eMedicine Specialties > Pediatrics: General Medicine > Rheumatology

Fibrodysplasia Ossificans Progressiva (Myositis Ossificans): Treatment & Medication

Author: Robert J Pignolo, MD, PhD, Assistant Professor of Medicine, Director, Ralston-Penn Clinic for Osteoporosis and Related Bone Disorders, Department of Medicine, Division of Geriatric Medicine, Associate Director, Structure-Function Biomechanical Core, Penn Center for Musculoskeletal Disorders, University of Pennsylvania School of Medicine
Coauthor(s): Frederick S Kaplan, MD, Isaac and Rose Nassau Professor of Orthopedic Molecular Medicine, Chief, Division of Orthopedic Molecular Medicine, Director, Center for Research in FOP and Related Disorders, The University of Pennsylvania School of Medicine; Consulting Surgeon, Department of Orthopedic Surgery, Hospital of The University of Pennsylvania; Eileen M Shore, PhD, Research Associate Professor, Departments of Orthopaedic Surgery and Genetics, University of Pennsylvania School of Medicine
Contributor Information and Disclosures

Updated: Jul 30, 2009

Treatment

Medical Care

Flare-ups of fibrodysplasia ossificans progressiva (FOP) are sporadic and unpredictable, and the rate of individual disease progression widely varies. Several large studies on the natural history of fibrodysplasia ossificans progressiva have confirmed that predicting the occurrence, duration, or severity of an fibrodysplasia ossificans progressiva flare-up is impossible, although characteristic anatomic patterning has been described.

A brief description of agents to be considered during a fibrodysplasia ossificans progressiva exacerbation is below. For a complete description, including dosing and potential major side effects, refer to the current treatment guidelines at International Fibrodysplasia Ossificans Progressiva.

Flare-ups
Widespread favorable anecdotal reports from the fibrodysplasia ossificans progressiva community suggest that a brief 4-day course of high-dose corticosteroids, started within the first 24 hours of a flare-up, may help reduce the intense inflammation and tissue edema seen in the early stages of the disease. The use of corticosteroids should be restricted to the extremely early symptomatic treatment of flare-ups that affect major joints, the jaw, or the submandibular area. Corticosteroids should not generally be used for the symptomatic treatment of flare-ups that involve the back, neck, or trunk due to the long duration and recurring nature of these flare-ups and the difficulty in assessing the true onset of such flare-ups.  

The dose of corticosteroids depends on body weight. A typical dose of prednisone is 2 mg/kg/d, administered as a single daily dose for no more than 4 days. The potentially dangerous nature of flare-ups in the submandibular region may dictate a slightly longer use of corticosteroids with an appropriate taper for the duration of the flare-up or until the acute swelling subsides.
 
When prednisone is discontinued, a nonsteroidal anti-inflammatory drug (NSAID) or cox-2 inhibitor (in conjunction with a leukotriene inhibitor) may be used symptomatically for the duration of the flare-up.
 
The use of mast cell inhibitors and aminobisphosphonates are less well-defined and should be used at the physician’s discretion. 
  
Pain management

Many fibrodysplasia ossificans progressiva flare-ups, especially those around the hips and knees, are extremely painful and may require a brief course of well-monitored narcotic analgesia in addition to the use of NSAIDs, cox-2 inhibitors, and oral or intravenous glucocorticoids. Other types of transient pain syndromes may be caused by neuropathies resulting from acute flare-ups, transient bursitis, inflammation of osteochondromas, arthritis, and muscle fatigue.  
 
Muscle relaxants

Areas of relatively healthy skeletal muscle bordering the acute fibrodysplasia ossificans progressiva lesion are subject to metabolic changes that lead to muscle spasm and fiber shortening. The judicious short-term use of muscle relaxants such as cyclobenzaprine (Flexeril), metaxalone (Skelaxin), or Lioresal (Baclofen) may help to decrease muscle spasm and maintain more functional activity.

Surgical Care

Attempts to surgically remove heterotopic bone risks provoking explosive and painful new bone growth. Biopsies of fibrodysplasia ossificans progressiva lesions are never indicated and may cause additional heterotopic ossification.

Activity

Falls suffered by patients with fibrodysplasia ossificans progressiva can lead to severe injuries and flare-ups. Patients with fibrodysplasia ossificans progressiva have a self-perpetuating fall cycle. Minor soft tissue trauma often leads to severe exacerbations of fibrodysplasia ossificans progressiva, which result in heterotopic ossification and joint ankylosis. Mobility restriction from joint ankylosis severely impairs balancing mechanisms and causes instability, resulting in more falls. Compared with people who do not have fibrodysplasia ossificans progressiva, falls in those with fibrodysplasia ossificans progressiva are more likely to result in severe head injuries, loss of consciousness, concussions, and neck and back injuries due to the inability to use the upper limbs to absorb the impact of a fall and to anatomic abnormalities of the cervical spine in individuals with fibrodysplasia ossificans progressiva.

