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A perspective on the control of myositis ossificans progressiva

Miosite ossificante progressiva: uma perspectiva no controle da doença
Durval B. Palhares, Lígia M. Leme
J Pediatr (Rio J) 2001;77(5):431-4

Objective: To report four cases of myositis ossificans progressiva, its form of presentation, in addition to new control and treatment options.

Description: The authors describe four cases of myositis ossificans progressiva, presenting its clinical manifestations, evolution, and available forms of control and treatment. The main congenital anomalies associated with myosistis ossificans progressiva are described, namely: hallux valgus, clinodactyly, short thumbs, exostosis, and syndactyly. The evolution and therapeutic responses of clinical improvement to oral ascorbic acid and biphosphonate in patients 1 and 4 are also described; patient 1 had a better response after receiving intravenous biphosphonate, while patients 2 and 3 showed clinical improvement after the administration of oral ascorbic acid.

Comments: Ascorbic acid relieves the pain and improves psychism in patients with myositis ossificans progressiva. Intravenous biphosphonate is an alternative to patients with significant worsening of the disease, especially those with ambulatory restrictions. The orientation towards avoiding recurrent trauma in myositis ossificans progressiva patients is important.


Myositis ossificans progressiva (MOP) or fibrodysplasia ossificans progressiva is a rare disease, with less than 1,000 cases described. It is autosomal dominant and presents variable clinical manifestations but most cases are sporadic(1). The disease was first described by Patin(2). Most MOP patients present peculiar characteristics of frequent congenital anomalies usually associated to the thumb and hallux, affecting patients at birth in 75 to 90% of cases. Other anomalies include adactyly, microdactyly, ankylosis of the interphalangeal joint, clinodactyly, narrow lumbar spinal canal, decreased humeral/epicondylar angle, and pseudoexostosis. Ectopic bone formation involves the tendons, fascia, and aponeurosis affecting skeletal striated muscles.

The physiopathology of the disease is not well-known. Early clinical manifestation is characterized by soft tissue ossification, especially of the neck(3); other areas, such as those of the lower limbs and dorsum can also be affected in early clinical status. The disease is characterized by frequent edemas as a result of inflammatory processes that cause ossification and, subsequently, restriction of motility of the affected region. Trauma is one of the factors for acutization of the disease, though there are reports of patients whose factor for the onset of the disease was not traumatism.

Several types of treatment have been suggested, including oral diphosphonate disodium etidronate (EDHP) with variable effects(4-6); steroids; isotretinoin; and so on. The treatments have shown little efficacy in controlling the disease. Diphosphonate compounds such as EDHP and chlodronate are inhibitors of bone metabolism and resistant to enzymatic hydrolysis. Their main pharmacological action is reduction of normal and abnormal bone reabsorption. The mechanism of action of diphosphonate compounds in prevention of heterotopic ossification is still not understood. Chemical and in vitro studies have shown that these drugs adsorb hydroxypatite crystals decreasing heterotopic bone formation during the active stage of the disease(7).

Palhares(8) observed that high doses of ascorbic acid controlled progression of the disease. We will also report the development of patients who were treated with ascorbic acid.

The prescribed medications are routinely used in cases of MOP and other diseases. The combination of ascorbic acid with diphosphonates was administered successfully to one patient (case 1) considering the particular benefits of either medication. Informed consent was obtained from the parents. The passing on of information to other colleagues allowed for parents of other MOP patients to seek our services for this treatment.

Our objective is to report four cases of MOP patients and suggest new control and treatment alternatives for the disease using ascorbic acid and diphosphonates.

Case report

Case 1

AGP, 16-year-old boy, born to full-term gestation without complications. Patient was asymptomatic up to 30 months of age and presented bilateral hallux valgus deformities and clinodactyly. Onset of symptoms occurred with intractable torticollis combined with intense pain and edema, contractures and ossification of upper limbs and chest. Six and a half years after onset of symptoms, treatment with ascorbic acid was initiated(8) allowing for remission of the status of pain, of edemas, and for stabilization of ossification (Figure 1). Patient remained asymptomatic until July of 2000 under continuous treatment with ascorbic acid at four daily doses of 500 mg and diphosphonate using alendronate sodium, which was later replaced by disodium etidronate (didronel®) at 400 mg per day due to epigastralgia. Subsequently, AGP presented MOP crisis with edema, pain, and left-side femoral ossification with restriction of knee flexion and coxofemoral joint. Investigation indicated that the crisis was caused by repeated trauma to the left thigh: while in school, the patient played with his friends in a game called "Paulistinha", in which two individuals face each other and try to hit each other's thigh with the knee for the effect of corked thigh. Due to the crisis, disodium etidronate dosage was adjusted to 800 mg per day; due to poor response to treatment, we started intravenous disodium chlodronate at 300 mg per day for five days. Patient presented good response following the first five applications for improvement of posture during walking, total remission of pain and gradual remission of edema. As a result, it was reported that patient presented noticeable improvement in the relationship with the family and in school performance. Patient will be administered five 300-mg injections of disodium chlodronate every month for five months for further improvement of walking.

