Total hip arthroplasty or hip replacement
surgery can result in a painful new bone formation known as heterotopic ossification. The incidence
of heterotopic ossification following total hip arthroplasty is estimated to be approximately 53%,
especially when risk factors, including a prior history of heterotopic ossification, prior
trauma/operations, ankylosing spondylitis, Paget’s disease or rheumatoid arthritis are
present.1,2 The pathophysiology is believed to involve the migration
of pluripotent mesenchymal cells into tissues surrounding the joint which then differentiate into
osteoblasts, which in turn form mature bone. 1 This formation results
in loss of range of motion of the affected joint as well as pain and inflammation experienced by the
In patients with high risk for the
development of this condition, prophylactic approaches include local radiation of the surgical area,
indomethacin or other NSAIDS for two to six weeks following surgery or the use of bisphosphonate
therapy such as etidronate. 1,
2 Etidronate is indicated for the
prevention of heterotopic ossification following total hip arthroplasty or spinal cord
Efficacy data from clinical trials of
etidronate in this setting is conflicting. Data from animal and in vitro models demonstrates the ability of etidronate to suppress the formation
of mature bone in non-osseous environments; it does not reverse already established heterotopic
bone. 4, 5 However, human trials have demonstrated that the use of etidronate in
long term prevention of heterotopic ossification following discontinuation does not differ
significantly from placebo.4 Moreover, once the
medication is removed, normal bone formation will resume in approximately three to six months.
3,4 A more recent study by Vasileiadis and colleagues demonstrated that
clinical outcomes in 56 total hip arthroplasty patients followed over 12 months did not differ
significantly in either Harris Hip Score or radiographic evidence of heterotopic ossification
between groups treated with etidronate or indomethacin.2 Significant differences
were noted with a greater incidence of adverse reactions (mostly GI upset) in the indomethacin group
and increased cost of therapy in the etidronate group.
In summary, etidronate is indicated for the
prophylaxis of heterotopic bone formation following total hip arthroplasty and appears to be at
least as effective as the use of indomethacin. However, long term data are equivocal between the
two groups and etidronate has a significantly greater cost.
1. Chao ST, Suh JH, Joyce MJ.
Treatment of heterotopic ossification. Orthopedics. 2007;
2. Vasileiadis GI,
Skellariou VI, Kelekis A, Galanos A et al. Prevention of
heterotopic ossification in cases of hypertrophic osteoarthritis submitted to total hip
arthroplasty. Etidronate or indomethacin? J Musculoskelet Neuronal
Interact. 2010; 10(2):159-165
3. Etidronate [package insert]. Morgantown, WV: Mylan
4. Hu HP,
Kuijpers W, Sloof TJJH, van Horn JR Versleyen DH. Effect of
bisphosphonate on induced heterotopic bone. Clin Ortho Rel Res. 1991; 272: 259-267.
Thomas BJ, Amstatz HC. Results of the administration
of diphosphonate for the prevention of heterotopic ossification after total hip arthroplasty. J Bone & Joint
Surg. 1985; 67(3): 400-403.