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Scientific Articles:
Mohit Bhandari, Sohail Bajammal, Gordon H. Guyatt, Lauren Griffith, Jason W. Busse, Holger Schünemann, and Thomas A. Einhorn
Effect of Bisphosphonates on Periprosthetic Bone Mineral Density After Total Joint Arthroplasty. A Meta-Analysis
J Bone Joint Surg Am 2005; 87: 293-301 [Abstract] [Full text] [PDF]
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Electronic letters published:

[Read Letter to the Editor] Effect of bisphosphonates on periprosthetic bone mineral density after total joint arthroplasty.
Nitin. R Shetty, AJ Hamer, I Stockley, R Eastell, and JM Wilkinson.   (31 May 2005)
[Read Letter to the Editor] Dr. Bhandari and colleagues respond to Dr Shetty et al
Mohit Bhandari, M.D., Sohail Bajammal, M.D., Thomas Einhorn, M.D.   (31 May 2005)

Effect of bisphosphonates on periprosthetic bone mineral density after total joint arthroplasty. 31 May 2005
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Nitin. R Shetty,
Research Fellow
Department of Orthopaedics, Northern General Hospital, Sheffied, U.K.,
AJ Hamer, I Stockley, R Eastell, and JM Wilkinson.

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Re: Effect of bisphosphonates on periprosthetic bone mineral density after total joint arthroplasty.

shettynr{at}yahoo.com Nitin. R Shetty, et al.

To The Editor:

We read with interest the paper, “Effect of bisphosphonates on periprosthetic bone mineral density after total joint arthroplasty. A meta-analysis” by Bhandari et al (1). We were intrigued by the finding that the effect size of bisphosphonate therapy was greater for cemented versus uncemented implants, and in total knee arthroplasty (TKA) versus total hip arthroplasty (THA). We note that both of the TKA studies were made using cemented implants, but that in half of the THA studies uncemented implants were used. Could the authors clarify whether cementation and joint site were independent predictors of drug efficacy, or might the greater effect in cemented implants be due to the common variable effect of TKA.

The authors also state that in our study the effect of a single post- operative dose of pamidronate on femoral bone mineral density was lost at 6 months.(2) We feel that it is important to comment that this late loss of effect was due largely to a partial recovery in bone mass in the placebo group at this time-point, rather than a late fall in bone mass in the pamidronate group.

Finally, we agree with the authors’ comments that studies to date have used small samples and not included clinically relevant outcome measures and that the clinical relevance of the results are, as yet, unclear. As bone mineral density is a major determinant of bone strength it seems plausible that pharmacological preservation of bone mass might influence the risk of periprosthetic fracture. Direct evidence for a relationship between regional bone loss, focal osteolysis, and aseptic loosening is lacking. We believe that further work is required to determine whether regional bone loss is an independent predictor of implant failure. If such a relationship were confirmed, this would justify the establishment of larger scale trials using clinically relevant outcomes such as development of osteolytic lesions or rates of implant survival.

References:

(1) Mohit Bhandari, Sohail Bajammal, Gordon H. Guyatt, Lauren Griffith, Jason W. Busse, Holger Schünemann, and Thomas A. Einhorn Effect of Bisphosphonates on Periprosthetic Bone Mineral Density After Total Joint Arthroplasty. A Meta-Analysis J Bone Joint Surg Am 2005; 87: 293-301

(2) Wilkinson JM, Stockley I, Peel NFA, Hamer AJ, Elson RA, Barrington NA et al. Effect of pamidronate in preventing local bone loss after total hip arthroplasty: A randomized, double-blind, controlled trial. J Bone Miner Res 2001;16:556 -64.
Dr. Bhandari and colleagues respond to Dr Shetty et al 31 May 2005
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Mohit Bhandari, M.D.,
Orthopaedic Surgery
McMaster University,
Sohail Bajammal, M.D., Thomas Einhorn, M.D.

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Re: Dr. Bhandari and colleagues respond to Dr Shetty et al

bhandam{at}mcmaster.ca Mohit Bhandari, M.D., et al.

ID: 87/2/293

We read with great interest the comments raised by Shetty and colleagues on our paper ““Effect of bisphosphonates on periprosthetic bone mineral density after total joint arthroplasty. A meta-analysis” by Bhandari et al (2005; 87(2): 293-301).

We have indicated in the discussion section of the paper that “Our subgroup analyses should be interpreted with caution. These analyses are inherently underpowered, and differences may be the result of chance alone. Investigators have suggested that tests of interaction between different subgroups can limit erroneous conclusions; however, tests of interaction are often underpowered. Thus, our findings that bisphosphonates exert a differential effect on total knee arthroplasties and arthroplasties with cement should be considered exploratory.” We agree, with Shetty and colleagues that the effect of cementation could be confounded by the site of arthroplasty. Meta-regression analysis could potentially answer this question. However, the limited number of studies make such an analysis difficult.

Regarding the comment on the effect of pamidronate, we reported that in the context of discussing the potential influence of industry funding on study results. We stated “In the current review, one trial was funded by a commercial entity(1) and, in another trial, the drugs were given free by a commercial entity(2). The industry- funded trial demonstrated a significant benefit of the commercial entity’s product, but Wilkinson, et al, reported no significant effects of pamidronate at six months(2).” We indicated that pamidronate had no significant effects, eliminating the risk of bias of industry funding, without elaborating on the explanation of absence of effects, whether fall in bone mass in the pamidronate group or recovery in bone mass in the placebo group. We thank the authors for highlighting this point.

Finally, we thank the authors for emphasizing our suggestion of the importance of further work in this field. As we indicated in the paper, “Whether improvements in bone mineral density improve quality of life and function and decrease the risk of revision surgery remains unknown. The current meta-analysis does, however, provide important hypotheses that suggest a biological rationale for the role of bisphosphonates in this patient population”. We look forward to hearing about a sufficiently sized, methodologically sound study to assess clinically relevant end points in this topic.

Sincerely yours,

Mohit Bhandari, M.D., Sohail Bajammal, M.D., Thomas Einhorn, M.D.

References:

1. Lyons A. Effects of alendronate in total hip arthroplasty (Abstractt) Journal of Bone and Joint Surgery-British Volume. Vol.81 Suppl 3, pp.313, 1999.

2. Wilkinson JM, Stockley I, Peel NF, Hamer AJ, Elson RA, Barrington NA, Eastell R. Effect of pamidronate in preventing local bone loss after total hip arthroplasty: a randomized, double-blind, controlled trial. J.Bone Miner Res. 2001;16:556-64.