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
*╩To whom correspondence should be addressed.
Abstract: Using an experimental model of type╩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╩mg/kg,╩s.c., 3-days-a-week basis from the 5th week after ovariectomy (OVX)). The osteopenia that developed for the first 12╩weeks after OVX was almost completely normalized by subsequent PTH pulsing (20╩mg/kg,╩s.c., 5-days-a-week) for 8╩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╩U/kg per day, s.c., 5-days-a-week, for 8╩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