Bone mineral and collagen quality in humeri of ovariectomized cynomolgus monkeys given rhPTH(1-34) for 18 months.
A recent study of ovariectomized monkeys, treated with recombinant human parathyroid hormone (rhPTH)(1-34) at 1 or 5 mg/kg/day for 18 months or for 12 months followed by 6 months withdrawal from treatment, showed significant differences in the geometry and histomorphometry of cortical bone of the midshaft humerus. To determine the extent to which the rapid bone turnover and cortical porosity induced by rhPTH(1-34) in ovariectomized monkeys modified mineral content, mineral crystal maturity and collagen maturity (cross-link distribution) in the cortical periosteal and endosteal regions, cross-sections of the cortical bone of the mid-humerus, were examined using Fourier transform infrared imaging (FTIRI). FTIRI analyses demonstrated that rhPTH(1-34) altered bone mineral and collagen properties in a dose-dependent manner. Mineral crystal maturity and collagen cross-link ratio (pyridinoline/dehydro-dihydroxylysinonorleucine) on both endosteal and periosteal surfaces decreased relative to ovariectomized animals, consistent with new bone formation. These changes were partially sustained after withdrawal of the higher dose of rhPTH(1-34), suggesting a prolonged after-effect on bone properties for at least two bone remodeling cycles. In conclusion, treatment of ovariectomized monkeys with rhPTH(1-34) had significant effects on cortical bone mineral-to-matrix ratio, mineral crystal maturity, and collagen cross-link ratio. These were fully reversible when the 1-microg rhPTH(1-34) treatment was withdrawn, but only partially reversed when the 5-microg rhPTH(1-34) dose was withdrawn.
Paschalis
Eleftherios P
EP
Mineralized Tissues Laboratory, Hospital for Special Surgery, New York, New York 10021, USA. paschalise@hss.edu
Burr
David B
DB
Mendelsohn
Richard
R
Hock
Janet M
JM
Boskey
Adele L
AL
D000818:Animals; D015519:Bone Density / Q000187:drug effects*; D016723:Bone Remodeling / Q000187:drug effects / Q000502:physiology; D003094:Collagen / Q000737:chemistry / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D006811:Humerus / Q000187:drug effects* / Q000378:metabolism*; D008252:Macaca fascicularis; D010052:Ovariectomy; D010053:Ovary / Q000502:physiology; D010281:Parathyroid Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D017550:Spectroscopy, Fourier Transform Infrared
D010281:Parathyroid Hormone; D010446:Peptide Fragments; D011994:Recombinant Proteins; D003094:Collagen