Intermittent parathyroid hormone (PTH) treatment and age-dependent effects on rat cancellous bone and mineral metabolism.
In recent years, intermittent PTH treatment has been investigated extensively for its efficacy in preventing osteoporotic fractures and to improve fracture healing and implant fixation. Although these tasks concern patients of all ages, very little is known about whether aging impacts the bone anabolic response to PTH. Female Sprague-Dawley rats of 1, 3, and 13 months of age were either treated by hPTH-(1-34) or by vehicle solution (CTR) for 1 week. As main outcome measures, we determined the effects on static and dynamic histomorphometry of cancellous bone. In addition, we measured gene expression in femur and serum parameters reflecting bone turnover and mineral metabolism. There was a profound decrease in bone formation rate (BFR) with aging in CTR rats, whereas PTH treatment resulted in a significant relative 1.5-, 3-, and 4.7-fold increase in BFR, without altering indices of bone resorption. Aging decreased and PTH increased mRNA levels for bone matrix proteins and growth factors in a gene-specific manner. In younger animals, PTH-induced a marked stimulation in the mineral apposition rate with no effect on osteoblast number, whereas the latter was increased in older animals (1.0-, 1.7-, and 3.1-fold). Treatment with PTH in young rats led to a significant increase in trabecular number (1.6-2.6/mm, p < 0.05), whereas older rats demonstrated increases in trabecular thickness only (52.8-77.8 microm, p < 0.001). Although PTH increased bone formation at all ages, we found significant age-related differences in the cellular and molecular mechanisms involved in the bone anabolic response to the hormone.
Friedl
Gerald
G
Department of Orthopedics and Orthopedic Surgery, Medical University of Graz, A-8036 Graz, Austria.
Turner
Russell T
RT
Evans
Glenda L
GL
Dobnig
Harald
H
D000375:Aging / Q000187:drug effects* / Q000502:physiology; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects* / Q000502:physiology; D002113:Calcification, Physiologic / Q000187:drug effects* / Q000502:physiology; D004334:Drug Administration Schedule; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D005260:Female; D005269:Femur / Q000187:drug effects* / Q000473:pathology / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D044162:Parathyroid Hormone-Related Protein / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D016326:Extracellular Matrix Proteins; D036341:Intercellular Signaling Peptides and Proteins; D044162:Parathyroid Hormone-Related Protein; D010446:Peptide Fragments; D012333:RNA, Messenger; C054296:parathyroid hormone-related protein (1-34)