Intratrabecular tunneling increases trabecular number throughout the skeleton of ovariectomized rhesus monkeys treated with parathyroid hormone 1-84.
Daily treatment of ovariectomized (OVX) adult rhesus monkeys with human parathyroid hormone (PTH) 1-84 for 16 months increases trabecular bone volume (BV/TV), number (Tb.N) and connectivity at lumbar vertebra-3 (L3) and thoracic vertebra-10. We proposed that the increased Tb.N and connectivity was achieved by stimulation of intratrabecular tunneling. Using histomorphometry to determine frequency of events, we have now quantified intratrabecular tunneling at L3 and extended it to investigate the effects of PTH(1-84) treatment on trabecular bone at the proximal femur, distal radius and iliac crest of these animals. At L3, tunneling frequency was low in control sham and OVX animals ( approximately 0.05/mm(2)) but increased significantly in PTH(1-84)-treated animals (0.27, 0.49 and 0.95/mm(2) with the 5, 10 and 25 microg/kg doses, respectively). Very similar tunneling frequencies were observed at all skeletal sites in all groups. Iliac crest biopsies were also collected at baseline and after 6 months of treatment and showed significant time- and dose-related increases in tunnels. Although the pattern and magnitude of response varied slightly from site to site, PTH(1-84) treatment significantly increased Tb.N, as well as BV/TV and bone formation rate at all skeletal sites. A modest but statistically significant increase in trabecular thickness occurred only at the iliac crest. In summary, intratrabecular tunneling is rare in control monkeys, but increased substantially with PTH(1-84) treatment. This phenomenon provides a plausible explanation for the PTH(1-84)-induced increase in Tb.N observed in OVX monkeys. Moreover, these analyses allowed a comparison of the effects PTH(1-84) treatment on trabecular bone at multiple locations.
Miller
M A
MA
NPS Pharmaceuticals, Bedminster, New Jersey, USA.
Bare
S P
SP
Recker
R R
RR
Smith
S Y
SY
Fox
J
J
D000818:Animals; D016723:Bone Remodeling / Q000502:physiology*; D001842:Bone and Bones / Q000033:anatomy & histology* / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008253:Macaca mulatta; D010012:Osteogenesis / Q000502:physiology; D010052:Ovariectomy; D010281:Parathyroid Hormone / Q000494:pharmacology*
D010281:Parathyroid Hormone