Systemic dihydrotestosterone enhances periimplant mineralization around titanium implants

U. Maus; M. Lühmann; S. Andereya; H. Schmidt; G. Zombory; C. Siebert; C. Niedhart

doi:10.1055/s-0037-1621664

Osteologie, Table of Contents

Osteologie 2012; 21(01): 23-28
DOI: 10.1055/s-0037-1621664

Original and review articles

Schattauer GmbH

Systemic dihydrotestosterone enhances periimplant mineralization around titanium implants

Die systemische Applikation von Dihydrotestosteron erhöht die periimplantäre Mineralisation um Titanimplantate

Authors

U. Maus

¹Department of Orthopedic Surgery, University of Mainz, Germany

²OZOM – Orthopedic Center Oldenburger Münsterland, St. Antonius-Stift, Emstek, Germany
M. Lühmann

³Department of Trauma Surgery, Medical center city region Aachen, Würselen, Germany
S. Andereya

⁴Department of Orthopedic Surgery and Traumatology, University of Aachen, Germany
H. Schmidt

³Department of Trauma Surgery, Medical center city region Aachen, Würselen, Germany
G. Zombory

⁴Department of Orthopedic Surgery and Traumatology, University of Aachen, Germany
C. Siebert

⁵Department of Orthopedic Surgery and Sport injuries, Medical school Hannover – Annastift e.V., Hannover, Germany
C. Niedhart

⁴Department of Orthopedic Surgery and Traumatology, University of Aachen, Germany

Abstract

Zusammenfassung

Trotz Verbesserungen der Einheilung von Titan-implantaten durch Oberflächenmodifikationen kann die postoperative Rehabilitation durch Phasen der Ent- oder Teilbelastung verzögert sein, um eine Osseointegration der Implantate ermöglichen. Außerdem wird die postoperative Rehabilitation gerade bei älteren Patienten durch die reduzierte Muskelfunktion beeinflusst. Androgene spielen eine wichtige Rolleals anabole Substanzen des Knochenstoffwechsels und erhöhen Muskelkraft und Aktivität. Ziel der vorliegenden Studie war die Evaluation der Effekte einer systemischen Vorbehandlung mit Androgenen auf die Osseointegration von Ti6Al4VA-Implantaten bei 20 Sprague-Dawley Ratten. Zur Vorbehandlung wurde den Tieren zwei Tage vor der Operation entweder ein Placebo oder 1 mg 5β-Androstan-17β-ol-one (DHT) subkutan injiziert. Die Ti6Al4VA-Implantate wurden beidseits pressfit in die Femura implantiert. Nach 14 Tagen wurden die Tiere euthanisiert, die Proben in Methylmetacrylat eingebettet und histologisch sowie histomorphometrisch untersucht. Die biomechanische Untersuchung mittels Ausrissversuch ergab inkonsistente Ergebnisse ohne signifikante Unterschiede. Die histologische Untersuchung ergab einen direkten Kontakt zwischen mineralisiertem Knochen bzw. Osteoid und Implantatoberfläche. In der Gruppe, die mit DHT vorbehandelt wurde, zeigte sich ein signifikant höherer Anteil an mineralisiertem Gewebe am Knochen-Implantat-Interface (51,24 ±10,48 % vs. 39,50 ±9,31 %, p < 0,05), während der Anteil an Osteoid signifikant geringer war (33,11 ±7,76 % vs. 47,59 ±7,76 %, p < 0,01). Die präoperative Vorbehandlung mit DHT führte zu einer verbesserten Mineralisation des periimplantären Osteoids um Ti6Al4VAImplantate. Die systemische Applikation von DHT könnte daher eine mögliche Option darstellen, um gleichzeitig die Osseointegration der Implantate zu verbessern und die postoperative Rehabilitation durch die Erhöhung der Muskelkraft zu verkürzen.

