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Abstract

Background: Cartilage and subchondral bone have recently been considered an osteochondral unit. The treatment of osteo-chondral lesions is still challenging, but better subchondral bone repair may result in higher quality repaired cartilage.

Hypotheses: Alendronate accelerates bone formation in osteochondral defects and affects the quality of the repaired cartilage.

Study Design: Controlled laboratory study.

Methods: Osteochondral defects were made on the left trochleas of 50 rabbits, which were assigned to 1 of 3 groups: control, ALN (weekly subcutaneous injection of 0.14 mg/mL alendronate), and ALN-S (alendronate injection in the first 8 weeks only). They were evaluated at 4, 8, 24, and 52 weeks. Bone repair was evaluated with microcomputed tomography and histologic evaluation. Cartilage repair was evaluated with ultrasound and histologic analyses.

Results: At 4 weeks, the defects were filled, and cartilage-like repair tissue was observed in the ALN group, whereas the defects were incompletely filled in the control group. Alendronate treatment enhanced early bone formation and mineralization in the osteochondral defect for the first 8 weeks. The continuous injection of alendronate for 24 weeks resulted in delayed bone remodeling, but the rabbits in the ALN-S group showed good integrity of the subchondral bone plate, without delayed remodeling. At 52 weeks, the ALN-S group had a columnar arrangement of chondrocytes that had less fibrillation and looked superior to those in the ALN and control groups. Ultrasound analysis showed better quality of repaired cartilage of the ALN and ALN-S group than the control group.

Conclusion: Alendronate accelerated bone formation without inhibiting its mineralization but thereafter inhibited bone remodeling in an osteochondral defect. The withdrawal of alendronate at 8 weeks avoided the delayed remodeling and showed better sub-chondral bone repair. At 52 weeks, better subchondral bone repair resulted in better cartilage quality.

Clinical Relevance: Alendronate administered in the early period accelerates bone formation and improves the quality of the repaired cartilage.

Keywords

cartilage repair subchondral bone repair remodeling osteochondral defect bisphosphonate

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References

Armstrong CG

. An analysis of the stresses in a thin layer of articular cartilage in a synovial joint.Eng Med.1986;15(2):55–61.

Azuma Y

Oue Y

Kanatani H

Ohta T

Kiyoki M

Komoriya K

. Effects of continuous alendronate treatment on bone mass and mechanical properties in ovariectomized rats: comparison with pamidronate and etidronate in growing rats.J Pharmacol Exp Ther.1998;286(1): 128–135.

Balena R

Toolan BC

Shea M

, et al. The effects of 2-year treatment with the aminobisphosphonate alendronate on bone metabolism, bone histomorphometry, and bone strength in ovariectomized nonhuman primates.J Clin Invest.1993;92(6):2577–2586.

Brittberg M

Lindahl A

Nilsson A

Ohlsson C

Isaksson O

Peterson L

. Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation.N Engl J Med.1994;331(14):889–895.

Cao Y

Mori S

Mashiba T

, et al. Raloxifene, estrogen, and alendro-nate affect the processes of fracture repair differently in ovariecto-mized rats.J Bone Miner Res.2002;17(12):2237–2246.

Ding M

Danielsen CC

Hvid I

. The effects of bone remodeling inhibition by alendronate on three-dimensional microarchitecture of sub-chondral bone tissues in guinea pig primary osteoarthrosis.Calcif Tissue Int.2008;82(1):77–86.

Dombrecht EJ

De Tollenaere CB

Aerts K

, et al. Antioxidant effect of bisphosphonates and simvastatin on chondrocyte lipid peroxidation.Biochem Biophys Res Commun.2006;348(2):459–464.

Gerstenfeld LC

Sacks DJ

Pelis M

, et al. Comparison of effects of the bisphosphonate alendronate versus the RANKL inhibitor denosumab on murine fracture healing.J Bone Miner Res.2009;24(2):196–208.

Hattori K

Ikeuchi K

Morita Y

Takakura Y

. Quantitative ultrasonic assessment for detecting microscopic cartilage damage in osteoar-thritis.Arthritis Res Ther.2005;7(1):R38–46.

10.

Hattori K

Takakura Y

Ishimura M

Tanaka Y

Habata T

Ikeuchi K

. Differential acoustic properties of early cartilage lesions in living human knee and ankle joints.Arthritis Rheum.2005;52(10):3125–3131.

11.

Hayami T

Pickarski M

Wesolowski GA

, et al. The role of subchon-dral bone remodeling in osteoarthritis: reduction of cartilage degeneration and prevention of osteophyte formation by alendronate in the rat anterior cruciate ligament transection model.Arthritis Rheum.2004;50(4):1193–1206.

12.

Iwata K

Li J

Follet H

Phipps RJ

Burr DB

. Bisphosphonates suppress periosteal osteoblast activity independently of resorption in rat femur and tibia.Bone.2006;39(5):1053–1058.

13.

