Effects of intramuscular administration of glycosaminoglycan polysulfates on signs of incipient hip dysplasia in growing pups

We tested the hypothesis that treatment of growing, susceptible (to hip dysplasia) pups by IM administration of glycosaminoglycan polysulfates would mitigate the signs of incipient hip dysplasia. In 1 experiment, 7 pups, selected at random from 2 litters, were administered glycosaminoglycan polysulfates (2.5 mg/kg of body weight, IM) twice weekly, and 7 control pups from the same litters were given sterile buffered 0.9% saline solution from the age of 6 weeks to 8 months. Hip joints were examined by radiography, with pups in the standard, limbs-extended position. At 8 months of age, all pups in this experiment did not manifest femoral head subluxation radiographically. The Norberg angle, a measure of coxofemoral congruity, improved from a mean +/- SEM value of 102 degrees +/- 1 degree in controls to 106 degrees +/- 1 degree in treated pups (P = 0.008). Pups were not subjected to necropsy. In the second experiment, 8 pups were selected at random from 2 litters and were administered 5 mg of glycosaminoglycan polysulfates/kg, IM, twice weekly from 6 weeks to 8 months of age. Similarly, 8 control pups were administered saline solution. At 8 months of age, hip joints were examined by radiography with pups in the standard position; at necropsy, intra-articular tissues were evaluated macroscopically and biochemically. Of 8 treated pups, none had subluxation radiographically, whereas 4 of 8 control dogs had femoral head subluxation. Mean Norberg angle on the radiographs was 109.7 degrees +/- 1.6 degrees for the treated group and was 101.5 degrees +/- 1.6 degrees for controls, representing a mean improvement in coxofemoral congruity of 8.2 degrees in the treated pups. The radiographic diagnosis (normal vs dysplastic) and the Norberg angle measurements were significantly (P = 0.04 and 0.002, respectively) different for treated and control pups. At necropsy, 1 of 8 treated pups had cartilage degeneration, whereas 4 of 8 control pups had cartilage degeneration. The mean pathologic score determined for the hip joints of treated pups was 1.6 +/- 0.8, whereas for those of controls, the score was 3.3 +/- 1.2 (P = 0.09). Normal (disease-free) pups had hip pathologic scores of zero. The mean fibronectin content of femoral head articular cartilage was reduced from 2.19 +/- 0.61 microg/mg in nontreated pups to 0.59 +/- 0.56 microg/mg for treated pups (P = 0.04). Fibronectin content was used as a measure of the extent of cartilage degeneration, and the cartilage of disease-free hip joints contained 0.32 +/- 0.03 microg/mg. The mean proteoglycan content of the cartilage was unaffected by drug treatment. A trend was evident for lower synovial fluid volume and lower ligament volume (more normal volumes) in treated pups, but the differences were not statistically significant. Hip joint laxity was assessed by use of a distraction method during radiogaphy of pups in experiments 1 and 2. The differences in laxity determinations between the treated and control pups were not statistically significant. Taken together, the data indicated that IM administration of gycosaminoglycan polysulfates from 6 weeks to 8 months of age in growing pups that were susceptible to hip dysplasia resulted in less sublaxation, as determined from the standard radiographic projection. Treated pups had closer coxofemoral congruity when they were 8 months old (P < 0.05); at necropsy, the joint pathologic scores of treated pups indicated a trend toward improvement (P < 0.09), but the differences were not statistically significant. The mechanism of action for this drug effect is unknown.