HETEROTOPIC OSSIFICATIONSBY: CHRISTINA BROWN

Radiation Therapy as Prophylaxis for

Heterotopic Ossification

“HO was first described in 1883 by Reidel and in Dejerne and Ceillier reported that HO frequency occurred amongst soldiers who had experienced spinal cord trauma as combatant in WW1” (Shehab, 2012).

Also known as heterotopic bone formation it is the presence of bone in soft tissue where bone normally does not exist.

It is a benign condition and not to be confused with bone forming tumors such as osteosarcoma and osteochondroma.

“This usually occurs by initial cartilage formation, followed by endochondral ossification” (Miner , 2013).

Normal Ossification

Medical School, D. U. (2012). Limb development. Retrieved from https://web.duke.edu/anatomy/embryology/limb/limb.html

Mesenchyme begins to condense into chondrocytes Chondrocytes form a model of the prospective bone Blood vessels invade the center of the model, where osteoblasts localize, and proliferation is restricted to the ends

(epiphyses) Chondrocytes toward the shaft (diaphysis) undergo hypertrophy and apoptosis as they mineralize the surrounding

matrix. Growth of the long bones continues into early adulthood 

Heterotopic Ossification

“The development of heterotopic ossification is related to the interplay between complex local and systemic factors that lead to the increased activity of osteoblasts and the preferential differentiation of pluripotent mesenchymal cells into bone forming osteoblast” (Sullivan, 2013).

Three conditions are required for the formation of ectopic bone:\

Osteogenic precursors An inducing agent (example: trauma) A permissive environment

Causes of Heterotopic Ossification

Trauma such as fracture total hip athroplasy, or direct muscular trauma

Neurogenic causes such as spinal cord injury or central nervous system injury

Or rare hereditary condition known as Myocitis Ossificans Progresssiva

Myocitis Ossificans Progresssiva

“FOP is a severely disabling musculoskeletal disease characterized by extensive formation of endochondral bone within soft connective tissues. This heterotopic bone formation is the most clinically relevant feature of FOP” (Shen, 2009).

extremely rare disease The onset is usually in the first 10 years it may begin in utero, but only rarely after the age of 20. It seems that trauma may be a precipitating factor

Clinical presentation Symptoms may appear as early as 3 weeks or as late as 12

weeks after the musculoskeletal trauma, spinal cord injury, or other precipitating event.

Loss of joint mobility and resulting loss of function Nerve entrapment Pressure ulcers Pain Ankylosis: a stiffness of a joint due to abnormal adhesion and

rigidity of the bones of the joint. Swelling

“significant loss of function when it forms adjacent to joints, major blood vessels or nerves, and can complicate the use of prostheses following amputation” (Alfieri, 2012)

Radiation therapy to as Prophylaxis for Hip Arthroplasty Hip athroplasty is a surgical procedure in which the hip joint is

replaced by a prosthetic implant.

“Recent reports have noted higher rates of heterotopic ossification (HO) with surface replacement arthroplasty (SRA) than with traditional total hip arthroplasty in the absence of postoperative HO prophylaxis.” (Kruser, 2012)

Radiation therapy to as Prophylaxis for Hip Arthroplasty Total hip arthroplasty (THA) is the standard treatment of

symptomatic, severe hip osteoarthritis SRA offers the advantage of conservation of more femoral

bone stock. Surgical technique and the amount of local tissue trauma can

impact the likelihood of HO Radiation prophylaxis consisted of 7.5 Gy prescribed to

midplane with routine shielding of the acetabular bone In-growth surface delivered postoperatively in all patients

within 72 hours of surgery preferable the next day. Typical Energy was 6 MV or 10 MV Median field size was 5 cm (4.9–6.7) by 12 cm (9.1–14.3).

Radiation therapy to as Prophylaxis for Acetabular Fractures Fractures of the acetabulum occur when the head of the

femur is driven into the pelvis. This is caused either by a blow on the side or by a blow in the

front of the knee Pins and screw are usually used for surgical repair “Disabling ossification occurs in approximately 5% of

nonoperatively treated patients , but after operative treatment, the incidence increases substantially “(Blokhuis, 2008).

Radiation therapy to as Prophylaxis for Acetabular Fractures

Side effects of radiation of heterotopic Ossification A 26-year old Caucasian man sustained multiple injuries in a

motorcycle accident in 2001. presented with a right posterior hip dislocation and acetabular

fracture as well as an open right distal tibia and fibular fracture which necessitated a below-knee amputation

He was surgically treated and within 72 hours, received post operative prophylactic RT to the right hip including the acetabulum, femoral head and neck, as well as the greater trochanter.

Treatment involved an open 8 × 15 field using anteroposterior-posteroanterior (AP/PA) 6-MV photons to 7Gy in one fraction, without bone shielding.

7 years later shooting pains Ct of the pelvis revealed a large soft tissue mass in the right iliac wing

measuring 15 × 14 × 15.4cm with intra-pelvic and extra-pelvic extension

“Core biopsy of mass revealed high grade sarcoma with cartilaginous differentiation suggestive of chondroblastic osteosarcoma” (Farris, 2012).

ResourcesAlfieri,, K. (2012). Blast injuries and heterotopic ossification. Logo of bonejointres, 1(8), Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3626224/

Blokhuis, T. (2008). Is radiation superior to indomethacin to prevent heterotopic ossification in acetabular fractures?: A systematic review. 467(1), doi: Clinical Orthopaedics and Related Research

Farris, M. (2012). Osteosarcoma following single fraction radiation prophylaxis for heterotopic ossification. Radiation Oncology (London, England), 7(140), Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3488033/

Medical School, D. U. (2012). Limb development. Retrieved from https://web.duke.edu/anatomy/embryology/limb/limb.htmlMiner , J. (2013). The role of endothelial-mesenchymal transition in heterotopic ossification. 27(8),

Shehab, D. (2012). Heterotopic ossification. Journal of Nuclear Medicine, 3(3), Retrieved from http://jnm.snmjournals.org/content/43/3/346.full.pdf

Shen, Q. (2009). The fibrodysplasia ossificans progressiva r206h acvr1 mutation activates bmp-independent chondrogenesis and zebrafish embryo ventralization.Journal of Clinical Investigation, 119(11), 3462–3472. Retrieved from http://www.jci.org/articles/view/37412

Sullivan, M. (2013). Heterotopic ossification after central nervous system trauma. Bone & Joint Research, 2(3), 51-57. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3626201/