Awareness of Heterotopic Ossification in Total Joint Arthroplasty: A Primer


Michelle J Lespasio, DNP, JD, ANP; AJ Guarino, PhD

Perm J 2020;24:19.211 [Full Citation]
E-pub: 02/07/2020


Heterotopic ossification (HO) is the presence of normal bone in soft tissue where bone should not exist. After direct musculoskeletal trauma of the surrounding soft tissue, HO is hypothesized to develop from a dysfunction of normal lamellar bone formation and remodeling that appears in nonskeletal areas of the body. Acquired HO related to total joint arthroplasty (TJA) of the hip and knee forms outside the joint capsule and can be a challenging condition when it impairs the essential healing process after elective surgery. Although HO is rare after elective TJA and thus clinically immaterial, when clinically relevant HO develops, patients may experience the following: 1) limited ambulation, 2) restricted range of motion, and 3) severe pain and discomfort that may lead to loss of function. Ultimately, patients with clinically relevant HO after elective TJA may require additional treatment, including medication, radiation therapy, manipulation under anesthesia, surgical excision of the HO, and possibly revision TJA. Awareness of HO and an understanding of the associated risk factors along with the various management options will enable health care practitioners and their patients to optimize their surgical outcomes.


The goal of this article is to describe heterotopic ossification (HO) after total joint arthroplasty (TJA), its risk factors, and management, to increase awareness of this condition so that physicians can optimize their surgical outcomes. See the Sidebar: Advance Organizer Quiz to Retrieve, Use and Organize the Materials Presented in this Article.

HO is the presence of bone in soft tissue where bone does not normally exist. This condition develops from dysfunction of normal lamellar bone formation and remodeling (inhibition), which presents in areas of soft tissue (nonskeletal) in the body.1 All bone, including HO, has its own vascular supply of blood vessels. Because of the associated vascularity, HO bone can grow at 3 times the normal rate, causing destruction and pain in the joints.2 Mature HO shows cancellous bone growth (eg, trabecular or spongy, light, porous bone) enclosing numerous large spaces, as well as mature lamellar bone, blood vessels, and bone marrow with minimal production of normal blood cells.3


The 4 types of HO are presented in Table 1. Of the 4 types described, acquired HO is most frequently observed and is the focus of this article. The 3 less common forms are 1) neurogenic HO, which can develop in patients with paraplegia after spinal cord injury; 2) genetic HO, such as myositis ossificans progressiva, a rare hereditary form of HO, which generally has a poor prognosis (most patients with this condition die early owing to related complications of restrictive lung disease and pneumonia); and 3) idiopathic HO, the causes of which remain unknown and ambiguous.

In direct musculoskeletal trauma, acquired HO may develop in patients with injuries related to fractures (eg, acetabular, dislocations), blast injuries, and burns.4 Similarly, soft-tissue trauma related to elective TJA might also lead to the acquired type of HO.5 HO after TJA of the hip and knee can be challenging because extra-articular heterotopic ossifications formed outside the joint capsule may impair the essential healing process necessary for a successful surgical outcome. Local trauma to soft tissue produced by TJA is hypothesized to disrupt the normal balance of bone formation and inhibition, possibly by inducing inflammatory dynamics needed to stimulate the production of HO: 1) osteogenic precursor cells, 2) inducing agents, and 3) a permissive soft-tissue environment.6 When normal lamellar bone develops pathologically in muscle, tendons, and other areas of soft tissue, this progression of HO may limit patients’ ambulation, reduce their range of motion, and, because of severe pain and discomfort, cause loss of function. Patients in whom clinically relevant HO develops may be subjected to additional treatment, including additional medication, radiation therapy, manipulation of the affected knee joint under anesthesia (MUA), surgical excision of the HO, and possibly revision TJA.3



The incidence of acquired HO in TJA varies greatly from one patient population to another. The incidence of HO after total hip arthroplasty (THA) varies widely from 0.6% to 90% (when evaluated in high-risk populations),7 although the consensus is that the incidence of HO is approximately 53% in THA (of which one-third of cases are clinically meaningful).8 Although HO is thought to be underreported, the overall incidence of HO after total knee arthroplasty (TKA) is about 15%.9

Risk factors for postoperative HO include excess weight, age older than 65 years, the presence of excessive osteophytes noted preoperatively, previous HO, and posttraumatic arthritis.10,11 Often, however, the HO that forms after TJA is clinically immaterial, causing it to be ignored and go unreported.12


