Calcium deficiency-induced secondary hyperparathyroidism and osteopenia are rapidly reversible with calcium supplementation in growing rabbit pups

Abstract

The reversibility of osteopenia secondary to isolated Ca deficiency (CaDef) is still not clear. We studied the effect of severe CaDef on Ca homeostasis and bone accrual in a 'hypercalcaemic' animal, the rabbit, during the post-weaning period and its reversibility on Ca supplementation. Male Belgian 5-week-old rabbit pups were fed CaDef diet (0.026 % Ca) for 10 weeks. As compared with those fed with a normal chow diet (0.45 % Ca), CaDef pups developed significant hypocalcaemia (P < 0.05), hypocalciuria (urinary Ca 76 (SEM 12) v. 17 (SEM 1) mg/l; P < 0.005), hypophosphataemia (serum inorganic P 100 (SEM 6) v. 65 (SEM 4) mg/l; P < 0.005), secondary hyperparathyroidism (SHPT) (serum intact parathyroid hormone human equivalent 18.2 (SEM 1.4) v. 125.0 (SEM 4.5) pg/ml; P < 0.001) and elevated serum calcitriol levels (34.0 (SEM 3.9) v. 91.0 (SEM 1.0) pg/ml; P < 0.005). Elevated urinary C-terminal telopeptide of class I collagen (P < 0.005) and total serum alkaline phosphatase (P < 0.005) suggested increased bone turnover. There was a significantly lower gain in bone mineral density (BMD) and bone mineral content (BMC) in the whole body and lumbar spine in vivo, and various sub-regions of the femur and tibia in vitro. Supplementation of adequate Ca (0.45 % Ca) after 15 weeks on the normal diet resulted in rapid catch-up growth, and resolution of SHPT. Rapid gain in various BMD and BMC parameters continued at 30 weeks of age, and both were comparable with those in rabbits on a normal diet. We conclude that Ca deficiency-induced SHPT and poor bone accrual in growing rabbit pups are rapidly reversible with Ca supplementation. The present study indicates that early intervention may be a more appropriate window period for human nutritional corrective measures.