Hypothesis 3:

	Neoplasia is a consideration in causing Bonnie's lameness.  Specifically, osteosarcoma is a malignant mesenchymal tumor of primitive bone cells. We believe that osteosarcoma could be the cause of this lameness because of Bonnie's signalment and clinical signs.  Bonnie is six years old and is within the age range of peak incidence for this disease, which is between the ages of five and nine years.  85% of all canine bone tumors are osteosarcomas.  Osteosarcomas are prevalent in Labrador retrievers, giving her a high breed incidence.  The location of Bonnie's lameness appears to be the stifle joint, and a prevalent site of osteosarcoma is the either the proximal tibia or the distal femur.  Both of these locations are associated with the site of attachment of the cranial cruciate ligament.     
	Bonnie's sudden onset of pain and lameness with no history of trauma could be explained by the presence of a pathologic fracture.  Many times a pathologic fracture is the first clinical sign seen in a dog with osteosarcoma.  The pain caused by this fracture could lead to Bonnie's partial weight bearing lameness and to the pain on manipulation of the stifle.  Because of the close proximity of the cranial cruciate ligament a fracture in this area could cause dissociation of the ligament from the weakened bone.  
	Dogs with early osteosarcoma are initially in good health as seen with Bonnie.  An aggressive tumor such as an osteosarcoma will present with focal soft tissue swelling, as is the case with Bonnie's stifle.  Bonnie presented with effusion of the left stifle joint with distension of the joint capsule.  The pathophysiology of this effusion is that a pathologic fracture near the joint would lead to disruption of the vascular supply, which causes plasma exudation and leads to acute edema.  Then inflammatory cells migrate into this exudate and release inflammatory mediators, which cause vasodilation and further exacerbate the edema.  Both the inflammatory mediators and the joint capsule distension will cause the clinical sign of lameness.  The inflammatory mediators increase nociceptor response.  The distension of the joint capsule causes lameness by increasing pressure on the fibrous joint capsule, where the nociceptors are abundant.  This increased pressure causes mechanical stimulation and thus the clinical lameness.
	Bonnie's lameness is a result of pain.  The pathophysiology of pain due to an osteosarcoma is likely due to microfractures or disruption or the periosteum induced by oteolysis of cortical bone with tumor extension from the medullary canal.  The lameness worsens, and a moderately firm to soft, variably painful swelling may arise at the site.  Dogs may present with acute severe lameness associated with pathologic fractures.  The pathologic fracture would lead to torn soft tissue, periosteum and disruption of nerves and vessels.  This would lead to inflammatory mediators such as prostaglandins infiltrating the site of the fracture.  Both the mechanical and chemical stimulation of the nociceptors in the tissue as a result of the fracture would lead to pain.
Osteosarcoma would be easily diagnosed on radiographs.  Osteosarcomas appear on radiographs as an aggressive bone tumor with focal soft tissue swelling.  The metaphysis is the most common location for this neoplasm, but it can be located in other parts of the bone.  There would be evidence of cortical and medullary bone lysis and disorganized new bone formation that invades the surrounding tissues.  In 50% of the cases a sunburst appearance occurs as periosteal new bone radiates out from the tumor.  A pathologic fracture could be visible.  It is also possible that joint involvement would be seen.  Metastasis is very common and usually arises very early in the course of the disease.  Although less than five percent of dogs have radiographically detectable pulmonary metastasis at presentation, approximately ninety percent will die with metastatic disease, usually to the lungs.  When suspecting osteosarcoma, it is important to also radiograph the lungs to check for metastasis in order to aid in prognosis and developing a management plan.  The tumor foci would appear as rounded discrete opacities in the lungs.  If radiographic evidence points to osteosarcoma, further investigation of the disease can be accomplished through a bone biopsy.