Withdrawal of parathyroid hormone treatment causes rapid resorption of newly formed vertebral cancellous and endocortical bone in old rats.
When administered intermittently, parathyroid hormone (PTH) is a strong anabolic agent, increasing both bone mass and bone mechanical strength and competence. This study evaluates the fate of PTH-induced bone in vertebral bodies after withdrawal of PTH treatment in normal old rats. Sixty-seven 21-month-old male rats were treated with 62 microg/kg/day PTH(1-34) for 8 weeks, followed by saline or bisphosphonate (risedronate, 5 microg/kg twice a week) for another 8 weeks. The rats were scanned by dual-energy X-ray absorptiometry at intervals. The bone mineral content (BMC) of L2-5 increased by 33% during the PTH treatment. The BMC started decreasing shortly after withdrawal of PTH and continued to decline during the 8 weeks after withdrawal of PTH. Risedronate, however, prevented this decrease in BMC. All rats were labeled with tetracycline and calcein 3 weeks and 1 week before the cessation of PTH therapy. In the cancellous bone, PTH increased the mineralized surface: 32.9% +/- 2.8% (mean +/- standard error of the mean) vs. controls 12.0% +/- 1.5%, the mineral appositional rate (0.65 +/- 0.02 to 0.88 +/- 0.06 microm/day), and the cancellous bone volume (BV/TV: 14.5% +/- 0.7% to 27.5% +/- 1.7%). Withdrawal of PTH induced a fast and pronounced bone resorption, decreasing both the extent of the fluorochrome labels and the cancellous bone volume to control values. Risedronate prevented this resorption. In the cortical bone of the vertebral shell, PTH induced large increases in the endocortical mineralized surface, mineral appositional rate, and cortical area. The endocortical fluorochrome labels were, however, resorbed after withdrawal of PTH. Risedronate maintained both the fluorochrome labels and the cortical area. At the periosteum, the response to PTH was less evident, however, and hardly any labeling was seen at the periosteum facing the vertebral canal either in the controls or in the PTH-treated rats. The compressive strength of the vertebral body specimens increased with PTH treatment whether measured in newtons (317 +/- 23 to 623 +/- 54 N), normalized to cross-sectional area (23.0 +/- 1.4 to 44.7 +/- 2.5 N/mm2), or to ash content per millimeter height (58 +/- 2 to 76 +/- 2 N x mm/mg). Withdrawal of PTH decreased the compressive strength and competence to control values. Risedronate, however, maintained the PTH-induced mechanical strength and competence. The study discloses that even in very old rats withdrawal of PTH treatment causes a rapid and pronounced decline in the bone mass deposited during PTH treatment; treatment with risedronate can, however, maintain the PTH-induced bone properties in the axial skeleton of old rats.
Ejersted
C
C
Department of Connective Tissue Biology, Institute of Anatomy, University of Aarhus, Denmark.
Oxlund
H
H
Eriksen
E F
EF
Andreassen
T T
TT
D015502:Absorptiometry, Photon; D000818:Animals; D001696:Biomechanical Phenomena; D015519:Bone Density / Q000187:drug effects; D001862:Bone Resorption / Q000139:chemically induced*; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004548:Elasticity; D012968:Etidronic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D008159:Lumbar Vertebrae / Q000187:drug effects* / Q000473:pathology; D008297:Male; D010281:Parathyroid Hormone / Q000009:adverse effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D000068296:Risedronic Acid; D013375:Substance Withdrawal Syndrome; D016474:Weight-Bearing
D002121:Calcium Channel Blockers; D010281:Parathyroid Hormone; D000068296:Risedronic Acid; D012968:Etidronic Acid