Summary

Despite the improvement of titanium implants by surface modification, postoperative rehabilitation can be prolonged to permit the osseointegration of the implant. Furthermore, muscular weakness of elderly patients lengthens the period of rehabilitation. Androgens play an important role as anabolic agent in bone metabolism and also increase muscular strength and activity. We evaluated the effects of systemic androgen pre-treatment on the osseointegration of Ti6Al4VA-implants in 20 rats, which received either no treatment or 1 mg 5β-Androstan-17β-ol-one (DHT) subcutaneously two days before surgery. Ti6Al4VA implants were inserted press-fit into the femur bilaterally. After 14 days histological and histomorphometrical analysis was performed after embedding specimens in methylmetacrylate. Biomechanical analysis was conducted by a pull-out test, which showed very inconsistent data without significant differences. Histology showed bone and implant in close contact and wide seams of osteoid in direct contact with the implant surface. Stimulation with DHT significantly increased the bone content at the bone-implant interface (51.24 ±10.48 % vs. 39.50 ±9.31 %, p < 0.05), while the ratio of osteoid was significantly reduced (33.11 ±7.76 % vs. 47.59 ±7.76 %, p < 0.01). Preoperative stimulation with DHT improved mineralization of periimplant osteoid around Ti6Al4VA implants. Systemic DHT therefore may represent a solution leading to both improved osseo integration and shortened rehabilitation thanks to muscular strengthening.

