title: Calcitonin alters bone quality in beagle dogs.
abstract: Because of its antiresorptive properties, calcitonin is widely used to prevent and treat osteoporosis. A stimulatory effect of calcitonin on osteoblasts has also been reported; however, a recent histologic study points to a negative effect of calcitonin on mineralization of cancellous bone. The present experiment was performed to determine whether the observed histological signs of alterations in mineralization are also observed in cortical bone and whether this results in changes in mechanical properties, mineral densities, or mineral properties of canine bone. Sixteen female adult beagle dogs were randomly allocated to receive either human calcitonin at a dose of 0.25 mg/dog (50 IU, n = 8) or vehicle (mannitol, n = 8) every other day for 16 weeks. At the end of the study, the dogs were euthanized. Both tibiae, L1 and L5 vertebrae, and iliac crest bone samples were excised and defleshed. Torsional mechanical properties of tibial diaphyses and compressive strengths of vertebrae were measured. Bone mineral densities (BMD) of tibiae and vertebrae were measured by using dual-energy X-ray absorptiometry. Ultrastructural mineral characteristics of iliac crest bone were determined by gravimetry and Fourier transform infrared spectroscopy (FTIR). Bone histomorphometry was performed in the cortical envelope of the iliac crest. Tibiae from dogs treated with calcitonin withstood significantly less maximum torque until failure, required less torsional energy to reach the maximum torque, and had less torsional stiffness than the tibiae from dogs treated with vehicle (p < 0.05). Cancellous cores of vertebrae from calcitonin-treated dogs withstood less compressive mechanical loading than did vertebral cores from vehicle-treated animals (p < 0.05). Dogs treated with calcitonin had less BMD of both tibiae and vertebrae than vehicle-treated animals (p < 0.05). Bones from calcitonin-treated dogs had significantly less ash content, which correlated with the lower phosphate-to-amide I (detected by FTIR) and greater carbonate-to-phosphate ratios than did bones from vehicle-treated dogs (p < 0.05). Calcitonin-treated dogs exhibited a decrease in bone formation and mineralization rates and an increase in mineralization lag time. These results point to a negative effect of calcitonin on bone quality. These findings are intriguing and call for further studies addressing whether the observed abnormalities are transient or permanent.
authors.affiliation: Department of Surgery, University of Kentucky, Lexington, USA.
authors.forename: D
authors.initials: D
authors.lastname: Pienkowski
authors.forename: T M
authors.initials: TM
authors.lastname: Doers
authors.forename: M C
authors.initials: MC
authors.lastname: Monier-Faugere
authors.forename: Z
authors.initials: Z
authors.lastname: Geng
authors.forename: N P
authors.initials: NP
authors.lastname: Camacho
authors.forename: A L
authors.initials: AL
authors.lastname: Boskey
authors.forename: H H
authors.initials: HH
authors.lastname: Malluche
mesh_terms: D015502:Absorptiometry, Photon; D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D002113:Calcification, Physiologic / Q000187:drug effects; D002116:Calcitonin / Q000494:pharmacology*; D004285:Dogs; D007085:Ilium / Q000033:anatomy & histology / Q000000981:diagnostic imaging / Q000187:drug effects; D008903:Minerals / Q000032:analysis; D017550:Spectroscopy, Fourier Transform Infrared; D013977:Tibia / Q000033:anatomy & histology / Q000000981:diagnostic imaging
chemical_list: D008903:Minerals; D002116:Calcitonin