Dosisabhängige Prophylaxe des frühen periprothetischen Knochenschwundes durch Alendronat

Zusammenfassung

Studienziel: Ein periprothetischer Knochenschwund tritt in den ersten 6 Monaten nach Hüfttotalendoprothetik (TEP) auf und ist weitgehend auf die Folgen des operativen Traumas, die postoperative Minderbelastung und die veränderte Krafteinleitung durch die Prothese zurückzuführen. Ziel dieser prospektiven, randomisierten, offenen und endpunktverblindeten Studie ist die Prophylaxe des frühen periprothetischen Knochenschwundes um den Schaft durch eine orale Bisphosphonattherapie. Methode: 66 gesunde Patienten mit unzementierter TEP und unterdurchschnittlicher lumbaler Knochendichte (BMD) (negativer T-score) wurden postoperativ mit Alendronat behandelt: n = 21 erhielten 10 Wochen 10 mg/d (A), n = 21 5 Wochen 20 mg/d (B), n = 24 ohne Therapie als Kontrollgruppe (KG). Die periprothetische BMD wurde mittels DEXA nach dem 2., 4., 6. und 12. Monat in den Regionen n. Gruen (ROI) bestimmt und prozentual auf den postoperativen Ausgangswert bezogen. Ergebnisse: In KG fand sich ein signifikanter Knochenverlust in allen ROI während der ersten Monate und in ROI 7 zeigte sich ein Defizit von 29 % nach einem Jahr. In B wurde der Knochenschwund komplett bis zum 2 Monat verhindert, in ROI 7 fand sich noch nach einem Jahr ein signifikanter Unterschied zu KG. In A erfolgte in allen ROI über 12 Monate ein signifikant geringerer Knochenschwund als in KG. Schlussfolgerung: Mit Alendronat ist eine Prophylaxe des frühen periprothetischen Knochenschwundes möglich. Die Therapie sollte sich über mindestens 10 Wochen erstrecken und mit einer Dosierung von 20 mg/d beginnen.

Abstract

Aim: Periprosthetic bone loss occurs in the first six months after total hip arthroplasty (THA) and is felt to be largely the result of initial operative irritation, immobilization, and stress shielding. This study (a prospective, randomized, open, blinded endpoint evaluation) aims at preventing bone loss around the stem with an oral bisphosphonate. Method: 66 healthy subjects with uncemented THA and low lumbar bone mass density (BMD) (negative T score) were treated post-operatively with alendronate as follows: n = 21 with 10 mg/d for 10 weeks (A), n = 21 20 mg/d for 5 weeks (B), n = 24 no treatment for controls (C). The periprosthetic BMD in the Gruen zones (ROI) was measured after the 2nd, 4th, 6th, and 12th month by DEXA as a percentage of the value measured one week after surgery. Results: In C, there was significant bone loss in all ROI during the first months and a deficit of 29 % in ROI 7 following one year. In B, bone loss was completely prevented up to the second month, in ROI 7, a significant difference in comparison to C was registered for the entire year. In A, significant bone loss reduction during 12 months was seen. Conclusion: Alendronate, therefore, is capable of preventing initial periprosthetic bone loss. A dosage of 20 mg/d is required initially with daily treatment lasting at least 10 weeks.

