12 week-old male (castrated) and female commercial cross (for meat production) pigs, Sus scrofa
domesticaPorcine reproductive and respiratory syndrome virus (PRRSv) negative herd
Historical mortality; 2% in the nursery phase of production (3-13 weeks of age)
40% mortality from weeks 9-12 in the nursery with no response to antimicrobial therapy
Clinical signs included sudden death, seizure like activity, lameness with joint enlargement, and weakness with muscle fasciculations.
Swollen joints with increased synovial fluid, swollen chondro-costal junctions, multiple fracture
calluses on ribs, rib bones were soft and rubbery and bent 20-30 degrees before breaking
Rib bone, costochondral junction (slide Bd): Physeal cartilage is
diffusely thickened and irregular resulting in flaring of the distal metaphysis.Â Hypertrophic chondrocytes are
arranged in poorly organized columns and there are multiple islands of retained cartilage within the metaphysis.
Long tongues of cartilage remain within the primary spongiosa that are often surrounded by variably thick seams of
unmineralized osteoid which are lined by cuboidal osteoblasts.Â Chondrocytes within retained cores are variably
degenerate and occasionally lost.Â There is disorganization of primary spongiosa with multifocal fractures and areas
of hemorrhage and fibrin accumulation.Â Osteoclasts are often associated with secondary spongiosa, many of which
are present within Howships lacunae, and marrow spaces are often devoid of marrow elements and contain
moderate numbers of mesenchymal cells and variable amounts of fibrous connective tissue.Â There is multifocal
thinning of cortical bone with increased numbers of associated osteoclasts, and the periosteum is variably thickened.
Rib bone, costochondral junction: Failure of endochondral ossification
with hyperplasia of physeal cartilage and retention of cartilage cores (nutritional osteodystrophy; Rickets)
Serum Vitamin D Vitamin D analysis in serum from 10 pigs reveals no detectable (<2.0 ng/ml) amount of 25-hydroxy vitamin D3.
|Normal reference range for serum Vitamin D|
|Age of animal||25-OH-D3 (ng/ml)|
|Identification||Bone Ash||Bone density||Bone Calcium||Bone Phosphorus|
|Pig 1||0.26||1.29 g/ml||32%||16%|
|Pig 2||0.33||1.2 g/ml||36%||18%|
|Pig 3||0.37||1.27 g/ml||38%||18%|
|Pig 4||0.29||1.08 g/ml||34%||18%|
|Pig 5||0.33||1.09 g/ml||40%||18%|
|Swine; rib bone, normal references|
|Bone ash||58-62 %|
|Bone density||1.4-1.5 g/ml.|
|Bone ash Calcium||32-39%|
|Bone ash Phosphorus||13-22%|
Negative for SIV, Mycoplasma hyopneumoniae, and PRRS (lung)
Negative for Erysipelothrix rhusiopathiae, Mycoplasma hyorhinis (joint fluid)
Lung, liver, spleen, and joint fluid; No significant growth
Metabolic bone disease broadly categorizes disturbances related to bone formation and remodeling.Â Rickets and osteomalacia are metabolic bone diseases associated flawed bone mineralization in growing and adult animals, respectively.(5) The pathogenesis is similar for these diseases and is linked to imbalances of phosphorus or vitamin D.3 In some instances, there are inherited forms of rickets associated with vitamin D metabolism or renal function.Â However, most reported cases of rickets in production animal medicine are outright diet mixing errors.Â Swine are particularly sensitive to rickets development because of rapid growth and confined facilities.(5)
Swine rickets has not garnished much attention in the last few decades as most nutritional programs provide adequate phosphorus and vitamin D required for normal bone growth and homeostasis.Â However, current industry practice for diet composition in market swine is tailored for lean muscle mass growth, not bone formation.
Variations in quality or quantity of feed ingredients can cause clinical signs and lesions compatible with rickets.Â This old and well characterized disease process can be easily overlooked and forgotten.Â Investigation of recent cases of metabolic bone disease/acute deaths with high morbidity and mortality presented to the Iowa State University Veterinary Diagnostic Laboratory (VDL) ultimately led to the discovery of a feed with a base mix product inadequate in Vit D3 and recall of that product.
Vitamin D can be synthesized in the skin from 7-dehydrocholesterol following ultraviolet light exposure or be supplied in the diet.Â Dietary supplementation of vitamin D is considered a necessary practice for swine.Â Following skin conversion or small intestinal absorption, vitamin D is hydroxylated to 25(OH)D in the liver with biologically active vitamin D, 1,25(OH)D, produced thereafter in the kidney.Â The main activity of 1,25(OH)D is to regulate small intestinal calcium absorption along with lesser phosphorus absorption and inhibit parathyroid hormone.(4)
Lack of calcium absorption results in calcium mobilization from bone to maintain the finely regulated physiologic homeostasis of blood calcium concentration.Â The result of inadequate deposition or excess mobilization is metabolic bone disease.(3) If bone reserves of calcium are exhausted or delayed in release, hypocalcaemia can result in death.
