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Polyostotic in a domestic shorthair cat Anne Fawcett, Richard Malik, C Rolfe Howlett, Michelle M McDonald, John Culvenor, Roy Pool and Graeme S Allan Journal of Feline Medicine and Surgery 2014 16: 432 DOI: 10.1177/1098612X14530216

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Downloaded from jfm.sagepub.com at UNSW Library on June 10, 2014 Journal of Feline Medicine and Surgery (2014) 16, 432–440 CASE REPORT

Polyostotic hyperostosis in a domestic shorthair cat

Clinical presentation: An 11-year-old male neutered domestic shorthair cat was presented for investigation of weight loss and inappetence. On physical examination there was palpable enlargement and thickening of many bones, and this finding was confirmed radiographically. Anne Fawcett Proposed diagnosis: Based on clinical, radiological and histopathological findings, a polyostotic bone BA(Hons) BSc(Vet)(Hons) BVSc(Hons) MVetStud1,2 disease, best described as generalised idiopathic hyperostosis, was diagnosed. This condition has not been reported in cats previously. Canine and human diseases with similarities to this presentation are discussed. Richard Malik DVSc DipVetAn MVetClinStud PhD FACVSc FASM3 Clinical report C Rolfe Howlett swollen back legs’ and was ‘very thin’. How - BVSc PhD MACVSc FBSE4 ever, the officer was unable to perform a Michelle M McDonald An 11-year-old male neutered domestic short- complete physical examination due to the BMedSci PhD5 hair cat (3.0 kg) was presented with inappe- cat’s fractious nature. John Culvenor tence and weight loss. It had been adopted The owners reported that the cat appeared BVSc MVSt FACVSc6 in Japan as a stray with two presumed litter- to have had lifelong valgus deformity of both Roy Pool mates, all found together in a cardboard box, carpi and had never jumped up higher than 7 DVM PhD when the litter was approximately 8 weeks of 30 cm. The cat had a history of chronic con - Graeme S Allan age. At 3 years old an elevation of one of the stipation (untreated) and, more recently, MVSc FACVSc DipACVR DVSc8 cat’s liver enzymes (not specified in the his - dysphagia, specifically difficulty prehending 1Sydney Animal Hospitals tory) was detected during dry food. Both cats lived – Inner West, a routine health screen. strictly indoors and both 1a Northumberland Avenue, The cat was fed Hill’s l/d ate dry urinary s/o Stanmore, NSW 2048, Australia for 2 years subsequently, (Royal Canin) and 2Faculty of Veterinary but the owners could not canned Hill’s c/d diet, Science, University of recall whether the diet Sydney, Camperdown, presumably due to a NSW 2006, Australia was discontinued due to urinary tract condition of 3Centre of Veterinary normalisation of liver one or both cats which Education, B22 University of Sydney, Camperdown, enzyme activity or for was not explained in the NSW 2006, Australia convenience. case notes from overseas. 4 Vetnostics, 60 Waterloo One of the littermates Vaccinations were cur- Road, North Ryde, NSW 2113, Australia was euthanased due to rent and there was no 5Garvan Institute of Medical advanced chronic kidney history of trauma. Research, Darlinghurst, disease at approximately NSW 2010, Australia Physical examination 6North Shore Veterinary 9 years of age. The owners Specialist Centre, relocated to Australia in The cat was alert and 64 Atchinson Street, Crows Nest, NSW 2065, Australia 2007 with the remaining responsive on presenta- 7Department of two cats, then 9 years old. tion. Physical examina- Pathobiology, College of On arrival, a veteri - tion was difficult due to Veterinary Medicine and Biomedical Sciences, Texas narian for the Australian the cat’s aggressive A&M University, College Quarantine Inspection behaviour. It was thin Station, TX 7784, USA 8 Service noted that this (body condition score Veterinary Imaging Figure 1 The cat on presentation. Note the marked Associates, St Leonards, particular cat had carpal valgus and plantigrade hindlimb stance 2/5). Palpation revealed NSW 1590, Australia ‘deformed front legs, extensive thickening of Corresponding author: Anne Fawcett, [email protected] Date accepted: 17 February 2014

