J Bone Metab.  2019 Feb;26(1):13-18. 10.11005/jbm.2019.26.1.13.

Is There a Role of Pharmacological Treatments in the Prevention or Treatment of Osteonecrosis of the Femoral Head?: A Systematic Review

• Lee YJ
• Cui Q
• Koo KH

• KMID: 2440640
• DOI: http://doi.org/10.11005/jbm.2019.26.1.13

Abstract

BACKGROUND
Various pharmacological treatments have been suggested to treat osteonecrosis of the femoral head. However, their practicability remains a controversial issue.
METHODS
We systemically reviewed articles published during last 20 years to assess the efficacy and safety of the pharmacological treatments.
RESULTS
To date, enoxaparin, statins, bisphosphonates, iloprost and acetylsalicylic acid have been practiced for the treatment of osteonecrosis. However, none of them were proven to be effective by high level studies, and most of them have adverse reactions.
CONCLUSIONS
No pharmacological prevention or treatment of osteonecrosis is recommendable at this moment.

Keyword

Bone remodeling; Diphosphonates; Drug therapy; Osteonecrosis

MeSH Terms

Aspirin
Bone Remodeling
Diphosphonates
Drug Therapy
Enoxaparin
Head*
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Iloprost
Osteonecrosis*
Aspirin
Diphosphonates
Enoxaparin
Iloprost

Figure

• 

  Fig. 1 Pathogenesis of femoral head osteonecrosis.

Reference

1. Schneider W, Knahr K. Total hip replacement in younger patients: survival rate after avascular necrosis of the femoral head. Acta Orthop Scand. 2004; 75:142–146.

2. Hungerford DS. Treatment of osteonecrosis of the femoral head: everything's new. J Arthroplasty. 2007; 22:91–94.

3. Shibatani M, Fujioka M, Arai Y, et al. Degree of corticosteroid treatment within the first 2 months of renal transplantation has a strong influence on the incidence of osteonecrosis of the femoral head. Acta Orthop. 2008; 79:631–636.

4. Arlet J. Nontraumatic avascular necrosis of the femoral head. Past, present, and future. Clin Orthop Relat Res. 1992; (277):12–21.

5. Shigemura T, Nakamura J, Kishida S, et al. Incidence of osteonecrosis associated with corticosteroid therapy among different underlying diseases: prospective MRI study. Rheumatology (Oxford). 2011; 50:2023–2028.

6. Hungerford DS. Osteonecrosis: avoiding total hip arthroplasty. J Arthroplasty. 2002; 17:4 Suppl 1. 121–124.

7. Kang JS, Park S, Song JH, et al. Prevalence of osteonecrosis of the femoral head: a nationwide epidemiologic analysis in Korea. J Arthroplasty. 2009; 24:1178–1183.

8. Yuan HF, Guo CA, Yan ZQ. The use of bisphosphonate in the treatment of osteonecrosis of the femoral head: a meta-analysis of randomized control trials. Osteoporos Int. 2016; 27:295–299.

9. Li D, Yang Z, Wei Z, et al. Efficacy of bisphosphonates in the treatment of femoral head osteonecrosis: A PRISMA-compliant meta-analysis of animal studies and clinical trials. Sci Rep. 2018; 8:1450.

10. Koo KH, Jeong ST, Jones JP Jr. Borderline necrosis of the femoral head. Clin Orthop Relat Res. 1999; (358):158–165.

11. Glueck CJ, Freiberg RA, Sieve L, et al. Enoxaparin prevents progression of stages I and II osteonecrosis of the hip. Clin Orthop Relat Res. 2005; (435):164–170.

12. Glueck CJ, Freiberg RA, Wissman R, et al. Long term anticoagulation (4–16 years) stops progression of idiopathic hip osteonecrosis associated with familial thrombophilia. Adv Orthop. 2015; 2015:138382.

