l-Carnitine Fumarate and Isovaleryl-l-Carnitine Fumarate Accelerate the Recovery of Bone Volume/Total Volume Ratio after Experimetally Induced Osteoporosis in Pregnant Mice

Anabolic skeletal agents have recently broadened the therapeutic options for osteoporosis by directly stimulating bone formation and improving bone turnover, bone density, bone size, and bone microarchitecture. We recently demonstrated that two new l-carnitine derivatives, l-carnitine fumarate (LC) and isovaleryl-l-carnitine fumarate (Iso-V-LC), stimulated osteoblast proliferation and differentiation. We here investigated, by histomorphometry in a mouse model of osteoporosis, the impact of these compounds on the repair of trabecular bone and the osteoblast involvement in this process. Fifty-nine inbred adult female CD1 mice in pregnancy were assigned to four treatment groups: (1) controls, mice fed a standard normocalcemic pre- and postpartal diet; (2) Hypo, mice fed a low-calcium isocaloric prepartal diet and a standard postpartal diet; (3) LC, mice fed a group 2-type diet supplemented post-partum with LC; (4) Iso-V-LC, mice fed a group 2-type diet supplemented post-partum with Iso-V-LC. Bone volume/total volume ratio (BV/TV), bone perimeter, osteoblast surface/bone surface, and osteoblast number/bone surface were measured from sections of L3 and L4 vertebral bodies obtained from animals killed on the day of delivery (controls and Hypo) and on days 7, 14, and 21 after delivery (all groups). BV/TV and all osteoblast-based indexes were significantly higher in LC and Iso-V-LC than in Hypo mice at each time point, and Iso-V-LC at the end of the treatment attained levels observed in controls. In conclusion, Iso-V-LC and, to a lesser extent, LC accelerated the recovery of normal BV/TV level after a hypocalcemic diet.