Cyclical treatment of osteopenic ovariectomized adult rats with PTH(1–34) and pamidronate

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Abstract
Administration of PTH(1–34) at low intermittent doses stimulates bone formation in vivo. However, the new bone is quickly resorbed after drug withdrawal.(24) Following the concept of lose, restore, and maintain,(27) we studied the possibility of maintaining the PTH(1–34)‐mediated new bone by APD post‐treatment and the effect of a second PTH(1–34)‐APD cycle in osteopenic ovariectomized (OVX) adult rats. Eighty OVX rats (6‐months‐old, 3 months after OVX) and 10 sham‐operated rats were divided into nine groups. One OVX group was killed as baseline (BL). Five OVX groups were injected with PTH(1–34) (20 μg/kg/day, subcutaneously) for 3 weeks (5 days/week). The remaining two OVX groups and the sham group (S) were injected with saline as controls. One PTH(1–34) group (A) and one control group (B) were then killed. Three PTH(1–34) groups were post‐treated with APD injections (250 μg/kg/day, subcutaneously) for 5 days; the remaining PTH(1–34) group, the other control group, and group S were injected with saline; and all these groups were left untreated for 3 weeks. At the end, one PTH‐APD group (C), the PTH‐saline group (D), and the saline‐saline group (E) were killed. Another PTH‐APD cycle was applied to the remaining two PTH‐APD groups, with group F killed after the second PTH treatment and group G killed after two complete cycles. We found a 90% increase in cancellous bone volume (Cn.BV/TV) and a 28% increase in trabecular thickness (Tr.Th) in group A over group B. Group C had a 78% increase in Cn.BV/TV and a 64% increase in Tr.Th over group E, but groups D and E were not different. Group G had another 15% increase in Cn.BV/TV over group C, but groups F and C were not significantly different. The results showed that APD post‐treatment did maintain the PTH(1–34)‐mediated new bone and that the effect of a second PTH(1–34)‐APD cycle was minor, probably due to the prolonged inhibitory effect of APD on bone formation.
Funding Information
  • Medical Research Council
  • Ciba-Geigy, Canada