Bone functional changes in intact, ovariectomized, and ovariectomized, hormone-supplemented adult cynomolgus monkeys (Macaca fascicularis) evaluated by serum markers and dynamic histomorphometry.
Several parameters of bone mass and function were investigated in three experiments involving intact, ovariectomized, or hormone-supplemented ovariectomized female cynomolgus monkeys. Ovariectomized animals had increased serum levels of alkaline phosphatase and acid phosphatase compared with intact and hormone-supplemented animals. Vertebral bone mass measured ex vivo by dual-photon absorptiometry was reduced by 11-19% in ovariectomized animals compared with intact and hormone-supplemented animals. The most dramatic effects observed with ovariectomy were markedly increased (30-60%) bone formation rates in vertebral cancellous bone, primarily caused by higher activation frequency of basic multicellular units of bone. In addition, combined resorption and reversal periods were decreased and formation period increased in untreated ovariectomized animals. Changes in static histomorphometry parameters were less dramatic, cancellous bone volume being 1-14% lower in ovariectomized animals compared with intact or ovariectomized hormone-supplemented animals. The data indicate that changes in bone resorption are primarily responsible for the lower bone mass of estrogen deficiency and increased bone mass in hormone-supplemented animals. Bone changes in ovariectomized cynomolgus monkeys resemble those in women after menopause and similarly respond positively to hormone supplementation. As such, cynomolgus monkeys are an excellent model for studying the basic mechanisms of osteoporosis and for the development of suitable therapeutic regimens.
Jerome
C P
CP
Comparative Medicine Clinical Research Center, Bowman Gray School of Medicine, Wake Forest University, Winston-Salem, North Carolina.
Carlson
C S
CS
Register
T C
TC
Bain
F T
FT
Jayo
M J
MJ
Weaver
D S
DS
Adams
M R
MR
D000135:Acid Phosphatase / Q000097:blood; D000367:Age Factors; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D015415:Biomarkers; D015519:Bone Density / Q000187:drug effects; D001842:Bone and Bones / Q000187:drug effects / Q000473:pathology* / Q000503:physiopathology*; D004032:Diet; D004195:Disease Models, Animal; D015914:Estrogen Replacement Therapy; D005260:Female; D006801:Humans; D008252:Macaca fascicularis; D015675:Osteocalcin / Q000097:blood; D015663:Osteoporosis, Postmenopausal / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D010052:Ovariectomy / Q000009:adverse effects*
D015415:Biomarkers; D015675:Osteocalcin; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase