Teriparatide increases bone formation in modeling and remodeling osteons and enhances IGF-II immunoreactivity in postmenopausal women with osteoporosis.
Transiliac bone biopsies were obtained from 55 women treated with teriparatide or placebo for 12-24 months. We report direct evidence that modeling bone formation at quiescent surfaces was present only in teriparatide-treated patients and bone formation at remodeling sites was higher with teriparatide than placebo.


BACKGROUND
Recombinant teriparatide [human PTH(1-34)], a bone formation agent for the treatment of osteoporosis when given once daily subcutaneously, increases biochemical markers of bone turnover and activation frequency in histomorphometry studies.


METHODS
We studied the mechanisms underlying this bone-forming action of teriparatide at the basic multicellular unit by the appearance of cement lines, a method used to directly classify surfaces as modeling or remodeling osteons, and by the immunolocalization of IGF-I and IGF-II. Transiliac bone biopsies were obtained from 55 postmenopausal women treated with teriparatide 20 or 40 microg or placebo for 12-24 months (median, 19.8 months) in the Fracture Prevention Trial.


RESULTS
A dose-dependent relationship was observed in modeling and mixed remodeling/modeling trabecular hemiosteons. Trabecular and endosteal hemiosteon mean wall thicknesses were significantly higher in both teriparatide groups than in placebo. There was a dose-dependent relationship in IGF-II immunoreactive staining at all bone envelopes studied. The greater local IGF-II presence after treatment with teriparatide may play a key role in stimulating bone formation.


CONCLUSIONS
Direct evidence is presented that 12-24 months of teriparatide treatment induced modeling bone formation at quiescent surfaces and resulted in greater bone formation at remodeling sites, relative to placebo.
Ma
Yanfei L
YL
Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana 46285, USA. ma_Linda@lilly.com
Zeng
Qingqiang
Q
Donley
David W
DW
Ste-Marie
Louis-Georges
LG
Gallagher
J Christopher
JC
Dalsky
Gail P
GP
Marcus
Robert
R
Eriksen
Erik Fink
EF
D000368:Aged; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D016723:Bone Remodeling / Q000187:drug effects* / Q000502:physiology; D001842:Bone and Bones / Q000737:chemistry / Q000187:drug effects; D003710:Demography; D004305:Dose-Response Relationship, Drug; D005260:Female; D006253:Haversian System / Q000254:growth & development / Q000648:ultrastructure*; D006801:Humans; D007150:Immunohistochemistry; D007335:Insulin-Like Growth Factor II / Q000737:chemistry / Q000378:metabolism*; D010012:Osteogenesis / Q000187:drug effects*; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D017698:Postmenopause; D019379:Teriparatide / Q000627:therapeutic use*
D050071:Bone Density Conservation Agents; D019379:Teriparatide; D007335:Insulin-Like Growth Factor II