DOI: 10.1177/1098612X14530216 432 JFMS CLINICAL PRACTICE Downloaded from jfm.sagepub.com at UNSW Library on June 10, 2014 © ISFM and AAFP 2014 C A S E R E P O R T / Polyostotic hyperostosis in a cat

Figure 3 Close-up of the paw pads, showing the peeling epithelial surface diagnostic possibilities included acromegaly, generalised , osteopetrosis or a disorder of calcium metabolism. Laboratory testing

Figure 2 Marked thickening of the hock with fur loss over A complete blood count revealed a mild neu- x 9 bony prominences trophilia (16.4 10 /l; reference interval [RI] x 9 x 2–13 10 /l) and marginal monocytosis (0.8 9 x 9 10 /l; RI <0.7 10 /l). Serum biochemical the mandible and long bones. Range of abnormalities included hypernatraemia (164 motion of the proximal appendicular joints mmol/l; RI 144–158 mmol/l), hyperchloraemia was markedly reduced. There was pro- (125 mmol/l; RI 106–123 mmol/l), increased nounced carpal valgus (Figure 1) and marked urea (26.4 mmol/l; RI 5–15 mmol/l) consistent thickening of the hocks (Figure 2). Abdominal with dehydration and likely pre-renal azo- palpation revealed a large column of hard fae- taemia, and increased alkaline phosphatase (51 ces in the colon. All paw pads had a peeling mmol/l; RI 5–10 mmol/l) concentrations. Total epithelial surface (Figure 3). The cat was mild- A notable thyroxine concentration was unremarkable (13 ly hypothermic (rectal temperature 36.7°C). radiographic nmol/l; RI 10–61 nmol/l). Urinalysis revealed The patient was considered to have gener- reduced concentrating ability (urine specific alised skeletal disease, most likely due to an feature was gravity 1.028), mild proteinuria (1+) and inborn error of bone metabolism. At that time marked haematuria (4+). Based on failure to our conclusions were that the history was not bilaterally adequately concentrate urine in the face of consistent with hypervitaminosis A and other symmetrical dehydration, a diagnosis of chronic kidney disease (IRIS stage 1A) was made. uniform The serum parathyroid hormone concentra- thickening of tion (28.6 pg/ml; RI 22–168 pg/ml), 25- hydroxy-vitamin D3 concentration (106 the mandibular nmol/l; RI 88–168) and insulin-like growth factor-1 (395 µg/l; RI <800 µg/l) were all rami. normal. Serology for leishmaniasis (Kalazar ELISA), ehrlichiosis (Ehrlichia canis IFA) and anaplasmosis (complement fixation test) were all negative. In-house serology for feline immunodeficiency virus (FIV) antibodies and feline leukaemia virus (FeLV) antigen (Anigen Rapid FIV Ab/FeLV Ag Test Kit, Bionote) was negative. Diagnostic imaging Radiographs of the appendicular and axial skeleton were obtained under general anaes- thesia. A notable radiographic feature of the Figure 4 Ventrodorsal images taken in March 2009 included bilater- radiograph of the head demonstrating thickened ally symmetrical uniform thickening of the mandibular rami mandibular rami (Figure 4) (thickness from

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Figure 5 Lateral radiograph of the skull and cervical spine. Note the thickened skull and Figure 6 Mediolateral view of the left forelimb. The humerus, mandibles and the coarse trabecular pattern in the vertebrae radius, ulna and metacarpals all demonstrate hyperostosis

