Extraskeletal Ossification

Extraskeletal ossification, also known as heterotopic ossification, is a condition where bone tissue grows in places where it normally shouldn’t be found—in soft tissues like muscles, tendons, or other connective tissue outside the skeleton.

Table of contents

• What is extraskeletal ossification?
• Types of extraskeletal ossification
• What causes this condition?
• Who is affected?
• Signs and symptoms
• Where does it occur in the body?
• Related genetic conditions

heterotopic ossification, HO, myositis ossificans

What is extraskeletal ossification?

Extraskeletal ossification occurs when bone tissue develops in soft tissues where bone typically wouldn’t grow. These pieces of bone that form outside the skeleton are called extraskeletal bone fragments. This is different from normal bone growth because it happens in muscles, fat tissue, or connective tissue rather than in the skeleton itself^[1][2].

The bone that forms is real, mature bone—complete with hard tissue, blood vessels, and bone marrow elements. It can be thought of as a tissue repair process that has gone wrong^[6]. For most people, these bone fragments are small and don’t cause many problems. However, larger pieces of bone can restrict movement and cause serious complications^[3].

These abnormal bone fragments can grow surprisingly fast—up to three times as quickly as normal bone. This rapid growth can lead to stiffness and pain, especially when the bone forms near joints^[5].

Types of extraskeletal ossification

There are two main types of extraskeletal ossification: nongenetic and genetic^[3].

Nongenetic extraskeletal ossification can affect people of all ages. Sometimes it occurs with no known cause, but more often it’s a response to some sort of trauma. That trauma can be an injury, or it may be the trauma of surgery. This type tends to be limited and usually develops within 3 to 12 weeks after the triggering event. In some cases, bone fragments can grow in as little as a few days, or they may appear several months later^[3][5].

Genetic extraskeletal ossification is far less common. These types are more likely to cause malformations in the spine, hands, or feet. Genetic forms can be progressive soon after birth and continue throughout life, and they tend to be more severe than nongenetic forms^[2][3].

What causes this condition?

The causes of extraskeletal ossification fall into two main categories: traumatic and neurogenic^[1].

Traumatic causes include bone fractures, joint replacement surgery, muscular trauma, joint dislocation, and severe burns. One of the most common triggers is total hip or joint replacement surgery. Between 28% and 61% of people who have a hip replaced will develop some form of extraskeletal bone growth, often around the metal hardware used during surgery^[5][1].

Neurogenic causes involve injuries to the nervous system, including stroke, spinal cord injury, traumatic brain injury, and brain tumors. The exact cause and mechanism of neurogenic extraskeletal ossification are not fully understood^[1].

Other health conditions that may lead to extraskeletal ossification include polio, tetanus, syringomyelia (a fluid-filled cyst in the spinal cord), multiple sclerosis, carbon monoxide poisoning, and tumors in the spine^[5].

Several risk factors increase the likelihood of developing this condition. These include muscle spasticity, older age, pressure ulcers, the presence of deep vein thrombosis (blood clots in deep veins), having a tracheostomy (a breathing tube in the windpipe), long bone fractures, prior injury to the same area, swelling, immobility, long-term coma, and severity of injury^[1].

Who is affected?

Anyone can develop nongenetic extraskeletal ossification, but you’re most likely to develop it if you have a history of injuries or surgeries. Up to 3 in 4 people who have this condition can point to trauma that led to it^[3].

The condition commonly affects specific groups of people. About 2 to 3 in 10 people with spinal cord injuries develop extraskeletal ossification. Among those with head trauma, 1 or 2 in 10 people with closed-head injury are affected. People who have total hip replacement may develop it, though it’s usually minor when it occurs. More than 9 in 10 people who have amputation after traumatic injury develop the condition^[3][8].

About half of all people with nongenetic extraskeletal ossification are adults in their 20s and 30s. Men are slightly more likely than women to develop it. However, in the total hip replacement population, the condition is twice as common in males versus females, though women older than 65 years are also at risk^[1][3][5].

Genetic types are extremely rare. Experts estimate that fewer than 5,000 people worldwide have the genetic diseases that cause extraskeletal ossification^[3].

Signs and symptoms

The symptoms of extraskeletal ossification vary depending on where the bone grows, how severe the condition is, and how far it has progressed^[3].

In its early stages, the condition often causes pain, swelling, and tenderness in the affected area. The onset of larger masses often resembles any inflammatory reaction—fairly suddenly, a warm and swollen area becomes obvious. If the person has feeling in the area, it will be painful. Sometimes people develop a fever that is usually higher at nighttime than during the day^[3][5].

As the condition progresses, you may notice a bump under the skin. The bump may grow quickly into a large lump that you can’t easily move with your fingers. It may be tender to the touch. The bone that grows is usually jagged or sharp, so it will probably feel sore when touched^[3][5].

In later stages, the lump hardens. If the bone fragment grows near a joint—such as the hip, knee, shoulder, or elbow—it will eventually become painful and difficult to move or bend as it should. The abnormal bone can restrict your range of motion by blocking the natural movement of bones and joints^[3][5].

With genetic forms of extraskeletal ossification, people may have a misshapen big toe, spinal malformations, and structural problems in the fingers. As the genetic condition progresses, most people experience severe symptoms^[3].

Where does it occur in the body?

• Hip
• Elbow
• Shoulder
• Knee
• Thigh
• Pelvis
• Neck or head
• Fingers

Extraskeletal ossification can affect any part of the body, but it’s most likely to occur in areas that are most likely to get injured. The most common sites depend on the underlying cause^[1][3].

After total joint replacement surgery, the condition most commonly occurs around the hips, knees, elbows, and shoulders^[1].

After spinal cord injury, the hips and knees are most commonly affected. About 20 to 29% of patients with spinal cord injury develop extraskeletal ossification^[8].

After traumatic brain injury, the hips, elbows, shoulders, and knees are commonly affected. About 5 to 20% of people with traumatic brain injury develop the condition^[8].

After stroke or severe burns, the elbows are commonly affected. The probability increases when the burned area is more than 20% of body surface area^[8].

When chronic muscular trauma leads to extraskeletal ossification—traditionally known as traumatic myositis ossificans—the most common sites are the quadriceps femoris muscle (front of the thigh) and the brachialis muscle (front of the upper arm)^[1].

Less commonly, extraskeletal ossification may occur in incisions, kidneys, uterus, corpora cavernosum (part of the penis), and the gastrointestinal tract^[1].

Related genetic conditions

Rarely, certain genetic diseases cause extraskeletal ossification^[1][3].

Fibrodysplasia ossificans progressiva (FOP), which used to be widely known as myositis ossificans progressiva, is among the rarest genetic conditions. It affects approximately 1 in 1 million people worldwide. The condition is characterized by muscle tissue and connective tissue such as tendons and ligaments gradually being replaced by bone. This process generally becomes noticeable in early childhood, starting with the neck and shoulders and proceeding down the body and into the limbs. People with FOP are generally born with malformed big toes, which helps distinguish this disorder from other bone and muscle problems^[7].

Progressive osseous heteroplasia (POH) is another rare genetic disease that causes abnormal and extraskeletal bone growth^[3][5].

Other genetic forms include Albright’s hereditary osteodystrophy, pseudohypoparathyroidism, pseudopseudohypoparathyroidism, and primary osteoma cutis^[1][2].