Jackson DW

Lalor PA

Aberman HM

Simon TM

. Spontaneous repair of full-thickness defects of articular cartilage in a goat model: a preliminary study.J Bone Joint Surg Am.2001;83(1):53–64.

14.

Kuroki H

Nakagawa Y

Mori K

Ikeuchi K

Nakamura T

. Mechanical effects of autogenous osteochondral surgical grafting procedures and instrumentation on grafts of articular cartilage.Am J Sports Med.2004;32(3):612–620.

15.

Kuroki H

Nakagawa Y

Mori K

, et al. Acoustic stiffness and change in plug cartilage over time after autologous osteochondral grafting: correlation between ultrasound signal intensity and histological score in a rabbit model.Arthritis Res Ther.2004;6(6):R492–504.

16.

Kuroki H

Nakagawa Y

Mori K

, et al. Maturation-dependent change and regional variations in acoustic stiffness of rabbit articular cartilage: an examination of the superficial collagen-rich zone of cartilage.Osteoarthritis Cartilage.2006;14(8):784–792.

17.

Kuroki H

Nakagawa Y

Mori K

, et al. Sequential changes in implanted cartilage after autologous osteochondral transplantation: postoperative acoustic properties up to 1 year in an in vivo rabbit model.Arthroscopy.2007;23(6):647–654.

18.

Li C

Mori S

Li J

, et al. Long-term effect of incadronate disodium (YM-175) on fracture healing of femoral shaft in growing rats.J Bone Miner Res.2001;16(3):429–436.

19.

Lietman SA

Miyamoto S

Brown PR

Inoue N

Reddi AH

. The temporal sequence of spontaneous repair of osteochondral defects in the knees of rabbits is dependent on the geometry of the defect.J Bone Joint Surg Br.2002;84(4):600–606.

20.

Mainil-Varlet P

Aigner T

Brittberg M

, et al. Histological assessment of cartilage repair: a report by the Histology Endpoint Committee of the International Cartilage Repair Society (ICRS).J Bone Joint Surg Am.2003;85(Suppl 2):45–57.

21.

Matsusue Y

Yamamuro T

Hama H

. Arthroscopic multiple osteo-chondral transplantation to the chondral defect in the knee associated with anterior cruciate ligament disruption.Arthroscopy.1993;9(3): 318–321.

22.

Minas T

Gomoll AH

Rosenberger R

Royce RO

Bryant T

. Increased failure rate of autologous chondrocyte implantation after previous treatment with marrow stimulation techniques.Am J Sports Med.2009;37(5):902–908.

23.

Mori K

Hattori K

Habata T

, et al. Measurement of the mechanical properties of regenerated articular cartilage using wavelet transformation. In: Tissue Engineering for Therapeutic Use 6.Tokyo, Japan: Elsevier; 2002: 133–142.

24.

Muehleman C

Li J

Abe Y

, et al. Effect of risedronate in a minipig cartilage defect model with allograft.J Orthop Res.2009;27(3): 360–365.

25.

Nishitani K

Nakagawa Y

Gotoh T

Kobayashi M

Nakamura T

. Intraoperative acoustic evaluation of living human cartilage of the elbow and knee during mosaicplasty for osteochondritis dissecans of the elbow: an in vivo study.Am J Sports Med.2008;36(12):2345–2353.

26.

Orriss IR

Key ML

Colston KW

Arnett TR

. Inhibition of osteoblast function in vitro by aminobisphosphonates.J Cell Biochem.2009;106(1):109–118.

27.

Peter CP

Cook WO

Nunamaker DM

Provost MT

Seedor JG

Rodan GA

. Effect of alendronate on fracture healing and bone remodeling in dogs.J Orthop Res.1996;14(1):74–79.

28.

Radin ER

Paul IL

Rose RM

. Pathogenesis of primary osteoarthritis.Lancet.1972;1(7765):1395–1396.

29.

Schlichting K

Schell H

Kleemann RU

, et al. Influence of scaffold stiffness on subchondral bone and subsequent cartilage regeneration in an ovine model of osteochondral defect healing.Am J Sports Med.2008;36(12):2379–2391.

30.

Sen C

Gunes T

Erdem M

Koseoglu RD

Filiz NO

. Effects of calcito-nin and alendronate on distraction osteogenesis.Int Orthop.2006;30(4):272–277.

31.

Steadman JR

Rodkey WG

Rodrigo JJ

. Microfracture: surgical technique and rehabilitation to treat chondral defects.Clin Orthop Relat Res.2001;391(Suppl):S362–369.

32.

Van Offel JF

Schuerwegh AJ

Bridts CH

Stevens WJ

De Clerck LS

. Effect of bisphosphonates on viability, proliferation, and dexamethasone-induced apoptosis of articular chondrocytes.Ann Rheum Dis.2002;61(10):925–928.

33.

Wright TM

Maher SA

. Current and novel approaches to treating chondral lesions.J Bone Joint Surg Am.2009;91(Suppl 1):120–125.

Positive Effect of Alendronate on Subchondral Bone Healing and Subsequent Cartilage Repair in a Rabbit Osteochondral Defect Model

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