Aminobutane bisphosphonate

Sprague-Dawley (male, 250-280 g, immobilization-induced bone loss via unilateral sciatic neuroctomy)^[2]

0.01 mg P per kg; 0.10 mg P per kg; 1.0 mg P per kg

s.c.; 2 consecutive days prior to surgery

Increased femoral ash weight in both intact and immobilized limbs in a dose-dependent manner at 10 and 20 days post-surgery (p < 0.05) compared to vehicle controls.
Abolished the immobilization-induced decrease in femoral ash weight at 10 days with 0.10 mg P per kg dose.
Reduced the percentage difference in femoral ash weight/length between intact and immobilized limbs from 11.5% in vehicle controls to 7.0% with 0.10 mg P per kg and 4.8% with 1.0 mg P per kg at 20 days.
Reduced femoral length in both limbs from 36.6 mm to 35.6 mm (intact) and 36.4 mm to 35.6 mm (immobilized) at 20 days with 1.0 mg P per kg dose (p < 0.05).
Increased trabecular bone volume to 52.1% (intact) and 41.0% (immobilized) at 10 days with 0.10 mg P per kg dose, compared to 17.9% (intact) and 7.9% (immobilized) in vehicle controls (p < 0.05).
Increased trabecular bone volume in a dose-dependent manner at 20 days: 22.9% (intact) and 15.5% (immobilized) with 0.01 mg P per kg; 37.6% (intact) and 35.4% (immobilized) with 0.10 mg P per kg; 71.6% (intact) and 68.1% (immobilized) with 1.0 mg P per kg (all p < 0.05 vs vehicle).
Eliminated the difference in trabecular bone volume between intact and immobilized limbs at 20 days with 0.10 and 1.0 mg P per kg doses.
Reduced osteoclast number per mm trabecular surface in both limbs at 20 days with all doses compared to vehicle controls (p < 0.05), eliminating the difference between intact and immobilized limbs seen in vehicle controls.
Reduced eroded surface in both limbs at 20 days with 0.01 mg P per kg (12.1% intact, 12.3% immobilized) and 1.0 mg P per kg (16.1% intact, 15.8% immobilized), and in immobilized limbs with 0.10 mg P per kg (17.7%) compared to vehicle controls (p < 0.05).
Reduced osteoid surface to 0.4% (intact) and 0.1% (immobilized) at 10 days with 0.10 mg P per kg dose, compared to 6.0% (intact) and 2.4% (immobilized) in vehicle controls (p < 0.05).
Decreased osteoid surface in a dose-dependent manner at 20 days: 1.3% (intact) with 0.01 mg P per kg; 0.2% (intact) and 0.3% (immobilized) with 0.10 mg P per kg; 0.2% (intact) and 0.1% (immobilized) with 1.0 mg P per kg (all p < 0.05 vs vehicle).
Reduced mineral apposition rate in intact limbs by 14% (0.82 μm/day and 0.83 μm/day, respectively) with 0.10 and 1.0 mg P per kg doses compared to vehicle controls (0.97 μm/day; p < 0.05), but did not further reduce rates in immobilized limbs.