Radiation Therapy as Prophylaxis for HETEROTOPIC OSSIFICATIONS BY

Radiation Therapy as Prophylaxis for HETEROTOPIC OSSIFICATIONS BY: CHRISTINA BROWN

Heterotopic Ossification q “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 WW 1” (Shehab, 2012). q Also known as heterotopic bone formation it is the presence of bone in soft tissue where bone normally does not exist. q It is a benign condition and not to be confused with bone forming tumors such as osteosarcoma and osteochondroma. q “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. 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 q “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). q Three conditions are required for the formation of ectopic bone: ü Osteogenic precursors ü An inducing agent (example: trauma) ü A permissive environment

Causes of Heterotopic Ossification q Trauma such as fracture total hip athroplasy, or direct muscular trauma q Neurogenic causes such as spinal cord injury or central nervous system injury q Or rare hereditary condition known as Myocitis Ossificans Progresssiva

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

Clinical presentation q 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. q Loss of joint mobility and resulting loss of function q Nerve entrapment q Pressure ulcers q Pain q Ankylosis: a stiffness of a joint due to abnormal adhesion and rigidity of the bones of the joint. q Swelling v “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 q Hip athroplasty is a surgical procedure in which the hip joint is replaced by a prosthetic implant. q “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 q Total hip arthroplasty (THA) is the standard treatment of symptomatic, severe hip osteoarthritis q SRA offers the advantage of conservation of more femoral bone stock. q Surgical technique and the amount of local tissue trauma can impact the likelihood of HO q Radiation prophylaxis consisted of 7. 5 Gy prescribed to midplane with routine shielding of the acetabular bone q In-growth surface delivered postoperatively in all patients within 72 hours of surgery preferable the next day. q Typical Energy was 6 MV or 10 MV q 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 q Fractures of the acetabulum occur when the head of the femur is driven into the pelvis. q This is caused either by a blow on the side or by a blow in the front of the knee q Pins and screw are usually used for surgical repair q “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 q A 26 -year old Caucasian man sustained multiple injuries in a motorcycle accident in 2001. q 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 q 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. q Treatment involved an open 8 × 15 field using anteroposteriorposteroanterior (AP/PA) 6 -MV photons to 7 Gy in one fraction, without bone shielding. q 7 years later shooting pains q Ct of the pelvis revealed a large soft tissue mass in the right iliac wing measuring 15 × 14 × 15. 4 cm with intra-pelvic and extra-pelvic extension q “Core biopsy of mass revealed high grade sarcoma with cartilaginous differentiation suggestive of chondroblastic osteosarcoma” (Farris, 2012).

Resources Alfieri, , K. (2012). Blast injuries and heterotopic ossification. Logo of bonejointres, 1(8), Retrieved from http: //www. ncbi. nlm. nih. gov/pmc/articles/PMC 3626224/ 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/PMC 3488033/ Medical School, D. U. (2012). Limb development. Retrieved from https: //web. duke. edu/anatomy/embryology/limb. html Miner , 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 r 206 h acvr 1 mutation activates bmp-independent zebrafish embryo ventralization. Journal of Clinical Investigation, 119(11), 3462– 3472. http: //www. jci. org/articles/view/37412 chondrogenesis and Retrieved from 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/PMC 3626201/