CLINTON F. PICKETT D.O., Orthopaedic Resident
FREEMAN MILLER M.D., Attending Pediatric Orthopaedic Surgeon
RICHARD KRUSE D.O., Attending Pediatric Orthopaedic Surgeon
May 9, 1996
CLINICAL CASE PRESENTATION
THE ALFRED I. DUPONT INSTITUTE
A nine year-old male with a diagnosis of cerebral palsy spastic quadriplegia presented for a follow-up exam. This patient was non-ambulatory and non-verbal. Patient had good head control and was capable of sitting if propped up. There was a wind-blown posture with the left hip being adducted and subluxated 30- 40 percent. On 9\95 patient underwent bilateral release of iliopsoas, gracilis, adductor longus, distal hamstrings and right tensor facia lata release. Four weeks later the patient still required valium and analgesics due to pain and muscle spasms. At that time a firm mass was palpated in the left groin. On 11\95 The patient was still having pain . Four months post-op the patient was able to start aquatic therapy. Seven months post-op the patient had increased range of motion with less pain.
Heterotopic bone formation was first described in 1692 when Guy Patin described myositis ossificans progressiva in children.(1) Better understanding and descriptions came about and in 1918 Dejerine and Ceillier described heterotopic ossification as a complication of intermedullary gunshot wounds during World War I(2) . They postulated the etiologies of local edema and a neurogenic factor . In 1961 Damanski associated improved post-trauma care with decreased incidence of heterotopic ossification(3). Descriptions of HO in children have been described following ilio-psoas release(11,12,13), posterior rhizotomy and femoral osteotomy (10), spinal cord injury(4), and spinal fusion (4,12) in recent literature.
Confusion surrounds the subject of heterotopic ossification regarding definition, etiology, incidence, and treatment. Heterotopic ossification(HO) is the formation of lamellar bone ( which may mature with time) where bone does not usually form in soft tissues. Myositis ossificans is a condition in which HO occurs in muscles and other soft tissues(21). There are three types of myositis ossificans circumscripta, myositis ossificans progressiva, and localized traumatic myositis ossificans (21).Ectopic calcification is mineralization of soft tissue structures usually due to physical or chemical trauma such as calcific tendonitis-histologically the deposits are not bone forming(4).
Etiologies of HO include trauma , neurogenic, and myositis ossificans progressiva. Traumatic etiologies include after spinal fusions , total hip arthroplasty, ORIF of acetabular fractures, soft tissue releases about the hips and burns. Neurogenic etiologies include closed head trauma, spinal cord injury, CNS infections, tumors, strokes, tetnus, polio, tabes dorsalis, multiple sclerosis, and following a selective posterior rhizotomy. Myositis ossificans progressiva is a rare autosomal dominant disease which begins in early infancy which initially involves the muscles of the back, neck, and shoulders and then progresses to immobilize the patient in early life(4).
Pathophysiology of HO is unclear. Histologic studies of heterotopic bone reveal the percentage of osteoblasts is typically double that of normal bone indicating that the bone being formed is metabolically active(14). One distinguishing feature is that the new bone and mature bone lacks periosteum(15). Heterotopic bone is often diffuse and does not always follow anatomic planes of tissue. Bone morphogenic protein is a potential inducer of undifferentiated mesenchymal cells which are precursors of cartilage and bone forming elements. It has been theorized that BMP may induce inappropriate differentiation of pluripotential cells, mesenchymal cells or fibroblasts into osteoprogenitor cells(5). Fujimori et al(6) studied the role of BMP and interleukin-1 in a rat model which had collagen induced arthritis . Non-osteogenic cells such as transitional epithelial cells from the urinary bladder(7), various sarcoma viruses, and t-lymphocyte mitogens have been associated with HO(7,15). The possible associatiion of prostaglandin E2 with heterotopic ossification has been studied in a rat burn model(8).
Evaluation of a patient includes an adequate physical exam. The initial clinical finding is decreased range of motion. There may be localized tissue hyperemia, swelling and tenderness to palpation. Initial onset is usually 4-16 weeks but ranges from two to fifty-two weeks(14). In addition to pain there may be increased spasticity of the limb. Differential diagnosis is infection(14,9),tumor, thombophlebitis(14,9),reflex sympathetic dystrophy, and many patients will have multiple and complex problems(14). Traumatic type of HO is found near focus of trauma. Neurogenic type of HO is found below the level of spinal cord injury usually on the side of spastic muscles.