For children, redirection of activity to less physically interactive play may be helpful. Complete avoidance of high-risk circumstances may reduce falls but may also compromise a patient’s functional level and independence and may be unacceptable to many.

Medication

Anti-inflammatory Agent

Corticosteroids are indicated as first-line treatment at beginning of flare-ups.


Prednisone

Decreases inflammation by suppressing migration of polymorphonuclear leukocytes and reversing increased capillary permeability.

Adult

Pediatric

2 mg/kg PO qd for no more than 4 days, then switch to NSAID for pain relief

Coadministration with estrogens may decrease clearance; concurrent use with digoxin may cause digitalis toxicity secondary to hypokalemia; phenobarbital, phenytoin, and rifampin may increase metabolism of glucocorticoids (consider increasing maintenance dose); monitor for hypokalemia with coadministration of diuretics

Documented hypersensitivity; viral infection, peptic ulcer disease, hepatic dysfunction, connective tissue infections, and fungal or tubercular skin infections; GI bleeding or ulceration

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Abrupt discontinuation of glucocorticoids may cause adrenal crisis; hyperglycemia, edema, osteonecrosis, myopathy, peptic ulcer disease, hypokalemia, osteoporosis, euphoria, psychosis, myasthenia gravis, growth suppression, and infections may occur with glucocorticoid use

More on Fibrodysplasia Ossificans Progressiva (Myositis Ossificans)

Overview: Fibrodysplasia Ossificans Progressiva (Myositis Ossificans)
Differential Diagnoses & Workup: Fibrodysplasia Ossificans Progressiva (Myositis Ossificans)
Treatment & Medication: Fibrodysplasia Ossificans Progressiva (Myositis Ossificans)
Follow-up: Fibrodysplasia Ossificans Progressiva (Myositis Ossificans)
Multimedia: Fibrodysplasia Ossificans Progressiva (Myositis Ossificans)
References
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References

  1. Cohen RB, Hahn GV, Tabas JA, et al. The natural history of heterotopic ossification in patients who have fibrodysplasia ossificans progressiva. A study of forty-four patients. J Bone Joint Surg Am. Feb 1993;75(2):215-9. [Medline].

  2. Kaplan FS, Glaser DL, Shore EM, et al. The phenotype of fibrodysplasia ossificans progressiva. Clin Rev Bone Miner Metab. 2005;3:183-188.

  3. Kaplan FS, Groppe J, Pignolo RJ, Shore EM. Morphogen receptor genes and metamorphogenes: skeleton keys to metamorphosis. Ann N Y Acad Sci. Nov 2007;1116:113-33. [Medline].

  4. Shore EM, Xu M, Feldman GJ, et al. A recurrent mutation in the BMP type I receptor ACVR1 causes inherited and sporadic fibrodysplasia ossificans progressiva. Nat Genet. May 2006;38(5):525-7. [Medline].

  5. Kaplan FS, Xu M, Seemann P, Connor JM, Glaser DL, Carroll L, et al. Classic and atypical fibrodysplasia ossificans progressiva (FOP) phenotypes are caused by mutations in the bone morphogenetic protein (BMP) type I receptor ACVR1. Hum Mutat. Mar 2009;30(3):379-90. [Medline].

  6. Kaplan FS, Le Merrer M, Glaser DL, et al. Fibrodysplasia ossificans progressiva. Best Pract Res Clin Rheumatol. Mar 2008;22(1):191-205. [Medline].

  7. Rocke DM, Zasloff M, Peeper J, Cohen RB, Kaplan FS. Age- and joint-specific risk of initial heterotopic ossification in patients who have fibrodysplasia ossificans progressiva. Clin Orthop Relat Res. Apr 1994;243-8. [Medline].

  8. Schaffer AA, Kaplan FS, Tracy MR, et al. Developmental anomalies of the cervical spine in patients with fibrodysplasia ossificans progressiva are distinctly different from those in patients with Klippel-Feil syndrome: clues from the BMP signaling pathway. Spine (Phila Pa 1976). Jun 15 2005;30(12):1379-85. [Medline].

  9. Deirmengian GK, Hebela NM, O'Connell M, Glaser DL, Shore EM, Kaplan FS. Proximal tibial osteochondromas in patients with fibrodysplasia ossificans progressiva. J Bone Joint Surg Am. Feb 2008;90(2):366-74. [Medline].

