Relation between the development of osteoporosis and osteonecrosis following glucocorticoid in a rabbit model

There has been a recent increase in the number of patients suffering from bone and joint diseases, as a consequence of corticosteroids administration. There are more patients treated with low dose of GCs under long-term conditions in clinical, such as effect of GCs on Rheumatoid arthritis, Crohn's disease and Asthma patients. Hence, it was difficult for doctor to determine which problem occur first - OP or ON; however, there was no clinical report previously in the literature, and there was no effective animal model of OP and ON about low dose GCs. This study was conducted to develop rabbit models of glucocorticoid (GC)-induced femoral head ON and OP and to investigate the temporal relationship between the occurrence of the two events following administration of glucocorticoids.

Fifty six, 6 months old female rabbits were randomly divided into the GC group and control group (C). Rabbits received gluteal injections of methylprednisolone sodium succinate once a day for 4 weeks, while normal saline solution in the control group. Rabbits were sacrificed at 0, 2, 4, and 8 weeks. Hip magnetic resonance imaging was performed before the rabbits were sacrificed. Serum calcium (Ca), phosphorus (P), total cholesterol, and triglyceride levels were also measured. The bone mineral density (BMD) of femoral head and the femoral shaft were measured by dual-energy X-ray absorptiometry. The trabecular parameters of the femur and the 4(th) lumbar vertebrae (L4) were measured with a micro-computed tomography (μ-CT). Also, the femoral head was stained with hematoxylin-eosin staining.

At 4 weeks in the GC group, the BMD of the femur reduced 33% and 22% in the femoral head and shaft; there was irregular intermediate to high T2-weighted images signals; μ-CT showed microfractures and cystic changes in the femoral head and L4 at 4 weeks. At 8 weeks in the GC group, the classical "line-like sign" indicating ON of the femoral head was observed in 64.3% of the rabbits.

A rabbit model of GC-induced OP and ON was developed by repetitive injection with small doses of GCs in the gluteal region. OP was observed at 4 weeks while ON developed at 8 weeks and followed a clear temporal pattern.