Treatment

It is not expected that the cause of O.I. can be eliminated in the near future. Therefore O.I. can not be cured at the moment. However, careful treatment can alleviate the circumstances.Treatments are aimed at reducing the impact of the consequences and at the prevention of complications. Often this calls for an integral management plan, which may encompass: orthopedic treatment of fractures, hearing improvement, dental intervention, physical therapy, psychological assistance, genetic counselling and DNA testing, social advisory, ergotherapy with advice on crutches and wheelchairs and other equipment, sometimes also dietary advice.

Attention should be given to the prevention of osteoporosis, as people with O.I. are more vulnerable to this than other people. Recently several types of bisphosphonates have been used as drugs with apparently good results, but it is still too early to draw conclusions.

Bisphophonates

There are two main cell groups in the bone. The osteoblasts, which make bone, and the osteoclasts that break down the bone (bone resorption). Both types of cells are very active, even in the adult, and work together to keep the bone intact and responding to stress. Current knowledge suggests that bisphosphonates slow down the process of bone resorption by shortening the life of the osteoclasts and prolonging the life of the osteoblasts, thus tilting the balance towards the production of bone. The prolonged osteoblast still produces mutant collagen. Thus, the patient is still making "O.I. bone," but resorbing less of it.

Early treatment studies have reported an increase in bone density, an increase in cortical bone width, a decrease in cortical bone porosity, and areduction in bone pain. It is still controversial as to whether this also results in a decrease in the number of fractures. Some animal studies of bisphosphonate treatment have shown that the femurs were less elastic, which would not be desirable in people with O.I. It is also not clear at this time whether the bisphosphonates will have the same effect on the bone of the spine, which is mainly trabecular, and the bone of long bone, which is mainly cortical.

Bisphosphonates are not metabolized in the body. Fifty percent of the medication goes directly to the bone, and 50 percent is excreted in the urine. Current studies are just beginning to measure how long bisphosphonates remain in the body, which will affect how often treatment is administered. Typically, treatment is repeated every 3-4 months for intravenous bisphosphonates, and weekly for oral bisphosphonates.

Pamidronate is given by slow intravenous infusion over 3-4 hours. Treatment takes 1-3 days. In South America and Europe, pamidronate is also available for oral administration. Zoledronate is given by a rapid intravenous injection of approximately 5-15 minutes. Alendronate (Fosamax®) and risedronate (Actonel) are given by mouth. Current directions include a weekly dose, with specific guidelines regarding taking it first thing in the morning on an empty stomach, at least 30 minutes before eating or laying down. The weekly dose appears to provide similar benefits to the daily regimen, but with less gastrointestinal discomfort.

One short-term side effect reported by the Shriners Hospital for Children, in Montreal, Quebec, Canada, after treating more than 200 children with pamidronate is a flu-like syndrome, including high fever, during the first day after the first treatment. Some babies react with decreased blood cells, but return to normal values in 48-72 hours.
A more recently reported intermediate-term side effect, reported by groups in both Canada and Australia, is slow bone healing of osteotomy cuts. The Australian researchers have discontinued use of bisphosphonates for several months before surgeries in which osteotomies will be required.

Persons taking alendronate or risedronate can have gastric discomfort or even severe burning of the esophagus (the tube connecting the mouth with the stomach) if the drug is not taken properly or if the individual has a history of gastric disturbance (such as ulcer or gastric reflux). Additional problems that have been seen in adults and described in medical literature include muscle pain, eye irritation and headaches.

There is some evidence that bisphosphonates may cause birth defects if taken at the time of conception or during pregnancy. There is no evidence that they affect fertility in people who have been taking them.

At this time, there is no evidence that bisphosphonates cause dental problems. They do not improve Dentinogenesis Imperfecta (D.I.) when the treatment is started after three years of age. Whether bisphosphonate treatment for infants will lead to a reduction in the seriousness of D.I. is under investigation. There is some concern that bisphosphonates might decrease the effectiveness of orthodontic treatments, but this is only beginning to be studied

In  recent years, the research use of bisphosphonates as a treatment for children and adults with O.I., is attracting a lot the medical and parental interest. Although these drugs are approved by the U.S. Food and Drug Administration (FDA) for the treatment of adults with Paget’s disease of bone, Osteoporosis, or other conditions, this differs for the treatment of people with O.I.

