Intravenous bisphosphonates in osteoporosis and jaw osteonecrosis: comment on the article by Delmas et al

Article

Reference

Intravenous bisphosphonates in osteoporosis and jaw osteonecrosis:

comment on the article by Delmas et al

LANDIS, Basile Nicolas, HUGENTOBLER, Max Anselme

LANDIS, Basile Nicolas, HUGENTOBLER, Max Anselme. Intravenous bisphosphonates in osteoporosis and jaw osteonecrosis: comment on the article by Delmas et al. Arthritis and Rheumatism , 2006, vol. 54, no. 11, p. 3720-1;authorreply3721-2

DOI : 10.1002/art.22202 PMID : 17075888

Available at:

http://archive-ouverte.unige.ch/unige:36920

Disclaimer: layout of this document may differ from the published version.

1 / 1

Markus M. J. Nielen, MSc

Dirkjan van Schaardenburg, MD, PhD Willem F. Lems, MD, PhD

Rob J. van de Stadt, PhD Margret H. M. T. de Koning Jan van Breemen Institute Amsterdam, The Netherlands Henk W. Reesink, MD, PhD Moud R. Habibuw

Sanquin Blood Bank North West Region Amsterdam, The Netherlands

Irene E. van der Horst-Bruinsma, MD, PhD Jos W. R. Twisk, PhD

Ben A. C. Dijkmans, MD, PhD VU University Medical Centre Amsterdam, The Netherlands

1. Merlino LA, Curtis J, Mikuls TR, Cerhan JR, Criswell LA, Saag KG. Vitamin D intake is inversely associated with rheumatoid arthritis: results from the Iowa Women’s Health Study. Arthritis Rheum 2004;50:72–7.

2. Holick MF. Vitamin D: photobiology, metabolism, mechanism of action, and clinical applications. In: Favus, MJ, editor. Primer on the metabolic bone diseases and disorders of mineral metabolism.

5th ed. New York: Raven Press; 2003. p. 129–37.

3. Nielen MM, van Schaardenburg D, Reesink HW, van de Stadt RJ, van der Horst-Bruinsma IE, de Koning MH, et al. Specific autoantibodies precede the symptoms of rheumatoid arthritis: a study of serial measurements in blood donors. Arthritis Rheum 2004;50:380–6.

4. Twisk JW. Applied longitudinal data analysis for epidemiology: a practical guide. Cambridge (UK): Cambridge University Press; 2003.

5. Van Soesbergen RM, Lips P, van den Ende A, van der Korst JK.

Bone metabolism in rheumatoid arthritis compared with post- menopausal osteoporosis. Ann Rheum Dis 1986;45:149–55.

6. Kroger H, Penttila IM, Alhava EM. Low serum vitamin D metabolites in women with rheumatoid arthritis. Scand J Rheu- matol 1993;22:172–7.

7. Aguado P, del Campo MT, Garces MV, Gonzalez-Casaus ML, Bernad M, Gijon-Banos J, et al. Low vitamin D levels in outpatient postmenopausal women from a rheumatology clinic in Madrid, Spain: their relationship with bone mineral density. Osteoporos Int 2000;11:739–44.

8. Als OS, Riis B, Christiansen C. Serum concentration of vitamin D metabolites in rheumatoid arthritis. Clin Rheumatol 1987;6:238–43.

9. Cantorna MT, Hayes CE, Deluca HF. 1,25-Dihydroxycholecalcif- erol inhibits the progression of arthritis in murine models of human arthritis. J Nutr 1998;128:68–72.

10. Larsson P, Mattsson L, Klareskog L, Johnsson C. A vitamin D analogue (MC 1288) has immunomodulatory properties and sup- presses collagen-induced arthritis (CIA) without causing hypercal- caemia. Clin Exp Immunol 1998;114:277–83.

11. Tsuji M, Fujii K, Nakano T, Nishii Y. 1 ␣-hydroxyvitamin D3 inhibits type II collagen-induced arthritis in rats. FEBS Lett 1994;337:248–50.

DOI 10.1002/art.22202

Intravenous bisphosphonates in osteoporosis and jaw osteonecrosis: comment on the article by Delmas et al

We congratulate Delmas and colleagues (1) on their article showing the efficacy of intravenous ibandronate treat-

ment for patients with osteoporosis, as assessed by bone mineral density. New-generation bisphosphonates (NGBs), which initially were used for patients with metastatic bone malignancies, rapidly became used for other bone pathologies such as osteoporosis and Paget’s disease (2,3). Adding to the discussion by Delmas et al, we would like to bring up a potential safety concern about intravenous NGB treatment that has also recently been highlighted by the American College of Rheumatology (4).