Endoprothetik - Bisphosphonat - Alendronat - Knochendichte - DEXA

Arthroplasty - Hip - Densitometry - Alendronate - Bisphosphonate

Literatur

• 1 Aspenberg P, van der Vis H. Migration, particles, and fluid pressure - a discussion of causes of prosthetic loosening.  Clin Orthop. 1998;  352 75-80
• 2 Bryan J M. Altered load history affects periprosthetic bone loss following cementless total hip arthroplasty.  J Orthop Res. 1996;  14 (5) 762-768
• 3 Cohen B, Rushton N. Accuracy of DEXA measurement of bone mineral density after total hip arthroplasty.  J Bone Joint Surg (Br). 1995;  77-B 479-483
• 4 Kerner J. Correlation between pre-operative periprosthetic bone density and post-operative bone loss in THA can be explained by strain-adaptive remodelling.  J Biomechanics. 1999;  32 695-703
• 5 Petersen M M. The relation between trabecular bone strength and bone mineral density assessed by dual photon and dual energy x-ray absorptiometry in the proximal tibia.  Calcif Tissue Int. 1996;  59 (4) 311-314
• 6 Sarin V K. DXA-derived section modulus and bone mineral content predict long-bone torsional strength.  Acta Orthop Scand. 1999;  70 (1) 71-76
• 7 Fleisch H. Bisphosphonate bei Knochenerkrankungen. Vom Labor zum Patienten. Hans Huber Bern; 1998
• 8 Hansson L, Hedner T, Dahlöf B. Prospective randomized open blinded end-point (PROBE) Study. A novel design for intervention trials.  Blood Pressure. 1992;  1 113-119
• 9 Hennigs T H. Risikofaktor für periprothetischen Knochenschwund: Perioperative DXA-Messung der LWS für Planung und Prophylaxe in der Hüftendoprothetik.  Osteologie. 2000;  9 Suppl 1 74
• 10 Gruen T A, McNeice G M, Amstutz H C. „Modes of failure” of cemented stem-type femoral components: a radiographic analysis of loosening.  Clin Orthop. 1979;  141 17-27
• 11 Huiskes R, Weinans H, van Rietbergen B. The relationship between stress shielding and bone resorption around total hip stems and the effects of flexible materials.  Clin orthop. 1992;  274 124-134
• 12 Maloney W J. The Otto Aufranc Award. Skeletal response to well fixed femoral components inserted with and without cement.  Clin Orthop. 1996;  333 15-26
• 13 Silva M J, Reed K L, Robertson D D. Reduced bone stress as predicted by composite beam theory correlates with cortical bone loss following cemented total hip arthroplasty.  J Orthop Res. 1999;  17 (4) 525-531
• 14 Sychterz C J, Engh C A. The influence of clinical factors on periprosthetic bone remodeling.  Clin Orthop. 1996;  322 285-292
• 15 Kobayashi S. Poor bone quality or hip structure as risk factors affecting survival of total-hip arthroplasty.  Lancet. 2000;  355 (9214) 1499-1504 (1497)
• 16 Broos P, Fourneau I. Host factors that affect outcome of total hip arthroplasty.  Lancet. 2000;  355 (9214) 1479-1480
• 17 Engh C A, Sychterz C, Engh C. Factors affecting femoral bone remodeling after cementless total hip arthroplasty.  J Arthroplasty. 1999;  14 (5) 637-644
• 18 Rubash H E, Sinha R K, Shanbhag A S, Kim S Y. Pathogenesis of bone loss after total hip arthroplasty.  Orthop Clin North Am. 1998;  29 (2) 173-186
• 19 Ingle B M. Changes in bone mass and bone turnover following ankle fracture.  Osteoporos Int. 1999;  10 (5) 408-415
• 20 Petersen M M. Loss of bone mineral of the hip assessed by DEXA following tibial shaft fractures.  Bone. 1997;  20 (5) 491-495
• 21 Kiratli B J. Measurements of bone mineral density by dual-energy x-ray absorptiometry in patients with the Wisconsin hip, an uncemented femoral stem.  Xyz. 1996;  11 (2) 184-193
• 22 Kröger H, Venesmaa P, Jurvelin J. Bone density at the proximal femur after total hip arthroplasty.  Clin Orthop. 1998;  352 66-74
• 23 Wixson R L. Maintenance of proximal bone mass with an uncemented femoral stem: analysis with dual energy x-ray absorptiometry.  J Arthroplasty. 1997;  12 365-372
• 24 Nishii T, Sugano N, Masuhara K. Longitudinal evaluation of time related bone remodeling after cementless total hip arthroplasty.  Clin Orthop. 1996;  339 121-131
• 25 Trevisan C. Periprosthetic bone density around fully hydroxyapatite coated femoral stem.  Clin Orthop. 1997;  340 109-117
• 26 Spittlehouse A J, Smith T W, Eastell R. Bone loss around 2 different types of hip prostheses.  J Arthroplasty. 1998;  13 (4) 422-427
• 27 Rosenthall L, Bobyn J D, Brooks C E. Temporal changes of periprosthetic bone density in patients with a modular noncemented femoral prosthesis.  J Arthroplasty. 1999;  14 (1) 71-76
• 28 Cummings S R, Black D M, Thompson D E. Effect of Alendronate on risk of fracture in women with low bone density but without vertebral fractures: Results from the Fracture Intervention Trail.  JAMA. 1998;  280 2077-2082
• 29 Meraw S J, Reeve C M. Qualitative analysis of peripheral peri-implant bone and influence of alendronate sodium on early bone regeneration.  J Periodontol. 1999;  70 (10) 1228-1233
• 30 Denissen H, Martinetti R, van Lingen . Normal osteoconduction and repair in and around submerged highly bisphosphonate-complexed hydoxyapatite implants in rat tibiae.  J Periodontol. 2000;  71 (29) 272-286
• 31 Wang X. Short-term effects of bisphosphonates on the biomechanical properties of canine bone.  J Biomed Mater Res. 1999;  44 (4) 456-460
• 32 Shanbhag A S. The John Charnley Award. Inhibition of wear debris mediated osteolysis in a canine total hip arthroplasty model.  Clin Orthop. 1997;  344 33-43
• 33 Adami S, Mian M, Gatti P. Effects of two oral doses of alendronat in the treatment of Paget’s disease of bone.  Bone. 1994;  15 (4) 415-417
• 34 Sabokbar A. Bisphosphonates in bone cement inhibit PMMA particle induced bone resorption.  Ann Rheum Dis. 1998;  57 (10) 614-618