Feline Hypertrophic Osteopathy: A Collection of Seven Cases in Taiwan
Between October 2003 and May 2004, seven cats were diagnosed with severe and extensive hypertrophic osteopathy of the appendicular skeleton without detectable underlying causes. All cats showed similar clinical signs of pain with progressive lameness of the limbs. One cat died shortly after presentation, whereas conditions of the others resolved after medical treatment and a change in diet. Regression of the bone lesions was observed radiographically in all surviving six cases.
Introduction
Hypertrophic osteopathy (HO) is radiographically characterized by periosteal bony proliferation affecting the diaphyses of long bones. The new bone formation usually starts at the distal portion of the limbs; it is symmetrical with nodular, spiculated, or palisade patterns; and it leads to irregular outlines of the involved bones. Hypertrophic osteopathy may cause limb soreness and result in ambulant disability.1–4
Hypertrophic osteopathy usually occurs secondary to a variety of underlying diseases and is more commonly documented in humans and dogs than in cats.4 In humans, a number of disorders have been linked with HO development, including cyanotic congenital heart defects, neoplasia, pulmonary diseases, and gastrointestinal diseases.1,5 In dogs, HO is a common paraneoplastic syndrome, often associated with primary or metastatic lung tumors.4
Many other species including (but not limited to) cats, horses, and cows have also been documented with HO. In cats, reports are limited and highly sporadic. Almost all reported feline HO cases have been associated with neoplasia.6–12
The precise pathogenesis of HO has yet to be determined. Increased circulation to the extremities secondary to neurogenic or humorally mediated mechanisms is thought to play a major role in new bone formation.1,7 Current studies in humans suggest that vascular endothelial growth factor and platelet-derived growth factor may be key elements in the development of HO.5,13,14 The treatment for HO is to eliminate the underlying causes.1,4,6 Most reports of cases showing relief of clinical signs and regression of bony changes were in those who had received complete surgical resection of causative tumors.1,4,6
This report describes a collection of seven cats, residing within a specific geographical area, with proliferative bone lesions presented within a relatively short period of time. The appendicular bony proliferation patterns in the cats are consistent with the diagnosis of HO. The possible etiology is also discussed.
Case Report
Signalment and Clinical Findings
Seven cats, four male and three female, from the Taipei area of Taiwan were presented or referred between October 2003 and May 2004 for an unusual illness of the limbs [Table 1]. All cats suffered from similar clinical signs for a period of 1 to 21 weeks. Clinical signs included discomfort or pain when being touched on the limbs, reluctance to move, progressive lameness, and swelling of the affected limbs without pitting edema [Figure 1]. Five of the cats showed anorexia with prominent weight loss, while the other two maintained normal mentation and physical status despite showing discomfort of limbs. Mean age of the cats was 5.7 years (range 1.5 to 11 years), and no breed or sex predisposition was seen. The anal temperatures at presentation were all normal. Blood pressures were measured repeatedly, and all of the measurements were within normal limits. Thoracic auscultation and percussion were unremarkable in all seven cats.
The main diet for all cats was the same commercial feline dry food for a relatively long period of time, ranging from 1 to 10 years. Of the seven cases, only two cats (case nos. 1, 4) were regularly vaccinated. Histories of conjunctivitis and feline lower urinary tract disease were documented in case nos. 1 and 5, respectively.
Radiography
Appendicular radiographs of all seven cats showed extensive and similar patterns of periosteal new bone formation of the long bones; however, the degree of the periosteal reaction and the number of bones involved were variable [Table 2]. The bony reactions were symmetrical and primarily displayed as a palisade pattern without involving the underlying cortex. The observed exostoses appeared primarily on the diaphysis of the long bones [Figures 2A, 2B]. In case no. 2, the bones adjacent to the elbow and tarsal joints were involved, but the joint surfaces were intact [Figure 3]. The prominent new bone formation pattern of the long bones was consistent with the diagnosis of HO in all seven cats. No signs of tumors, masses, or pulmonary abnormalities were observed in the thoracic or abdominal survey radiographs in any cats. Renal sizes acquired from abdominal radiography revealed smaller kidneys (<1.6 times the length of the second lumbar vertebral body) in case nos. 2 and 7.
Blood Examinations
Complete blood cell counts, serum biochemical profiles, and selected hormone tests were performed. Abnormalities included a lowered packed cell volume (PCV) in four cats (case nos. 2, 3, 5, 7), elevated urea nitrogen and creatinine in five cats (case nos. 2, 3, 4, 6, 7), and lowered total calcium levels in two cats (case nos. 2, 3) [Table 3]. Other serum biochemical results including alanine aminotransferase, alkaline phosphatase, glucose, albumin, and phosphate were all within normal ranges.
