title: [Ovariectomy and calcium/vitamin D2/D3 deficient diet as a model of osteoporosis in the spine of Sprague-Dawley rats].
abstract: BACKGROUND
  Osteoporosis is a widespread disease characterised by low bone mass and structural deterioration of bone resulting in an increased susceptibility to fractures. Osteoporosis affects women more frequently than men; every second woman older than 50 years suffers from an osteoporotic fracture, frequently a vertebral fracture. The aim of this study was to induce osteoporosis in rats to establish an osteoporotic small-animal model that simulates the human pathology particularly in the spine. Therefore, bone density parameters, which are routinely determined in the spine of osteoporotic patients, were investigated by Dual-Energy X-ray Absorptiometry (DEXA).
  
  
  METHODS
  Fourteen-week-old female Sprague-Dawley rats (n = 50) were either sham-operated (control group: sham) or ovariectomised (experimental group). Ovariectomised rats were further divided into two groups; one received calcium/vitamin D2/D3 deficient diet (OVX + diet), and the other received subcutaneous steroid injections (dexamethasone 0.3 mg/kg body weight) twice a month (OVX + steroid). Rats were scanned by DEXA at three time points (Month = M, 0 M, 1 M and 3 M). DEXA measurement of the spine delivered T-value, Z-value, bone mineral content (BMC), and the scanned area. Fifteen female patients at an age of 57-72 years were scanned in 8-10 regions of the spine (150 measurements). T-values and Z-values were pre-calculated based on patient databases. Statistical analysis was performed using two-way ANOVA followed by Bonferroni correction, with significance considered at p < 0.05.
  
  
  RESULTS
  T-value and Z-value of both rat groups were compared with the patient data as well as with each others. Both treated rat groups revealed significantly lower T- and Z-values than controls. Despite the significant difference, the reference line (-2.5 for T-value and -1.5 for Z-value) was only reached by the OVX + diet group. On the other hand, the sham group showed an increase in BMC over time, while no change was seen in OVX + diet or OVX + steroid. Bone area demonstrated a significant increase up to M3. However, the increase in bone area within the OVX + diet group was notably higher than in both sham and OVX + steroid groups. Patients showed significantly lower T- and Z-values than sham and OVX + steroid but insignificant ones when compared with OVX + diet.
  
  
  CONCLUSIONS
  A reproducible vertebral osteoporosis can be generated in a rat model by combination of ovariectomy with administration of a calcium/vitamin D3 deficient diet. T- and Z-values of this experimental group mimicked values obtained from osteoporotic patients, reflecting a simulation of their pathology. Interestingly, the increase in bone area over time with the steady BMC results in lower mineral density (BMD) of the OVX + diet group. Therefore, this rat model presents a reliable experimental set-up that may serve as a tool to better understand and treat osteoporosis.
authors: Klinik und Poliklinik für Unfallchirurgie, Universitätsklinikum Gießen und Marburg GmbH, Gießen. gudrun.schlewitz@chiru.med.uni-giessen.de
authors: G
authors: G
authors: Schlewitz
authors: P
authors: P
authors: Govindarajan
authors: N
authors: N
authors: Schliefke
authors: V
authors: V
authors: Alt
authors: W
authors: W
authors: Böcker
authors: T
authors: T
authors: Elkhassawna
authors: U
authors: U
authors: Thormann
authors: K S
authors: KS
authors: Lips
authors: N Y
authors: NY
authors: Hemdan
authors: D
authors: D
authors: Zahner
authors: R
authors: R
authors: Schnettler
authors: C
authors: C
authors: Heiss
mesh_terms: D000818:Animals; D002118:Calcium / Q000172:deficiency*; D002762:Cholecalciferol / Q000172:deficiency*; D004195:Disease Models, Animal; D004872:Ergocalciferols / Q000172:deficiency*; D005260:Female; D010024:Osteoporosis / Q000000981:diagnostic imaging* / Q000503:physiopathology; D010052:Ovariectomy; D011859:Radiography; D051381:Rats; D017207:Rats, Sprague-Dawley; D013122:Spinal Diseases / Q000000981:diagnostic imaging* / Q000503:physiopathology
chemical_list: D004872:Ergocalciferols; D002762:Cholecalciferol; D002118:Calcium