J . small Anim. Pract. (1979) 20,491-500.

Scurvy as a cause of osteodystrophy Two case reports

MARIA VAANANEN A N D L. WIKMAN College of Veterinary Medicine, Helsinki, Finland

ABSTRACT

Two cases of hypertrophic osteodystrophy (HOD) showed the character- istic stigmata of scurvy. The effective treatment, for both patients, was ascorbic acid. The clinical and radiographic findings and a discussion of the possible causes of hypovitaminosis C are presented.

INTRODUCTION

The experiments of Innes (1 93 1) and Naismith (1958) clearly seem to indicate that dogs are independent of an exogenous supply of vitamin C. Nevertheless, skeletal changes typical of scurvy have been reported in young dogs (Meier et al., 1957; Holmes 1962). Grondalen (1976), Rendano, Dueland & Sifferman (1977) and Alexander (1 978) consider the pathogenesis of hypertrophic osteodystrophy (HOD) to be obscure and in fact claim it to be multifactorial.

In the autumn of 1977 the present authors diagnosed two cases of HOD, where the clinical and radiographic symptoms strongly resembled those seen in infantile scurvy (Muller-Barlow). The effective treatment was 3000 mg of ascorbic acid intravenously daily.

CASE REPORTS

Patient I A 5-month-old German Shepherd was suffering from fever, diarrhoea and

anorexia for several days. Because treatment with tetracyclines and acetosalicylic

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49 2 M. VAANANEN A N D L. W I K M A N

acid did not relieve the symptoms, the dog was referred to the Small Animal Clinic at the College of Veterinary Medicine in Helsinki.

The dog had been fed mainly homemade food with fish added three or four times a week. It had been given mineral supplement (Ca: P ratio 6 : 1) and vitamin B preparations daily. The owner had been treating the diarrhoea with sour milk preparations, without permanent success. The dog had not been vaccinated against distemper nor contagious hepatitis.

Upon clinical examination the following features were noted: temperature 40°C, severe diarrhoea, swelling of the distal joints of the limbs and inability to stand. The dog yelped loudly upon palpation of the legs and the pain was of equal severity in all legs.

Radiographic findings were pronounced and bilaterally symmetrical in the lower metaphyses of the radius and ulna and in both metaphyses of the tibia and femur. A ring of increased density around the centres of ossification was evident. Transverse linear radiolucent defects were seen adjacent to the metaphyses, together with minimal infractions of the metaphyses. Calcifying subperiosteal haematomata and an overall osteoporosis were found.

The dog was given 500 mg of ascorbic acid i.v., 0.6 g phenylbutazone, an intestinal antibiotic and a suspension of penicillin-streptomycin. The diet was corrected according to NRC recommendations (Anon., 1972) and the treatment was continued for 4 days, The pain seemed to decrease a little and the dog was able to stand. However, on the fourth day, there was a severe relapse with high fever, inability to stand and swelling over the distal joints of the limbs. The diarrhoea also recurred and the clinical condition of the dog was estimated as very severe. As the usual amount of ascorbic acid, given in HOD (500 mg/day), did not have any demonstrable effect, it was decided to increase the dose gradually to 3000 mg/day i.v. and to discontinue all other medication.

The clinical condition of the dog improved steadily and it exhibited only slight discomfort when walking, the appetite became excellent and the diarrhoea sub- sided (Fig. 1). After 2 weeks of this treatment the dog was discharged from the clinic with a treatment of 2500 mg of ascorbic acid daily per os. Dietary instruc- tions were given according to NRC recommendations. The dog has been well ever since and their has been no recurrence of the condition. However, 2 months after being discharged, the owner reported polydipsia and sore lips. After an examina- tion of the patient the dose of ascorbic acid was reduced to 500 mg/day and these symptoms disappeared (Fig. 2).

During the course of the disease there was no bleeding from the gums, ecchymoses of the skin nor melaena, all of which are seen in infantile scurvy of children. During recovery the metaphyses assumed, radiographically, a more homogenous appearance. Ossification began in the zone of disorganization, the lattice seemed to disappear slowly and normal trabecular bone was being formed. The mineralized haematomata seemed to decrease and were obviously under- going very active resorption (Fig. 3).

