Dietary-Related Skeletal Changes in a Shetland Sheepdog Puppy
A commercially available, renal failure diet was used to manage suspected renal failure in a 10-week-old Shetland sheepdog puppy. Rickets subsequently developed, possibly from low phosphorous intake and an increased calcium to phosphorus ratio. Decreased dietary calcium in addition to decreased phosphorus may have played a role in decreasing bone mineral density. Lethargy, decreased long bone growth, angular limb deformity, and osteopenia occurred, but these signs resolved within 3 months with nutritional management.
Introduction
Many factors contribute to bone mass and growth, including nutrition. In response to inadequate intake of multiple nutrients, the structure of bone becomes compromised. Growing animals show effects of nutritional stresses more acutely than mature animals, as they have less skeletal mass and are depositing and remodeling bone at a rapid rate.1
Dietary-induced rickets is a disease of the developing skeleton characterized by defective mineralization of bone as well as the cartilaginous portion of the growth plate.2 The disease combines defective calcification of the epiphyseal cartilage, delay in maturation and arrangement of cartilage cells, and a failure to remodel freshly deposited bone. These defects eventually weaken the diaphysis of long bones and may lead to bending deformities.2 Metaphyseal regions are widened from accumulation of newly formed cartilage that fails to mineralize.2 The disease arises most commonly from inadequate intake or endogenous production of vitamin D, but rickets lesions can also occur secondary to decreased phosphorous intake or an increased calcium to phosphorus ratio.1–6
Case Report
A 10-week-old, intact female Shetland sheepdog was examined by the referring veterinarian for a 4-day history of vomiting and lethargy. The only abnormalities found on serum biochemical analysis included a marked increase in blood urea nitrogen [BUN] (142 mg/dL; reference range 21 to 30 mg/dL) and creatinine (4.5 mg/dL; reference range 0.5 to 0.6 mg/dL) and hypocalcemia (7.1 mg/dL; reference range 10.5 to 12.1 mg/dL).7 Phosphorus was not measured. The urine was isosthenuric (specific gravity of 1.012; reference range 1.001 to 1.070), but the puppy had received some intravenous (IV) fluids. Differential diagnoses included acute renal failure or prerenal azotemia. With IV fluid therapy, the puppy’s appetite and attitude improved, and it was discharged on a commercially available, dry renal failure diet (99 grams per day).a
Ten weeks later, the puppy (at 20 weeks of age) was referred to the University of Illinois Veterinary Teaching Hospital (UI-VTH) for evaluation of an abnormal gait and failure to grow. The skeletal abnormalities in the limbs developed subsequent to the episode of renal failure. At presentation, the 4.3-kg puppy appeared shorter than normal, had a body condition score of 3/5, and a poor hair coat. Prominent metaphyses were noted in the distal aspect of the long bones [Figure 1]. No pain was elicited on palpation of the bones and joints. Varus deformation was symmetrical in both thoracic limbs, and the range of flexion was decreased symmetrically in both carpi.
On a serum biochemical profile, hypophosphatemia (2.8 mg/dL; reference range 7.2 to 10.1 mg/dL) and mildly elevated BUN (20.8 mg/dL; reference range 7 to 19 mg/dL) were noted.7 The serum intact parathyroid hormone (PTH) concentration was low (1.7 pmol/L; reference range 2 to 13 pmol/L), whereas ionized calcium was normal (1.44 mmol/L; reference range 1.25 to 1.45 mmol/L). A complete blood count (CBC) was within normal limits. A urinalysis was not obtained at presentation. Abdominal ultrasonography was performed to investigate the previously suspected renal disease, and the architecture of the kidneys appeared normal. Lateral and anterior-posterior radiographs of both tibia and radii were obtained. Metaphyseal flaring was especially obvious in the proximal metaphyses of both radii and tibia, as well as in the distal metaphysis of both ulnae [Figure 2]. The physes generally appeared thickened and irregular, with hazy borders. A cup-shaped area of decreased mineralization was found in the distal metaphyseal region of both thoracic limbs.
Based on the clinical findings, differential diagnoses included metabolic bone disease, growth hormone deficiency, and congenital hypothyroidism. The clinical abnormalities were believed to be secondary to nutritional bone disease associated with dietary management of the puppy during the preceding 10 weeks. The therapeutic diet fed to this puppy is recommended as a nutritional aid for dogs with renal failure and moderate heart disease, but it is below National Research Council (NRC) recommendations for growth, especially with respect to phosphorous and protein content.b,c The puppy was started on a dry, commercially available puppy diet designed for use in growing puppies.d The amount initially recommended was 160 grams per day. This food was fed throughout the observation period, and the owners were instructed to follow the manufacturers’ feeding recommendations as body weight increased.
