Heterotopic ossification

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Heterotopic ossification
Heterotopic Ossification Hip1.JPG
Heterotopic ossification around the hip joint in a patient who has undergone hip arthroplasty

Heterotopic ossification (HO) is the process by which bone tissue forms outside of the skeleton in muscles and soft tissue. [1]

Contents

Symptoms

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.[ citation needed ]

Causes

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 arthroplasty (joint replacement) or a severe fracture of the long bones of the lower leg will develop heterotopic ossification, but is uncommonly symptomatic. Between 50% and 90% of patients who developed heterotopic ossification following a previous hip arthroplasty will develop additional heterotopic ossification.[ citation needed ]

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. [2]

There are also rare genetic disorders causing heterotopic ossification such as fibrodysplasia ossificans progressiva (FOP), a condition that causes injured bodily tissues to be replaced by heterotopic bone. Characteristically exhibiting in the big toe at birth, it causes the formation of heterotopic bone throughout the body over the course of the sufferer's life, causing chronic pain and eventually leading to the immobilisation and fusion of most of the skeleton by abnormal growths of bone.[ citation needed ]

Another rare genetic disorder causing heterotopic ossification is progressive osseous heteroplasia (POH), is a condition characterized by cutaneous or subcutaneous ossification.

Diagnosis

Heterotopic ossification of the elbow, after comminuted fracture and arthroplasty. Heterotopic Ossification Elbow1.JPG
Heterotopic ossification of the elbow, after comminuted fracture and arthroplasty.
Heteropic ossification of the elbow, after comminuted fracture and arthroplasty. Heterotopic Ossification Elbow2.JPG
Heteropic ossification of the elbow, after comminuted fracture and arthroplasty.

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.[ citation needed ]

The only definitive diagnostic test in the early acute stage is a bone scan, which will show heterotopic 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. [3]

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. [4]

Treatment

There is no clear form of treatment. Originally, bisphosphonates were expected to be of value after hip surgery but there has been no convincing evidence of benefit, despite having been used prophylactically. [5]

Depending on the growth's location, orientation and severity, surgical removal may be possible.

Surgical removal of a Heterotopic Ossification fusing the right Humerus and Radius following a severe TBI and complete fracture of the Ulna. Heterotopic Ossification removal 2011.jpg
Surgical removal of a Heterotopic Ossification fusing the right Humerus and Radius following a severe TBI and complete fracture of the Ulna.

Radiation Therapy.

Elbow heterotopic ossification radiation therapy field, status post surgery. Heterotopic Ossification Elbow RT.JPG
Elbow heterotopic ossification radiation therapy field, status post surgery.

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. [6]

Other possible treatments.

Certain antiinflammatory agents, such as indomethacin, ibuprofen and aspirin, have shown some effect in preventing recurrence of heterotopic ossification after total hip replacement. [7]

Conservative treatments such as passive range of motion exercises or other mobilization techniques provided by physical therapists or occupational therapists 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 physical and occupational therapy in conjunction with pharmacological treatment. [8] 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. [9]

See also

Related Research Articles

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A head injury is any injury that results in trauma to the skull or brain. The terms traumatic brain injury and head injury are often used interchangeably in the medical literature. Because head injuries cover such a broad scope of injuries, there are many causes—including accidents, falls, physical assault, or traffic accidents—that can cause head injuries.

<span class="mw-page-title-main">Injury in humans</span> Physiological wound caused by an external source

An injury is any physiological damage to living tissue caused by immediate physical stress. Injuries to humans can occur intentionally or unintentionally and may be caused by blunt trauma, penetrating trauma, burning, toxic exposure, asphyxiation, or overexertion. Injuries can occur in any part of the body, and different symptoms are associated with different injuries.

<span class="mw-page-title-main">Spinal cord injury</span> Injury to the main nerve bundle in the back of humans

A spinal cord injury (SCI) is damage to the spinal cord that causes temporary or permanent changes in its function. It is a destructive neurological and pathological state that causes major motor, sensory and autonomic dysfunctions.

<span class="mw-page-title-main">Arachnoiditis</span> Inflammation of the arachnoid mater

Arachnoiditis is an inflammatory condition of the arachnoid mater or 'arachnoid', one of the membranes known as meninges that surround and protect the central nervous system. The outermost layer of the meninges is the dura mater and adheres to inner surface of the skull and vertebrae. The arachnoid is under or "deep" to the dura and is a thin membrane that adheres directly to the surface of the brain and spinal cord.

<span class="mw-page-title-main">Ossification</span> Development process in bones

Ossification in bone remodeling is the process of laying down new bone material by cells named osteoblasts. It is synonymous with bone tissue formation. There are two processes resulting in the formation of normal, healthy bone tissue: Intramembranous ossification is the direct laying down of bone into the primitive connective tissue (mesenchyme), while endochondral ossification involves cartilage as a precursor.

