title: PTH (1-34), but not strontium ranelate counteract loss of trabecular thickness and bone strength in disuse osteopenic rats.
abstract: PTH and strontium ranelate (SrR) have both been shown to reduce bone loss induced by immobilization. PTH is a potent bone anabolic agent, whereas SrR has been suggested to be an antiresorptive as well as a bone anabolic agent. The aim of the study was to investigate whether PTH, SrR, and PTH and SrR in combination could counteract immobilization-induced bone loss in a rat model. Immobilization was induced by injecting 4IU Botox (BTX) into the muscles of the right hind limb. Seventy-two female Wistar rats, 3-months-old, were divided into the following groups: Baseline, Controls, BTX, BTX+PTH, BTX+SrR, and BTX+PTH+SrR (n=12 in each group). PTH was given as injections (SC) at a dosage of 60μg/kg/d, and SrR as 900mg/kg/d in the diet. The experiment lasted for 4weeks. BTX resulted in lower trabecular bone formation rate (-68%) and periosteal bone formation rate (-91%), and a higher fraction of osteoclast-covered surfaces (+53%) compared with controls. This was accompanied by significantly lower trabecular bone volume fraction (-24%), trabecular thickness (-16%), and bone strength (-14% to -32% depending on site). PTH alone counteracted immobilization-induced losses in trabecular (4-fold increase vs. BTX) and periosteal (5-fold increase vs. BTX) bone formation rate, trabecular thickness (+25% vs. BTX) and femoral neck strength (+24% vs. BTX). In contrast, SrR did not influence BTX-induced loss of bone formation rate, trabecular bone volume fraction, trabecular thickness, or bone strength. Finally, no additive effect was found when PTH and SrR treatments were combined. In conclusion, PTH counteracted loss in bone architecture and bone strength in immobilized rats, whereas as no effect of SrR was found. Moreover, no additional effect was found by combining PTH with SrR.
authors.affiliation: Department of Biomedicine, Aarhus University, Aarhus, Denmark. mb@ana.au.dk
authors.forename: Annemarie
authors.initials: A
authors.lastname: Brüel
authors.forename: Jens Bay
authors.initials: JB
authors.lastname: Vegger
authors.forename: Anders Christer
authors.initials: AC
authors.lastname: Raffalt
authors.forename: Jens Enevold Thaulov
authors.initials: JE
authors.lastname: Andersen
authors.forename: Jesper Skovhus
authors.initials: JS
authors.lastname: Thomsen
mesh_terms: D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001696:Biomechanical Phenomena; D001835:Body Weight / Q000187:drug effects; D001851:Bone Diseases, Metabolic / Q000503:physiopathology*; D001842:Bone and Bones / Q000187:drug effects* / Q000503:physiopathology; D005260:Female; D009929:Organ Size / Q000187:drug effects; D009942:Organometallic Compounds / Q000494:pharmacology*; D010281:Parathyroid Hormone / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013876:Thiophenes / Q000494:pharmacology*; D014057:Tomography, X-Ray Computed
chemical_list: D009942:Organometallic Compounds; D010281:Parathyroid Hormone; D013876:Thiophenes; C081587:strontium ranelate; D000469:Alkaline Phosphatase