title: A rat osteoporotic spine model for the evaluation of bioresorbable bone cements.
abstract: BACKGROUND
  As the aging population increases, the rising prevalence of osteoporosis-related spine fractures will have a dramatic impact on health care. At present, mainstay treatment relies on systemic medications intended to prevent diminishing bone mineral density (BMD) and bone mass. However, an adjunctive treatment strategy is to target specific areas of the skeletal system that are prone to clinically significant osteoporotic fractures. We term this strategy the "local treatment of osteoporosis" or osteoplasty. Potential use of osteoplasty involves the percutaneous injection of bioresorbable and bioactive bone cements into bones at risk of sustaining osteoporotic fractures. Calcium sulfate (CaSO(4)) is among the candidate bioresorbable bone cements with the material attributes desirable for potential application with osteoplasty, yet previous studies on the osteoconductive properties of CaSO(4) have been limited to animal models exhibiting normal bone biology and architecture. However, osteoporotic bone physiology may potentially interfere with the material properties of common osteoconductive biomaterials, such as that of CaSO(4). To further test this hypothesis, a suitable animal model is needed to evaluate the in vivo behavior of potential biomaterials in osteoporotic bone.
  
  
  OBJECTIVE
  The purpose of this study is to evaluate the caudal (proximal tail) rat vertebral body as an appropriate system for the in vivo evaluation of bone cement performance in the osteoporotic spine.
  
  
  METHODS
  (1) Micro-computed tomography radiomorphometry study and (2) biomechanical vertebral compression analysis.
  
  
  METHODS
  Female Sprague Dawley rats were ovarectomized (OVX) at age 8 weeks and subsequently maintained on a low-calcium diet for 3 months. Normal nonovarectomized female rats (NL) of similar age and size were maintained on regular rodent feed. Micro-CT analysis was performed on both the lumbar and caudal vertebrae (levels 5-7) of both groups. The following bone radiomorphometric parameters were determined: bone mineral density (BMD), average cortical thickness (ACT), average trabecular thickness (TbTh), and average trabecular spacing (TbSp). Strength and stiffness of both NL and OVX vertebral bodies were assessed under axial compression at 0.1 mm/s, whereas displacement (mm) and force (N) were measured at 10 Hz until completion to failure. After the implantation of an injectable form of CaSO(4) bone cement into caudal vertebrae, radiomorphometric analysis of cement volume, based on its unique CT absorption profile, was performed over the 8-week time period, as well as the subsequent bone response of both NL and OVX caudal vertebrae to CaSO4.
  
  
  RESULTS
  OVX caudal vertebrae showed an 18% decrease in BMD, a 28% decrease in diaphyseal ACT, a 55% decrease in TbTh, and a 2.4-fold increase in TbSp compared with NL (p<.05). Additionally, lumbar vertebrae exhibited a 21% decrease in BMD, a 24% decrease in anterior body ACT, a 48% decrease in TbTh, and a 4.7-fold increase in TbSp (p<.05). Failure testing of OVX caudal vertebral bodies revealed a 29% decrease in strength and a 60% decrease in stiffness compared with NL (p<.01). After implantation into OVX caudal vertebrae, CaSO(4) cement exhibited a 50% decrease in initial cement volume at 2 weeks and complete resorption by 4 weeks, whereas CaSO(4) injected into NL vertebrae exhibited a 79% decrease in initial cement volume at 4 weeks, trace amounts at 6 weeks, and complete resorption by 8 weeks. At 8 weeks, NL vertebrae implanted with CaSO(4) cement exhibited increased cortical bone thickness compared with NL sham vertebrae. This CaSO(4) cement-mediated bone augmentation was altered in osteoporotic vertebrae that exhibited porous irregular cortical bone not noted in cement-treated NL vertebrae or OVX sham vertebrae.
  
  
  CONCLUSIONS
  Future investigation of potential biomaterials intended for the local treatment of osteoporosis will require their study within an appropriate osteoporosis animal model. The OVX rat caudal spine exhibits pathologic bone changes consistent with the osteoporosis phenotype, including decreased BMD, diminished trabecular network density, cortical thinning, and decreased mechanical strength. These derangements in bone microarchitecture and physiology may contribute toward the accelerated cement resorption and altered bone response to CaSO4 observed in this study. Important advantages of the OVX rat caudal spine are the rapid and minimally invasive surgical exposure of the vertebral body and the ease of cement injection. We propose that the OVX rat caudal spine represents a valuable and cost-effective tool in the armamentarium of investigators evaluating biomaterials designed for implantation into the osteoporotic spine.
authors.affiliation: Department of Orthopaedic Surgery, University of California-San Diego, 350 Dickinson Street, Mail Code 8894, San Diego, CA 92103, USA.
authors.forename: Mark L
authors.initials: ML
authors.lastname: Wang
authors.forename: Jennifer
authors.initials: J
authors.lastname: Massie
authors.forename: Andrew
authors.initials: A
authors.lastname: Perry
authors.forename: Steven R
authors.initials: SR
authors.lastname: Garfin
authors.forename: Choll W
authors.initials: CW
authors.lastname: Kim
mesh_terms: D000042:Absorption; D000818:Animals; D001843:Bone Cements / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D015519:Bone Density; D002133:Calcium Sulfate / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use; D019245:Compressive Strength; D004195:Disease Models, Animal; D005260:Female; D015552:Injections, Intralesional; D008159:Lumbar Vertebrae / Q000000981:diagnostic imaging / Q000378:metabolism; D010024:Osteoporosis / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000209:etiology; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013131:Spine / Q000000981:diagnostic imaging / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D013623:Tail; D014057:Tomography, X-Ray Computed
chemical_list: D001843:Bone Cements; D002133:Calcium Sulfate