the axial to abaxial surface of the rami was 19 mm [left] and 20 mm [right]). The mandibu- lar bone was smoothly mar- ginated with homogeneous radiopacity. There was no evi- dence of cancellous bone in either mandibular ramus, all bone appearing to be cortical in morphology. In the skull the frontal bone and the cal- varium were uniformly thick- ened (5 mm and 6 mm, respectively) (Figure 5). In the forelimbs the humeri, radii, ulnae, metacarpals and phalanges of the manus were all affected in a similar man- ner, except that a narrow Figure 8 Ventrodorsal radiograph of the pelvis. A coarse medulla was present in affect- trabecular pattern is visible in the pelvis ed bones of the appendicular skeleton. The humeri meas- ured 24 mm and 26 mm diam- eter, and the paired bones of joints of the appendicular skeleton and the the antebrachii measured Figure 7 Lateral radiograph adjacent epiphyses appeared to be spared the of the right stifle and hock. 24 mm and 28 mm diameter (Table 1). The femur, tibia, fibula, proliferative changes in the long bones, Increase in diaphyseal bone volume appeared calcaneus and metatarsals although signs of degenerative remodelling have demonstrable to be cortical in origin and expansion hyperostosis were present in many joints, resulting in appeared both concentric and eccentric, with osteoarthritis. In the axial skeleton the ribs florid new bone being laid down on both the appeared wider than normal for a cat. periosteal and endosteal surfaces of long bone The cat’s littermate was radiographed for diaphyses (Figure 6). Similar changes affected comparison. There were no signs of increased the femurs, tibiae, fibulae, metatarsal bones bone thickening or opacity, trabecular thick- and phalanges of the pes (Figure 7). The bones ening or degenerative joint disease, except for of the pelvis appeared wider than expected, signs of ankylosing spondylopathy of the with accentuation of trabeculae in the verte- lower lumbar vertebrae, which was consid- brae and pelvis (Figure 8). The diarthrodial ered a normal finding for a cat of this age.

Table 1 Relative bone measurements of the affected cat and the unaffected littermate

Mandible width Frontal bone thickness Calvarium thickness Humeral diameter Antebrachial diameter

Affected cat L19 mm, R20 mm 5 mm 6 mm L24 mm, R26 mm L24 mm, R28 mm

Unaffected cat L5 mm, R5 mm 2 mm 3 mm L11 mm, R11 mm L15 mm, R15 mm

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Sonographic examination of the abdomen changes were most consistent with pathologi- by an imaging specialist (GSA) revealed a cal fractures. striated pattern in the renal cortices, with Fourteen months after the initial presenta- recognisable corticomedullary architecture. tion, a bone biopsy was scheduled to further Foci of mineralisation were evident in the characterise the skeletal disorder. Repeat tho- renal parenchyma, with overall renal dimen- racic radiographs at this time failed to detect sions x in the sagittal plane measuring 19–20 any radiographic signs of pulmonary disease. mm 34–36 mm. No other sonographic At the time of writing, 4 years later, the abnormalities were detected in the abdomen. owners report that, aside from intermittent The appearance of the renal parenchyma was urinary tract infections, treated successfully considered consistent with chronic interstitial with antimicrobials, the cat remains bright nephritis. and alert and has a normal appetite. However, The skeletal Assessment and management the cat’s mobility remains abnormal and lim- changes ited, and body condition is suboptimal. The skeletal changes appeared to be long- Bone biopsy and labelling procedures standing and, although severe, seemed appeared to be unlikely to account for the cat’s presenting Oxytetracycline was used to label new bone complaints, which were considered referable long-standing deposition in order to determine bone turnover. to bacterial urinary tract infection secondary to and, although Oxytetracycline was administered at a dose inadequately concentrated urine. Regrettably rate of 21 mg/kg PO at 12 h intervals, 17 and 16 this was not confirmed by microscopy and severe, seemed days prior to bone biopsy, and again on days culture due to financial constraints. unlikely to 5 and 4 prior to biopsy, to label new bone and The cat was admitted for intravenous fluid thus permit an estimate of bone turnover. therapy (Hartmann’s solution; 6 ml/kg/h for account for The cat was premedicated with acepro- 24 h, then 3 ml/kg/h), antimicrobial therapy mazine (0.05 mg/kg) and butorphanol (0.2 (amoxicillin–clavulanic acid, 20 mg/kg PO) and the cat’s mg/kg). Anaesthesia was induced with nutritional support (1 can Hill’s a/d by syringe presenting propofol, given to effect, and maintained using daily, divided into four meals). Following isoflurane in oxygen following endotracheal 3 days of intravenous fluid therapy, the cat was complaints, intubation. Intravenous fluids (Hartmann’s discharged on Ipakitine (Vetoquinol), a stool solution) were administered perioperatively. softener and inorganic phosphate binder. The which were Following creation of dorsal skin incisions cat continued to gain weight (at this point considered and elevation of the gluteal muscles, bone weighing 3.4 kg). Serial radiographs revealed specimens were obtained from the crests of no progression of skeletal changes. referable to both iliac wings using a 15 mm diameter Over the following 3 months the cat present- trephine. The ilia were 4–5 mm thick. The ed with two further episodes of haematuria, bacterial bone samples were placed in fixative. The cat both of which were treated with an injectable urinary tract recovered uneventfully from anaesthesia. antibiotic (cefovecin, 8 mg/kg SC) for pre- infection. Histology and micromorphology sumptive urinary tract infections. When the of hyperostosis haematuria did not resolve on the second occa- sion a urine culture was performed, revealing Bone biopsies from both the affected cat and a heavy growth of Escherichia coli that was sus- an unrelated normal cat were fixed in 4% ceptible to cefovecin. A second injection was paraformaldehyde for 3–4 days before being given 14 days after the first. transferred to 70% ethanol. Biopsies were then One year after initial radiographic assess- scanned using a Skyscan MicroCT ( CT) at a μ ment, the cat was re-radiographed under resolution of 12 m. μ general anaesthesia (March 2010). The appear- Upon completion of CT analysis, the biop- μ ance of the mandibles, skull, vertebral column sies were decalcified for 8–10 weeks in 0.34 M and appendicular skeleton was essentially EDTA at pH 8.0 before being processed to unchanged. Measurements of the mandibular paraffin blocks. Samples were dehydrated in rami, humeri and antebrachii were similar to graded ethanols before being infiltrated with the measurements obtained 1 year earlier, xylene and then embedded in paraffin wax. suggesting that the bone condition was either Sections were stained using haematoxylin/ non-progressive or slowly progressive. There eosin and alcian blue/picrosirius red to assess 1 were two new findings – an area of increased bone morphology. A tartrate-resistant acid radiopacity in the dorsocaudal thorax, phosphatase (TRAP) stain was used to assess confluent with the crura of the diaphragm, osteoclast parameters. The second biopsy and what appeared to be bilaterally symmet- from the affected cat was processed to methyl- rical transverse fractures of both zygomatic methacrylate resin for undecalcified histology arches. The thoracic opacity had the appear- to assess bone formation through measuring ance of a neoplastic or inflammatory pul- interlabel distances between the serial oxytet- monary nodule, while the zygomatic arch racycline labels (Figure 9).