Radiographic findings of HO on plain films is evident at 4-6 weeks, usually trabeculation is absent. Payne and DeLuca(10) define HO in soft tissues as radiodensity 5 mm from the femoral shaft and not initially adjacent to the femur which is periosteal callus and HO is usually a flocculent pattern.Technetium three-phase bone scan is positive in the initial phase of HO and is 90% sensitive in 2-4 weeks after injury. Return to baseline is 7-12 months after injury(14). Bone scans may be used to assess the level of maturity of the HO. Computed tomography can differentiate native vs. ectopic bone by revealing the osseous architecture(14).Computed tomography may also be useful in planning surgical approach. Magnetic resonance imaging can demonstrate soft tissue swelling but receives only limited signal from calcified tissue(14). Ultrasound has been shown to detect HO earlier than plain radiographs in eight consecutive patients by Thomas and Amstutz (17).
Laboratory findings include changes in serum levels of alkaline phosphatase ,phosphate and calcium. Alkaline phosphatase may be as high as 3.5 times normal at 4 weeks post injury with peak levels measured at 12 weeks. Smaller volumes of ectopic bone (usually at the smaller joints) may not raise levels as significantly(18).Although non-specific, serum alkaline phosphatase may be the earliest ,least expensive test for early detection of HO. If fractures are not present this is an excellent presumtive test (9). Serum alkaline phosphatase elevation is accompanied by an increase in inorganic phosphate and is preceded by a transient decrease in serum calcium(8).Other researchers feel that these test are unreliable for screening(20).
Risk factors of HO include trauma, burns , neurologic injury, previous HO (which may or may not have been resected ), surgery about the hips, male sex(4),age over 60(4)and possibly genetic predisposition. Probable risk factors include diffuse idiopathic skeletal hyperostosis(DISH), Paget's disease(4). Forearm fractures in patients which are neurotraumatized or burned have substantially increased risk of developing HO. The elbow is the most frequently involved joint in burn patients. Burn-related HO was more related to the severity of the burn. Burns over 20% of the body with the majority of the burns being third degree(19). This may be evidence of a humeral mediated response or systemic effect of trauma. Performing hip soft tissue releases and spine surgery in children with cerebral palsy concomitantly may increase the risk of HO(15). Genetic risk factors once were thought to include those with positive HLA B18(18), HLA B27,HLADW7(9) for neurogenic HO. However follow-up studies have not confirmed these findings. Presently they have no predictive value(18).
Other risk factors include prior surgery for excision of HO, trochanteric osteotomy , length of surgery,(9)and pressure sores near proximal joints.
Incidence of Ho has been shown to occur generally in 10-20% of predisposed patients(9). Reported rates vary with type of treatment center ; acute care will see less incidence than rehabilitation units, since it is seen later. Acetabular fractures treated with ORIF may have as high as 60% incidence of HO however in many cases there may not be a limitation of motion and many will improve function with time. Spinal cord injuries have 20-25% incidence however 18-35% limit motion (4).Closed head injuries have 10-20% incidence with 10% developing loss of motion . Incidence of HO in elbow dislocations is about 3% but in fracture-dislocations it is 15-20 % (4). Payne and DeLuca (10) reported 27%incidence of HO with selective rhizotomy and subsequent femoral varus derotational osteotomy in spastic quadriplegics. Ho was not noted in diplegics, nor in patients who did not undergo rhizotomy during the same period. Patients with perthes disease who underwent adductor releases had a incidence of 6% of HO.
Classification of HO is well documented by Parkinson et al (22); DeLee(23);and Brooker(24). These classifications were used to describe HO after total hip arthroplasty. A classification developed by Krum and Miller(15) included radiographic and clinical criteria. Grade I was considered when there was no symptoms but radiographic evidence. Grade II was described as having mild-moderate symptoms of pain, irritability, limited range of motion. In grade III lesions hip function was severely limited. The radiographic classification A included those lesions in which the width of heterotopic ossification was less than half of the width of the femoral neck. With B lesions the width of HO was equal to half of the width to the entire width of the iplilateral femoral neck. Grade C heterotopic ossification has lesions greater than width of the ipsilateral femoral neck. Classification of HO about the elbow is described by Hastings and Graham(14). This three part classification focuses on functional limitation with consideration to the anatomic basis of HO distribution.
