BACKGROUND: Bisphosphonates are anticatabolic agents that inhibit bone resorption and are widely used to treat osteoporosis and bone metastases in adults. They are also used in young patients with diseases like osteogenesis imperfecta or juvenile osteoporosis. Bone modeling/remodeling is elevated in growing subjects, and inhibition of osteoclastic activity has been shown to interfere with growth. Thus, our objective was to evaluate the effect of alendronate (ALN) on growing animals. METHODS: Healthy male Wistar rats, aged 1 mo, received ALN or vehicle for 8 wk. Serum levels (calcemia, phosphatemia, and total alkaline phosphatase) were determined. Morphometric (rat: femur and tibia weight and length and hemimandible growth) and histomorphometric parameters (thickness of tibial epiphyseal cartilage and each cartilage zone, interradicular bone volume in the first lower molar, trabeculae volume, percentage of bone and cartilage, and osteoclast number in mandibular condyles) were assessed. RESULTS: ALN caused a significant decrease in femur and tibia length, tibial cartilage thickness, and longitudinal growth of hemimandibles. It increased interradicular bone volume and mandibular condyle trabeculae volume, increasing the percentage of cartilage and osteoclast number. CONCLUSION: These findings indicate that administration of ALN to growing animals alters the endochondral ossification process, and thus alters growth.
BACKGROUND:Bisphosphonates are anticatabolic agents that inhibit bone resorption and are widely used to treat osteoporosis and bone metastases in adults. They are also used in young patients with diseases like osteogenesis imperfecta or juvenile osteoporosis. Bone modeling/remodeling is elevated in growing subjects, and inhibition of osteoclastic activity has been shown to interfere with growth. Thus, our objective was to evaluate the effect of alendronate (ALN) on growing animals. METHODS: Healthy male Wistar rats, aged 1 mo, received ALN or vehicle for 8 wk. Serum levels (calcemia, phosphatemia, and total alkaline phosphatase) were determined. Morphometric (rat: femur and tibia weight and length and hemimandible growth) and histomorphometric parameters (thickness of tibial epiphyseal cartilage and each cartilage zone, interradicular bone volume in the first lower molar, trabeculae volume, percentage of bone and cartilage, and osteoclast number in mandibular condyles) were assessed. RESULTS:ALN caused a significant decrease in femur and tibia length, tibial cartilage thickness, and longitudinal growth of hemimandibles. It increased interradicular bone volume and mandibular condyle trabeculae volume, increasing the percentage of cartilage and osteoclast number. CONCLUSION: These findings indicate that administration of ALN to growing animals alters the endochondral ossification process, and thus alters growth.
Authors: Erin L Ealba; Andrew H Jheon; Jane Hall; Camille Curantz; Kristin D Butcher; Richard A Schneider Journal: Dev Biol Date: 2015-10-21 Impact factor: 3.582