Skeletal muscle injuries are the most common sports-related injuries and present a challenge in primary care and sports medicine. Most types of muscle injuries would follow three stages: the acute inflammatory and degenerative phase, the repair phase and the remodeling phase. Present conservative treatment includes RICE (rest, ice, compression, elevation), nonsteroidal anti-inflammatory drugs (NSAIDs) and physical therapy. However, if use improper, NSAIDs may suppress an essential inflammatory phase in the healing of injured skeletal muscle. Furthermore, it remains controversial whether or not they have adverse effects on the healing process or on the tensile strength. However, several growth factors might promote the regeneration of injured skeletal muscle, many novel treatments have involved on enhancing complete functional recovery. Exogenous growth factors have been shown to regulate satellite cell proliferation, differentiation and fusion in myotubes in vivo and in vitro, TGF-β1 antagonists behave as inhibitors of TGF-β1. They prevent collagen deposition and block formation of muscle fibrosis, so that a complete functional recovery can be achieved.

The etiology of heterotopic ossification (HO) is still obscure, it is difficult to devise an effective preventive or therapeutic approach. The options for the prevention of HO are still limited. The prophylactic effect of nonsteroidal anti-inflammatory drugs (NSAIDs) is insufficient. Moreover, NSAIDs increase the risk of nonunion and loosening in patients with multiple joint injuries. The present experimental study was designed to compare methylprednisolone with free radical scavengers for the prevention of HO. The model of Michelsson et al. was used to induce HO in the hind legs of 30 female New Zealand albino rabbits, weighing approx. 4 kg. The animals were randomized into three groups of 10 animals each, and received daily either placebo, a free radical scavenger cocktail [allopurinol and Nacetylcysteine (A/A)], or methylprednisolone in a randomized, double-blind fashion. Every four days, X-rays were obtained to measure the thickness and the length of new bone formation at the thigh. A statistically significant difference in thickness and length of newly formed bone was found between the three groups. In the placebo group HO increased from day 16 toward a medium length of 6 mm and a median thickness of 1.5 mm. In the A/A group, no signs of HO were found. In the methylprednisolone group, only one animal presented minor HO from day 32. Both free radical scavengers and methylprednisolone were found to inhibit HO, and may be considered effective measures for the prevention of heterotopic bone formation. However, it could not be demonstrated which of the two had the strongest inhibitory effect. Keywords: methylprednisolone; free radical scavengers; heterotopic ossification; prevention Strictly defined, heterotopic ossification (HO) is the formation of lamellar bone inside soft-tissue structures where bone normally does not exist. Myositis ossificans rather refers to a condition in which ectopic bone is formed within muscle or connective tissue following chemical or physical trauma.1-3 However, this term has fallen into disfavor because primary muscle inflammation is not necessarily a precursor, and ossification does not always occur in muscle tissue. For these reasons, the term heterotopic ossification has largely replaced myositis ossificans in the literature. 4 HO frequently complicates central nervous system disorders such as brain and spinal cord injuries, brain tumors, and encephalitis.5 HO is of common occurrence in orthopedic patients as a consequence of hip, knee, shoulder, and elbow arthroplasty. The reported incidence of HO after hip arthroplasty is as high as 53%. 6,7 Patients with a history of osteoarthritis, ankylosing spondylitis, diffuse idiopathic skeletal hyperostosis, and Paget's disease are at high risk for HO. The condition is also frequently present in burn patients, and has recently been reported to occur after long-term mechanical ventilation following trauma. 8Because nonsteroidal anti-inflammatory drugs (NSAIDs) have important systemic side effects and may increase the risk of ps...

The pathogenesis of heterotopic ossification is still unclear and the preventive therapies are usually insufficient. The present study was designed to investigate the possible preventive effect of free radical scavengers on the development of experimentally induced heterotopic ossification in a rabbit model and to compare free radical scavengers with indomethacin to determine whether they act synergistically. A standard immobilization-manipulation model was used to induce heterotopical ossification in the hind legs of 40 1-year-old female New Zealand albino rabbits. The animals were divided into four groups and received daily either placebo, a free radical scavenger cocktail [allopurinol and N-acetylcysteine (A/A)], indomethacin or the combination of A/A and indomethacin in a randomized double-blind fashion. Every 4 days an X-ray was taken and the thickness and length of new bone formation was measured at the thigh. A marked statistically significant difference was found between the four groups. In the groups that received A/A, either alone or combined with indomethacin, an inhibition of bone growth, both in thickness and in length was demonstrated. In this experimental model free radical scavengers had a superior inhibitory effect on heterotopic ossification than indomethacin. Free radicals could play an important role in the pathogenesis of heterotopic ossification. ß

FIGURE 1. (A and B) CT scan revealed an irregularly delineated sclerotic and translucent area at the distal tibial epiphysis. (C) Radiograph showing a sclerotic zone in the distal tibial epiphysis.