<span class="mw-page-title-main">Fibrodysplasia ossificans progressiva</span> Disease in which fibrous connective tissue turns into bone

Fibrodysplasia ossificans progressiva, also called Münchmeyer disease or formerly myositis ossificans progressiva, is an extremely rare connective tissue disease in which fibrous connective tissue such as muscle, tendons, and ligaments turn into bone tissue (ossification). It is the only known medical condition where one organ system changes into another. It is a severe, disabling disorder with no cure.

<span class="mw-page-title-main">Myositis ossificans</span> Disease in which muscle converts into bone

Myositis ossificans comprises two syndromes characterized by heterotopic ossification (calcification) of muscle. The World Health Organization, 2020, has grouped myositis ossificans together with fibro-osseous pseudotumor of digits as a single specific entity in the category of fibroblastic and myofibroblastic tumors.

<span class="mw-page-title-main">Spondylolysis</span> Defect or fracture in the pars interarticularis of the vertebral arch

Spondylolysis is a defect or stress fracture in the pars interarticularis of the vertebral arch. The vast majority of cases occur in the lower lumbar vertebrae (L5), but spondylolysis may also occur in the cervical vertebrae.

<span class="mw-page-title-main">ACVR1</span> Protein-coding gene

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<span class="mw-page-title-main">Harry Raymond Eastlack</span> American medical patient

Harry Raymond Eastlack, Jr. was the subject of the most recognized case of fibrodysplasia ossificans progressiva (FOP) from the 20th century. His case is also particularly acknowledged, by scientists and researchers, for his contribution to medical advancement. After living with a rare, disabling, and currently incurable genetic disease, Eastlack decided to have his skeleton and medical history donated to the Mütter Museum of the College of Physicians of Philadelphia in support of FOP research. His skeleton is one of the few FOP-presenting, fully articulated ones in existence, and it has proved valuable to the study of the disease.

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Progressive osseous heteroplasia is a cutaneous condition characterized by cutaneous or subcutaneous ossification.

The International Fibrodysplasia Ossificans Progressiva Association (IFOPA) is a US-based 501(c)(3) non-profit organization supporting medical research, education and communication for those afflicted by the rare genetic condition Fibrodysplasia Ossificans Progressiva (FOP). IFOPA's mission is to fund research to find a cure for FOP while supporting, connecting, and advocating for individuals with FOP and their families, and raising awareness worldwide. IFOPA is governed by a volunteer board of directors which may range in number from 9 to 15, at least one of whom must have FOP. The association's location is 1520 Clay St., Suite H2, North Kansas City, MO, 64116, part of the Kansas City, Missouri metropolitan area.

<span class="mw-page-title-main">Palovarotene</span> Chemical compound

Palovarotene, sold under the brand name Sohonos, is a medication used for the treatment of heterotopic ossification and fibrodysplasia ossificans progressiva. It is a highly selective retinoic acid receptor gamma (RARγ) agonist. It is taken by mouth.

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<span class="mw-page-title-main">Frederick Kaplan</span> American medical researcher

Frederick S. Kaplan is an American medical doctor specializing in research of musculoskeletal disorders such as fibrodysplasia ossificans progressiva (FOP).

<span class="mw-page-title-main">Eileen Shore</span> American medical researcher

Eileen M. Shore is an American medical researcher and geneticist specializing in research of muscoskeletal disorders such as fibrodysplasia ossificans progressiva.

References

  1. Brance ML, Cóccaro NM, Casalongue AN, Durán A, Brun LR. Extensive progressive heterotopic ossification post-Covid-19 in a man. Bone. 2022 Feb;155:116287. DOI: 10.1016/j.bone.2021.116287. PMID 34896358.
  2. Morley, John; Marsh, Sarah; Drakoulakis, Emmanuil; Pape, Hans-Christoph; Giannoudis, Peter V. (2005). "Does traumatic brain injury result in accelerated fracture healing?". Injury. 36 (3): 363. doi:10.1016/j.injury.2004.08.028. PMID   15710151.
  3. "Heterotopic Ossification – SCI InfoSheet #12" . Retrieved 2008-06-28.
  4. "Heterotopic Ossification". Archived from the original on 2008-05-05. Retrieved 2008-06-28.
  5. Metabolic Bone and Stone Disease. BEC Nordin, AG NEED, HA Morris: Churchill Livingstone, 1993. p 328-9
  6. Principles and Practice of Radiation Oncology Fifth Edition, Perez and Brady, Lippincott pp. 1955–56
  7. spinal cord injury information network – info sheet 12
  8. 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 Injured38: 1146–1150.
  9. Cipriano, C.A., Pill, S.G., Keenan, M.A. (2009). "Heterotopic ossification following traumatic brain injury and spinal cord injury". J Am Acad Orthop Surg17 (11): 689-697.