The signs and symptoms of HO after elective TJA usually appear within 3 to 8 weeks postoperatively,13,14 and most often HO presents as an incidental finding on plain radiographs. In patients with HO after THA, HO typically forms in the connective tissue between the muscle planes around the femoral neck and adjacent to the greater trochanter.8 After TKA, HO can form anterior to the distal femoral shaft in the quadriceps expansion.15 The most common complaint related to the development of HO is stiffness, and when a large amount is present, the stiffness may progress to ankylosis (abnormal stiffening causing immobility) in the affected joint.12 Many patients who demonstrate early or low-grade HO on plain films are asymptomatic, and pain is rarely a problem. On physical examination, reported pain, stiffness, loss of joint mobility, decreased ambulation, and resulting loss of function are the principal complications of HO.10 Fever, swelling, erythema, and occasional joint tenderness seen in early HO can be difficult to distinguish from other conditions (see next section on assessment).14


Although clinically relevant HO occurs infrequently after TJA, appropriate laboratory and imaging data (see Sidebar: Assessment of Heterotopic Ossification) should be obtained to confirm the diagnosis and distinguish HO from other diagnostic possibilities. The differential diagnosis of HO includes cellulitis, osteomyelitis, thrombophlebitis, deep vein thrombosis, septic arthritis, tumor, hematoma, and fracture.16

Conventional radiography followed by 3-phase bone scanning can be considered to confirm the diagnosis of HO, establish the extent and metabolic activity of HO, determine if medical treatment is warranted, and choose the appropriate time for surgical resection if needed.17 Serial quantitative bone scans to assess for presence and/or progression of acquired HO can serve as an aid to time the surgical intervention.14 Although rarely performed in the clinical setting, serum alkaline phosphatase levels can be used to detect early HO.14 Alkaline phosphatase levels generally become abnormal and increase 2 weeks after most injuries and are not specific to HO. In the typical case of HO, however, the alkaline phosphatase levels reach approximately 3.5 times their normal levels as early as 10 weeks after the inciting trauma, before returning to normal at about 18 weeks.14 Measurement of 24-hour urinary prostaglandin E2 excretions, also rarely assessed in the clinical setting, can help in detecting early HO.7 A sudden increase in prostaglandin E2 excretion points to the need for bone scanning.18



Currently there are no universal treatment strategies or guidelines for the prevention and management of patients with HO. However, for individuals identified as high risk for development of acquired HO, the following are possible treatment options and/or prophylactic measures:

1. serial quantitative bone scanning to assess status of HO and determine whether medical and/or surgical treatment is warranted

2. nonsteroidal anti-inflammatory agents, preferably indomethacin, to prevent and/or slow the progression of HO

3. radiation therapy to prevent or inhibit the progression of HO

4. manipulation under anesthesia to loosen stiff joints after TKA procedures in select patients

Researchers suggest that prophylactic measures against HO be administered within 24 to 48 hours after TJA for optimal deterrence of HO.10


Once clinically relevant HO is demonstrated, radiation therapy with or without MUA in TKA recipients, and/or with surgical resection of the HO (often used in conjunction with radiation therapy), can be considered to restore and preserve joint mobility and function. Surgical resection of HO is generally reserved for mature HO (recurrence and progression of HO can occur after “excision of” HO). In patients who underwent THA, MUA is not performed because of the risk of hip instability. In cases where these measures fail to produce optimal patient outcomes, revision TJA may be indicated.7


Despite the lack of consensus on standardized treatment guidelines for acquired HO established by the orthopedic community, various treatment options can be employed to possibly manage this condition. Health care professionals should be cognizant of and alert to the signs and symptoms of patients at risk of acquired HO, to ensure treatment optimization.

Disclosure Statement

The author(s) have no conflicts of interest to disclose.


The authors wish to graciously acknowledge the editors of this article whose contributions were invaluable to the clarity of explaining this condition.

Kathleen Louden, ELS, of Louden Health Communications performed a primary copy edit.

Author Affiliations

1 Department of Orthopedic Surgery, Boston Medical Center, MA

2 Simmons University, Boston, MA

Corresponding Author

Michelle J Lespasio, DNP, JD, ANP (

How to Cite this Article

Lespasio MJ, Guarino AJ. Awareness of heterotopic ossification in total joint arthroplasty: A primer. Perm J 2020;24:19.211. DOI:

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Keywords: clinically relevant heterotopic ossification, heterotopic ossification, joint stiffness, pathological bone growth, TJA, total joint arthroplasty


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