During the last 3 years, reports in the oromaxillofacial literature on avascular jaw osteonecrosis associated with NGB treatment have increased almost exponentially (5,6). NGBs have proved efficacious in oncology patients with bone involve- ment, and there is no doubt about the contribution of NGBs in improving the quality of life in patients experiencing bone metastases.

In contrast to patients with osteoporosis, oncology patients receive high doses of intravenous NGB and have been shown to be more prone to the development of jaw osteone- crosis. However, jaw osteonecrosis in patients with osteo- porosis who are receiving oral NGBs has repeatedly been reported (5,6). Whether these are isolated examples or are cases that suggest a broader clinical problem will become clearer within the next years.

The incidence of jaw osteonecrosis during or after NGB treatment remains unknown, but the rising number of reported cases causes considerable concern. The risk of jaw osteonecrosis seems to depend on the type and dose of NGB administered (5). The fact that osteoporosis patients are usually prescribed oral and lower doses of NGB could explain why these patients are less concerned about jaw osteonecrosis.

NGBs inhibit osteoclast activity but also have antiangiogenic effects, and, once incorporated into the bone, they are barely eliminated (7).

Considering the higher life expectancy of patients with osteoporosis compared with that of oncology patients, even lower doses of NGB could lead to the delayed occurrence of jaw osteonecrosis (5). Having said this, how early and aggres- sively NGBs should be prescribed to patients with osteoporosis might be weighed on an individual basis (8). According to the literature (6), the mean time of onset of osteonecrosis after starting intravenous NGB therapy is 1–3 years in oncology patients. Thus, the question of whether intravenous NGB treatment might increase the risk of avascular jaw osteonecro- sis developing in patients with osteoporosis remains unan- swered. Further reports from this intravenous administration study might clarify this issue.

Jaw osteonecrosis represents a severe complication, and currently, no curative treatment exists (5,6). Risk factors for jaw osteonecrosis are an oncologic situation and intrave- nous rather than oral administration of NGBs. Furthermore, recent studies clearly identified poor dental hygiene, periodon- tal pathologies, and particularly dental extractions during NGB treatment as factors that considerably increase the risk of jaw osteonecrosis (6,9).

Therefore, patients with chronic periodontal problems and foreseeable dental extractions should be identified before NGB treatment is started. If necessary, these patients should undergo a specialist dental or maxillofacial workup in order to treat all oral and dental problems before starting NGB ther-

3720 LETTERS

apy. This is particularly important when considering intrave- nous NGB treatment.

Basile N. Landis, MD Max Hugentobler, MD, DMD Hoˆpitaux Universitaires de Gene`ve Geneva, Switzerland

1. Delmas PD, Adami S, Strugala C, Stakkestad JA, Reginster JY, Felsenberg D, et al. Intravenous ibandronate injections in post- menopausal women with osteoporosis: one-year results from the Dosing Intravenous Administration Study. Arthritis Rheum 2006;

54:1838–46.

2. Drake WM, Kendler DL, Brown JP. Consensus statement on the modern therapy of Paget’s disease of bone from a Western Osteo- porosis Alliance symposium: Biannual Foothills Meeting on Osteo- porosis, Calgary, Alberta, Canada, September 9–10, 2000 [review].

Clin Ther 2001;23:620–6.

3. Bone HG, Hosking D, Devogelaer JP, Tucci JR, Emkey RD, Tonino RP, et al. Ten years’ experience with alendronate for osteoporosis in postmenopausal women. N Engl J Med 2004;350:

1189–99.

4. American College of Rheumatology Web Site. Hotline: Bisphos- phonate-associated osteonecrosis of the jaw. URL: http://www.

rheumatology.org/publications/hotline/0606onj.asp.

5. Woo SB, Hellstein JW, Kalmar JR. Narrative [corrected] review:

bisphosphonates and osteonecrosis of the jaws. Ann Intern Med 2006;144:753–61.

6. Marx RE, Sawatari Y, Fortin M, Broumand V. Bisphosphonate- induced exposed bone (osteonecrosis/osteopetrosis) of the jaws:

risk factors, recognition, prevention, and treatment. J Oral Maxil- lofac Surg 2005;63:1567–75.

7. Lin JH, Russell G, Gertz B. Pharmacokinetics of alendronate: an overview. Int J Clin Pract Suppl 1999;101:18–26.

8. Schousboe JT, Nyman JA, Kane RL, Ensrud KE. Cost-effectiveness of alendronate therapy for osteopenic postmenopausal women.

Ann Intern Med 2005;142:734–41.

