High Concentrations of Pamidronate in Bone Weaken the Mechanical Properties of Intact Femora in a Rat Model
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Abstract
Purpose: Bisphosphonates have been used to treat osteoporosis for more than ten years. However, complications associated with long-term administration of bisphosphonates, such as nonunion after pelvic insufficiency fracture or osteonecrosis of the jaw, have been recently reported in the literature. We investigated the relationships among the mechanical properties of the intact rat femur as well as healing fracture calluses and the intraosseous concentration of pamidronate (ICP), after long-term administration of pamidronate in a rat osteoporosis model. Materials and Methods: We performed bilateral ovariectomy in 25 3-month-old female Sprague-Dawley rats. Beginning three months after ovariectomy, disodium pamidronate (0.5mg/kg) was injected every month. After the six-month administration period, the left femoral shaft was fractured using the closed fracture technique. Five weeks after fracture, 23 rats were euthanized and both femora were removed. We checked the mechanical properties of the intact (right) and fractured (left) femora using a three-point bending technique. Intraosseous concentration of pamidronate was checked by high-performance liquid chromatography. Results: The mean ICP was 61.8±15.7ng/mg of bone. High ICP decreased the ultimate load to failure, stiffness, and ultimate stress of the intact femora (p=0.015, 0.027, 0.039, respectively). There was a tendency to decrease the ultimate load to failure in the healing callus when the ICP increased (p= 0.183). High ICP decreased the bone mineral density of the femoral head (p=0.005). Conclusion: High concentrations of pamidronate in intact bone decreased the bone mineral density and weakened the mechanical strength of the rat femora. The mechanical strength of the early healing callus was not correlated with concentration of pamidronate in the bone.
참고문헌 (22)
- Bone HG, "Ten year's experience with alendronate for osteoporosis in postmenopausal women", 350, pp.1189~1199 (2004)
- Fleisch H, "Bisphosphonates in bone disease. 4th ed." (2000), San Diego: Academic Press
- Odvina CV, "Severely suppressed bone turnover: a potential complication of alendronate therapy", 90, pp.1294~1301 (2005)
- Ott SM, "Long-term safety of bisphosphonates", 90, pp.1897~1899 (2005)
- Maerevoet M, "Osteonecrosis of the jaw and bisphosphonates", 353, pp.99~102 (2005)
- Marx RE, "Bisphosphonate-induced exposed bone (osteonecrosis", osteopetrosis) of the jaws: risk factors, recognition, prevention, and treatment, 2005, pp.63, 1567~1575
- Komatsubara S, "Long-term treatment of incadronate disodium accumulates microdamage but improves the trabecular bone microarchitecture in dog vertebra", 18, pp.512~520 (2003)
- Whyte MP, "Bisphosphonate-induced osteopetrosis", 349, pp.457~463 (2003)
- Einhorn TA, "Production of a standard closed fracture in laboratory animal bone", pp.97~101
- Hoggarth CR, "The pharmacokinetics and distribution of pamidronate for a range of doses in the mouse", pp.416~20
- Turner CH, "Basic biomechanical measurements of bone", pp.595~608
- King LE, "Extraction and measurement of pamidronate from bone samples using automated pre- column derivatization, high-performance liquid chromatography and fluorescence detection", 678, pp.325~330 (1996)
- Cao Y, "Raloxifene, estrogen, and alendronate affect the processes of fracture repair differently in ovariectomized rats", 17, pp.2237~2246 (2002)
- Goodship AE, "Use of a bisphosphonate to modulate fracture repair in ovine bone", pp.~5
- Koivukangas A, "Long-term administration of clodronate does not prevent fracture healing in rats", 408, pp.268~278 (2003)
- Li J, "Effect of bisphosphonate (incadronate) on fracture healing of long bones in rats", 14, pp.969~979 (1999)
- Yang KH, "Effect of the long-term administration of pamidronate on bone strength and fracture healing in a rat model", 40, pp.1043~1049 (2005)
- Lehman RA, "The effect of alendronate sodium on spinal fusion: a rabbit model", 4, pp.36~43 (2004)
- Glorieux FH, "Cyclic administration of pamidronate in children with severe osteogenesis imperfecta", 339, pp.947~952 (1998)
- Munns CF, "Delayed osteotomy but not fracture healing in pediatric osteogenesis imperfecta patients receiving pamidronate", 19, pp.1779~1786 (2004)
- Delmas PD, "Long-term effects of intravenous pamidronate in fibrous dysplasia of bone", pp.953~4
- Adamson BB, "Mineralisation defects with pamidronate therapy for Paget's disease", pp.1459~60