Bone parameters are improved with intermittent dosing of vitamin D3 and calcitonin.
Intermittent combination of an anabolic agent to promote bone formation and an antiresorptive agent that would prevent further bone loss is a theoretically attractive approach for restoring bone mass. We tested the potential of intermittently dosed calcitriol and calcitonin (CT) to restore bone properties in ovariectomized (Ovx) rats. Rats had Ovx or sham surgery at 8 weeks old and 4 weeks later were assigned to experimental groups: (1) sham vehicle, (2) Ovx vehicle, (3) Ovx + parathyroid hormone (PTH, 40 microg/kg), and (4) Ovx + calcitriol (2 microg/kg) + CT (2 microg/kg). Group 3 received PTH every week throughout the study, and group 4 received calcitriol at weeks 1, 3, 5, and 7 and CT at weeks 2, 4, 6, and 8. Dosing was carried out for 8 weeks with serum, and micro-computed tomographic analysis was done at 0, 4, and 8 weeks. Femurs and tibias were used for radiological analyses and for mechanical testing. Dosing with PTH improved bone mass and structure of cancellous bone at metaphyses of tibias and femurs as well as properties of cortical bone including geometry and strength. Intermittent dosing with calcitriol and CT was less potent in correcting loss of cancellous bone relative to treatment with PTH and had no effect on cortical bone parameters. However, intermittent dosing with calcitriol and CT was robust enough to improve cancellous bone mass and structure through bone formation without causing deleterious side effects. Our data provide additional evidence that therapies can be devised to ameliorate the skeletal defects associated with established osteoporosis.
Andresen
C J
CJ
World Wide Comparative Medicine, Pfizer Global Research and Development, Pfizer Inc., Eastern Point Road 8274-1312, Groton, CT 06340, USA.
Moalli
M
M
Turner
C H
CH
Berryman
E
E
Pero
R
R
Bagi
C M
CM
D015502:Absorptiometry, Photon; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D016723:Bone Remodeling; D001842:Bone and Bones / Q000378:metabolism*; D002116:Calcitonin / Q000378:metabolism*; D002762:Cholecalciferol / Q000378:metabolism*; D005260:Female; D005269:Femur / Q000473:pathology; D010053:Ovary / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013314:Stress, Mechanical; D013977:Tibia / Q000473:pathology; D014057:Tomography, X-Ray Computed / Q000379:methods
D015415:Biomarkers; D002762:Cholecalciferol; D002116:Calcitonin