Osteogenesis Imperfecta (OI)

Osteogenesis imperfecta (OI) is a genetic disorder characterized by brittle bones that break easily, often from little or no apparent cause. There are four primary forms of the disorder with extreme variation in severity from one individual to another.

How Common Is Osteogenesis Imperfecta?

While the number of people affected with OI in the United States is unknown, the best estimate suggests a minimum of 20,000 and possibly as many as 50,000.

A parent with a history of OI has a 50% chance of passing the gene, and therefore the disease, on to his or her children.

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What Causes Osteogenesis?

• Most cases of OI are caused by a dominant genetic defect in the formation of Type 1 collagen.
• Type 1 collagen is found in connective tissue such as skin, ligaments, tendons, bone, and the aorta.
• Some children with OI inherit the disorder from a parent. Other children are born with OI even though there is no family history of the disorder. In these children, the genetic defect occurred as a spontaneous genetic mutation.

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What Are the Symptoms of Osteogenesis Imperfecta?

There are 4 major subtypes of OI. The symptoms of AO can vary significantly depending on the subtype and even within the same subtype.

Type I (Mild)

• Most common and mildest type of OI.
• Bones predisposed to fracture, most before puberty.
• Normal or near-normal stature.
• Loose joints and low muscle tone.
• Sclera (whites of the eyes) usually have a blue, purple, or gray tint.
• Triangular face.
• Tendency toward spinal curvature.
• Bone deformity absent or minimal.
• Brittle teeth possible.
• Hearing loss possible, often beginning in early 20s or 30s.
• Collagen structure is normal, but the amount is less than normal.

Type II (Most Severe)

• Most severe form of OI.
• Frequently lethal at or shortly after birth, often due to respiratory problems. In recent years, some people with Type II have lived into young adulthood.
• Numerous fractures and severe bone deformity.
• Small stature with underdeveloped lungs.
• Collagen is improperly formed.

Type III (Severe and progressive)

• Bones fracture easily and are often present at birth.
• Short stature.
• Sclera (whites of the eyes) have a blue, purple, or gray tint.
• Loose joints and poor muscle development in arms and legs.
• Barrel-shaped rib cage.
• Triangular face.
• Spinal curvature.
• Respiratory problems possible.
• Bone deformity, often severe.
• Brittle teeth possible.
• Hearing loss possible.
• Collagen is improperly formed.

Type IV (Intermediate)

• Between Type I and Type III in severity.
• Bones fracture easily, most before puberty.
• Shorter than average stature.
• Sclera are white or near-white (i.e., normal in color).
• Mild to moderate bone deformity.
• Tendency toward spinal curvature.
• Barrel-shaped rib cage.
• Triangular face.
• Brittle teeth possible.
• Hearing loss possible.
• Collagen is improperly formed.

Collagen problems in OI:

Type 1:

• Decreased synthesis of pro-a1 chain (primary defect)
• Abnormal pro-a1 or pro-a2 chains

Type 2:

• Abnormally short pro-a1 chain
• Unstable triple helix
• Abnormal or insufficient pro-a2

Type 3:

• Altered structure of propeptides of pro-a2
• Impaired formation of triple helix

Type 4:

• Short pro-a2 chain
• Unstable triple helix

Consequence of collagen mutation in Osteogenesis Imperfecta:

1) The defective collagen rods form an abnormal mold into which bone is mineralized, resulting in weakened bones.

2) The badly formed collagen rods are more susceptible to the body's normal process that detects and destroys broken molecules. Thus, the amount of bone, however imperfect, is reduced further by osteoclasts (cells that break down bone) that remove the defective collagen rods.

3) The third and perhaps most important reason for the brittle bone in OI is that the cells that form bone -- the osteoblasts -- are themselves affected by the nearby presence of bad collagen molecules. Osteoblasts have great difficulty making abnormal collagen fibers and transferring them outside the cell. Thus, the cells are filled with vast quantities of imperfect collagen fibers that cannot be moved outside. Consequently, these cells become very inefficient in the way they make additional bone proteins and are very slow to divide and make new bone cells. However, the body demands that the bone cells make more bone, particularly during childhood, when new bone is needed to carry the increased stature and weight of a growing child. Unfortunately, the only bone that it can make still contains the defective fibers, so the strength is never improved. This spiral of ineffective bone formation is never-ending.

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How Is Osteogenesis Imperfecta Diagnosed?

• In most people the diagnosis is made from the pattern of fractures and on clinical features.
• Clinical geneticists can also perform biochemical (collagen) or molecular (DNA) tests that can help confirm a diagnosis of OI in some situations. Approximately 10 to 15 percent of individuals with mild OI who have collagen testing, and approximately 5 percent of those who have genetic testing, test negative for OI despite having the disorder.
• Alkaline Phosphatase levels are a marker for osteoblasts and cellular levels correlate with the mineralization potential of osteoblasts. Inorganic pyrophosphate is a potent inhibitor of mineralization of bone. Alk phos in osteoblasts and other cells can catalyze the hydrolysis of inorganic pyrophosphate at neutral pH, this enzyme could regulate mineralization by controlling the concentrations of pyrophosphate.(Braunwald 2001)
• Urinary markers for bone resorption: hydroxyproline, hydroxylysine, and hydroxy pyridinium collagen cross-links.
• Serum marker for bone resorption: n-telopeptide.
• X-rays may show characteristic abnormalities - the result of previous fractures. In many people with only mild or moderate OI the X-rays may appear normal at the time of the first few fractures. Later, in bones that have been the site of previous fractures, the bones may appear demineralized (less white on X-ray).
• Bone density measurements are usually unhelpful for the diagnosis of OI. They frequently give normal results in bones that have not previously been fractured.
• Serum vitamin D level.
• Indirectly test growth hormone levels with IGF-1 (somatomedin C)

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What Is the Best Treatment for FMS?

Conventional Treatment for Osteogenesis Imperfecta

Natural Treatment for Osteogenesis Imperfecta

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What Should You Do Next?

The doctors at The Connecticut Center for Health are quite experienced in how to treat osteogenesis imperfecta.

If you would like to learn more about natural medicine approaches to osteogenesis imperfecta, contact one of our clinics for a free consultation or an appointment.

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2. Braunwald, E. (2001). Harrison's principles of internal medicine. New York, McGraw-Hill Medical Publishing Division.
3. Castells, S., C. Colbert, et al. (1979). "Therapy of osteogenesis imperfecta with synthetic salmon calcitonin." J Pediatr 95(5 Pt 1): 807-11.
4. Cetta, G., L. Lenzi, et al. (1977). "Osteogenesis imperfecta: morphological, histochemical and biochemical aspects. Modifications induced by (+)-catechin." Connect Tissue Res 5(1): 51-8.
5. Iwamoto, J., K. Matsu, et al. (2003). "Effects of treatment with etidronate and alfacalcidol for osteogenesis imperfecta type I: a case report." J Orthop Sci 8(2): 243-7.
6. Jones, C. J., C. Cummings, et al. (1984). "A clinical and ultrastructural study of osteogenesis imperfecta after flavonoid (Catergen) therapy." S Afr Med J 66(24): 907-10.
7. Kurz, D. and E. J. Eyring (1974). "Effects of vitamin C on osteogenesis imperfecta." Pediatrics 54(1): 56-61.
8. Marini, J. C., E. Hopkins, et al. (2003). "Positive linear growth and bone responses to growth hormone treatment in children with types III and IV osteogenesis imperfecta: high predictive value of the carboxyterminal propeptide of type I procollagen." J Bone Miner Res 18(2): 237-43.