Histomorphometric and microCT analysis of bone biopsies from postmenopausal osteoporotic women treated with strontium ranelate.
Strontium ranelate is a new anti-osteoporotic treatment. On bone biopsies collected from humans receiving long-term treatment over 5 yr, it has been shown that strontium ranelate has good bone safety and better results than placebo on 3D microarchitecture. Hence, these effects may explain the decreased fracture rate.


BACKGROUND
Strontium ranelate's mode of action involving dissociation of bone formation and resorption was shown in preclinical studies and could explain its antifracture efficacy in humans.


METHODS
One hundred forty-one transiliac bone biopsies were obtained from 133 postmenopausal osteoporotic women: 49 biopsies after 1-5 yr of 2 g/d strontium ranelate and 92 biopsies at baseline or after 1-5 yr of placebo.


CONCLUSIONS
Histomorphometry provided a 2D demonstration of the bone safety of strontium ranelate, with significantly higher mineral apposition rate (MAR) in cancellous bone (+9% versus control, p = 0.019) and borderline higher in cortical bone (+10%, p = 0.056). Osteoblast surfaces were significantly higher (+38% versus control, p = 0.047). 3D analysis of 3-yr biopsies with treatment (20 biopsies) and placebo (21 biopsies) using microCT showed significant changes in microarchitecture with, in the strontium ranelate group, higher cortical thickness (+18%, p = 0.008) and trabecular number (+14%, p = 0.05), and lower structure model index (-22%, p = 0.01) and trabecular separation (-16%, p = 0.04), with no change in cortical porosity. The changes in 3D microarchitecture may enhance bone biomechanical competence and explain the decreased fracture rate with strontium ranelate.
Arlot
Monique E
ME
INSERM, Université Lyon 1, Lyon, France. Monique.Arlot@sante.univ-lyon1.fr
Jiang
Yebin
Y
Genant
Harry K
HK
Zhao
Jenny
J
Burt-Pichat
Brigitte
B
Roux
Jean-Paul
JP
Delmas
Pierre D
PD
Meunier
Pierre J
PJ
D000368:Aged; D001706:Biopsy; D016723:Bone Remodeling / Q000187:drug effects; D004311:Double-Blind Method; D005260:Female; D006651:Histocytochemistry; D006801:Humans; D007085:Ilium / Q000187:drug effects* / Q000473:pathology; D008875:Middle Aged; D009942:Organometallic Compounds / Q000009:adverse effects / Q000627:therapeutic use*; D010006:Osteoblasts / Q000187:drug effects / Q000473:pathology; D010012:Osteogenesis / Q000187:drug effects; D015663:Osteoporosis, Postmenopausal / Q000000981:diagnostic imaging / Q000188:drug therapy*; D017698:Postmenopause; D013876:Thiophenes / Q000009:adverse effects / Q000627:therapeutic use*; D013995:Time; D014057:Tomography, X-Ray Computed / Q000295:instrumentation / Q000379:methods
D009942:Organometallic Compounds; D013876:Thiophenes; C081587:strontium ranelate