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

Wetzsteon, Rachel J.; Kalkwarf, Heidi J.; Shults, Justine; Zemel, Babette S.; Foster, Bethany J.; Griffin, Lindsay; Strife, C. Frederic; Foerster, Debbie; Jean-Pierre, Darlene K; Leonard, Mary B.

doi:10.1002/jbmr.427

Cited by 54 publications

(56 citation statements)

References 55 publications

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“…20 Markedly elevated baseline trabecular BMD Z-scores (range=2.2-5.7) were observed solely in transplant recipients ,13 years of age. Therefore, trabecular BMD Z-scores were described separately for younger (age,13 years) and older (age$13 years) participants.…”

Section: Trabecular Bmdmentioning

confidence: 43%

“…Serum iPTH levels above the pediatric clinical target of 300 pg/ml 23 were associated with significantly higher trabecular BMD Z-scores compared with iPTH levels#300 pg/ml (P,0.05); however, this positive association was absent in older participants (test for interaction: P,0.05), which was previously reported. 20 Similar patterns were observed when iPTH was analyzed as a continuous variable; however, the results were not statistically significant. Table 3 summarizes the pQCT Z-scores in the transplant recipients at the time of transplantation and 12 months later compared with reference participants.…”

Section: Trabecular Bmdmentioning

confidence: 43%

“…pQCT results were compared with reference data generated in more than 700 concurrent healthy participants. 1,[19][20][21] The hypotheses were that glucocorticoid exposure and resolution of secondary hyperparathyroidism after renal transplantation would be associated with declines in trabecular BMD and increases in cortical BMD. 12,22 We also hypothesized that increases in muscle area after renal transplantation would be associated with increases in cortical dimensions.…”

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confidence: 50%

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Bone Density and Cortical Structure after Pediatric Renal Transplantation

Terpstra

Kalkwarf²,

Shults³

et al. 2012

Journal of the American Society of Nephrology

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The impact of renal transplantation on trabecular and cortical bone mineral density (BMD) and cortical structure is unknown. We obtained quantitative computed tomography scans of the tibia in pediatric renal transplant recipients at transplantation and 3, 6, and 12 months; 58 recipients completed at least two visits. We used more than 700 reference participants to generate Z-scores for trabecular BMD, cortical BMD, section modulus (a summary measure of cortical dimensions and strength), and muscle and fat area. At baseline, compared with reference participants, renal transplant recipients had significantly lower mean section modulus and muscle area; trabecular BMD was significantly greater than reference participants only in transplant recipients younger than 13 years. After transplantation, trabecular BMD decreased significantly in association with greater glucocorticoid exposure. Cortical BMD increased significantly in association with greater glucocorticoid exposure and greater decreases in parathyroid hormone levels. Muscle and fat area both increased significantly, but section modulus did not improve. At 12 months, transplantation associated with significantly lower section modulus and greater fat area compared with reference participants. Muscle area and cortical BMD did not differ significantly between transplant recipients and reference participants. Trabecular BMD was no longer significantly elevated in younger recipients and was low in older recipients. Pediatric renal transplant associated with persistent deficits in section modulus, despite recovery of muscle, and low trabecular BMD in older recipients. Future studies should determine the implications of these data on fracture risk and identify strategies to improve bone density and structure. During childhood and adolescence, skeletal development is characterized by increases in trabecular and cortical bone mineral density (BMD) and cortical dimensions. 1 Children with CKD have numerous risk factors for impaired bone acquisition, including growth failure, delayed puberty, malnutrition, acidosis, vitamin D deficiency, muscle deficits, and secondary hyperparathyroidism. Successful renal transplantation corrects many of the underlying abnormalities contributing to bone deficits in childhood CKD. However, immunosuppressive therapies and persistent hyperparathyroidism may impair recovery of bone structure and strength. The risk of fracture among adult renal transplant recipients increases in the months after transplantation and then gradually declines. 2 The

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Section: Trabecular Bmdmentioning

confidence: 43%

Section: Trabecular Bmdmentioning

confidence: 43%

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confidence: 50%

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Bone Density and Cortical Structure after Pediatric Renal Transplantation

Terpstra

Kalkwarf²,

Shults³

et al. 2012

Journal of the American Society of Nephrology

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“…Current guidelines recommend that bone turnover, mineralization, volume, strength, and growth be assessed in all adults and children with CKD, and the bone biopsy is the gold standard for the diagnosis of renal osteodystrophy (3,4). Because this is an invasive technique used primarily in the research setting, circulating biomarkers are often used to assess bone turnover, and estimates of bone volume and density are often obtained from imaging studies (5)(6)(7). To date, however, only one study has evaluated the relationship between imaging data and bone histomorphometry in patients on dialysis; in this study, differences in bone density, as assessed by in vivo quantitative computed tomography (QCT), were noted between adult patients on dialysis with high and low bone turnover (8).…”

