Do estrogen and alendronate improve metaphyseal fracture healing when applied as osteoporosis prophylaxis?

Abstract

Osteoporosis is accompanied by predominantly metaphyseal fractures with a delayed and qualitatively reduced healing process. This study addressed the question of whether fracture healing in the context of osteoporosis prophylaxis is improved with estrogen (E) or alendronate (ALN). Thirty-six ovariectomized and 12 sham-operated 12-week-old rats received soy-free (osteoporotic C, sham), E-, or ALN- supplemented diets. After 10 weeks, a metaphyseal tibia osteotomy and standardized T-plate fixation were performed. After a 5-week healing process, the fracture callus was evaluated qualitatively by biomechanical bending test and quantitatively in microradiographic sections. The time course of callus formation was examined using fluorochrome-labeled histological sections. Administration of E improved the biomechanical properties of callus (stiffness [N/mm]: sham: 110.2 ± 76.07, C: 41.28 ± 33.70, E: 85.72 ± 47.24, ALN: 72.07 ± 34.68). The resistance to microfracturing seen in E-treated animals was significantly enhanced and even superior to sham (yield load [N] sham: 27.44 ± 9.72, C: 21.04 ± 12.47, E: 42.85 ± 13.741, ALN: 25.28 ± 6.4•) (* P < 0.05 vs. sham group, 1 P < 0.05 vs. C group, • P < 0.05 vs. E group). Trabecular bone in particular was improved, indicating the presence of physiological endosteal bridging (Tr.Dn [%] sham: 10.53 ± 18.9, C: 1.01 ± 0.14, E: 24.13 ± 34.09 1, ALN: 3.99 ± 8.3•). ALN did not help bone healing, as shown by mechanical tests. Compared to the C group, statistically, ALN did not show worse properties. The induction of callus formation under ALN treatment was slightly delayed (Tt.Cl [mm2] sham: 3.68 ± 0.66, C: 3.44 ± 0.42, E: 3.69 ± 0.58, ALN: 3.06 ± 0.56). Osteoporotic metaphyseal fracture healing was qualitatively and quantitatively improved by E prophylaxis. The process of fracture healing occurred nearly physiologically (shamlike). Notably, ALN hardly improved metaphyseal callus properties when assessed as osteoporosis prophylaxis, but to a lesser extent than E.