PTH (1–34), but not strontium ranelate counteract loss of trabecular thickness and bone strength in disuse osteopenic rats

• Published in: Bone (New York, N.Y.) Vol. 53; no. 1; pp. 51 - 58
• Main Authors: Brüel, Annemarie, Vegger, Jens Bay, Raffalt, Anders Christer, Andersen, Jens Enevold Thaulov, Thomsen, Jesper Skovhus
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Inc 01.03.2013; Elsevier
• Subjects: Alkaline Phosphatase - metabolism; Animals; Biological and medical sciences; Biomechanical Phenomena; Body Weight - drug effects; Bone and Bones - drug effects; Bone and Bones - physiopathology; Bone Diseases, Metabolic - physiopathology; Diseases of the osteoarticular system; Female; Fundamental and applied biological sciences. Psychology; Histomorphometry; Immobilization; Mechanics; Medical sciences; Organ Size - drug effects; Organometallic Compounds - pharmacology; Orthopedics; Osteoporosis. Osteomalacia. Paget disease; Parathyroid Hormone - pharmacology; PTH; Rat; Rats; Rats, Wistar; Strontium ranelate; Thiophenes - pharmacology; Tomography, X-Ray Computed; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Strontium ranelate; Immobilization; Mechanics; Rat; Histomorphometry; PTH; Antiosteoporotic; Diseases of the osteoarticular system; Rodentia; Vertebrata; Mammalia; Animal; Morphology; Spongious bone; Osteopenia; Strength; Teriparatide
• ISSN: 8756-3282; 1873-2763
• DOI: 10.1016/j.bone.2012.11.037

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 4 IU 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 60 μg/kg/d, and SrR as 900 mg/kg/d in the diet. The experiment lasted for 4 weeks. 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.