A structural approach to the assessment of fracture risk in children and adolescents with chronic kidney disease

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Abstract

Children with chronic kidney disease (CKD) have multiple risk factors for impaired accretion of trabecular and cortical bone. CKD during childhood poses an immediate fracture risk and compromises adult bone mass, resulting in significantly greater skeletal fragility throughout life. High-turnover disease initially results in thickened trabeculae, with greater bone volume. As disease progresses, resorption cavities dissect trabeculae, connectivity degrades, and bone volume decreases. Increased bone turnover also results in increased cortical porosity and decreased cortical thickness. Dual-energy X-ray absorptiometry (DXA)-based measures of bone mineral density (BMD) are derived from the total bone mass within the projected bone area (g/cm ²), concealing distinct disease effects in trabecular and cortical bone. In contrast, peripheral quantitative computed tomography (pQCT) estimates volumetric BMD (vBMD, g/cm ³), distinguishes between cortical and trabecular bone, and provides accurate estimates of cortical dimensions. Recent data have confirmed that pQCT measures of cortical vBMD and thickness provide substantially greater fracture discrimination in adult dialysis patients compared with hip or spine DXA. The following review considers the structural effects of renal osteodystrophy as it relates to fracture risk and the potential advantages and disadvantages of DXA and alternative measures of bone density, geometry, and microarchitecture, such as pQCT, micro-CT (μCT), and micro magnetic resonance imaging (μMRI) for fracture risk assessment.

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Most cited references 63

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Pathogenesis of bone fragility in women and men.

Ego Seeman (2002)

There is no one cause of bone fragility; genetic and environmental factors play a part in development of smaller bones, fewer or thinner trabeculae, and thin cortices, all of which result in low peak bone density. Material and structural strength is maintained in early adulthood by remodelling; the focal replacement of old with new bone. However, as age advances less new bone is formed than resorbed in each site remodelled, producing bone loss and structural damage. In women, menopause-related oestrogen deficiency increases remodelling, and at each remodelled site more bone is resorbed and less is formed, accelerating bone loss and causing trabecular thinning and disconnection, cortical thinning and porosity. There is no equivalent midlife event in men, though reduced bone formation and subsequent trabecular and cortical thinning do result in bone loss. Hypogonadism contributes to bone loss in 20-30% of elderly men, and in both sexes hyperparathyroidism secondary to calcium malabsorption increases remodelling, worsening the cortical thinning and porosity and predisposing to hip fractures. Concurrent bone formation on the outer (periosteal) cortical bone surface during ageing partly compensates for bone loss and is greater in men than in women, so internal bone loss is better offset in men. More women than men sustain fractures because their smaller skeleton incurs greater architectural damage and adapts less effectively by periosteal bone formation. The structural basis of bone fragility is determined before birth, takes root during growth, and gains full expression during ageing in both sexes.

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Increased incidence of hip fractures in dialysis patients with low serum parathyroid hormone.

M. Coco, H. Rush (2000)

To study the complications of renal osteodystrophy in patients with end-stage renal disease, we reviewed the incidence of hip fractures in our outpatient dialysis population from 1988 to 1998. One thousand two hundred seventy-two patients were treated for a total of 4,039 patient-years; 56 hip fractures were documented during this period. The incidence of hip fractures was many times greater in the dialysis patients than in the general population in each of the age-, race-, and sex-matched subgroups. The 1-year mortality rate from the hip fracture event was nearly two and a half times greater in the dialysis patients compared with the general population. The incidence of hip fractures in the first half of the decade was similar to that observed in the second half. When parathyroid hormone (PTH) levels were evaluated, we determined that patients with lower serum PTH levels were more likely to sustain a hip fracture than patients with higher PTH levels (P: < 0.006). In addition, we determined that patients with lower PTH levels had an earlier mortality than patients with higher PTH levels (P: < 0.03). We conclude that despite more aggressive therapy directed toward bone health in our dialysis patients in recent years, the incidence of hip fractures and their devastating morbidity and mortality remained unchanged over the past decade. Lower PTH levels may predispose to earlier mortality.

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Basic biomechanical measurements of bone: a tutorial.

C Turner, D B Burr (1993)

Although bone densitometry is often used as a surrogate to evaluate bone fragility, direct biomechanical testing of bone undoubtedly provides more information about mechanical integrity. Like any other specialized field, biomechanics contains its own techniques and vocabulary. This article serves as a guide to biomechanical principles and testing techniques for bone specimens.

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Author and article information

Contributors

Mary B. Leonard: leonard@email.chop.edu

Journal

Journal ID (nlm-ta): Pediatr Nephrol

Journal ID (iso-abbrev): Pediatr. Nephrol

Title: Pediatric Nephrology (Berlin, Germany)

Publisher: Springer Berlin Heidelberg (Berlin/Heidelberg )

ISSN (Print): 0931-041X

ISSN (Electronic): 1432-198X

Publication date (Electronic): 11 July 2007

Publication date PMC-release: 11 July 2007

Publication date (Print): 2007

Volume: 22

Issue: 11

Pages: 1815-1824

Affiliations

GRID grid.239552.a, ISNI 0000000106808770, Departments of Pediatric and Epidemiology, University of Pennsylvania School of Medicine, , The Children’s Hospital of Philadelphia, ; 34th Street and Civic Center Blvd, CHOP North, Room 1564, Philadelphia, PA 19104 USA

Article

Publisher ID: 490

DOI: 10.1007/s00467-007-0490-6

PMC ID: 6949198

PubMed ID: 17622566

SO-VID: 6737eef7-9811-47e8-b11a-90225d9ec628

License:

This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 26 September 2006

Date revision received : 20 March 2007

Date accepted : 20 March 2007

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ScienceOpen disciplines: Nephrology

Keywords: renal osteodystrophy,fracture,dxa,bone mineral density,bone

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ScienceOpen disciplines: Nephrology

Keywords: renal osteodystrophy, fracture, dxa, bone mineral density, bone

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A structural approach to the assessment of fracture risk in children and adolescents with chronic kidney disease

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Fracture and Structural Integrity

Most cited references 63

Pathogenesis of bone fragility in women and men.

Increased incidence of hip fractures in dialysis patients with low serum parathyroid hormone.

Basic biomechanical measurements of bone: a tutorial.

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Cited by 12

Most referenced authors 1,015