Schlüsselwörter

Knochen - Kalzifizierung - Titanlegierungen - Osseointegration

Keywords

Bone - calcification - titanium (alloys) - osseointegration

Full Text

References

References
1 Abraham D, Carpenter PC. Issues concerning androgen replacement therapy in postmenopausal women. Mayo Clin Proc 1997; 72 (11) 1051-1055.
2 Albrektsson T, Jacobsson M. Bone-metal interface in osseointegration. J Prosthet Dent 1987; 57: 597-607.
3 Albrektsson T, Johansson C, Lundgren AK. et al. Experimental studies on oxidized implants. A histomorphometrical and biomechanical analysis. Appl Osseointegration Res 2000; 1: 21-24.
4 Albrektsson T, Johansson C. Osteoinduction, osteoconduction and osseointegration. Eur Spine J 2001; 10: S96-S101.
5 Baran DT, Bergfeld MA, Teitelbaum SL, Avioli LV. Effect of testosterone therapy on bone formation in an osteoporotic hypogonadal male. Calcif Tissue Res 1978; 26: 103-106.
6 Burr DB. Muscle strength, bone mass and age-related bone loss. J Bone Miner Res 1997; 12: 1547-1551.
7 Collier JP, Mayor MB, Chae JC. et al. Macroscopic and microscopic evidence of prosthetic fixation with porous-coated materials. Clin Orthop Rel Res 1988; 235: 173-180.
8 Davidson BJ, Ross RK, Paganini-Hill A. et al. Total and free estrogens and androgens in postmenopausal women with hip fractures. J Clin Endocrinol Metab 1982; 54 (01) 115-120.
9 Dayer R, Rizzioli R, Kaelin A, Ammann P. Low protein intake is associated with impaired titanium implant osseointegration. J Bone Joint Surg 2005; 20: 258-264.
10 Dobs AS, Nguyen T, Pace C, Roberts CP. Differential effects of oral estrogen versus oral estrogen-androgen replacement therapy on body composition in post menopausal women. J Clin Endocrin Metabol 2002; 87: 1509-1516.
11 Frankle M, Borrelli J. The effects of testosterone propionate and methenolone enanthate on the healing of humeral osteotomies in the Wistar rat. J Invest Surg 1990; 3 (02) 93-113.
12 Gotfredsen K, Nimb L, Hjorting-Hansen E. et al. Histomorphometric and removal torque analysis for TiO2-blasted titanium implants. Clin Oral Impl Res 1992; 3: 77-84.
13 Gottlander M. On hard-tissue reactions to hydroxyapatite-coated titanium implants. PhD thesis, Dept of Biomaterials/Handicap research, University of Göteborg. Sweden: 1994: 1-192.
14 Hazan R, Brener R, Oron U. Bone growth to metal implants is regulated by their surface chemical properties. Biomaterials 1993; 14: 570-574.
15 Johansson CB, Han CH, Wennerberg A, Albrektsson T. A quantitative comparison of machined commercially pure titanium and titanium-aluminium-vanadium implants in rabbit bone. Int J Oral Maxillofac Implants 1998; 13 (03) 315-321.
16 Kasperk CH, Wergedal JE, Farley JR. Androgens directly stimulate proliferation of bone cells in vitro. Endocrinology 1989; 124: 1576-1578.
17 Kurth AH, Eberhardt C, Mueller S. et al. The bis-phosphonate ibandronate improves implant integration in osteopenic ovariectomized rats. Bone 2005; 37 (02) 204-210.
18 Lu TW, O´Connor JJ, Taylor SJG, Walker PS. Influence of muscle activity of the forces of the femur: comparison between in vivo measurements and calculation. Trans Orthop Res Soc 1997; 22: 721.
19 Maus U, Andereya S, Schmidt S. et al. Therapy effects of testosterone on the recovery of bone defects. Z Orthop Unfall 2008; 146: 59-63.
20 McCutchen JW, Collier JP, Mayor MB. Osseointegration of titanium implants in total hip arthroplasty. Clin Orthop Rel Res 1990; 261: 114-125.
21 Nilsson LP, Granström G, Albrektsson T. The effect of hyperbaric oxygen treatment of bone regeneration. An experimental study in the rabbit. Int J Oral Maxillofac Implants 1987; 3: 43-48.
22 Nishiguchi S, Kato H, Fujita H. et al. Titanium metals form direct bonding to bone after alkali and heat treatments. Biomaterials 2002; 22: 2525-2533.
23 Nordin BE, Robertson A, Seamark RF. et al. The relation between calcium absorption, serum dehydroepiandrosterone and vertebral mineral density in postmenopausal women. J Clin Endocrinol Metab 1985; 60: 651-657.
24 Piatelli A, Scarano A, Piatelli M, Calabrese L. Direct bone formation on sand-blasted titanium implants: an experimental study. Biomaterials 1996; 17: 1015-1018.
25 Pilliar RM. Porous-surface metallic implants surface for orthopaedic applications. J Biomed Mater Res 1986; 21: 1-33.
26 Raisz LG, Wiita B, Artis A. et al. Comparison of the effects of estrogen alone and estrogen plus androgen on biomechanical markers of bone formation and resorption in postmenopausal women. J Clin Endocrinol Metab 1996; 81: 37-43.
27 Tarsoly E, Janossy J, Kosztura L. Effect of testosterone on fracture healing in hypophysectomized rats. Acta-Histochem 1979; 65 (01) 25-33.
28 Vanderschueren D, Van Herck E, Suiker AMH. et al. Bone and mineral metabolism in the androgen resistant (testicular feminized) male rat. J Bone Miner Res 1993; 8: 799-807.
29 Vanderschueren D, Van Herck E, Suiker AMH. et al. Bone and mineral metabolism in aged male rats: short-and longterm effects of androgen deficiency. Endocrinology 1992; 130: 2906-2916.
30 Wang C, Eyre DR, Clark R. et al. Sublingual testosterone replacement improves muscle mass and strength, decreases bone resorption, and increases bone formation markers in hypogonadal men–a clinical research center study. J Clin Endocrinol Metab 1996; 81: 3654-3662.
31 Weenerberg A. On surface roughness and implant incorporation. PhD thesis, Dept of Biomaterials/ Handicap research, University of Göteborg. Sweden: 1996: 1-212.
32 Weisman Y, Cassorla F, Malozowski S. et al. Sex-specific response of bone cells to gonadal steroids: modulation in perinatally androgenized females in testicular feminized rats. Steroids 1993; 58: 126-133.