Microstructural, Densitometric and Metabolic Variations in Bones from Rats with Normal or Altered Skeletal States

Andrew N Luu,Brian D Snyder,Vahid Entezari,Shima Aran,Claudio Rosso,Lorenzo Anez-Bustillos,Francisco J Araiza Arroyo,Ara Nazarian,Hani A Awad

doi:10.1371/journal.pone.0082709

Abstract

BackgroundHigh resolution μCT, and combined μPET/CT have emerged as non-invasive techniques to enhance or even replace dual energy X-ray absorptiometry (DXA) as the current preferred approach for fragility fracture risk assessment. The aim of this study was to assess the ability of µPET/CT imaging to differentiate changes in rat bone tissue density and microstructure induced by metabolic bone diseases more accurately than current available methods.MethodsThirty three rats were divided into three groups of control, ovariectomy and vitamin-D deficiency. At the conclusion of the study, animals were subjected to glucose (18FDG) and sodium fluoride (Na18F) PET/CT scanning. Then, specimens were subjected to µCT imaging and tensile mechanical testing. ResultsCompared to control, those allocated to ovariectomy and vitamin D deficiency groups showed 4% and 22% (significant) increase in 18FDG uptake values, respectively. DXA-based bone mineral density was higher in the vitamin D deficiency group when compared to the other groups (cortical bone), yet μCT-based apparent and mineral density results were not different between groups. DXA-based bone mineral density was lower in the ovariectomy group when compared to the other groups (cancellous bone); yet μCT-based mineral density results were not different between groups, and the μCT-based apparent density results were lower in the ovariectomy group compared to the other groups. ConclusionPET and micro-CT provide an accurate three-dimensional measurement of the changes in bone tissue mineral density, as well as microstructure for cortical and cancellous bone and metabolic activity. As osteomalacia is characterized by impaired bone mineralization, the use of densitometric analyses may lead to misinterpretation of the condition as osteoporosis. In contrast, µCT alone and in combination with the PET component certainly provides an accurate three-dimensional measurement of the changes in both bone tissue mineral density, as well as microstructure for cortical and cancellous bone and metabolic activity.

Highlights

Fragility fractures occurring at multiple skeletal sites affect approximately 1.5 million in the United States annually [1], where four out of ten white women aged 50 or older will suffer a fracture due to osteoporosis
We find relevant to establish significant biochemical and structural differences between osteoporosis and osteomalacia, as a means to provide better treatment options for each pathologic condition
The 18FDG positron emission tomography (PET) imaging intent was to quantify the metabolic activity of the bone, whereas the Na18F PET imaging aimed to quantify the osteoblastic activity within the bone

Summary

Introduction

Fragility fractures occurring at multiple skeletal sites affect approximately 1.5 million in the United States annually [1], where four out of ten white women aged 50 or older will suffer a fracture due to osteoporosis. The World Health Organization identifies individuals at risk for these types of fractures based on their areal bone mineral density (aBMD) measured by dual energy X-ray absorptiometry (DXA) at the hip, lumbar spine or forearm, compared to normal reference values [6]. Such aBMD-based fracture predictions have been shown to lack sensitivity and specificity [7,8,9,10,11]. ΜCT alone and in combination with the PET component certainly provides an accurate three-dimensional measurement of the changes in both bone tissue mineral density, as well as microstructure for cortical and cancellous bone and metabolic activity

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