Structural Organization of Bone
The same organization is true of bone. The steel rods that support the building are collagen rods in bone. The cement that surrounds and supports the rods is formed by minerals (including calcium and phosphorous) from the blood that crystallize and surround the rods. These minerals give the bones strength while the collagen rods provide resiliency.
Diseases that interfere with the ability of calcium and phosphorous to be deposited around the collagen rods yield bones that bend, but do not necessarily break. These diseases are usually diagnosed as "rickets" and are seen in patients who are deficient in vitamin D. Diseases in which the steel rods (collagen rods) are abnormal produce brittle bones and fall under the category of osteogenesis imperfecta (OI). To understand OI, it is essential to understand why the collagen rods are abnormal and how the abnormal rods affect the structure of bone.
Normal versus OI Collagen Rods
The collagen rods that make up OI bone do not give the skeleton full strength because the quantity or shape of the rods is abnormal. There is a defect in the structure or numbers of collagen molecules. Such defects are the result of a mutation (a change) in the DNA (the genetic code) within a gene that makes collagen and often causes severe OI. When such a mutation occurs, a defective blueprint is produced that tells the cell to produce deformed collagen, resulting in bad collagen fibers. Even though the body still makes some good collagen fibers, these fibers attach to bad fibers so that the rods and, consequently, the bone never becomes very strong.
In OI, the collagen fibers that form the rods are either "kinked" or broken, so that the structure is inherently unstable. Between one-half to three-quarters of all collagen fibers that are formed are defective. The more severe the defect in the collagen fiber, the weaker the collagen rod, the greater the severity of OI. As more patients with OI are studied, researchers will be better able to predict how severe a new case of OI will be based on the location of the weakness within the collagen fiber.
In contrast to the more severe forms of OI, mild or Type I OI does not result from the production of bad collagen fibers. Instead, it results from the underproduction of otherwise normal collagen fibers. In these patients, the mutation inactivates or knocks out the function of one of the two collagen genes that we all inherit (one from each parent). The presence of only half the number of collagen fibers and rods has a moderate effect on bone strength, but it is not as severe as the malformation of bone from a normal number of bad collagen fibers.
Consequence of a Collagen Mutation
This phenomenon probably explains why children who are growing rapidly sustain the majority of fractures. They need more strength than the skeleton can provide. When growth stops after sexual maturation, this demand for bone cell activity is relieved. Then bone cells can concentrate on making enough bone matrix just to maintain bone mass without having to form new bone for growth. Because the bone cells catch up to a limited extent, fractures decrease in frequency.
This fact sheet is adapted with permission from an article by David Rowe, M.D., University of Connecticut Health Center, entitled, "Promising Strategies to Treat OI With Somatic Gene Therapy," Breakthrough, 22(1), Winter 1997.
This information is brought to you by the NIH Osteoporosis and Related Bone Diseases~National Resource Center (ORBD~NRC) and the Osteogenesis Imperfecta Foundation
National Institutes of Health
The National Resource Center is supported by the National Institute of Arthritis and Musculoskeletal and Skin Diseases with contributions from the National Institute of Child Health and Human Development, National Institute of Dental and Craniofacial Research, National Institute of Environmental Health Sciences, NIH Office of Research on Women's Health, Office of Women's Health, PHS, and the National Institute on Aging. The Resource Center is operated by the National Osteoporosis Foundation, in collaboration with the Paget Foundation and the Osteogenesis Imperfecta Foundation.