title: Trabecular reorganization in consecutive iliac crest biopsies when switching from bisphosphonate to strontium ranelate treatment.
abstract: BACKGROUND
  Several agents are available to treat osteoporosis while addressing patient-specific medical needs. Individuals' residual risk to severe fracture may require changes in treatment strategy. Data at osseous cellular and microstructural levels due to a therapy switch between agents with different modes of action are rare. Our study on a series of five consecutively taken bone biopsies from an osteoporotic individual over a six-year period analyzes changes in cellular characteristics, bone microstructure and mineralization caused by a therapy switch from an antiresorptive (bisphosphonate) to a dual action bone agent (strontium ranelate).
  
  
  RESULTS
  Biopsies were progressively taken from the iliac crest of a female patient. Four biopsies were taken during bisphosphonate therapy and one biopsy was taken after one year of strontium ranelate (SR) treatment. Furthermore, serum bone markers and dual x-ray absorptiometry measurements were acquired. Undecalcified histology was used to assess osteoid parameters and bone turnover. Structural indices and degree of mineralization were determined using microcomputed tomography, quantitative backscattered electron imaging, and combined energy dispersive x-ray/µ-x-ray-fluorescence microanalysis.
  
  
  CONCLUSIONS
  Microstructural data revealed a notable increase in bone volume fraction after one year of SR treatment compared to the bisphosphonate treatment period. Indices of connectivity density, structure model index and trabecular bone pattern factor were predominantly enhanced indicating that the architectural transformation from trabecular rods to plates was responsible for the bone volume increase and less due to changes in trabecular thickness and number. Administration of SR following bisphosphonates led to a maintained mineralization profile with an uptake of strontium on the bone surface level. Reactivated osteoclasts designed tunneling, hook-like intratrabecular resorption sites. The appearance of tunneling resorption lacunae and the formation of both mini-modeling units and osteon-like structures within increased plate-like cancellous bone mass provides additional information on the mechanisms of strontium ranelate following bisphosphonate treatment, which may deserve special attention when monitoring a treatment switch.
authors.affiliation: Musculoskeletal Quantitative Imaging Research Group, Department of Radiology, University of California San Francisco, San Francisco, California, United States of America.
authors.forename: Björn
authors.initials: B
authors.lastname: Jobke
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: Burghardt
authors.forename: Burkhard
authors.initials: B
authors.lastname: Muche
authors.forename: Michael
authors.initials: M
authors.lastname: Hahn
authors.forename: Jutta
authors.initials: J
authors.lastname: Semler
authors.forename: Michael
authors.initials: M
authors.lastname: Amling
authors.forename: Sharmila
authors.initials: S
authors.lastname: Majumdar
authors.forename: Björn
authors.initials: B
authors.lastname: Busse
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D001706:Biopsy; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007085:Ilium / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009942:Organometallic Compounds / Q000627:therapeutic use*; D015663:Osteoporosis, Postmenopausal / Q000150:complications / Q000188:drug therapy* / Q000473:pathology; D016103:Spinal Fractures / Q000188:drug therapy / Q000209:etiology; D013876:Thiophenes / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D055114:X-Ray Microtomography
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D009942:Organometallic Compounds; D013876:Thiophenes; C081587:strontium ranelate