title: Bone structure and remodelling in stroke patients: early effects of zoledronate.
abstract: BACKGROUND
  We have reported that after an acute stroke, intravenous zoledronate prevented bone loss in the hemiplegic hip. Participants from the trial also volunteered for trans-iliac bone biopsy, to assess the early effects of stroke and zoledronate on iliac bone remodelling.
  
  
  METHODS
  Patients with acute stroke were randomly assigned to a single intravenous dose of zoledronate 4 mg or placebo within 5 weeks of stroke. Biopsies from 14 patients (3 female, 11 male, mean age 71+/-11) were suitable for analysis. These were taken at mean 10 weeks (+/-2) post-stroke, and included 5 patients who had received zoledronate. Histomorphometry was performed on undecalcified sections using light and fluorescence microscopy. Static and dynamic indices of remodelling were compared to a local reference range from healthy controls. Osteoclasts and their precursors were identified on frozen sections using tartrate resistant acid phosphatase (TRAP) staining. Dual-energy x-ray absorptiometry (DXA) of the proximal femora was performed at baseline and 6 months later.
  
  
  RESULTS
  The eroded surface in cancellous bone (ES/BS) was significantly higher in stroke patients than controls (5.7% vs. ref 1.6%, p<0.0001). Although ES/BS did not differ between zoledronate and placebo-treated groups, there were significantly fewer osteoclasts and their precursors in zoledronate-treated individuals (p=0.023). Bone formation indices (osteoid surface, OS/BS and mineralising surface, MS/BS) were significantly lower in stroke patients than controls and although OS/BS was higher in the zoledronate group than the placebo group (p=0.033), MS/BS was not different (p=0.924). There were no differences between hemiplegic and unaffected sides for any histomorphometric parameter despite asymmetric reductions in hip bone mineral density (p=0.013).
  
  
  CONCLUSIONS
  Stroke patients had higher resorption indices and lower bone forming surfaces than controls, consistent with uncoupling of bone remodelling. These findings are preliminary and a larger study is required to evaluate the contributions of gender, age and hemiplegic status to the remodelling imbalance. Zoledronate therapy was associated with a reduction in osteoclastic cell numbers consistent with its known mode of action in bone.
authors.affiliation: Division of Bone Research, Department of Medicine, University of Cambridge, Box 157, Addenbrooke's Hospital, Cambridge, England, CB2 2QQ, UK. kp254@nhs.net
authors.forename: Kenneth E S
authors.initials: KE
authors.lastname: Poole
authors.forename: Shobna
authors.initials: S
authors.lastname: Vedi
authors.forename: Irene
authors.initials: I
authors.lastname: Debiram
authors.forename: Collette
authors.initials: C
authors.lastname: Rose
authors.forename: Jon
authors.initials: J
authors.lastname: Power
authors.forename: Nigel
authors.initials: N
authors.lastname: Loveridge
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Warburton
authors.forename: Jonathan
authors.initials: J
authors.lastname: Reeve
authors.forename: Juliet
authors.initials: J
authors.lastname: Compston
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000627:therapeutic use*; D016723:Bone Remodeling / Q000187:drug effects*; D004164:Diphosphonates / Q000627:therapeutic use*; D005260:Female; D006429:Hemiplegia / Q000209:etiology; D006615:Hip; D006801:Humans; D007085:Ilium / Q000187:drug effects* / Q000473:pathology; D007093:Imidazoles / Q000627:therapeutic use*; D008297:Male; D008856:Microscopy, Fluorescence; D008875:Middle Aged; D010010:Osteoclasts / Q000187:drug effects; D010024:Osteoporosis / Q000209:etiology / Q000517:prevention & control*; D020521:Stroke / Q000150:complications*; D000077211:Zoledronic Acid
chemical_list: D050071:Bone Density Conservation Agents; D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid