported significantly higher OPG levels in children on dialysis compared to controls [13,17]. Swolin-Eide et al [14][15][16], who reported OPG levels within the healthy reference intervals in pediatric patients with various stages of CKD, found that at the end of a 3-year follow-up almost 50% of them had OPG levels above the reference intervals. These authors hypothesized that a compensatory mechanism had developed in these patients for maintaining adequate bone mass; the concept of such a mechanism was supported by the normal bone mineral density of these patients [16].…”

Section: Discussionsupporting

confidence: 94%

“…In childhood, the interpretation of bone mineral measurements is more complex than in adults because of more dynamic changes in growing bones. In fact, studies regarding OPG [13][14][15][16][17] and RANKL [17,18] in the pediatric population with CKD are few, and no studies have assessed the relationship of the OPG/RANKL system with FGF-23. Findings from one animal study have shown that OPG may play a key role in mediating the response of FGF-23 to an oral phosphate load in bone cells [19].…”

Section: Abbreviationsmentioning

confidence: 99%

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Serum osteoprotegerin, RANKL and fibroblast growth factor-23 in children with chronic kidney disease

et al. 2011

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Osteoprotegerin (OPG), receptor activator of the nuclear factor κB ligand (RANKL) and fibroblast growth factor-23 (FGF-23) play a central role in renal osteodystrophy. We evaluated OPG/RANKL and FGF-23 levels in 51 children with chronic kidney disease (CKD) [n = 26 stage 3 or 4 (CKD3-4) and n = 25 stage 5 (CKD5)] and 61 controls. Any possible association with intact parathyroid hormone (iPTH) and bone turnover markers was also investigated. The OPG levels were lower in the CKD3-4 group (p < 0.001) and higher in the CKD5 group (p < 0.01) than in the controls, while RANKL levels did not differ. The FGF-23 levels were higher in both patient groups (p < 0.0001), while the levels of phosphate and iPTH were higher only in the CKD5 group (p < 0.0001). There were independent positive correlations between OPG and RANKL (β = 0.297, p < 0.01) and FGF-23 (β = 0.352, p < 0.05) and a negative correlation with the bone resorption marker TRAP5b (β = -0.519, p < 0.001). OPG was positively correlated with iPTH (R = 0.391, p < 0.01). An independent positive correlation between FGF-23 and phosphate (β = 0.368, p < 0.05) or iPTH (β = 0.812, p < 0.0001) was noted. In conclusion, we found that higher OPG levels in patients with CKD stage 5 correlated with the levels of RANKL, FGF-23, iPTH, and TRAP5b. These findings may reflect a compensatory mechanism to the negative balance of bone turnover. High FGF-23 levels in early CKD stages may indicate the need for intervention to manage serum phosphate (Pi) levels.

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Section: Discussionsupporting

confidence: 94%

Section: Abbreviationsmentioning

confidence: 99%

Serum osteoprotegerin, RANKL and fibroblast growth factor-23 in children with chronic kidney disease

et al. 2011

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“…Most studies of bone health in pediatric CKD used DXA and yielded inconsistent results, reporting decreased [28–32], normal [25, 33–35], or increased BMD [36, 37] compared to controls. These studies utilized varying methods to adjust for growth failure and different reference samples to generate Z-scores.…”

Section: Discussionmentioning

confidence: 99%

Assessment of dual-energy x-ray absorptiometry measures of bone health in pediatric chronic kidney disease