Growing pigs with classic rickets will have weak bones that bend before they break.Â Enlarged growth plates can give the appearance of swollen joints.(1) Osteomalacia is usually seen in late finishing or adult swine since this is a condition of increased absorption of previously formed bone.Â Fractured femurs, vertebrae, or ribs at load out or at slaughter occur with increased frequency when there is osteomalacia.Â Lactational osteoporosis has similar features but occurs in lactating or newly-weaned sows.Â These aforementioned clinical signs are classical for metabolic bone disease.Â However, there are atypical presentations that can result in sudden death without premonitory signs.(2)
Chronic nutrient imbalances can have acute clinical manifestations other than pathologic fractures or rubbery or weak bones.Â Somewhat more unusual is the rather abrupt onset of clinical signs associated with acute hypocalcemia.Â In clinical observations from recent cases, growing pigs unexpectedly develop one or more of the following clinical signs: tremors, tetany, seizure-like muscle fasciculations, weakness, lameness, painful gait with reluctancy to move, and bone fractures (macroscopic and/or microscopic).Â Often, the first clinical sign observed in affected animals in our cases was acute death.Â In a large population of pigs, many of these clinical signs may occur simultaneously.
- Most common mechanisms of rickets in growing pigs:
- Inadequate dietary supplementation of vitamin D3
- Inadequate absorption of phosphorus due to low phosphorus in diet, phosphorus unavailable as phytate, or
- inadequate phytase usage
- Imbalance of feed calcium to phosphorus ratio; improper formulation of Ca:P ratio in diet (should be roughly 1.2:1)(2)
1.Â Rib bone: Physeal chondrodystrophy with delayed endochondral ossification.
2.Â Rib bone: Fibrous osteodystrophy.
3.Â Rib bone: Cortical osteopenia.
It is common for rickets to present with focally thickened physeal cartilage, as in this case,
which represents pockets of disorganized retained hypertrophied chondrocytes within areas of normal endochondral
ossification.Â This represents a timeline of variations of adequate and inadequate dietary vitamin D, and can look
similar to osteochondrosis; however, rickets also presents with trabecular disruption, hemorrhage, and infractions(1,5).
The moderator discussed the fact that that in rickets, the physeal cartilage is not hyperplastic, indicating proliferation of chondrocytes, but rather a failure of resorption of normal chondrocytes, and they are thus considered retained.Â For this reason conference participants preferred the term of physeal chondrodystrophy.Â This presents as a failure of orderly maturation of physeal chondrocytes, disorganization of columns of chondrocytes, irregular retention of hypertrophied chondrocytes, rare mineralized longitudinal septa formation, disorganized and thickened primary and secondary trabeculae without normal mineralized longitudinal septa, and secondary and tertiary trabeculae lined by hypertrophied osteoblasts and many osteoclasts forming howships lacunae.Â In mammals, failure of endochondral ossification occurs because blood vessels can only penetrate into the physis when there is apoptosis of chondrocytes and mineralization of the longitudinal septa, which does not occur properly due to decreased available serum ionized calcium(1).
The presence of a flared metaphysis with course spicules of chondro-osseous tissue and fibrosis in the perichondrial groove and cutback zone is due to the presence of unmineralized bone matrix that cannot be bound by osteoclasts, which are only able to bind and resorb mineralized bone.Â This is the reason for the presence of prominent thickening along costal-chondral junctions, colloquially known as rachitic rosary(1,5).
The cortex is composed mostly of woven bone with increased cortical porosity, and the cortical osteopenia is due to increased cortical lysis as a result of the attempt at calcium resorption.Â In the diaphysis, the marrow fibrosis and increased osteoclasts is mostly intracortical and endocortical, but there is some classic peritrabecular fibrous connective tissue.Â Conference participants interpreted this as fibrous osteodystrophy (FOD).Â FOD occurs along with rickets due to hypocalcemia from decreased resorption from bone and absorption from the intestines and resultant secondary hyperparathyroidism.Â In the early stages of FOD, fibrous proliferation can be subtle and the fibrous connective tissue begins and is oriented around bone spicules.Â This is in contrast to myelofibrosis, where fibrous connective tissue is oriented toward the middle of the marrow cavities(1,5).
In addition to decreased dietary phosphorus or vitamin D, rickets in young animals or osteomalacia in adults can be the result of chronic fluorosis.Â It is also theoretically possible to be caused by low dietary calcium with normal dietary vitamin D.
1.Â Carlson CS, Wesibrode, SE.Â Bones, joints, tendons, and ligaments.Â In: McGavin MD, Zachary JF, eds.Â Pathologic Basis of Veterinary Disease.Â 5th ed.Â St.Â Louis, MO:Mosby; 2011:926-7, 948-50.
2.Â Crenshaw TD: 2001, Calcium, phosphorus, vitamin D and vitamin K.Â In: Swine Nutrition, Lewis, A.Â J.Â and Southern, L.Â L., 2nd: pp.Â 187-212.Â CRC Press LLC, Boca Raton, FL.
3.Â Dittmer KE, Thompson KG: 2011, Vitamin D metabolism and rickets in domestic animals: a review.Â Vet Pathol 48:389-407.
4.Â Moe SM: 2008, Disorders involving calcium, phosphorus, and magnesium.Â Prim Care 35:215-2vi.
5.Â Thompson K.Â Bones and joints.Â In: Maxie MG, ed.Â Jubb, Kennedy and Palmers Pathology of Domestic Animals.Â 5th ed.Â Vol 1, New York, NY: Elsevier Saunders; 2007:75-80.