Both the affected puppy and her littermate were examined 3 weeks later (at 23 weeks of age). The affected puppy’s hair coat had improved, and her activity level had increased, yet she was still smaller and weighed less than her littermate [Table 1; Figure 3]. Prominent metaphyses and angulation of the forelimbs persisted on physical and radiological examination [Table 1]. The radiographic appearance of all tibial and radial physes had improved (i.e., they were thinner, with more distinct borders). The cup-shaped area of demineralization on the ulnar metaphyses was markedly decreased [Figure 4].
Results of a serum biochemical profile showed that the serum phosphorous concentration had increased dramatically (9.6 mg/dL; reference range 7.2 to 10.1 mg/dL), mild hypocalcemia persisted (9.3 mg/dL; reference range 9.8 to 12.4 mg/dL), and the BUN was slightly elevated (20.1 mg/dL; reference range 7 to 19 mg/dL).7 Urine specific gravity was 1.028. The PTH concentration was not repeated. Whole-body bone mineral composition was analyzed in both dogs via dual-energy X-ray absorptiometry (DEXA).e Positioning and landmarks were kept constant throughout all evaluations. Bone mineral density (BMD) of a standardized region of interest (first cervical vertebra [C1] through the 13th thoracic vertebra [T13]) was also determined in each dog initially and measured sequentially in the affected puppy. Although the affected puppy had been fed an appropriate diet for 3 weeks prior to performing the DEXA, the BMDs measured of the whole-body analysis (0.483 gm/cm2) and in the region of interest (0.350 gm/cm2) were both lower than those of the normal littermate (0.593 gm/cm2 and 0.453 gm/cm2, respectively) [Figure 5]. Because of the dramatic radiographic improvement following institution of an appropriate diet, other potential differential diagnoses to explain the growth abnormalities observed in this puppy were considered less likely and were not pursued further.
At a 15-week recheck (at 35 weeks of age), the puppy was still markedly smaller and weighed less than the normal littermate. The distal metaphyseal regions were less prominent, and the limb angulations had resolved [Table 1]. Serum biochemical analysis and urinalysis were normal. On a DEXA scan, the puppy’s whole-body composition BMD (0.607 gm/cm2) and the region-of-interest BMD (0.443 gm/cm2) had increased.
Both dogs were reevaluated 10 months (at 19 months of age) after initial presentation. Both dogs were similar in size and weight [Table 1; Figure 6]. A CBC, serum biochemical profile, and a urine specific gravity were normal. All growth plates appeared closed on radiographs of the radii. Joint alignment remained within normal limits [Table 1]. Bone mineral densities as whole-body composition and over a region of interest were similar in both dogs [Figure 5].
Discussion
The clinical and radiographic findings described in this puppy were consistent with dietary-induced rickets. Radiographic lesions consistent with rickets are most prominent at epiphyseal growth plates. Metaphyses are usually widened from the accumulation of newly formed cartilage that fails to mineralize. Decreased calcification of the hypertrophic zone produces a ragged and cup-shaped appearance of metaphyseal borders.2 The puppy described in this case report had radiographic abnormalities (i.e., flaring of the metaphyses, bowing of long bones, and poor epiphyseal cartilage mineralization) consistent with rickets.
Rickets in dogs has most commonly been associated with vitamin D deficiency, although naturally occurring cases are rare.2–4 A definitive diagnosis of vitamin D-deficient rickets is made by detecting reduced concentrations of the storage form of vitamin D in the blood.2 Although vitamin D concentrations were not evaluated in this case, PTH levels were below the reference range. In both nutritional hyperparathyroidism (i.e., calcium deficiency) and vitamin D-deficient rickets, PTH concentrations are often markedly elevated in an attempt to maintain ionized calcium concentrations.2 In this case, PTH concentrations were likely decreased in an attempt to conserve phosphorus. Vitamin D deficiency was also unlikely in this case, because the commercial renal diet fed to the puppy contained vitamin D concentrations that were above the recommended minimum for growth [Table 2]. In general, vitamin D-deficient rickets has become rare, as most commercial pet foods contain between two and 10 times more vitamin D than the minimal requirements recommended by the Association of American Feed Control Officials (AAFCO).8–11
Congenital inborn errors in vitamin D metabolism may cause similar skeletal lesions and have been documented in a Saint Bernard dog.12 All signs in this dog resolved with administration of a synthetic analogue of the active form of vitamin D (i.e., dihydrotachysterol).12 If the puppy described in this report had suffered from inborn errors in vitamin D metabolism, no improvement would have occurred with a change of diet, so this defect was considered unlikely.
