Heterotopic ossification
Heterotopic ossification (HO) is the process by which bone tissue forms outside of the skeleton
The skeleton is the body part that forms the supporting structure of an organism. There are two different skeletal types: the exoskeleton, which is the stable outer shell of an organism, and the endoskeleton, which forms the support structure inside the body.In a figurative sense, skeleton can...



During the early stage, an x-ray will not be helpful because there is no calcium in the matrix. (In an acute episode which is not treated, it will be 3– 4 weeks after onset before the x-ray is positive.) Early laboratory tests are also not very helpful; alkaline phosphatase will be elevated at some time, but in patients who have had fractures or spine fusion recently, this is not diagnostic. The values will often be quite high but unless weekly tests are done this peak value may not be detected. Initially the value may be only slightly elevated. The only definitive diagnostic test in the early acute stage is a bone scan
Bone scan
A bone scan or bone scintigraphy is a nuclear scanning test to find certain abnormalities in bone which are triggering the bone's attempts to heal. It is primarily used to help diagnose a number of conditions relating to bones, including: cancer of the bone or cancers that have spread to the bone,...

. When the initial symptoms are an acute inflammatory process with swelling and increased temperature, the differential diagnosis is thrombophlebitis. It may be necessary to do a bone scan and a venogram to differentiate which is present, and it is even possible that both could be present simultaneously. The swelling tends to be more proximal with little or no foot/ankle edema; whereas, in thrombophlebitis the swelling is more uniform throughout the leg.


Heterotopic ossifications will develop in 10% to 80% of cases with varying severity after surgery or trauma to the hip and lower legs. About every third patient who has to face heterotopic ossification following total hip arthoplasty (replacement) or severe fracture of the long bones of the lower extremities will develop pain and dysfunction resulting from extensive heterotopic ossification. Heterotopic ossification jeopardizes functional outcome, impairs rehabilitation and is costly because of secondary surgical procedures. Pain first arises a few days after surgery with calcified structures appearing as blurred contours on x-rays at 3 to 6 weeks postoperatively. Patients with heterotopic ossification after a previous hip arthoplasty are at greatest risk of developing additional heterotopic ossification, with incidence between 50% and 90%.

It has also been shown that patients who sustained traumatic brain injuries undergo heterotopic ossification, which may been a reason for the clinical perception that TBIs cause accelerated fracture healing.


In addition, the bone scan will show heterotopic ossification seven to ten days earlier than an x-ray. The three-phase bone scan is perhaps the earliest method of detecting heterotopic bone formation. However, in some cases, an abnormality may be detected in the early phase which does not necessarily mean it will go on to form heterotopic bone. Another finding, often misinterpreted as early heterotopic bone formation, is an increased (early) uptake around the knees or the ankles in an early spinal cord injured patient. It is not clear exactly what this means because these patients do not develop heterotopic bone formation. It has been hypothesized that this may be related to the autonomic nervous system and its control over circulation.


The effect of Didronel, a bisphosphonate, ehtylhydroxydiphosphonets (EHDP), is to prevent calcium from being deposited in the bony matrix that has already been formed. EHDP (Didronel) does this by inhibiting the conversion of amorphous calcium phosphate to hydroxyapatite crystals which prevents mineralization of the bone matrix. Therefore, it is essential to make the diagnosis as soon as possible (preferably before any calcium shows up on x-ray) and start the Didronel immediately. Didronel will do nothing to remove calcium that has already been deposited. It is a preventative drug, and has no effect on existing ossification. It also has no effect on the underlying process which produces the bony matrix. There are no known side effects that would prohibit usage. Many physicians recommend prophylactic use of Didronel in all acute spinal cord injuries, but because of the cost this may not be practical. Some patients complain of nausea the first week, but this is rarely severe enough to stop treatment and usually subsides in a few days. There is no uniform agreement on how long Didronel should be continued. In most cases, there will be a brief flare-up of the heterotopic ossification following discontinuation of Didronel, and some cases an increase in the amount of calcium deposited. There are no completely reliable tests to indicate that the heterotopic ossification is inactive and treatment can be safely stopped. However, if the treatment is continued long enough this additional calcium deposition will be of minimal clinical significance. The patient needs to be observed closely for signs of recurrence whenever treatment is discontinued.

EHDP (Didronel) has been used for the prevention of postoperative heterotopic ossification, but the outcome has been contradictory. Indomethacin, a prostaglandin synthase inhibitor is an anti-inflammatory drug which also suppresses mesenchymal cells, and is effective in patients at high risk, when administered in different doses immediately after surgery for about 3 to 6 weeks, but non-steroidal anti-inflammatory drugs may trigger gastrointestinal or renal side effects, including bleeding. Recommended dosage for EHDP is 20 mg per kilogram per day for two weeks prior to surgery and 10 mg per kilogram per day postoperatively. However, some patients, particularly those with total hip replacement, must be maintained on 20 mg per kilogram per day postoperatively because the lower dosage will not be enough to prevent recurrence.
Radiation Therapy.

Prophylactic radiation therapy for the prevention of heterotopic ossification has been employed since the 1970s. A variety of doses and techniques have been used. Generally, radiation therapy should be delivered as close as practical to the time of surgery. A dose of 8 Gray in a single fraction within 24–48 hours of surgery has been used successfully. Treatment volumes include the peri-articular region, and can be used for hip, knee, elbow, shoulder, jaw or in patients after spinal cord trauma.

Single dose radiation therapy is well tolerated and is cost effective, without an increase in bleeding, infection or wound healing disturbances.

Other possible treatments.
Certain antiinflammatory agents, such as indomethacin, ibuprofen and aspirin, have shown some effect in preventing reoccurrence of heterotopic ossification after total hip replacement.

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