Strontium ranelate does not stimulate bone formation in ovariectomized rats.
BACKGROUND
Strontium ranelate (SrR) is suggested to function as a dual-acting agent in the treatment of postmenopausal osteoporosis with anti-resorptive and anabolic skeletal benefits. We evaluated the effects of SrR on the skeleton in ovariectomized (OVX) rats and evaluated the influence of dietary calcium.


METHODS
Three-month old virgin female rats underwent ovariectomy (OVX, n = 50) or SHAM surgery (SHAM, n = 10). Four weeks post-surgery, rats were treated daily by oral gavage with distilled water (10 ml/kg/day) or SrR (25 or 150 mg/kg/day) for 90 days. Separate groups of animals for each dose of SrR were fed a low (0.1%) or normal (1.19%) calcium (Ca) diet. Static and dynamic histomorphometry, DXA, mu-CT, mechanical testing, and serum and skeletal concentrations of strontium were assessed.


RESULTS
SrR at doses of 25 and 150 mg/kg/day did not increase bone formation on trabecular or periosteal bone surfaces, and failed to inhibit bone resorption of trabecular bone regardless of Ca intake. There were no improvements in bone mass, volume or strength with either dose of SrR given normal Ca.


CONCLUSIONS
These findings demonstrate that SrR at dosages of 25 and 150 mg/kg/day did not stimulate an anabolic bone response, and failed to improve the bone biomechanical properties of OVX rats.
Fuchs
R K
RK
Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, IN, USA. rfuchs@iupui.edu
Allen
M R
MR
Condon
K W
KW
Reinwald
S
S
Miller
L M
LM
McClenathan
D
D
Keck
B
B
Phipps
R J
RJ
Burr
D B
DB
D015502:Absorptiometry, Photon; D000818:Animals; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D001862:Bone Resorption / Q000503:physiopathology / Q000517:prevention & control; D001842:Bone and Bones / Q000378:metabolism; D002136:Calcium, Dietary / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical / Q000379:methods; D005260:Female; D005269:Femur / Q000187:drug effects / Q000503:physiopathology; D008159:Lumbar Vertebrae / Q000187:drug effects / Q000503:physiopathology; D009942:Organometallic Compounds / Q000493:pharmacokinetics / Q000494:pharmacology*; D010012:Osteogenesis / Q000187:drug effects*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D013324:Strontium / Q000097:blood; D013876:Thiophenes / Q000493:pharmacokinetics / Q000494:pharmacology*
D050071:Bone Density Conservation Agents; D002136:Calcium, Dietary; D009942:Organometallic Compounds; D013876:Thiophenes; C081587:strontium ranelate; D013324:Strontium