Therapeutic renal diets generally differ from diets designed for growth, in that their phosphorous, calcium, and protein content is restricted. The protein in renal diets is of high quality; however, the renal therapeutic diet initially fed in this case did not meet absolute daily NRC requirements for growth with respect to phosphorus, calcium, and protein [Tables 2, 3]. Energy intake was also inadequate based on the reported amount fed [Table 3]. In addition, the calcium to phosphorus ratio was abnormal. Because the clinical signs of the affected puppy were consistent with deficiencies of nutrients known to be lacking in the diet and improvement of signs occurred in response to nutritional correction of these deficiencies, diet was thought to be the most likely cause of the orthopedic disturbances. A definitive diagnosis of rickets requires histopathology, and a bone biopsy would have provided valuable information regarding the underlying pathological process causing the changes seen in this case. However, for practical reasons and after considering the clinical improvement following empirical dietary change, this procedure was not performed. Additional support for a presumptive diagnosis of dietary-related skeletal changes was obtained from DEXA scans.13 The use of DEXA scans in this case allowed a direct comparison between the two littermates and objective evaluation of the improvement after corrective dietary changes.
Young, growing animals have an increased requirement for calcium to mineralize newly formed cartilage and osteoid.8 Decreased calcium absorption, either from low dietary calcium content or poor bioavailability, can cause a decrease in calcium available for mineralization. Reduced circulating calcium causes a compensatory rise in PTH, which eventually increases osteoclasia and synthesis of active vitamin D metabolites.8 Vitamin D metabolites and PTH stimulate calcium and phosphate reabsorption from bone.8,14 Skeletal deformities such as bowing of the long bones and calcaneus, compression fractures of cancellous bone, and greenstick fractures of the long bones can result from hypocalcemia.8 Low dietary calcium intake may have contributed to the low BMD seen clinically in this case. However, in pure calcium deficiency, bony changes do not usually occur at the growth plates, as seen in this puppy.8 In cases of skeletal disease secondary to decreased calcium intake, PTH concentration would also usually be increased. In the puppy of this report, PTH was low. Low dietary calcium intake combined with an adequate supply of vitamin D during growth results in poor bone mineralization, but cartilage mineralization is undisturbed.14 In cases of nutritional calcium deficiency with decreased mineralization, providing an appropriate diet will result in sufficient mineralization within 3 weeks.8 In this case, calcium contributed to decreased BMD. Bone mineral density was not measured at initial evaluation, and although the BMD in the puppy of this study was still lower than the normal littermate’s after having been on an appropriate diet for 3 weeks, there was already a marked improvement in BMD noted radiographically. The expected difference between the two dogs would have been greater if BMD had been measured on initial presentation. Although calcium contributed to decreased BMD, it would not be responsible for changes occurring at the growth plate in this case.
Although calcium makes up 40% of the bone mineral, phosphorus accounts for nearly 60%.2 Hypophosphatemia eventually slows bone matrix deposition and osteoblast initiation of mineralization, thereby preventing rapid bone growth.2 Over time, decreased serum phosphorus leads to a rise in 1, 25 (OH)2 vitamin D concentrations and an eventual increase in calcium concentrations. Parathormone concentration declines secondary to the hypercalcemia and enhances calcium and reduces phosphorous clearance.14 Reduced dietary phosphorus can cause histological changes in bone that are consistent with rickets.1 Rickets has been documented in a group of research puppies fed diets containing <0.17% of phosphorus on a dry-matter basis. Growth abnormalities were noted consistently in puppies consuming diets containing <0.25% phosphorus on a dry-matter basis.6
In addition to appropriate absolute mineral content, the calcium to phosphorus ratio affects bone metabolism. The AAFCO-recommended calcium to phosphorus ratio for growth is 1:1; however, a range of 1.0:1 to 2.0:1 is accepted.10,15 In one study, Great Danes fed a diet with an increased calcium content (3.11 g/100 g dry matter) without an increase in phosphorus (0.87 g/100 g dry matter; calcium to phosphorus ratio of 3.57:1) developed skeletal disturbances typical of rickets.5 These lesions resolved after 3 weeks of appropriate nutritional management.5 In the same study, dogs fed increased levels of calcium (3.1 g/100 g dry matter) and phosphorus (2.77 g/100 g dry matter) with a normal calcium to phosphorus ratio (1.12:1) had normal mineralization of bone.5 The normal ratio was thought to be important in that it allowed for the formation of calcium-phosphorous complexes required to calcify osteoid.5 In the case described in this report, the commercial renal diet fed contained only 0.25 g/100 g dry matter of phosphorus and 0.80 g/100 g of calcium, and it had an elevated calcium to phosphorus ratio of 3.2:1.f The decreased phosphorous intake and abnormal calcium to phosphorus ratio were thought to be responsible for the decreased bone mineralization and the other clinical signs consistent with rickets.