S C U R V Y AS A C A U S E OF OSTEODYSTROPHY 493

FIG. 1. Patient 1 . Four-month-old German Shepherd, after a week of treatment with ascorbic acid. The dog is still severely ill but is able to walk. The swellings above the joints

are clearly seen (arrowed).

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FIG. 2. Patient 1, the same dog as in Fig. 1 after 2 months of treatment with ascorbic acid. The swellings above the carpal joints have almost disappeared and the dog seems clinically

well.

Patient 2 A 4-month-old, male Great Dane, which had been suffering from similar

symptoms to patient 1, arrived at the clinic 1 week after the onsetlof symptoms. The dog had not been walking and the temperature had been around 39°C. Upon clinical examination the following symptoms were noted: stiffness, reluctance to walk and marked pain and tenderness over the joints, especially over the knees and hooks, which were swollen. A particular enlargement of the frontal bone was

FIG. 3. Patient 1, antero-posterior view of right radius/ulna during disease. (a) At the beginning periosteal haematomas (arrowed) are seen around the metaphyseal regions. Thickness of epiphyseal lines is normal. (b) A week later periosteal reactions are more extensive. More calcification is seen. Note swellings of soft tissue (arrowed) medially. (c) Radiographical findings 2 months after treatment with ascorbic acid. In the antero- posterior aspect the periosteal haematomas are resorbed. On the lateral aspect a calcified

haematoma (arrowed) is seen caudally on ulna.

496 M . VAANANEN AND L . W I K M A N

evident. Radiographic findings were similar, but more severe, than those of patient 1 (Fig. 4).

The dog was immediately given 3000 mg of ascorbic acid intravenously and no other treatment was prescribed for the following days. Forty-eight hours after commencement of treatment the dog was able to stand when lifted to its feet and it was willing to walk a little. The improvement continued and after 4 days there was no fever, the appetite was sufficient and the dog was able to walk. As the improvement persisted the dog was discharged after 12 days of treatment, with a prescription of 2500 mg of ascorbic acid daily per 0s. Dietary instructions were given according to NRC recommendations.

After a month the dog was re-examined and appeared clinically healthy. Blood samples and radiographs were obtained and the dog was sent home, with the same prescription as before for 4 weeks.

LABORATORY FINDINGS

The serum values of calcium, phosphorous and alkaline phosphatase are shown in Table 1. The values for calcium and phosphorus can be considered normal. The high value of phosphorous in patient 2, after the treatment, was attributed to

TABLE 1. Serum values of Ca, P, Afos and SAA (serum ascorbic acid) initially and 2 months after treatment

Initially Two months after treatment

Ca P Afos Ca P Afos SAA mmol/l mmol/l I.U. mmol/l mmol/l I.U. mg/100 ml

Patient 1 2.5 2.6 294 2.7 2.42 171 0.5 Patient2 2.5 2.1 555 2.8 3.22 403 0.7

incomplete adherence to the dietary instructions. The values of alkaline phospha- tase are higher than normally, in growing dogs, but there is a diminishing trend as the dogs recover. The SAA-values, taken after clinical recovery, were below the mean values obtained by Meier et al. (1975) and Grondalen (1 976) being 0.8-2-0 mg/100 ml and 0.93 mg/100 ml respectively. Otherwise haematology and blood chemistry were normal.

FIG. 4. Patient 2, antero-posterior view of right radius/ulna during disease. (a) At the beginning of treatment the patient was unable to stand. The radiograph shows a scorbutic lattice at the distal end of radius/ulna. No periosteal reactions are yet to be seen. (b) Radiographical findings 1 week later. Scorbutic lattice (arrowed) is more clearly seen. (c) After 1 month of intensive treatment with ascorbic acid the lattice has disappeared. On the lateral aspect, however, a calcified haematoma (arrowed) can be seen caudally on ulna.

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DISCUSSION

The predominant trait of scurvy is a failure in the biosynthesis of collagen resulting from hypovitaminosis C (Kivirikko & Risteli, 1976). The collagen bundles in the intracellular ground substance disappear and the ground substance becomes thin and watery in appearance.