  10. Adegbite NS, Xu M, Kaplan FS, Shore EM, Pignolo RJ. Diagnostic and mutational spectrum of progressive osseous heteroplasia (POH) and other forms of GNAS-based heterotopic ossification. Am J Med Genet A. Jul 15 2008;146A(14):1788-96. [Medline].

  11. Pignolo RJ, Foley, KL. Non-hereditary heterotopic ossification. Implications for injury, arthropathy, and aging. Clin Rev Bone Miner Metabol. 2005;3:261-266.

  12. [Guideline] Morrison WB, Dalinka MK, Daffner RH, et al. Expert Panel on Musculoskeletal Imaging. Soft tissue masses. [online publication]. Reston (VA): American College of Radiology (ACR);. 2005;6 p.

  13. Kitterman JA, Kantanie S, Rocke DM, Kaplan FS. Iatrogenic harm caused by diagnostic errors in fibrodysplasia ossificans progressiva. Pediatrics. Nov 2005;116(5):e654-61. [Medline].

  14. Kaplan FS, Strear CM, Zasloff MA. Radiographic and scintigraphic features of modeling and remodeling in the heterotopic skeleton of patients who have fibrodysplasia ossificans progressiva. Clin Orthop Relat Res. Jul 1994;238-47. [Medline].

  15. Kaplan FS, Xu M, Glaser DL, et al. Early diagnosis of fibrodysplasia ossificans progressiva. Pediatrics. May 2008;121(5):e1295-300. [Medline].

  16. Pignolo RJ, Suda RK, Kaplan FS. The fibrodysplasia ossificans progressiva lesion. Clin Rev Bone Miner Metabol. 2005;3:195-200.

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Further Reading

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Keywords

fibrodysplasia ossificans progressiva, FOP, myositis ossificans circumscripta, soft tissue ossification, heterotopic ossification, HO, progressive osseous heteroplasia, nonhereditary heterotopic ossification, NHHO, soft connective tissue swelling, trauma, blunt muscle trauma, malformation of the great toes, toe malformation, neck stiffness, pneumonia, heart failure, diagnosis, treatment

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Contributor Information and Disclosures

Author

Robert J Pignolo, MD, PhD, Assistant Professor of Medicine, Director, Ralston-Penn Clinic for Osteoporosis and Related Bone Disorders, Department of Medicine, Division of Geriatric Medicine, Associate Director, Structure-Function Biomechanical Core, Penn Center for Musculoskeletal Disorders, University of Pennsylvania School of Medicine
Robert J Pignolo, MD, PhD is a member of the following medical societies: American College of Physicians, American Geriatrics Society, American Society for Bone and Mineral Research, Gerontological Society of America, and National Osteoporosis Foundation
Disclosure: Nothing to disclose.

Coauthor(s)

Frederick S Kaplan, MD, Isaac and Rose Nassau Professor of Orthopedic Molecular Medicine, Chief, Division of Orthopedic Molecular Medicine, Director, Center for Research in FOP and Related Disorders, The University of Pennsylvania School of Medicine; Consulting Surgeon, Department of Orthopedic Surgery, Hospital of The University of Pennsylvania
Frederick S Kaplan, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American Society for Bone and Mineral Research, American Society for Microbiology, Johns Hopkins Medical and Surgical Association, and Orthopaedic Research Society
Disclosure: Nothing to disclose.

Eileen M Shore, PhD, Research Associate Professor, Departments of Orthopaedic Surgery and Genetics, University of Pennsylvania School of Medicine
Eileen M Shore, PhD is a member of the following medical societies: American Society for Bone and Mineral Research and Royal Society of Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from financial planner; Avanir Pharma Stock Investment from financial planner ; WebMD Salary and stock Employment and investment from financial planner

Managing Editor

David D Sherry, MD, Director, Clinical Rheumatology, Attending Physician, Pain Management, The Children's Hospital of Philadelphia; Professor of Pediatrics, University of Pennsylvania
David D Sherry, MD is a member of the following medical societies: American College of Rheumatology and American Pain Society
Disclosure: Nothing to disclose.

CME Editor

Daniel Rauch, MD, FAAP, Director, Pediatric Hospitalist Program, Associate Professor, Department of Pediatrics, New York University School of Medicine
Daniel Rauch, MD, FAAP is a member of the following medical societies: Ambulatory Pediatric Association, American Academy of Pediatrics, and Society of Hospital Medicine
Disclosure: Baxter Honoraria Consulting

Chief Editor

Lawrence K Jung, MD, Chief, Division of Pediatric Rheumatology, Children's National Medical Center
Lawrence K Jung, MD is a member of the following medical societies: American Association for the Advancement of Science, American Association of Immunologists, American College of Rheumatology, Clinical Immunology Society, and New York Academy of Sciences
Disclosure: Nothing to disclose.

 
 
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