Medication Summary

The goals of pharmacotherapy are to reduce morbidity and prevent complications.

Class Summary

Nonsteroidal anti-inflammatory drugs (NSAIDs) have analgesic, anti-inflammatory, and antipyretic activities. Their mechanism of action is not known, but they may inhibit cyclooxygenase activity and prostaglandin synthesis. Other mechanisms may exist as well, such as inhibition of leukotriene synthesis, lysosomal enzyme release, lipoxygenase activity, neutrophil aggregation, and various cell-membrane functions.^{[18, 21, 22, 23, 24, 25, 26, 27, 28]}

Indomethacin (Indocin, Indochron E-R)

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An indoleacetic acid derivative and NSAID, indomethacin is related structurally and pharmacologically to sulindac. Theoretically, indomethacin decreases inflammation associated with heterotopic ossification (HO) and quiets the spastic muscles driven by pain. The effect is thought to be due to inhibition of the synthesis of prostaglandin. Indomethacin is known to be highly potent in preventing HO after total hip replacement, due to one of the most potent inhibitors of the cyclooxygenase enzyme, which catalyzes the formation of prostaglandin precursors (endoperoxides) from arachidonic acid.

Class Summary

Analogs of pyrophosphate, these act by binding to hydroxyapatite in bone-matrix, thereby inhibiting the dissolution of crystals. Bisphosphonate derivatives prevent osteoclast attachment to the bone matrix and inhibit osteoclast recruitment and viability.^[15]

Etidronate disodium (Didronel)

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The role of etidronate disodium (EHDP) in preventing heterotopic ossification (HO) has been studied extensively. The literature to date does not adequately support the efficacy of its use in patients with brain injuries. EHDP is a bisphosphonate that reportedly retards formation, growth, and dissolution of hydroxyapatite crystals; therefore, it is thought to limit ectopic soft-tissue calcification by preventing conversion of calcium phosphate compounds in hydroxyapatite crystals. EHDP often is used to retard HO once it is discovered; the drug is thought to be more effective if given prophylactically or in the earlier stages of formation. EHDP does not dissolve established calcification.

An active HO process is often painful, and treatment with agents such as EHDP is often effective in reducing the inflammatory aspects of the HO process and in quieting the spastic muscles driven by pain. Therefore, EHDP is the mainstay of drug treatment, reducing the incidence and severity of ectopic bone formation with minimal side effects. Effective prophylactic treatment should be initiated as soon as possible. Optimal drug dose and length of treatment have not been established adequately in TBI.

Follow-up

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Media Gallery

This radiograph clearly demonstrates fairly extensive heterotopic ossification at the bilateral hip regions. The extensive bone formation shown here makes it easy for the viewer to understand why a patient with HO could present with complaints such as pain, swelling, palpable mass, and decreased range of motion.

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