et al. 2012

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Background Dual-energy X-ray absorptiometry (DXA) techniques are limited in childhood chronic kidney disease (CKD) by the confounding effect of short stature and opposing parathyroid hormone effects on trabecular and cortical bone. Peripheral quantitative computed tomography (pQCT) is not subject to these limitations. Methods Lumbar spine (LS) and whole-body (WB) DXA and tibia pQCT scans were obtained in 88 stage 4–5 CKD and >650 healthy participants, ages 5–21 years. Sex- and race-specific Z-scores were generated for bone mineral density (BMD) and bone mineral content (BMC) by DXA, relative to age and adjusted for height Z-score (LS-BMD-Z and WB-BMC-Z), and compared to pQCT Z-scores for trabecular BMD (TrabBMD-Z) for age and cortical BMC (CortBMC-Z) for age and tibia length. Results LS-BMD-Z [0.50 (95% C.I. 0.28, 0.73), p<0.0001] and TrabBMD-Z [0.53 (0.27, 0.79), p<0.0001] were greater in CKD, and WB-BMC-Z [−0.36 (−0.53, −0.19), p<0.0001] and CortBMC-Z [−0.48 (−0.70, −0.27), p<0.0001] were lower, compared to reference participants. Z-scores were correlated at trabecular (LS-BMD-Z and TrabBMD-Z: R=0.36) and cortical (WB-BMC-Z and CortBMC-Z: R=0.64) sites in CKD; similar to correlations in reference participants. Conclusions Lumbar spine and whole-body DXA suggested greater trabecular BMD and lower cortical BMC in CKD, consistent with pQCT results; however, correlations were modest. Studies are needed to identify methods that predict fracture in childhood CKD.

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“…This effect was illustrated in a study of pediatric renal transplant recipients: Areal BMD Z ‐scores relative to chronologic age were 1 to 2 SD lower than areal BMD Z ‐scores relative to height age 10. Accordingly, prior DXA studies in children with CKD yielded variable and inconsistent results, reporting decreased,11–16 normal,17–20 or increased15, 20–22 areal BMD compared with controls.…”

Section: Introductionmentioning

confidence: 99%

Volumetric bone mineral density and bone structure in childhood chronic kidney disease

Wetzsteon

Kalkwarf

Shults

et al. 2011

Journal of Bone and Mineral Research

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Chronic kidney disease (CKD) is associated with increased fracture risk and skeletal deformities. The impact of CKD on volumetric bone mineral density (BMD) and cortical dimensions during growth is unknown. Tibia quantitative computed tomography scans were obtained in 156 children with CKD [69 stage 2–3, 51 stage 4–5, and 36 stage 5D (dialysis)] and 831 healthy participants, ages 5–21 years. Sex-, race-, and age- or tibia length-specific Z-scores were generated for trabecular BMD (TrabBMD), cortical BMD (CortBMD), cortical area (CortArea) and endosteal circumference (EndoC). Greater CKD severity was associated with higher TrabBMD-Z in younger participants (p < 0.001), compared with healthy children; this association was attenuated in older participants (interaction p < 0.001). Mean CortArea-Z was lower (p < 0.01) in CKD 4–5 [−0.49 (95% C.I. −0.80, −0.18)] and 5D [−0.49 (−0.83, −0.15)], compared with healthy children. Among CKD participants, parathyroid hormone (PTH) levels were positively associated with TrabBMD-Z (p < 0.01), and this association was significantly attenuated in older participants (interaction p < 0.05). Higher levels of PTH and biomarkers of bone formation (bone-specific alkaline phosphatase) and resorption (β-CTX) were associated with lower CortBMD-Z and CortArea-Z, and greater EndoC-Z (r = 0.18–0.36; all p ≤ 0.02). CortBMD-Z was significantly lower in CKD participants with PTH levels above vs. below the upper limit of the KDOQI CKD stage-specific target range: −0.46 ± 1.29 vs. 0.12 ± 1.14, p < 0.01. In summary, childhood CKD and secondary hyperparathyroidism were associated with significant reductions in cortical area and CortBMD, and greater TrabBMD in younger children. Future studies are needed to establish the fracture implications of these alterations and to determine if cortical and trabecular abnormalities are reversible.

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Children with chronic kidney disease: a 3‐year prospective study of growth, bone mass and bone turnover

Abstract: A normal BMD does not exclude mineral bone disorder in patients with CKD, yet the BMD Z-scores were well preserved and most markers of bone turnover were within the reference intervals.

Cited by 13 publications

References 28 publications

Serum osteoprotegerin, RANKL and fibroblast growth factor-23 in children with chronic kidney disease

Serum osteoprotegerin, RANKL and fibroblast growth factor-23 in children with chronic kidney disease

Assessment of dual-energy x-ray absorptiometry measures of bone health in pediatric chronic kidney disease

Volumetric bone mineral density and bone structure in childhood chronic kidney disease

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