Scientific Testing for Osteogenesis Imperfecta (OI) and other Bone Disorders
	The following information pertains to the tests that could help to identify OI. Some of the limitations of the biochemical and DNA testing are mentioned here as well. For further information, please see the OI medical journals on our web site and the OI Child Advocacy web site.

DISCLAIMER: Please note that Protect Our Families.com is not licensed to give medical advice. The following information is research gathered that you may wish to share with your doctor.

• Skin Fibroblast Biopsy - for OI
  
  To take a skin fibroblast biopsy, a small circle will be punched out of the skin. A pediatric dermatologist should perform this biopsy and he will use a topical anesthesia to minimize pain. Sometimes one or two stitches are used to close the area. The sample should be taken from the forearm and should not be taken in the diaper area.
  
  The dermatologist will then place the sample in a sterile, sealed container and send it to a lab to be cultured so that the skin fibroblast cells can grow and produce collagen. There are only a few labs in the United States that can perform this test.
  
  The collagen is then isolated and protein studies are completed - gel electrophoresis. A protein will migrate various distances through a gel based on its size, number of charges, and shape. A big protein doesn't go very far and small proteins move the furthest.
  
  In some forms of OI, the collagen defect involves the structure of the collagen molecule (malformed). These collagens may behave differently in the gel. In type I OI, the defect is that normal collagen is produced but in decreased amounts. A standard gel electrophoresis does not provide a measurement of quantity.
  
  There are no strength tests done on the collagen. A weak, defective collagen that behaves normally in the gel would also result in a negative OI diagnosis.
  
  NOTE: The skin biopsy has a accuracy rate between 85-87%, which means that it is possible to have a false negative result, where the patient actually does have OI but receives a negative test result. Undetected strains, including mild OI, may fall into the 13-15% error ratio or the patient may simply have OI based on other genes or quantity of collagen that the test is not capable of identifying. Truly, a clinical diagnosis of evaluating the patient, family history and x-rays is the best and most thorough way to diagnose OI.
  
  For more information about the skin biopsy test, please contact:
  
  Dr. Peter Byers
  Melanie Pepin at 206-543-5464
  e-mail: mpepin@u.washington.edu
  Additional information about the skin biopsy can be found at:
  http://www.pathology.washington.edu/clinical/collagen/faq.php
  
  Information about the cost for collagen and molecular testing per the University of Washington's web site: http://www.pathology.washington.edu/clinical/collagen/billing.php
  
  
• DNA blood test - for OI
  
  To take a DNA sample, a doctor will take a few small tubes of blood and send it to a lab for DNA testing. There are only a few labs in the United States that can do this testing.
  
  To sequence the DNA for OI, white blood cells or cheek cells are used. It is easier to extract the DNA from these cells. In 1996, when DNA sequencing for OI was first done, it was a comparison test. In other words, a family member known to have OI would have their DNA sequence compared with the patient. The DNA was sequenced for COLA1A and COLA2A. In order to detect OI using this method, two people in the family would have to have the same DNA defect. Now the tests being done are absolute/isolated diagnoses (i.e., the genes are not compared to someone in your family, but rather against a library of OI genes).
  
  There are over two hundred different defects for OI. Confidently diagnosing OI from a DNA sequence or from biochemical studies is very difficult.
  
  NOTE: The OI DNA test has a accuracy rate between 60 - 94%, based on the type classification of OI. That means that it is possible to have a false negative result, where the patient actually does have OI but receives a negative test result. Mild OI Type and Type IV fall into the 60% error ratio where the patient may have OI but the test is unable to determine it either due to testing limitations based or that the test is not capable of identifying other genes that may be a factor in causing OI. Truly, a clinical diagnosis of evaluating the patient, family history and x-rays is the best and most thorough way to diagnose OI.
  
  See the following article:
  
  Prockop DJ, Korkko J, Kinnarney M, Ala-Kokko L: Direct DNA Testing Of Collagen I Genes In Osteogenesis Imperfecta. Proceedings of the 7th International Conference on Osteogenesis Imperfecta. Montreal, Canada, 1999.
  
  For more information about the OI DNA blood test please contact:
  
  Matrix DNA Diagnostics
  Tulane University Health Sciences Center
  TB-28, Tidewater Room 2140
  1430 Tulane Ave.
  New Orleans, LA 70112-2899
  Darwin J. Prockop, MD, PhD, Laboratory Director
  Information & appointments:
  Charlene Crain, MBA, BSMT (ASCP),Laboratory Supervisor
  Telephone: (504) 988-7706
  Fax: (504) 988-7704
  Web Site: www.som.tulane.edu
  www.som.tulane.edu/gene_therapy/matrix/matrix_dna_diagnostics.shtml
  
  
• DEXA Bone Mineral Density Scan
  
  DEXA Bone scans are available at most hospitals. It will need to be arranged in advance for babies and toddlers to be sedated so they will remain still for the imaging process. The scan only takes about fifteen minutes and the radiologist will note the level of bone density and osteopenia noted. Comparison data for young children is limited but certain hospitals do offer DEXA scans with pediatric software and age comparative reference values.
  
  
• Metabolical blood tests - for bone disorders other than OI
  
  You may wish to discuss with your doctor about taking a blood test for some of the following metabolic deficiencies:
  
  Complete Blood count (CBC) - white cells, red cells, platelets
  Alkaline Phosphatase
  Calcium
  Copper
  Chloride
  Creatinine
  Magnesium
  Phosphorous
  Phosphate Parathormone
  Parathyroid hormone (PTH)
  Vitamin C
  Vitamin D (2 types): 25-hydroxy-vitamin D and 1,25 dihydroxy vitamin D
  Zinc
  

Our personal recommendation is to get a DEXA bone density scan and metabolic blood test done on your child as soon as possible. It's important that these tests be done as soon as possible as to when the fractures occured as the condition may be due to a deficiency which may correct itself over time. The other positive aspect is that the DEXA results and metabolic blood test results would be back within a few days whereas the OI skin biopsy test and DNA test take two to three months to be completed. Often times, CPS requires that the baby stay in foster care until the OI tests are back. This frequently means that the child has to stay in foster care for at least three months due to the time required to grow and cultivate skin cells. Instead we highly recommend that you establish that your child has osteopenia (lower bone density) by a DEXA bone density scan or by evaluation of the x-rays by a mild OI expert doctor. It also can help to get the vitamin/mineral blood test in case the baby's fragile bones could be due to a metabolic bone disorder, such as Vitamin D deficiency Rickets.