Figure 1 -
Chest x-ray in left oblique view; extensive soft tissue ossification

Case 2

RHNB, 15 years and 6 months old girl, born to full-term gestation without complications. Father had MOP. Patient was reported asymptomatic until five years of age but with clinical stigmata of the disease: adduction contracture of the left-side thumb, clinodactyly, osteophyte of the left-hand thumb, and bilateral hallux valgus deformities. At six years of age, patient complained of pain and restriction of movements in the neck. It was reported that patient woke up during the night feeling pain on the affected areas. X-ray findings indicated supraclavicular ossification. Following the start of treatment with ascorbic acid, the mother of the patient reported improvement in psyche, normal sleep, and interruption of inflammatory processes. We administered a previously reported treatment(11) of continuous ascorbic acid at 500 mg per day, four times daily combined with two-week treatment of disodium chlodronate at 20/mg/kg/day, followed by 10-week disodium chlodronate at 10 mg/kg/day observing a 12-week interval between cycles.

Case 3

RD, 17-year old patient born in Belarus , former Soviet Union. Treatment of patient was oriented by correspondence. Patient was asymptomatic until 14 years of age, when a bone tumor on the left-side of the mandible was diagnosed; patient was submitted to plastic surgery. Subsequently, patient presented progression of the disease with other ossifications to the shoulders and limbs. In addition to physical examination findings, patient presented apathy, disturbed sleep, and pain to areas affected by ossification. RD had prominent facial asymmetry with left-side hypertrophy and hypoplastic ear lobes, short and wide thumbs, femoral head luxation, and right-side femoral exostosis, small and wide feet with short first metatarsus. Three years after manifestation of the disease (September, 1997), patient started continuous treatment with ascorbic acid at 500 mg, four times daily. After approximately eight months of treatment (June, 1998), the mother of the patient reported significant improvement with partial reduction of ossifications, no pain, improvement in sleep and especially in psyche with better school performance. Patient was admitted to a medical school.

Case 4

GLG, six-year-old boy, born to full-term gestation without complications. Early symptomatology appeared in the neonatal period with edema on the neck followed by calcifications, restriction of movement, and difficulty to open the mouth. Patient presented clinodactyly, sindactyly, spinal column alterations, and mild restriction of movement of lower limbs (Figure 2). Diagnosis was established in 1997. Alkalyne phosphatase at 335 IU/l (ref: 90-300 IU/l). Five months prior to this study, we began treatment with ascorbic acid at 500 mg, four times daily and disodium etidronate at 200 mg per day, 12 week treatment cycle. In October of 2000, disodium etidronate dosage was increased to 400 mg per day and we are monitoring the patient for improvement for a minimum of one year of treatment.

Figure 2 -
X-ray in cervical and thoracic view, showing the initial distribution of soft tissue ossification: neck, shoulders (interscapular), and thorax


Early and correct diagnosis of MOP is fundamental for indication of proper management of the disease. Despite the limited pharmacological options, awareness of clinical manifestations of the disease can allow for diagnosis without unnecessary biopsy and surgical procedures, and intramuscle and intravenous injections, which can deteriorate prognosis for the disease. In this sense, unnecessary trauma can originate or exacerbate the inflammatory processes of MOP, which precede ectopic calcifications. Intramuscular vaccines such as diphtheria-pertussis-tetanus, measles, hepatitis B, and so on can be applied subcutaneously(9). Dental treatment should be carried out with caution, avoiding anesthesia, especially of the mandible, in order to prevent temporomandibular joint ankylosis(10). Prophylaxis of dental cavities is essential to avoid need for more aggressive procedures.

Following trauma, patients can present edema, mild local heat, increase in VHS and serum alkaline phosphatase (case 4). MOP can be identified in X-rays approximately two to four weeks after the onset of the process. Calcification start on the extremities and progresses towards the center; this characteristic differentiates MOP from osteosarcoma. Computed tomography can be used to help delineate, in MOP, the central radiolucency encompassed by peripheral density(13).

As to the treatments that have been reported, the use of diphosphonates is effective on established ossifications(11).

The administration of ascorbic acid in MOP apparently acts on stabilizing the disease(8). According to reports of the relatives of patients in this study, controlling painful symptomatology produces effects on improving comfort, quality of life, relationships, sleep, and school performance.

Decrease in ossifications while in the transition stage or, in other words, during the inflammatory process (as in cases 1 and 3) has been attributed to the action of ascorbic acid on modulating synthesis of procolagen type III(8).

In cases of severe MOP with restriction of movements and gastric intolerance (case 1), the use of intravenous diphosphonate can be indicated and present good results, as reported by Alpigiani et al.(12) in three patients who recovered motor ability being administered 300 mg per day of dichloromethylenbiphosphonic acid ten times per month during five months.

Repetitive trauma is the most important exacerbating factor of the disease, even when high doses of ascorbic acid are administered as in patient 1. Even considering the limitations, the most appropriate physical activity for MOP patients is swimming; patients can adapt to the motility they still have and exercise without lesions related to direct impact or trauma.

Differential diagnosis of MOP is obtained with idiopathic calcinosis, dermatomyositis, tumoral idiopathic calcinosis, and calcium metabolism diseases. Presence of ossification of the soft tissue, axial skeleton, and of anomalies of the extremities are a more clear indication for diagnosis of MOP.

Young MOP patients should be monitored and oriented in order to avoid trauma. It is our opinion that combined oral or intravenous ascorbic acid and diphosphonate can be an alternative for long-term control of, and decrease in, ectopic calcifications allowing for significant improvement of the quality of life. In patients with severe clinical status and restriction of movements, the use of intravenous diphosphonate was the alternative that allowed for faster improvement of the clinical status.

Title of the article: "A perspective on the control of myositis ossificans progressiva"
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