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Unaffected cat Affected cat

Entire sample

Sliced image Figure 9 Image demonstrating the interlabel distance that was measured to generate mineral apposition rate. The red lines depict the distances measured between the two fluorescent labels (pale green) incorporated into the bone matrix (blue). Original magnification x 20

Analysis of the three-dimensional structure Sliced image of both the trabecular and cortical compart- ment was performed on each biopsy within a 300 slice central region of interest, approxi- mately 3.6 mm in diameter. Trabecular bone volume of total volume (BV/TV) was increased by 45% in the affected cat as com- Figure 10 Images of the pared with the control. Trabecular architec- three-dimensional model of ture was also considerably altered, with a each biopsy generated from CT scans. Note the loss of 140% increase in trabecular thickness and a μnormal trabecular bone clearly appreciated in Figure 10. Cortical bone 40% reduction in trabecular number. These structure, greatly thickened in the biopsies was also dramatically altered, trabeculae and reduced alterations in trabecular bone distribution are trabecular number in the both in volume and appearance, with 29% affected cat compared with more cortical bone volume in the affected cat. the unaffected cat This finding at the tissue level is consistent with the radiological findings of increased cortical thickening, along with increases in cancellous bone volume. x 10 The decalcified histological sections of corti- cal compacta and cancellous bone of the cat with hyperostosis, compared with the control cat, revealed marked differences in density and architecture. Cortical thickness of the affected cat measured 0.8 mm compared with 0.5 mm for the control cat. While the number of bony trabecular systems was reduced in the x 30 affected cat as compared with the control cat, bony trabeculae in the hyperostotic cat were stouter and had a haphazard arrangement that lacked the normal architectural pattern for cancellous bone seen in the control cat. Patchy areas of periosteal new bone deposition, and cortical and cancellous bone remodelling activity were present in the affected cat but x 40 absent in the control. Goldner’s trichrome- stained bone specimens revealed wide, poorly mineralised bone deposits on bone surfaces in the affected cat (Figure 11). In the cat with the hyperostotic skeleton, the Figure 11 Representative images of undecalcified sections resorption spaces in the cortical bone were of bone from the affected cat. Sections are stained with increased as compared with the normal litter- Goldner’s trichrome. Osteoid is red, mineralised bone matrix is green and nuclei are purple. Note the large amount of mate. While the numbers of bony trabeculae of osteoid covering the bone surfaces cancellous bone were reduced, the thickness of

