The effects of chronic vitamin D deficiency on the skeleton in the adult rabbit

Albino rabbits were fed a 1.0% Ca, 0.5% P, vitamin D-deficient diet for 11.7 to 31.3 mo. Control rabbits were fed either this diet with the addition of 2.2 units/gm of vitamin D 3 or a standard laboratory rabbit ration. Serum levels of 25-OH-D and 1,25-(OH) 2D were both undetectable in all vitamin D-deficient rabbits but were present at levels typically found in other species in the control rabbits. Vitamin D deficiency resulted in elevated serum PTH values but did not produce significant changes in serum Ca levels, femur length, femur ash weight to body weight ratio, or tibial breaking strength. The vitamin D-deficient rabbits could be readily separated into two distinct subgroups. Four of these rabbits were normo-phosphatemic (P = 3.7 ± 0.4 mg/dl) whereas the other five were severely hypophosphatemic (P = 0.8 ± 0.2 mg/dl). During the last 10 days of the study the control and normo-phosphatemic vitamin D-deficient rabbits were in positive Ca and zero P balance. The hypophosphatemic vitamin D-deficient rabbits were in zero Ca and negative P balance. This negative P balance resulted from a net intestinal secretion, as urinary P excretion was negligible. Femur ash weight as a percentage of dry weight was decreased in hypophosphatemic but not the normophosphatemic vitamin D-deficient rabbits. Histomorphometric analyses indicated the bones from the normophosphatemic vitamin D-deficient rabbits were normal. In contrast, vertebral trabecular bone from the hypophosphatemic rabbits contained large amounts of osteoid that was not mineralizing, as indicated by a failure to take up the fluorescent label calcein. Similarly, tibial cortical bone from these rabbits was also not mineralizing properly and contained localized areas of high porosity near the endosteal surface. These results indicate that, on a 1.0% Ca, 0.5% P diet, chronic vitamin D deficiency in the adult rabbit results in intestinal P malabsorption with a resulting renal P conservation. Although some vitamin D-deficient rabbits are able to maintain normal serum P levels, in other rabbits serum P levels fall dramatically. The resulting hypophos-phatemia in these rabbits leads to inadequate skeletal mineralization and the classical signs of osteomalacia.