1. Salcido, Richard "Sal MD, EdD"

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Heterotopic Bone Ossification (HO): "It's Bone" is a quote from one of my mentors, the late Robert Hussey, MD, orthopedic surgeon and chief of Spinal Cord Medicine at Richmond Veterans Administration Medical Center in Virginia.

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Persons with spinal cord injury (SCI) endure morbidities to nearly every body system, including the central and peripheral nervous, cardiopulmonary, urologic, and musculoskeletal systems. In addition, they have joint mobility dysfunction, related atrophy, and contractures of neurogenic, myogenic, arthrogenic, and osteogenic origin.1,2


Patients often present with indolent, painful, swollen, red, and indurated major joints and extremities, including pressure ulcers (PrUs).3-5 Such signs and symptoms are often conflated with infection, trauma, deep vein thrombosis, and deep tissue injury. Diagnostic tests used to explain these symptoms include X-ray, magnetic resonance imaging, computed tomography, and bone scan. The interpretation of these studies, in the SCI, brain injury, and amputee population, often unexpectedly reveals HO in the deep tissues or in the muscle or joint-"it's bone!"


Heterotopic Bone Ossification

Heterotopic ossification was first reported by El Zahrawi (Albucasis) in 1000 CE.1,3 He noted that "stony hard prominences occasionally developed during fracture healing, requiring surgical removal to restore normal function, a standard of practice that endures."3,5 Isaacson et al6 noted that 1000 years later, the exact mechanism for this ectopic bone formation is not known. Current literature defines HO as extraskeletal bone formation in nonosseous tissue (muscle, fascia, subcutaneous, and cartilaginous tissues). As a pathologic bone genitor, HO has been described as a "hybrid of cortical and cancellous bone."3,4


The exact etiology of HO is not well understood. The clinical typology of HO is characterized by 3 subtypes:3,4 (1) traumatic results from fracture-dislocations, military high-velocity war wounds, blast injuries, limb salvage, and amputations; (2) neurogenic HO is related to SCI and traumatic brain injury,2 neuroarthropathy (Charcot joints),7 diabetes, and tabes dorsalis associated with late diagnosis and untreated neurosyphilis; (3) genic HO is known as fibrodysplasia ossificans progressiva (FOP),8 when a "molecular short circuit" allows unchecked bone growth where it does not belong. Thus, FOP is attributable to the ACVR1/ALK2 gene mutation that aberrantly transforms tendons, ligaments, and skeletal muscles to HO. The HO fuses the spine, ribs, shoulder, and hips. This phenomenon has been described as "trapping persons in their own spine or the development of a shadow spine."8 And, HO nodules can place focal pressure on the subjacent tissues putting tissues at risk.3-6


Heterotopic Bone Ossification and PrUs

Heterotopic bone ossification impedes normal joint function and wound healing and also predisposes patients to an increased risk of PrUs.


In a group of 131 SCI patients followed up for chronic symptoms over a 2-year period, 62 (47%) developed HO of the hip, and 63% of the cohort developed HO in a unilateral hip joint. The methodology used in this clinical study demonstrated a high correlation between HO of the hip and PrUs and HO ([script phi] = 0.69, P < .001).1


Injuries from improvised explosive devices, including blast injuries, traumatic brain injury, SCI, traumatic amputations, and polytrauma, are associated with the formation of HO and, if present, may require multiple surgeries and prolong rehabilitation secondary to delays in prosthetic fitting, the development of PrUs, and chronic nonhealing wounds. Potter3 identified a 64.6% rate of HO in a war-wounded cohort of patients demonstrating significantly higher rates of HO formation than civilian trauma populations.


Diagnoses Prevention and Treatment

Diagnosing HO requires a high index of suspicion. It is a great imitator of infection, deep vein thrombosis, acute arthritic conditions, and even deep tissue injury or impending PrUs. From a diagnostic perspective, 3-phase technetium Tc 99m methylene diphosphonate bone scanning is the most sensitive, followed by computed tomography scans. X-ray is very specific, but not sensitive (found late in the disease). High levels of alkaline phosphates on liver function tests are sensitive, but not specific. C-reactive protein levels are an indirect marker of inflammation.9


Pharmacologic management using nonsteroidal anti-inflammatory agents and bisphosphonates is aimed at reducing inflammation and the development of osteogeneses. Intraoperative radiation also has been used in orthopedic procedures.3-5,9 Prevention through gentle range of motion is usually effective if initiated early. The treatment strategies for HO are supportive and focused on restoring function of the involved joints and soft tissues. Surgical removal of the HO is predicated on the need for functional restoration and activities of daily living, sitting, standing, and prevention of repeated PrUs.1,2,9


Richard "Sal" Salcido, MD, EdD

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6. Isaacson BM, Weeks SR, Potter K, Pasquina PF, Bloebaum RD. Relationship between volumetric measurements of heterotopic ossification in wounded service members and clinically available screening tools. J Prosthet Orthot 2012; 24: 138-43. [Context Link]


7. Nakajima A, Tsuge S, Aoki Y. Intra-articular giant heterotopic ossification following total knee arthroplasty for Charcot arthropathy. Case Rep Orthop 2013; 2013: 472378. [Context Link]


8. Kaplan FS. The skeleton in the closet. Gene 2013; 528: 7-11. [Context Link]


9. Mavrogenis AF, Soucacos PN, Papagelopoulos PJ. Heterotopic ossification revisited. Orthopedics 2011; 34: 177. [Context Link]