Linear growth and long bone development depend on the production of osteoid within which mineral deposition can take place.16 Decreased osteoid production will in turn result in a smaller volume of bony matrix available to be mineralized, and this ultimately leads to decreased BMD.16 Insufficient intake of both protein and energy can result in growth retardation and ultimately cessation and weight loss.16 Studies in animals and humans strongly suggest that low protein intake impairs bone development and decreases preservation of bone integrity with aging.17 The protein and energy intake in this case was below NRC requirements for growth at some instances during this puppy’s development [Table 3]. Therefore, it is possible that these deficiencies may have contributed to the skeletal abnormalities seen in this case.
The puppy described in this case report showed an improvement in bone mineralization, growth plate flaring, and energy level when a proper growth diet was instituted. Based upon response to the diet, it appeared that decreased phosphorous intake and an increased calcium to phosphorus ratio resulted in the growth disturbances observed. Decreased calcium intake may also have contributed to the decreased BMD. It was unknown if concurrent protein-calorie malnutrition simply decreased osteoid production or also decreased the concentration and the effects of growth mediators such as insulin-like growth factor-1.
Conclusion
A 10-week-old Shetland sheepdog being fed a renal therapeutic diet developed clinical and radiographic changes compatible with rickets. The diet contained phosphorous, energy, and protein concentrations that did not meet the published NRC requirements for growth, and absolute daily requirements were also inadequate. Bony lesions were attributed to an inadequate phosphorous intake and increased calcium to phosphorus ratio. Decreased calcium intake and protein caloric malnutrition may have also contributed to the orthopedic changes and low body weight of the puppy, both of which improved when the puppy was switched to an appropriate diet designed for growth.
Prescription Diet Canine k/d; Hill’s Pet Nutrition, Inc., Topeka, KS 66601
National Research Council Data, 1985; National Academy Press, Washington DC 20418
National Research Council Data, 1974; National Academy Press, Washington DC 20418
Science Diet Puppy; Hill’s Pet Nutrition, Inc., Topeka, KS 66601
Hologic QDR2000; Hologic, Inc., Waltham, MA 02425
Data from Hill’s Key to Clinical Nutrition, 2004; Hill’s Pet Nutrition, Inc., Topeka, KS 66601
Acknowledgment
The authors thank the owners of Sonoma and Shadow for providing the opportunity to reevaluate Sonoma and for allowing comparisons with her littermate.
Citation: Journal of the American Animal Hospital Association 42, 1; 10.5326/0420057
Citation: Journal of the American Animal Hospital Association 42, 1; 10.5326/0420057
Citation: Journal of the American Animal Hospital Association 42, 1; 10.5326/0420057
Citation: Journal of the American Animal Hospital Association 42, 1; 10.5326/0420057
Citation: Journal of the American Animal Hospital Association 42, 1; 10.5326/0420057
Citation: Journal of the American Animal Hospital Association 42, 1; 10.5326/0420057
A 20-week-old, female Shetland sheepdog with varus deformation of the forelimbs and swelling proximal to the carpi.
The affected dog (right) and normal littermate (left) at 23 weeks of age after the affected dog had been fed an appropriate growth diet for 3 weeks. Note the difference in size, the dramatic bowing of the forelimbs, and swelling proximal to the carpi of the affected dog compared to the normal littermate.
Lateral radiograph of the left forelimb of the dog in Figure 2 at 23 weeks of age, after the puppy had been fed an appropriate growth diet for 3 weeks. Note the dramatic improvement in skeletal mineralization. The growth plate is thinner, and the area of cartilaginous demineralization is almost gone (arrow).
Bone mineral density (BMD) measured by dual-energy X-ray absorptiometry of the affected dog and its normal littermate. The overall body composition BMD (affected BMD) and the BMD of a standardized region of the thoracic spine (affected region BMD) of the affected puppy are both lower than the corresponding measurements of the normal littermate (normal BMD, normal region BMD) early in the clinical course. Overall and regional BMDs of the affected puppy increased after the diet was changed and reached values comparable to those of the normal littermate by 10 months.
The affected dog (right) and normal littermate (left) at 19 months of age (10 months after initial presentation). The limb angulations have completely resolved, and the body weight of the affected dog was comparable to its littermate.