Total tetraiodothyroninea levels were within normal limits in five cats and not measured in the remaining two cats (case nos. 2, 7). Plasma parathyroid hormone (PTH) concentrations were measured using an immunoradiometric assayb in case nos. 3, 4, and 5. All tested cats showed increased secretion from the parathyroid gland.15 Serological testsc for feline leukemia virus and feline immunodeficiency virus were performed in all cats except case no. 2. All cats were negative. Serum (from case nos. 1, 3–7) and viscera (from the deceased cat [case no. 2]) samples were tested for feline coronavirus via reverse transcriptase polymerase chain reaction.16 Only case no. 2 showed positive reaction [Table 3].
Other Examinations
Urinalyses (including specific gravity, pH, protein, glucose, ketones, blood, nitrate, bilirubin, and urobilinogen) were within the normal ranges in all cases. Abdominal ultrasonography was performed in case nos. 2–5 and 7 with no suspected mass formations identified. Synovial analysis and aerobic bacterial culture of multiple joints were carried out in case no. 2 with no detected abnormalities. Biopsy of the proliferative bone was performed in case no. 7 by the referring veterinarian. Exostosis composed of osteoid cells without tumor cell involvement was diagnosed histopathologically. Direct ophthalmoscopy was carried out in case nos. 1, 3, and 5 without detection of abnormalities or vascular changes of the retinas.
Food Analysis
Food samples collected from households for two of the cats were sent to two independent laboratories for analysis. Calcium (inductively coupled plasma optical emission spectroscopy [ICP/OES] method), phosphate (ICP/OES method), and vitamin A (high-performance liquid chromatography [HPLC] method) levels in one sample were 10200 ppm, 11900 ppm, and 58 IU/g, respectively. At the second laboratory, total vitamin A, retinol, and β-carotene levels (all by HPLC method) in sample 1 were 5834 IU/100 g, 1657 μg/100 g, and 187.3 μg/100 g, respectively. In sample 2, these concentrations were 7871 IU/100 g, 2348 μg/100 g, and 25.62 μg/100 g, respectively.
Treatment/Outcome
Supportive treatment including appropriate fluid therapy and electrolyte correction was administered according to the results of the blood examinations. Case no. 2 was treated with oral prednisoloned (0.8 mg/kg per os q 24 hours) with limited effect on pain relief. Since all cats had a common dietary source, a change in diet was implemented. For cats with renal insufficiency (case nos. 2, 3, 4, 7), a renal prescription diete was prescribed [Table 1].
Most cats showed clinical and hematological (PCV, urea nitrogen, and creatinine) improvement within 2 to 4 weeks after initiation of treatments and discontinuation of the original food. The owner of case no. 5 reported that all symptoms were significantly relieved within 1 week after changing the diet. Only one cat (case no. 2) died of renal failure after 2 weeks of aggressive fluid and supportive treatment. Necropsy was performed, and major pathological findings were renal medullary fibrosis and parathyroid gland hyperplasia. The exostotic hypertrophic bones of limbs formed a clear resting line from the periosteum without involving the articular spaces [Figure 4].
Follow-up
The follow-up period ranged between 10 months and 2 years. During follow-up, cats were examined, radiography was repeated, and routine blood work was performed intermittently (case nos. 3, 4, 5, 7) [Table 1]. No signs of anemia or renal insufficiency were detected in cats during the follow-up period. The calcium and PTH levels were not followed in these cats.
Generally, the radiographic bony proliferation in each cat (except case no. 2) ceased after diet change and supportive treatment, and the palisade character of the bone gradually remodeled to a smoother outline [Figures 5A, 5B]. In the three cats followed for >2 years (case nos. 3, 5, 7), variable degrees of HO regression were observed, and complete remission was detected in some areas of the involved bones.
Telephone follow-up interviews were conducted for case nos. 1 and 6 for 10 months after diagnosis [Table 1]. At the time of last contact, the cats were clinically normal and exhibited no signs of orthopedic problems. In general, all six cats that survived the acute stage of illness were free of clinical signs of HO for a minimum of 10 months.
Discussion
Over the years, a number of HO cases—most commonly in dogs—have been reported in the veterinary literature. Over 90% occurred in association with intrathoracic tumors.4,17 Meanwhile, fewer than 10 cases of domestic cats with HO have been reported over the last 30 years, all of which were associated with neoplasia in the thoracic or abdominal cavity with or without lung metastasis.6–12 In this report, seven cats residing in the Taipei area of Taiwan were presented with HO within a short period of time. The cats showed similar clinical symptoms and orthopedic radiographic characteristics. To our knowledge, a high incidence of feline HO within a specific geographical area has never been reported.
A definite mechanism in the development of HO is still unclear. The most accepted theory is that increased blood flow to the limbs stimulates an overgrowth of vascular connective tissue, which subsequently causes periosteal proliferation. Neural or humoral factors mediated by increased blood circulation in the limb secondary to the underlying disease are thought to play major roles in HO formation.1,5,18 The neurogenic mechanism suggests that a nervous reflex exists, with afferent fibers originating in the thorax and efferent pathways affecting the circulation of the limbs.19 The production of humoral or toxic factors from neoplastic cells has been hypothesized as an explanation in cases of HO without intrathoracic lesions.1,5
To determine the possible etiologies of HO in the seven cats described herein, some examinations and assays were performed based on findings of previously reported HO cases.4,6–12,17 The investigations included survey radiography, abdominal ultrasonography, cardiovascular/cardiopulmonary evaluation, comprehensive blood work, urinalysis, and virus screening. Data were collected both retrospectively and prospectively. Additional examinations including synovial analysis, proliferative bone biopsy, fundus examination, necropsy, and diet analysis in selected cases were also included in the hope of discovering unusual events in these cases. Long-term follow-up examinations or telephone interviews regarding the six live cats were conducted to evaluate the prognosis of HO.