436 JFMS CLINICAL PRACTICE Downloaded from jfm.sagepub.com at UNSW Library on June 10, 2014 C A S E R E P O R T / Polyostotic hyperostosis in a cat the remaining bony trabeculae was increased. Normal control Affected cat The normal architectural pattern of trabecular bone spanning the medullary cavity of the bones was absent in the hyperostotic cat. However, the adipose tissue and the thickness of bone lining cells in the affected cat were Entire biopsy x 1.2 similar to those of the control cat (Figure 12). Bone density was in agreement with µCT. TRAP-positive osteoclasts had an unre- markable histological appearance in both the affected and unaffected cats (Figure 13); however, increased numbers of osteoclasts 2 were present in the affected cat (21/mm ) as compared with the unaffected littermate 2 (6.9/mm ). This is compatible with increased bone remodelling activity. Trabecular bone Undecalcified sections were obtained only x 20 from the affected cat. Fluorescent labelling of active bone formation revealed numerous surfaces actively forming bone. The mineral apposition rate was calculated as being 1.38 m/day. We did not have access to a μ labelled bone biopsy from an age-matched normal cat for comparison, nor could we locate such data in the published literature. In Cortical bone addition to assessing bone formation, we per- x 20 formed a Goldner’s trichrome stain which demonstrates mineralising osteoid. The biop- sy from the affected cat showed many sites of non-mineralised osteoid (Figure 11). This sug- gests elevated bone turnover in the affected cat. Although we did not have control bone to Figure 12 Haematoxylin and eosin stained decalcified bone sections from the affected and unaffected cats. Note extensive changes in the trabecular and cortical architecture. The compare this with, such large amounts of marrow cells in the affected cat appear normal, but the trabecular bone appears corticalised active bone formation would not be expected when compared with the unaffected cat in a mature cat. Molecular genetics fragments were resolved on a 1% agarose gel Genomic DNA was isolated from whole blood and visualised with ethidium bromide. PCR from the affected cat and from an unrelated products were treated with 1 U Shrimp control cat. Using the UCSC cat genome Alkaline Phosphatase and 6 U Exonuclease I. assembly (felCat5), primers were designed All DNA sequencing was performed on a to amplify the coding exons of SOST 3730xl capillary sequencer. (chrE1:71795923-71808882) and adjacent There were a number of heterozygous and intronic regions. homozygous changes identified in both the Amplicons were generated using Taq DNA proband and control. Changes in SOST that Polymerase. Polymerase chain reaction (PCR) were likely to be pathogenic were not found.

Normal control Affected cat

Figure 13 Representative sections from the unaffected and affected cats stained with TRAP for osteoclasts and counterstained with haematoxylin. Osteoclasts appear red; nuclei and bone matrix appear purple. Osteoclast morphology did not appear altered in the affected cat. Original magnification x 30