In the growing skeleton impaired osteoid formation, in the metaphyses and in the periphery of the centres of ossification, delays growth. Because the deposition of calcium salts continues within the preformed osteoid-tissue an increased density will develop. This increased density is seen on radiographs as the ‘white line’ of scurvy adjacent to the epiphyseal plate. Osteolytic resorption, associated with remodelling during growth, will result in a generalized osteoporosis, with a translucent medullary pattern and thin cortices. Hence the metaphyseal border is especially liable to fractures upon minimal stress. Since deficiency of vitamin C also causes increased capillary fragility (Kivirikko & Risteli, 1976) subperiosteal haemmorhages appear with minimal injury to the bone. The calcification of these haematomata make them visible on radiographs.

The changes of HOD in our two cases show the characteristic stigmata of scurvy. The diagnosis was confirmed by the treatment, where ascorbic acid (3000 mg/day i.v.) alone relieved both clinical and radiographic signs.

It is generally assumed that dogs are able to synthesize an adequate amount of vitamin C in the liver (NRC, 1972). However, several mechanisms can cause hypovitaminosis C, as Holmes (1962) has suggested.

1. Failure to synthesize the vitamin. 2. Failure to absorb the vitamin from the site of synthesis. 3. Inability to utilize the vitamin at sites of growth. 4. Inability to store sufficient vitamin. 5 . Excessive loss by excretion in the urine. 6. Excessive requirements, exceeding supplies. 7. The presence of some factor antagonizing or interfering with the

He also states that several of these mechanisms may operate simultaneously. In our opinion the answer is to be found along these guidelines.

It would be logical to assume that the ability to synthesize vitamin C can be impaired during states of liver disease. The liver of young growing puppies will be under stress when they are vaccinated against distemper and HCC and the biosynthesis of vitamin C may temporarily be out of order. It is also possible that the mere growth, in large fast-growing breeds, requires such an enormous amount of collagen that the ability of the liver to produce a sufficient amount of vitamin C is exceeded. When the symptoms of scurvy in dogs are compared with those of children it has to be remembered that dogs grow much more rapidly than children during the first few months.

metabolism of the vitamin.

S C U R V Y AS A CAUSE OF OSTEODYSTROPHY 499

In addition to disturbances in vitamin C metabolism and mineral overloading, Grondalen (1976) suggests the presence of an infectious agent as an aetiological factor in HOD. The possibility of an infectious agent is concluded from the diarrhoea which is often present and the extremely elevated temperatures of such patients. According to her it seems possible that the diarrhoea promotes a slight malabsorption of minerals and vitamins from the intestines. She estimates the prognosis of the condition as being good and concludes that therapy is un- necessary. Several authors have also reported slight pneumonic reactions in their HOD-patients (Grondalen, 1976; Rendano et al., 1977). Vitamin C is necessary for the synthesis of glucocorticosteroids (Perek & Kendler, 1969) and for comple- ment fixation, which is of importance for non-specific immunity (Panda & Ray, 1970). Vitamin C deficiency, therefore, increases the risk of infection, which explains the existing broncho-pneumonia and enteritis seen in patients suffering from HOD. Hence the osteological changes, the pneumonia and the enteritis are manifestations of the same aetiological factor and have no causal relationship to each another. In our experience HOD definitely needs a specific therapy, even though the symptoms of elevated temperature and diarrhoea need no specific therapy, but will subside as recovery from HOD proceeds.

The larger breeds are getting more popular and the feeding of animals is, to an increasing extent, based on commercial dry-foods. Often the feeding regimen is also very one-sided. The vitamin C in food will keep for 3 4 months, but humidity and alterations in temperature will speed its deterioration. Therefore it would be advisable to supply vitamin C to dogs of the giant breeds during their most intensive period of growth at the age of &8 months. It would be important to be able to estimate the exact amount to be added and this merits further study. However, vitamin C is remarkably atoxic, water-soluble and does not accumulate in the body.

ACKNOWLEDGMENT

The authors wish to thank the Department of Anatomy and Embryology at the College of Veterinary Medicine of Finland for encouraging criticism during the work.

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