Section: Introductionmentioning

confidence: 44%

Micro-CT in the Assessment of Pediatric Renal Osteodystrophy by Bone Histomorphometry

Pereira

Bischoff

Yamaguchi

et al. 2016

Clinical Journal of the American Society of Nephrology

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Background and objectives Computed tomography (CT) measurements can distinguish between cortical and trabecular bone density in vivo. High-resolution CTs assess both bone volume and density in the same compartment, thus potentially yielding information regarding bone mineralization as well. The relationship between bone histomorphometric parameters of skeletal mineralization and bone density from microcomputed tomography (mCT) measurements of bone cores from patients on dialysis has not been assessed.Design, setting, participants, & measurements Bone cores from 68 patients with ESRD (age =13.960.5 years old; 50% men) and 14 controls (age =15.363.8 years old; 50% men) obtained as part of research protocols between 1983 and 2006 were analyzed by bone histomorphometry and mCT.Results Bone histomorphometric diagnoses in the patients were normal to high bone turnover in 76%, adynamic bone in 13%, and osteomalacia in 11%. Bone formation rate did not correlate with any mCT determinations. Bone volume measurements were highly correlated between bone histomorphometry and mCT (bone volume/tissue volume between the two techniques: r=0.70; P,0.001, trabecular thickness and trabecular separation: r=0.71; P,0.001, and r=0.56; P,0.001, respectively). Osteoid accumulation as determined by bone histomorphometry correlated inversely with bone mineral density as assessed by mCT (osteoid thickness: r=20.32; P=0.01 and osteoid volume: r=20.28; P=0.05). By multivariable analysis, the combination of bone mineral density and bone volume (as assessed by mCT) along with parathyroid hormone and calcium levels accounted for 38% of the variability in osteoid volume (by histomorphometry).Conclusions Measures of bone volume can be accurately assessed with mCT. Bone mineral density is lower in patients with excessive osteoid accumulation and higher in patients with adynamic, well mineralized bone. Thus, bone mineralization may be accurately assessed by mCT of bone biopsy cores. Additional studies are warranted to define the value of high-resolution CT in the prediction of bone mineralization in vivo.

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“…32 We subsequently completed a study in 170 children and adolescents with CKD and ESRD. Over an average follow-up of 1 year, 6.5% of participants sustained a fracture (incidence of 556/10,000 person-years), and lower baseline cortical volumetric bone mineral density (BMD) was associated with risk of subsequent fracture. 1 The sample size and follow-up duration were insufficient to define genderspecific incidence and identify risk factors for fracture.…”

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confidence: 45%

Fracture Burden and Risk Factors in Childhood CKD

Denburg

Kumar

Jemielita

et al. 2016

Journal of the American Society of Nephrology

110

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Childhood chronic kidney disease (CHD) poses multiple threats to bone accrual; however, the associated fracture risk is not well characterized. This prospective cohort study included 537 CKD in Children (CKiD) participants. Fracture histories were obtained at baseline, at years 1, 3, and 5 through November 1, 2009, and annually thereafter. We used Cox regression analysis of first incident fracture to evaluate potential correlates of fracture risk. At enrollment, median age was 11 years, and 16% of patients reported a prior fracture. Over a median of 3.9 years, 43 males and 24 females sustained incident fractures, corresponding to 395 (95% confidence interval [95% CI], 293-533) and 323 (95% CI, 216-481) fractures per 10,000 person-years, respectively. These rates were 2-to 3-fold higher than published general population rates. The only gender difference in fracture risk was a 2.6-fold higher risk in males aged $15 years (570/10,000 person-years, adjusted P=0.04). In multivariable analysis, advanced pubertal stage, greater height Z-score, difficulty walking, and higher average log-transformed parathyroid hormone level were independently associated with greater fracture risk (all P#0.04). Phosphate binder treatment (predominantly calcium-based) was associated with lower fracture risk (hazard ratio, 0.37; 95% CI, P=0.03). Participation in more than one team sport was associated with higher risk (hazard ratio, 4.87; 95% CI, 2.21-10.75; P,0.001). In conclusion, children with CKD have a high burden of fracture. Regarding modifiable factors, higher average parathyroid hormone level was associated with greater risk of fracture, whereas phosphate binder use was protective in this cohort.

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

Cited by 54 publications

References 55 publications

Bone Density and Cortical Structure after Pediatric Renal Transplantation

Bone Density and Cortical Structure after Pediatric Renal Transplantation

Micro-CT in the Assessment of Pediatric Renal Osteodystrophy by Bone Histomorphometry

Fracture Burden and Risk Factors in Childhood CKD

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