Submitted on November 20, 2006
Accepted on April 24, 2007
Glucocorticosteroid-induced osteoporosis in adult primiparous Goettingen miniature pigs: effects on bone mineral and mineral metabolism
Katharina Elisabeth Scholz-Ahrens1*, Günther Delling2, Bernd Stampa3, Andreas Helfenstein4, Hans-Jürgen Hahne4, Yahya Açil5, Wolfram Timm3, Rainer Barkmann3, Joachim Hassenpflug4, Jürgen Schrezenmeir1, and Claus-Christian Glüer6
1 ; Institute of Physiology and Biochemistry of Nutrition, Federal Research Centre for Nutrition and Food - Location Kiel, Kiel, Germany
2 Department of Osteopathology, University Medical Center Hamburg-Eppendorf, Germany, Germany
3 Medical Physics Research Group, Department of Diagnostic Radiology,, University Hospital Schleswig-Holstein, Campus Kiel, United States
4 Department of Orthopaedics, University Hospital Schleswig-Holstein, Campus Kiel, United States
5 Department of Oral and Maxillofacial Surgery, Kiel University, Germany, Germany
6 Medical Physics Research Group, Department of Diagnostic Radiology, University Hospital Schleswig-Holstein, Kiel, Germany
* To whom correspondence should be addressed. E-mail: katharina.scholz-ahrens{at}bfel.de.
Information on the pathophysiology of glucocorticoid-induced osteoporosis (GIO) is limited, since its clinical picture often reflects a combined effect of glucocorticoids (GC) and the treated systemic disease. In 50 healthy adult (30 month old) primiparous Goettingen minipigs we studied the short-term (8 months, n=30) and long-term effect of GC (15 months, n=10) on bone and mineral metabolism longitudinally and cross-sectionally, as compared to a control group (n=10). All animals on GC treatment received prednisolone orally (1.0 mg/kg body weight/d for 8 weeks, thereafter 0.5 mg/kg body weight/d). In the short-term GC reduced bone mineral density (BMD) at the lumbar spine by -47.5±5.1 mg/cm3 from baseline (P<0.001), which was greater (P<0.05) than the loss (ns) in the control group of -11.8±12.6 mg/cm3. Ca absorption decreased from baseline by -2488±688 mg/7d (P<0.001) compared to -1380±1297 mg/7d (ns) in the control group. Plasma bone alkaline phosphatase (BAP) decreased from baseline by -17.8±2.2 U/l (P<0.000), which was different (P<0.05) from the value of the control group of -1.43±4.8 U/l. In the long term, bone mineral content (BMC), trabecular thickness, mechanical stability, calcium absorption, 25-hydroxyvitamin D3, 1,25-dihydroxyvitamin D3 and PTH tended to be lower compared to the control group. There was a negative association between the cumulative dose of GC and BMD, which was associated with impaired osteoblastogenesis. In conclusion, the main outcomes after GC treatment are comparable to symptoms of GC-induced osteoporosis in human subjects. Thus, the adult Goettingen miniature pig appears to be a valuable animal model for GC-induced osteoporosis.