13. Chotanaphuti T, Thongprasert S, Laoruengthana A. Low molecular weight heparin prevents the progression of precollapse osteonecrosis of the hip. J Med Assoc Thai. 2013; 96:1326–1330.

14. Pritchett JW. Statin therapy decreases the risk of osteonecrosis in patients receiving steroids. Clin Orthop Relat Res. 2001; (386):173–178.

15. Pengde K, Fuxing P, Bin S, et al. Lovastatin inhibits adipogenesis and prevents osteonecrosis in steroid-treated rabbits. Joint Bone Spine. 2008; 75:696–701.

16. Ajmal M, Matas AJ, Kuskowski M, et al. Does statin usage reduce the risk of corticosteroid-related osteonecrosis in renal transplant population? Orthop Clin North Am. 2009; 40:235–239.

17. U.S. Food and Drug Administration. FDA Drug Safety Communication: Important safety label changes to cholesterol-lowering statin drugs. 2012. cited by 2019 Jan 7. Available from: http://www.fda.gov/drugs/drugsafety/ucm293-101.htm#dose.

18. Lai KA, Shen WJ, Yang CY, et al. The use of alendronate to prevent early collapse of the femoral head in patients with nontraumatic osteonecrosis. A randomized clinical study. J Bone Joint Surg Am. 2005; 87:2155–2159.

19. Agarwala S, Shetty V, Karumuri LK, et al. Patellar resurfacing versus nonresurfacing with patellaplasty in total knee arthroplasty. Indian J Orthop. 2018; 52:393–398.

20. Nishii T, Sugano N, Miki H, et al. Does alendronate prevent collapse in osteonecrosis of the femoral head? Clin Orthop Relat Res. 2006; 443:273–279.

21. Chen CH, Chang JK, Lai KA, et al. Alendronate in the prevention of collapse of the femoral head in nontraumatic osteonecrosis: a two-year multicenter, prospective, randomized, double-blind, placebo-controlled study. Arthritis Rheum. 2012; 64:1572–1578.

22. Lee YK, Ha YC, Cho YJ, et al. Does zoledronate prevent femoral head collapse from osteonecrosis? A prospective, randomized, open-label, multicenter study. J Bone Joint Surg Am. 2015; 97:1142–1148.

23. Pazianas M, Abrahamsen B. Safety of bisphosphonates. Bone. 2011; 49:103–110.

24. Jager M, Zilkens C, Bittersohl B, et al. Efficiency of iloprost treatment for osseous malperfusion. Int Orthop. 2011; 35:761–765.

25. Claßen T, Becker A, Landgraeber S, et al. Long-term clinical results after iloprost treatment for bone marrow edema and avascular necrosis. Orthop Rev (Pavia). 2016; 8:6150.

26. Pountos I, Giannoudis PV. The role of Iloprost on bone edema and osteonecrosis: safety and clinical results. Expert Opin Drug Saf. 2018; 17:225–233.

27. Albers A, Carli A, Routy B, et al. Treatment with acetylsalicylic acid prevents short to mid-term radiographic progression of nontraumatic osteonecrosis of the femoral head: a pilot study. Can J Surg. 2015; 58:198–205.

28. Sugano N, Atsumi T, Ohzono K, et al. The 2001 revised criteria for diagnosis, classification, and staging of idiopathic osteonecrosis of the femoral head. J Orthop Sci. 2002; 7:601–605.

29. Koo KH, Ahn IO, Kim R, et al. Bone marrow edema and associated pain in early stage osteonecrosis of the femoral head: prospective study with serial MR images. Radiology. 1999; 213:715–722.

30. Ha YC, Jung WH, Kim JR, et al. Prediction of collapse in femoral head osteonecrosis: a modified Kerboul method with use of magnetic resonance images. J Bone Joint Surg Am. 2006; 88:Suppl 3. 35–40.

31. Steinberg ME, Hayken GD, Steinberg DR. A quantitative system for staging avascular necrosis. J Bone Joint Surg Br. 1995; 77:34–41.