What is a Bisphosphonate?

Bisphosphonates are analogous to compounds that naturally occur in the human body, but are metabolized in a different manner. There are a number of versions of these compounds, each having slightly different characteristics including mode of administration and potency. Until recently, interest was focused exclusively on pamidronate (Aredia®, given by intravenous infusion) and alendronate (Fosamax®, available in tablet form). New and more potent bisphosphonates (risedronate and zoledronate) are now also being studied in relation to O.I. Zolendronate is in clinical trials at this time.

Rodding Surgery

Rodding surgery involves internal "splinting" of the long bones by means of the insertion of a metal rod. Under general anesthesia, a long bone (e.g., a leg or arm bone) may be cut in one or several places, straightened and "threaded" onto a metal rod. The surgery generally requires an incision long enough to expose the bone where it is deformed. Alternatively, small incisions can be made at the end of the deformed bone, and the rod may be introduced through the skin and moved through the bone under x-ray guidance. When the bone is acutely fractured, rodding can often be done without opening the fracture site.
Rodding is most often used to treat children with moderate to severe osteogenesis imperfecta. In teens and adults, rodding and other surgery is usually reserved for difficult fractures that are not healing well or for alignment problems.

Purpose of Rodding

Rodding is recommended to control repeated fractures of a long bone, and to improve bone deformities that interfere with function. A curved or bowed long bone is not in itself a reason for rodding unless it worsens, repeatedly fractures, becomes painful because of stress fractures, or interferes with function. Rodding does not necessarily prevent fractures; the bone may still fracture, but the rod will provide an internal splint that can help keep the bone in alignment. Fractures may also occur in an area of the bone that grows beyond the end of the rod. Rodding may allow the person to be more active after a fracture, and to avoid prolonged periods of casting and inactivity.  This, in turn, can help break cycles of inactivity leading to fractures. But not everyone with O.I. needs intramedullary rods.

Ambulation (walking) may be improved after rodding surgery, for example, if a child is ready to walk but is unable to progress because of repeated fractures. However, the severity of O.I., and not the technical results of surgery, is primarily responsible for whether ambulation is an appropriate goal. Rodding surgery by itself will not guarantee that the child with a severe form of O.I. will learn to walk.

Timing of Surgery

Babies with severe forms of O.I. have numerous fractures at birth and repeated fractures over the following months. The fractures are usually treated with splints or casts rather than surgery. Surgery may be needed over the following years if repeated fractures of one or more long bones occur. The timing of surgery depends on the size of the bone to be rodded. It has to have a large enough diameter to accept a rod. The bones in O.I. may be thin and flat, so they may appear wider in diameter on x-ray than they actually are. Children with moderately severe forms of O.I. also have numerous fractures at birth, but few new fractures until they start to stand and walk, which is when repeated fractures of the upper thigh bone (femur) may occur; at this time, surgery may be required.

Rodding is usually undertaken as a scheduled elective procedure. However, it can also be undertaken soon after a fracture to avoid a second period in a cast. The fracture may provide an opportunity to perform a rodding without opening the fracture site. http://www.oif.org/

Other treatments include hearing aids and early capping of teeth (due to dentinogenesis imperfecta). Patients require the use of a walker or wheelchair.  Pain may be treated with a variety of medication and exercise like walking, for those who can, and especially swimming promote muscle, bone and joints strength.

According to a theory, people with O.I. have a lack of vitamin D, which is consumed by food and the sun light. Because this vitamin is very vital for the bone health and the immune system, it is suggested to people with O.I., to be very active during the winter period, where they don’t “consume” enough sun light as they do in a summer season, and of course it is also suggested to avoid immobilization. Immobilization might be the most negative factor for this disease.

As for the adults with O.I., they should avoid smoking, excessive alcohol, caffeine consumption and steroid medication. All the above can increase the bone fragility.