Using data from the Mouse Phenome Database of the Jackson Laboratory, we screened 14 strains of mice in pilot experiments on the basis of their known constitutive phenotypes which might predispose to osteonecrosis: A/J, BALB/cJ, DBA/2J (higher platelet counts); AKR/J, C3H/HeJ (higher plasma fibrinogen); B6AF1/J, B6C3F1, BALB/cBy, C3HeB/FeJ, CB6F1/J, NMRI (higher body weight); BTBR-T+tf/tf (lower prothrombin time); and C57BL/6J, CeH/HeJ (lower bone mineral density). Various regimens of oral dexamethasone in the drinking water for up to 15 weeks, methylprednisolone by intraperitoneal injection, and high-fat diets were given to a total of 185 mice from both genders of 14 strains (129 of whom were evaluable at the scheduled time point for histologic examination after 3 to 12 weeks of glucocorticoid therapy), and all bones in the appendages were evaluated histologically. The entire skeleton was evaluated using standard x-ray techniques. Osteonecrosis was identified histologically in a few mice but not radiographically. Osteonecrosis was only observed in male BALB/cJ and C57BL/6J mice on low-folate diets given dexamethasone in the drinking water. In the few animals (only 8 of 129) where osteonecrosis was identified histologically, the only joints affected were distal femurs. Osteonecrosis was not observed in controls receiving water without dexamethasone.
To decrease glucocorticoid induced infections, sulfamethoxazole/trimethoprim (280 mg sulfamethoxazole and 56 mg trimethoprim per 450 mL drinking water, three days a week) and tetracycline (1000 mg/L, seven days a week) were added to the drinking water.27 (link),28 (link) The interindividual coefficient of variation in consumption of drinking water containing dexamethasone has been reported to have a coefficient of variation of ~ 20%.29 (link)
Remaining experiments employed male BALB/cJ mice on low-folate diets, antimicrobial prophylaxis, and dexamethasone (or saline control) in the drinking water. In these definitive experiments, we evaluated only the right and left stifle joints, only by histology. A confirmatory experiment was conducted in which twelve mice were assigned to the continuous dexamethasone treatment at 4 mg/L for the first week and 2 mg/L dexamethasone thereafter until week 12.
To decrease glucocorticoid induced infections, sulfamethoxazole/trimethoprim (280 mg sulfamethoxazole and 56 mg trimethoprim per 450 mL drinking water, three days a week) and tetracycline (1000 mg/L, seven days a week) were added to the drinking water.27 (link),28 (link) The interindividual coefficient of variation in consumption of drinking water containing dexamethasone has been reported to have a coefficient of variation of ~ 20%.29 (link)
Remaining experiments employed male BALB/cJ mice on low-folate diets, antimicrobial prophylaxis, and dexamethasone (or saline control) in the drinking water. In these definitive experiments, we evaluated only the right and left stifle joints, only by histology. A confirmatory experiment was conducted in which twelve mice were assigned to the continuous dexamethasone treatment at 4 mg/L for the first week and 2 mg/L dexamethasone thereafter until week 12.