With neoplasia being the most commonly reported cause of HO in cats and dogs, it is noteworthy that none of the seven cats were found with any sign of tumor growth upon physical examinations, radiographic surveys, or long-term follow-up.4,6–12 In addition, no sign of lung disease was detected in any of the cats. Other disorders associated with HO formation in humans, such as hepatic disease, intestinal disease, and mediastinal disease, also were not found in the affected cats.5,18
The most intriguing finding in our investigation was the identical commercial food that all cats had been eating for a relatively long period of time before the clinical signs appeared. Further support for a speculation of dietary relevance is the observation that all six surviving cats recovered from clinical signs within 1 to 4 weeks after a change in diet. The regression of HO was also documented radiographically during the follow-up period. While hypervitaminosis A has been reported to cause new bone formation of the cervical and thoracic spine in cats,20 levels of a select number of analyzed ingredients (including calcium, phosphorus, total vitamin A, retinol, and β-carotene) of the commercial cat food consumed by two of the seven cats were generally within recommended ranges. Thus, a definitive cause could not be identified. No previous publications in either human or veterinary medicine have reported a similar phenomenon, and no known food elements or additives have been proven to be linked with HO formation. Nonetheless, the possibility of the involvement of unidentified materials or toxins in the diet cannot and should not be ruled out.
Other less common findings were seen in the cats of this report. Many of the cats showed variable degrees of anemia and/or renal insufficiency; most conditions were either detected with an elevated PTH level or were diagnosed as parathyroid hyperplasia through necropsy. The cause of hyperparathyroidism in the six surviving cats was not known, because the renal insufficiency was transient and reversible. The more accurate method of measuring extracellular ionized calcium concentrations was not carried out to assess hyperparathyroidism.21 Important to note is that cats with secondary hyperparathyroidism will show signs of generalized osteopenia, which is very different from HO.22 In addition, no previous reports have shown evidence that HO is associated with feline renal failure, hyperparathyroidism, or calcium metabolism. The possibility of the involvement of calcium regulation mechanisms is relatively low.
While overall prognosis of previously reported cats with HO is poor with a high mortality,6,8–12 long-term outcomes (i.e., 10 months to 2 years) of the affected cats in this case report were mostly good after discontinuing the regular diet and administering supportive therapy. Regression and remission of the bony lesions were also observed in several of the cats included in this report, which indicates that the HO in these cats was readily reversed after elimination of the unidentified primary causes.
Conclusion
The occurrence of as many as seven feline cases of hypertrophic osteopathy over a relatively short period of time has never been reported. The feline HO of this report was not associated with neoplastic or pulmonary disorders, and the etiology was not determined.
SNAP T4 Test; IDEXX Laboratories, Inc., Westbrook, ME 04092
Intact Parathyroid Hormone; Nichols Institute Diagnostics, Chantilly, VA 20153
SNAP Combo FeLV Ag/FIV Ab test; IDEXX Laboratories, Inc., Westbrook, ME 04092
Prelon Tablets; Y F Chemical Corp., Taipei, Taiwan 24262
Feline k/d; Hill’s Pet Nutrition, Inc., Topeka, KS 66601
Citation: Journal of the American Animal Hospital Association 46, 5; 10.5326/0460346
Citation: Journal of the American Animal Hospital Association 46, 5; 10.5326/0460346
Citation: Journal of the American Animal Hospital Association 46, 5; 10.5326/0460346
Citation: Journal of the American Animal Hospital Association 46, 5; 10.5326/0460346
Citation: Journal of the American Animal Hospital Association 46, 5; 10.5326/0460346
The right hind limb of case no. 7. The swelling was firm and irregular on palpation.
Craniocaudal views of the right forelimb (A) and left forelimb (B) of case no. 3. Prominent periosteal reaction with a palisade pattern was observed.
Lateral view of the right hind limb of case no. 2. Prominent periarticular exostosis existed on the periosteum of the distal tibia, tarsus, and proximal metatarsus. Joint spaces did not appear to be involved.
Histopathological section of periosteal new bone of case no. 2. The exostotic hypertrophic bones of limbs formed a clear resting line (black arrows) on the periosteum (Hematoxylin and eosin stain, 40×; bar=100 μ).
Craniocaudal view of the right forelimb of case no. 4 at the time of presentation (A). Note the prominent HO involving the radius and ulna, which regressed by the time of follow-up 9 months after initial presentation (B).
Contributor Notes
