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Sci Rep. 2017 Sep 6;7(1):10721. doi: 10.1038/s41598-017-10817-w.

Avascular Necrosis of Femoral Head: A Metabolomic, Biophysical, Biochemical, Electron Microscopic and Histopathological Characterization.

Author information

1
Disease Biology Lab, Department of Biosciences, Sri Sathya Sai Institute for Higher Learning, Prasanthi Nilayam, Puttaparthi, Anantapur District, Andhra Pradesh, India.
2
Department of Orthopaedics, Sri Sathya Sai Institute of Higher Medical Sciences, Prasanthigram, Puttaparthi, Anantapur District, Andhra Pradesh, India. drprakashk@hotmail.com.
3
National Centre for Mass Spectrometry, CSIR-Indian Institute of Chemical Technology, Hyderabad, 500 007, India.
4
Advanced Technology Core, Baylor College of Medicine, One Baylor Plaza, Houston-77030, United States.
5
Raman Research Institute, C.V Raman Avenue, Sadashivanagar, Bengaluru, Karnataka, India.
6
Jan and Dan Duncan Neurological Research Institute, Baylor College of Medicine, One Baylor Plaza, Houston, 77030, United States.
7
Department of Orthopaedics, Sri Sathya Sai Institute of Higher Medical Sciences, Prasanthigram, Puttaparthi, Anantapur District, Andhra Pradesh, India.
8
Department of Pathology and Immunology, Baylor College of Medicine, One Baylor Plaza, Houston, 77030, United States.
9
Michael E. DeBakey Veteran Affairs Medical Center, Houston, Texas, United States.
10
Department of Pathology, M. S. Ramaiah Medical College and Hospital, Bengaluru, Karnataka, India.
11
Department of Biology and Cancer Research, 1200, W. Montgomery Rd, Tuskegee University, Tuskegee, AL, 36088, United States.
12
Department of Physics, Sri Sathya Sai Institute for Higher Learning, Prasanthi Nilayam, Puttaparthi, Anantapur District, Andhra Pradesh, India.
13
Disease Biology Lab, Department of Biosciences, Sri Sathya Sai Institute for Higher Learning, Prasanthi Nilayam, Puttaparthi, Anantapur District, Andhra Pradesh, India. svenketesh@sssihl.edu.in.

Abstract

Avascular necrosis of the femur head (AVNFH) is a debilitating disease caused due to the use of alcohol, steroids, following trauma or unclear (idiopathic) etiology, affecting mostly the middle aged population. Clinically AVNFH is associated with impaired blood supply to the femoral head resulting in bone necrosis and collapse. Although Homocysteine (HC) has been implicated in AVNFH, levels of homocysteine and its associated pathway metabolites have not been characterized. We demonstrate elevated levels of homocysteine and concomitantly reduced levels of vitamins B6 and B12, in plasma of AVNFH patients. AVNFH patients also had elevated blood levels of sodium and creatinine, and reduced levels of random glucose and haemoglobin. Biophysical and ultrastructural analysis of AVNFH bone revealed increased remodelling and reduced bone mineral density portrayed by increased carbonate to phosphate ratio and decreased Phosphate to amide ratio together with disrupted trabeculae, loss of osteocytes, presence of calcified marrow, and elevated expression of osteocalcin in the osteoblasts localized in necrotic regions. Taken together, our studies for the first time characterize the metabolomic, pathophysiological and morphometric changes associated with AVNFH providing insights for development of new markers and therapeutic strategies for this debilitating disorder.

PMID:
28878383
PMCID:
PMC5587540
DOI:
10.1038/s41598-017-10817-w
[Indexed for MEDLINE]
Free PMC Article

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