Lisa Michelle Katz
Hypertrophic Osteopathy
Hypertrophic osteopathy (HO, also Marie’s disease) is an uncommon disease in the horse that is characterized by bilateral, progressive, symmetric subperiosteal bony and fibrous connective tissue proliferation. Hypertrophic osteopathy has also been referred to as hypertrophic pulmonary osteopathy or osteoarthropathy because it is commonly associated with intrathoracic diseases; however, it is now recognized that the condition can arise secondary to extrathoracic diseases, and the term HO is considered to be more appropriate. In humans, the term hypertrophic osteoarthropathy is often used because synovial changes and joint involvement leading to a decreased range of motion have been recorded. However, in most domestic animals, including horses, the name HO is considered more appropriate because HO does not typically involve the articular surfaces, although in horses, bony proliferations can often be found around the joints.
Etiology and Pathogenesis
Primary and secondary forms of HO have been recognized in humans. Primary HO is a hereditary disease in which skeletal, neuromuscular, and dermatologic changes may be present, whereas secondary HO develops in association with a primary intrathoracic or extrathoracic lesion. Secondary HO in humans is generally associated with a primary lung condition, most often neoplastic, with complete resolution often occurring after treatment of the primary condition. Comparatively, only secondary HO has been described in horses and, as with humans, is most often associated with a primary intrathoracic lesion, although multiple types of primary extrathoracic lesions have also been described. It is interesting that thoracic neoplasia is uncommon in horses, with associated HO even more rarely reported. Comparatively, HO occurs in up to 10% of human patients with intrathoracic malignancies. Because of this reported rarity in horses, when HO is identified, it warrants thorough evaluation for both intrathoracic and extrathoracic disease.
Intrathoracic neoplastic conditions associated with HO in horses include squamous cell carcinoma, granular cell tumor, and metastatic tumors in the lung. Nonneoplastic intrathoracic conditions include abscesses, granulomas, pulmonary infarction, tuberculosis, pneumonia (tuberculosis or mycobacterial, or bacterial), pleuritis, inflammatory airway disease (IAD), fibrosing mediastinal lymphadenitis, rib fracture, fibrous pericarditis or epicarditis, equine multinodular pulmonary fibrosis, and mineralization of the proximal part of the descending aorta. At one point, tuberculosis was the most common cause of HO in horses, with the incidence of HO declining in conjunction with the decline of reported cases of tuberculosis. The link between HO and granulomatous conditions is well documented in the literature, with 40% of recorded cases of HO in horses related to granulomatous inflammatory conditions.
Hypertrophic osteopathy in horses has also been reported in association with extrathoracic lesions such as ovarian neoplasia, polycystic hepatic disease, pituitary adenoma, gastric squamous cell carcinoma, splenomegaly, and pregnancy. In addition, several reports describe horses in which an underlying disease was not identified; in humans, this is referred to as pachydermoperiostosis. Interestingly, in a high percentage of cases in which antemortem diagnostic testing failed to detect an intrathoracic lesion, a lesion was found on necropsy. For this reason, it has been hypothesized that for horses with no antemortem diagnosis or an antemortem diagnosis such as IAD or recurrent airway obstruction (RAO), an early-stage pulmonary granular cell tumor may have been missed. Horses with this stage of neoplasia often have no overt clinical signs or have mild respiratory signs compatible with IAD or RAO, with most pulmonary granular cell tumors diagnosed subsequently at postmortem examination.
The etiology of HO is unknown, but initially there is a rapid increase in blood flow to the distal portions of the limbs that results in fluid retention and leads to proliferation of vascular connective tissue with subsequent deposition of new bone perpendicular to the cortex. Vascular hyperplasia, edema, and excessive collagen deposition have been identified, all of which contribute to the development of the distal limb swelling, with periosteal proliferation that potentially further interrupts limb circulation and contributes to the worsening of edema. The precise cause of the increased blood flow is not known, but hypotheses include hormonal abnormalities, pulmonary arteriovenous shunting, periosteal hypoxia, and parasympathetic nerve stimulation.
The overall prevalence of HO in horses is low. The mean reported age of horses with a diagnosis of HO ranges from 5.4 to 8.8 years. There is no confirmed sex predisposition, although a slightly higher prevalence has been reported in male horses. In most reports, a wide range of breeds is affected, although in one report the disease affected horses more frequently than ponies.
