Differential effects of teriparatide and alendronate on bone remodeling in postmenopausal women assessed by histomorphometric parameters.
An 18-month randomized double-blind study was conducted in postmenopausal women with osteoporosis to compare the effects of once-daily teriparatide 20 microg with alendronate 10 mg on bone histomorphometry. Biopsies were obtained from 42 patients. Indices of bone formation were significantly higher after 6 or 18 months of teriparatide compared with alendronate treatment.


BACKGROUND
Alendronate and teriparatide increased BMD, assessed by DXA, by different mechanisms of action, supported by changes in biochemical markers of bone turnover. The purpose of this cross-sectional study was to explore the differential effects of these two osteoporosis treatments at the bone tissue level by examining bone histomorphometric parameters of bone turnover after either 6 or 18 months of treatment.


METHODS
Patients were a cohort from a randomized parallel double-blind study conducted to compare the effects of once-daily teriparatide 20 microg and alendronate 10 mg in postmenopausal women with osteoporosis. Transiliac crest bone biopsies were obtained after tetracycline double labeling from 42 patients treated for 6 months (n = 23) or 18 months (n = 14); 5 additional patients were biopsied from contralateral sides at 6 and 18 months. Biopsy specimens adequate for quantitative analysis were analyzed by 2D histomorphometry from 17 patients at 6 months (teriparatide, n = 8; alendronate, n = 9) and 15 patients at 18 months (teriparatide, n = 8; alendronate, n = 7). Data were analyzed by two-sample tests.


RESULTS
Histomorphometric indices of bone formation were significantly and markedly greater in the teriparatide group than in the alendronate group at 6 and 18 months, whereas indices of bone resorption were only significantly greater in the teriparatide group than in the alendronate group at 6 months. Bone formation and activation frequency were significantly lower at 18 months compared with 6 months in the teriparatide group, returning to levels comparable with untreated postmenopausal women. In the teriparatide group, the peak in histomorphometric bone formation indices coincided with peak levels for N-terminal propeptide of type I collagen, a biochemical marker of bone formation. The degree of mineralization was lower at 18 months than at 6 months with treatment in both groups but was not different between groups.


CONCLUSIONS
These results confirm the opposite mechanisms of action of teriparatide and alendronate on bone remodeling and confirm the bone formation effect of teriparatide.
Arlot
Monique
M
Laboratoire d'Histodynamique Osseuse and INSERM Unit 403, Faculty of Medicine R. Laennec, Lyon, France. Monique.Arlot@sante.univ-lyon1.fr
Meunier
Pierre J
PJ
Boivin
Georges
G
Haddock
Lillian
L
Tamayo
Juan
J
Correa-Rotter
Ricardo
R
Jasqui
Salomón
S
Donley
David W
DW
Dalsky
Gail P
GP
Martin
Javier San
JS
Eriksen
Erik Fink
EF
D015502:Absorptiometry, Photon; D000368:Aged; D019386:Alendronate / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D015519:Bone Density / Q000187:drug effects; D016723:Bone Remodeling / Q000187:drug effects*; D002113:Calcification, Physiologic / Q000187:drug effects; D005260:Female; D006801:Humans; D007085:Ilium / Q000473:pathology; D008875:Middle Aged; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy*; D017698:Postmenopause / Q000187:drug effects / Q000378:metabolism; D019379:Teriparatide / Q000627:therapeutic use*
D015415:Biomarkers; D019379:Teriparatide; D019386:Alendronate