Prognosis for recovery of motion after HO is worse in patients that have severe loss of ROM, severe persistent spasticity or poor neurologic recovery. Elevated levels of serum alkaline phosphatase 1-2 years post injury is a poor prognostic indicator . Minimal resorption of HO occurs after it has matured however nearly full range of motion may return .
Non-surgical management of HO includes recognition of risk factors. One should consider pharmacologic treatment. Agents used are diphosphonates and NSAIDs. Etidronate disodium, Ethane Hydroxy diphosphonate prevent or inhibit crystallization of hydrozyapatite, They do not interfere with formation of osteoid or existing osteoid. Side effects include GI disturbances, osteomalacia and rebound calcification of existing osteoid after treatment is discontinued. Naraghi no longer recommends diphosphonates for prophylaxis against HO(4). NSAIDS such as indomethicin, acetylsalicylic acid , and ibuprofen work by inhibiting cycloxygenase which probably interrupts the synthesis of PGE2, bone formation and fracture healing are suppressed. Efficacy has been demonstrated in the hips of adults. Acetylsalicylic acid has been reported to decrease progression in pediatric patients with HO following brain injury. Most common side effects of NSAIDS are GI disturbances, and interaction with other medicines , particularly anticoagulants.
Radiotherapy using a low-dose external beam radiation prevents cell proliferation(25)/ Dosage is usually 700rads x1 dose or 1000 rads in 4 divided doses (26). There has been reports of sarcomas induced by radiation, but not after receiving these recommended doses(27). Prophylaxtic post surgical debridement of HO dosage is 700-800 rads within 48-72 hours after surgery(14).
Physical therapy particularly stretching of spastic limbs has been postulated as an etiology of HO however Wharton and Morgan reported in a study of spinal cord injured patients , daily range of motion program improved range of motion in such patients(28).Garland(9) recommended up to three manipulations under anesthesia spaced one to two months apart for traumatic brain injured patients with HO In traumatic HO , passive stretching of the joints may lead to increase HO(4). Alteration of physical therapy should be made if patient is diagnosed with HO . Forceful passive ROM should be avoided and gentle ROM should be limited by the patients discomfort.
Surgical treatment should not be considered until the HO has matured . Many researchers feel that 6 months after initial trauma (without neural injuries) that HO can be resected. It should not be resected until it is considered mature bone(13). A specific amount of time to delay surgical resection of HO associated with with spinal cord injury is difficult to predict. Surgery is usually delayed at least one year , but should be performed at 1.5 to 2 years in young males with anklyosis or near ankylosis of the hip, radiographic evidence of progression of HO longer than 6 months, greater than moderate amounts of HO, severe spasticity, persistent elevation of serum alkaline phosphatase, continued uptake in bone scanning, and poor response to prophylactic medications. Procrastination longer than 2 years allows development of complications such as intraarticular joint ankylosis and fractures in the osteoporotic bone with initiation of joint motion after resection (29).In traumatic brain injury patients the natural history of neurologic recovery is the best index for surgical excision, recurrence, and functional outcome(30). The majority of motor recovery occurs by 1.5 years -- those patients with rapid neurologic recovery may have HO resected if the guidelines for monitoring the maturity of the bone are met(9).Surgery is mainly indicated for limb positioning in the neurologically compromised patient.
Techniques of surgery should be meticulous with adequate hemostasis, evacuation of bone dust, interposition of muscle, fat, fascia or silastic(14). More than one incision to decrease the dissection of soft tissue to reach the HO may be beneficial(14). Complications of surgical resection include recurrence, blood loss (this is especially true when HO has not matured, infection, and morbidity.
Heterotopic ossification is a well documented complication of spinal cord injuries, surgical release of the spastic hip muscles, and trauma. Local trauma is not a requisite of HO. Spinal fusion of cerebral palsy patients may also be associated with HO at the hip area. Orthopedists , physical therapists , and pain management teams should be aware of this complication when diagnosing and treating the cause of persistent post-op pain. Recognition of risk factors may warrant prophylaxtic treatment.