Pretreatment with anticatabolic agents blunts but does not eliminate the skeletal anabolic response to parathyroid hormone in oophorectomized mice.
Previous studies have indicated that bisphosphonate pretreatment can inhibit the anabolic actions of PTH. We examined the capacity of two anticatabolic agents with different mechanisms of action, alendronate and osteoprotegerin (OPG), to influence the anabolic activity of PTH. Oophorectomized mice were pretreated for 30 d with alendronate or OPG and then treated for 30 d with the respective anticatabolic alone or the respective anticatabolic plus PTH(1-34). Bones were analyzed by bone mineral density (BMD), microcomputed tomography, histology and histomorphometry, and biochemical bone markers. OPG pretreatment produced a greater inhibition of bone turnover and a greater increase in bone than alendronate. Increases in bone were sustained during subsequent treatment with vehicle or continued administration of the anticatabolic. Pretreatment with each anticatabolic blunted the capacity of PTH to increase BMD and bone volume and continued treatment with each anticatabolic agent also reduced the effectiveness of PTH. Although both anticatabolics decreased the maximal PTH effect, BMD and bone volume increased more when PTH was added than when only anticatabolics were used. These results demonstrate that mechanistically distinct anticatabolics may reduce PTH efficacy, that the characteristics of this inhibition may reflect the different modes of action of the anticatabolics, but that the addition of PTH still provides a skeletal benefit even if the anabolic effect is submaximal.
Samadfam
Rana
R
Calcium Research Laboratory and Department of Medicine, University Health Centre, McGill University, 687 Pine Avenue, Montréal, Québec, Canada.
Xia
Qingwen
Q
Goltzman
David
D
D019386:Alendronate / Q000008:administration & dosage / Q000627:therapeutic use*; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D001862:Bone Resorption / Q000517:prevention & control*; D001842:Bone and Bones / Q000187:drug effects* / Q000378:metabolism; D004359:Drug Therapy, Combination; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D008660:Metabolism / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000187:drug effects; D053244:Osteoprotegerin / Q000008:administration & dosage / Q000627:therapeutic use; D010052:Ovariectomy; D010281:Parathyroid Hormone / Q000494:pharmacology*
D050071:Bone Density Conservation Agents; D053244:Osteoprotegerin; D010281:Parathyroid Hormone; C506031:Tnfrsf11b protein, mouse; D019386:Alendronate