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Discussion palisades of new bone proliferation that over- lie relatively normal cortical bone. The Disorders that cause increased bone size in medullary cavity is unaffected. Typically, it is cats are uncommon. The maintenance of bones of the extremities that appear to be first healthy bone depends on normal bone remod- affected, so the paws become noticeably elling, with old bone being resorbed by osteo- swollen. Bone enlargement progresses proxi- 2 clasts and new bone formed by osteoblasts. mally, and can affect bones of the axial skele- Abnormally increased bone density reflects an ton. At least 10 cases of feline SHO have been 5 6 imbalance in bone turnover, which may be reported. In all but one case, the underlying 2 congenital or acquired. Diagnostic possi - pathology was determined and included tho- bilities for increased bone density in cats racic and abdominal neoplasia and, in one include osteopetrosis, FeLV-induced instance, a tuberculous granuloma in the medullary and secondary chest. hyper trophic osteodystrophy (SHO). SHO is an unlikely cause for the condition Osteopetrosis refers to a well characterised reported here for several reasons. The radio - bone disorder that causes increased bone den- graphic appearance of new bone is not consis- sity. Commonly it is an incidental finding and tent with SHO, being homogeneous, smoothly affected cats have increased medullary opaci- marginated and appearing to seamlessly 3 2 ty and endosteal thickening of the cortex. incorporate the cortex. Clinically the cat has In these two previous feline reports, the con- remained stable during 4 years of observation. dition was characterised by an increase in There is no radiographic evidence of progres- bone mass due to cortical thickening and min- sion of the bony changes, and thoracic radiog- eralisation within the medulla, without over- raphy and abdominal ultrasonography have 2,3 all enlargement of affected bones. In Wright failed to detect signs of persistent concurrent et al’s study, 10/11 affected cats died of an un - disease. We presume that the transient radio - related disease within 6 months of detection graphic lung lesion was inflammatory in of radiographic signs of osteopetrosis, raising origin as it resolved spontaneously, or second- the possibility that the condition is secondary arily to oxytetracycline administration. 3 to concurrent disease. A condition that is Two other conditions that are worthy of 7 radiographically similar to osteopetrosis has consideration are hypervitaminosis A, and 8 been reported following experimental inocu- Scottish Fold osteochondrodysplasia. In both 4 lation of kittens with FeLV. Wright et al there is bony proliferation causing bone proposed that osteopetrosis be replaced by enlargement, but the anatomical location of diffuse osteosclerosis when describing this proliferative changes is generally around the 3 disorder. joints of the appendicular skeleton in the case We make the distinction between disorders of Scottish Fold osteochondrodysplasia, while, that cause increased bone mass without over- in hypervitaminosis A, bony proliferation caus- all increase in bone size (osteosclerosis), and es ankylosing spondylopathy of the spine, ster- disorders that cause increased bone mass and num and elbows. The cat in this report did not increased bone size (hyperostosis), and pro- have folded ears and was not fed a diet likely pose that the condition that we have encoun- to induce hypervitaminosis A. Furthermore, tered in this cat is an example of generalised the anatomical distribution of bone changes in hyperostosis. Based on the morphologic this case is atypical for both Scottish Fold osteo- appearance of the bones of the cat in this chondrodysplasia and hypervitaminosis A. report, it is unlikely that the bone changes Regional hyperostosis is a feature of several were caused by osteopetrosis. conditions reported in dogs, but so far not SHO, generally regarded as a paraneoplas- replicated in domestic cats. Craniomandibular tic disorder (although not always the case), is osteopathy affects the rami of the mandibles, characterised by bilaterally symmetrical sub - the tympanic bullae and occasionally the long 9 periosteal new bone proliferation that affects bones. It is mostly seen in small dogs of terri- the diaphyses of any long bones of the er breeds, but has been reported in large 10 appendicular skeleton, especially distally. dogs. Its onset coincides with the period of Radio graphically it is recognised by irregular bone formation in juveniles; it is often self-

We distintinguish between disorders that cause increased bone mass without overall increase in bone size (osteosclerosis), and disorders that cause increased bone mass and increased bone size (hyperostosis), and propose that the condition encountered in this cat is an example of generalised hyperostosis.

