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Heterotopic ossification of varying severity can be caused by surgery or trauma to the hips and legs. About every third patient who has total hip arthoplasty (joint replacement) or a severe fracture of the long bones of the lower leg will develop heterotopic ossification. Between 50% and 90% of patients who developed heterotopic ossification following a previous hip arthoplasty will develop additional heterotopic ossification.
Heterotopic ossification often develops in patients with traumatic brain or spinal cord injuries, other severe neurologic disorders or severe burns, most commonly around the hips. The mechanism is unknown. This may account for the clinical impression that traumatic brain injuries cause accelerated fracture healing.
There is another variant called myositis ossificans progressiva, a rare, genetic disorder, in which there are recurrent episodes of inflammation around the big toe, which eventually lead to ossification in the area and deformity of the toe.
In traumatic heterotopic ossification (traumatic myositis ossificans), the patient may complain of a warm, tender, firm swelling in a muscle and decreased range of motion in the joint served by the muscle involved. There is often a history of a blow or other trauma to the area a few weeks to a few months earlier. Patients with traumatic neurological injuries, severe neurologic disorders or severe burns who develop heterotopic ossification experience limitation of motion in the areas affected.
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 not very helpful. Alkaline phosphatase will be elevated at some point, but initially may be only slightly elevated, rising later to a high value for a short time. Unless weekly tests are done, this peak value may not be detected. It is not useful in patients who have had fractures or spine fusion recently, as they will cause elevations.
The only definitive diagnostic test in the early acute stage is a bone scan, which will show hetertopic ossification 7 - 10 days earlier than an x-ray. The three-phase bone scan may be the most sensitive method of detecting early heterotopic bone formation. However, an abnormality detected in the early phase may not progress to the formation of heterotopic bone. Another finding, often misinterpreted as early heterotopic bone formation, is an increased (early) uptake around the knees or the ankles in a patient with a very recent spinal cord injury. 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.
When the initial presentation is swelling and increased temperature in a leg, the differential diagnosis includes thrombophlebitis. It may be necessary to do both a bone scan and a venogram to differentiate between heterotopic ossification and thrombophlebitis, and it is even possible that both could be present simultaneously. In heterotopic ossification, the swelling tends to be more proximal and localized, with little or no foot/ankle edema, whereas in thrombophlebitis the swelling is usually more uniform throughout the leg.
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. 
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 7-8 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. 
Conservative treatments such as passive range of motion exercises or other mobilization techniques provided by physiotherapists may also assist in preventing HO. A review article looked at 114 adult patients retrospectively and suggested that the lower incidence of HO in patients with a very severe TBI may have been due to early intensive physiotherapy in conjunction with pharmacological treatment.  Another review article also recommended physiotherapy as an adjunct to pharmacological and medical treatments because passive range of motion exercises may maintain range at the joint and prevent secondary soft tissue contractures, which are often associated with joint immobility. 
possible Treatments requiring research regulating calcitriol, the biologically active form of vitamin D. Calcitriol circulates as a hormone in the blood, regulating the concentration of calcium and phosphate in the bloodstream and promoting the healthy growth and remodeling of bone.
- "Does traumatic brain injury result in accelerated fracture healing?".
- "Heterotopic Ossification - SCI InfoSheet #12". Retrieved 2008-06-28.
- "Heterotopic Ossification". Archived from the original on 2008-05-05. Retrieved 2008-06-28. - Broken
- "Heterotopic Ossification". Archived from the original on 2008-05-05. Retrieved 2008-06-28.
- Template:Spinal cord injury information network - info sheet 12
- Template:Principles and Practice of Radiation Oncology Fifth Edition, Perez and Brady, Lippincott pp. 1955-56
- Simonsen, L.L., Sonne-Holm, S., Krasheninnikoff, M., Engberg, A.W. (2007). "Symptomatic heterotopic ossification after very severe traumatic brain injury in 114 patients: Incidence and risk factors". Injury, Int. J. Care Injured 38: 1146-1150.
- Cipriano, C.A., Pill, S.G., Keenan, M.A. (2009). "Heterotopic ossification following traumatic brain injury and spinal cord injury". J Am Acad Orthop Surg 17 (11): 689-697.