Tohru Fukushima, Takaya Nitta, Hiroshi Furuichi, Nobuo Izumo,
Tohru Fukuyama, Hiromichi Nakamuta and Masao Koida*
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Setsunan
University,
Nagaotohge-cho 45-1, Hirakata, Osaka 573-0101, Japan
*ﾊTo whom correspondence should be addressed.
Abstract: Using an experimental model of typeﾊ1 osteoporosis
under the chronic therapy with an anti-inflammatory steroid, the bone anabolic
effect of PTH(1-34) was evaluated by histomorphometrical and biomechanical
analysis. Wistar female rats (12-week-old) were ovariectomized and allowed
to develop an osteopenic model in the presence or absence of methylprednisolone
acetate (MPA: 0.1ﾊmg/kg,ﾊs.c., 3-days-a-week basis from the 5th week after
ovariectomy (OVX)). The osteopenia that developed for the first 12ﾊweeks
after OVX was almost completely normalized by subsequent PTH pulsing (20ﾊmg/kg,ﾊs.c.,
5-days-a-week) for 8ﾊweeks starting at the 13th week; the following characteristics
were observed: 1) proximal tibial metaphysis: recovered bone volume, rather
increased trabecular thickness and osteoid volume, and normalized eroded
surface; 2) 5th lumbar vertebra (L-5): partially recovered trabecular connectivity;
3) femur and 4th lumbar vertebra (L-4): recovered mechanical strength in
maximum elastic load and maximum elastic energy. The anabolic effect of
PTH(1-34) was not substantially modified by MPA. Salmon calcitonin (SCT:
10ﾊU/kg per day, s.c., 5-days-a-week, for 8ﾊweeks) was anabolic in limited
parameters: decreased number of osteoclasts, recovered maximum elastic load
in femur, and partially recovered maximum elastic load in L-4. The results
suggest that PTH(1-34) pulsing is able to recover OVX-induced osteopenia
in the structure and mechanical strength not only of the cancellous bone
but also of the cortical bone, and the anabolic effect can be clinically
expected even under steroid medication.
Keywords: PTH(1-34), Bone anabolic effect, Calcitonin, Steroid-induced
osteopenia