438 JFMS CLINICAL PRACTICE C A S E R E P O R T / Polyostotic hyperostosis in a cat limiting, and may regress and disappear has been postulated (but unproven) that the when bone growth is complete. There may be underlying mechanism is increased osteoblas- some crossover between craniomandibular tic activity. osteopathy and another condition of dogs, Camurati–Engelmann disease has morpho- metaphyseal osteopathy (formerly known as logical radiographic features of skull, pelvic 11,12 17 hypertrophic osteodystrophy). and long bone hyperostosis. Typically the In metaphyseal osteopathy the primary long bone changes affect the diaphyses with- radio graphic lesion is in the metaphyses of out metaphyseal or epiphyseal involvement. long bones of juvenile dogs, where osteonecro- The joints of the appendicular skeleton appear sis causes an irregular radiolucent zone in the normal. Unlike Van Buchem disease, the metaphysis roughly parallel to the growth mandible is spared. Camurati–Engelmann plate. As the disorder progresses a collar of disease is an autosomal dominant disorder extraperiosteal new bone proliferation devel- characterised by a molecular defect in the ops around the affected metaphysis, eventual- gene encoding transforming growth factor 19 ly becoming incorporated into the underlying beta-1. Affected individuals often have periosteum. Affected animals also exhibit signs Currently, painful extremities and fatigue easily. of dysfunction in other organs, due to a wide- is a mesenchymal disease spread immune-mediated vasculitis. In this we are unable that affects the skeleton and adjacent soft tis- 20 respect, metaphyseal osteopathy is a truly to determine sues. Its pathogenesis is unclear and it is polysystemic disorder, unlike craniomandibu- generally believed not to be inherited. lar osteopathy, but the proliferative metaphy- a single Affected individuals usually show extensive seal changes and occasional bone proliferation bone involvement. The flowing hyperostosis on the rami of the mandibles can create a simi- mechanism or ‘dripping candlewax’ pattern described as lar radiographic picture. Metaphyseal osteopa- or combination characteristic of melorheostosis is not always thy causes affected animals to be painful and present. Bone changes are not distributed unwell, but after appropriate treatment with of mechanisms symmetrically and may affect only one bone 21 cortico steroids the condition resolves and bone or bones of one limb. Patterns of hyper - formation returns to normal. responsible ostosis are variable, including osteoma-like, A third condition that produces regional for the bony cortical thickening and ‘dripping candlewax’. hyperostosis is the calvarial hyperostosis syn- In addition, soft tissue mineralisation such as 13 drome. This also affects juvenile dogs, to abnormalities myositis ossificans may be present. date limited to Bullmastiffs. Calvarial thicken- in this cat, but In the affected cat in this report the ing involving the frontal, parietal and occipi- increased urea concentration may be due to tal bones is an important radiographic feature. we anticipate muscle catabolism, although a renal compo- Proliferative bone changes affecting the dia- nent cannot be ruled out on account of the low physes of some bones of the appendicular a genetic basis. urine specific gravity and history of recurrent skeleton also occur in some dogs. It has been urinary tract infections. suggested that osteomyelitis may occur con- Currently, we are unable to determine a sin- currently with calvarial hyperostosis and gle mechanism or combination of mechanisms some cases have been treated successfully responsible for the bony abnormalities in this with antibiotics. patient, but we anticipate a genetic basis. In lions (Panthera leo) calvarial hyperostosis 14 Conclusions has been linked to hypovitaminosis A, a condition where hyperostosis of the occipital bone compresses the foramen magnum. The Disorders that cause bone sclerosis may be atlas is also thickened. divided into those causing increased bone In the human literature, several disorders density without modification of bone shape, present as diaphyseal hyperostosis and bear such as osteopetrosis, and those that cause some radiographic resemblance to this case; increased bone density with modification of namely, hyperostosis corticalis generalisata shape, such as metaphyseal osteopathy. In this 15,16 (Van Buchem disease), Camurati– report we describe a third subtype, a cat with Engelmann disease (progressive diaphyseal increased bone density and modification of 17 15 dysplasia) and melorheostosis. the size and shape of the osseous skeleton. By In Van Buchem disease there is hyperostosis convention, osteosclerosis refers to trabecular of the diaphyses of the long bones, mandible, bone thickening, and hyperostosis to cortical 18 calvarium, ribs and clavicles. The disease is bone thickening. Because the affected cat had described as being characterised by endosteal demonstrable cortical thickening we name the hyperostosis. Radiographically, affected bones syndrome hyperostosis. Although we have are thickened; in particular, the mandibles are anecdotal reports of several other similar impressively enlarged. The disease is inherit- examples of feline generalised hyperostosis, ed as an autosomal recessive trait. Bone this condition has not previously been report- growth is continuous throughout life, and it ed in cats.

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