9. Farrugia MC, Summerlin DJ, Krowiak E, Huntley T, Freeman S, Borrowdale R, et al. Osteonecrosis of the mandible or maxilla associated with the use of new generation bisphosphonates. Laryn- goscope 2006;116:115–20.

DOI 10.1002/art.22203

Reply

We thank Drs. Landis and Hugentobler for their letter highlighting the growing concern among physicians about the case reporting of osteonecrosis of the jaw (ONJ) in patients receiving treatment with bisphosphonates. At present, most reported cases of ONJ have been in oncology patients, with the vast majority of these cases being reported in cancer patients receiving high-dose intravenous (IV) bisphosphonate therapy in association with chemotherapy, radiotherapy, poor dental hygiene, or after a dental procedure. Published series of cases in more than 300 oncology patients have been extensively reviewed (1,2), with additional cases reported in patients with metastatic bone disease or multiple myeloma (3–19). In con- trast, few cases of ONJ have been reported in patients re- ceiving bisphosphonates for osteoporosis or osteopenia (1,2,13,18,20–22), and the occurrence of ONJ in this popula-

tion is thought to be very rare. The relationship between bisphosphonate therapy and ONJ in these patients remains unclear, and further investigation is warranted.

The Dosing Intravenous Administration (DIVA) study investigated the effects of ibandronate on bone mineral density and formed the basis of its registration as the first IV bisphos- phonate indicated for the treatment of postmenopausal osteo- porosis. We have been informed by F. Hoffmann-La Roche Ltd./GlaxoSmithKline that in all controlled clinical trials of patients with postmenopausal osteoporosis receiving iban- dronate (IV or oral), no cases of ONJ have been observed, and that the occurrence of this condition will be carefully moni- tored in future studies and in clinical practice.

As pointed out by Drs. Landis and Hugentobler, patients with chronic periodontal disease and those requiring dental extraction should be identified before bisphosphonate therapy is initiated, although there is no current guideline for their management.

Pierre D. Delmas, MD, PhD Hoˆpital Edouard Herriot Lyon, France

for the DIVA study investigators

1. Migliorati CA, Casiglia J, Epstein J, Jacobsen PL, Siegel MA, Woo SB. Managing the care of patients with bisphosphonate-associated osteonecrosis: an American Academy of Oral Medicine position paper. J Am Dent Assoc 2005;136:1658–68.

2. Woo SB, Hellstein JW, Kalmar JR. Systematic review: bisphos- phonates and osteonecrosis of the jaws. Ann Intern Med 2006;144:

753–61.

3. Durie BG, Katz M, Crowley J. Osteonecrosis of the jaw and bisphosphonates. N Engl J Med 2005;353:99–100.

4. Woo SB, Hande K, Richardson PG. Osteonecrosis of the jaw and bisphosphonates. N Engl J Med 2005;353:100.

5. Maerevoet M, Martin C, Duck L. Osteonecrosis of the jaw and bisphosphonates. N Engl J Med 2005;353:100–1.

6. Singhal S, Kut V, Tariman J, Rosen S, Benneett CL, Mehta J.

Pamidronate and zoledronate-associated osteonecrosis in my- eloma is an increasing and underrecognized problem [abstract].

Haematologica 2005;90 (Suppl 1):191.

7. Bagan JV, Jimenez Y, Murillo J, Hernandez S, Poveda R, Sanchis JM, et al. Jaw osteonecrosis associated with bisphosphonates:

multiple exposed areas and its relationship to teeth extractions:

study of 20 cases. Oral Oncol 2006;42:327–9.

8. Olson KB, Hellie CM, Pienta KJ. Osteonecrosis of jaw in patient with hormone-refractory prostate cancer treated with zoledronic acid [review]. Urology 2005;66:658.

9. Markiewicz MR, Margarone JE, Campbell JH, Aguirre A.

Bisphosphonate-associated osteonecrosis of the jaws. J Am Dent Assoc 2005;136:1669–73.

10. Marx RE, Sawatari Y, Fortin M, Broumand V. Bisphosphonate- induced exposed bone (osteonecrosis/osteopetrosis) of the jaws:

risk factors, recognition, prevention and treatment. J Oral Maxil- lofac Surg 2005;63:1567–75.

11. Bamias A, Kastritis E, Bamia C, Moulopoulos LA, Melakopoulos I, Bozas G, et al. Osteonecrosis of the jaw in cancer after treatment with bisphosphonates: incidence and risk factors. J Clin Oncol 2005;23:8580–7.

12. Melo MD, Obeid G. Osteonecrosis of the jaws in patients with a history of receiving bisphosphonate therapy. J Am Dent Assoc 2005;136:1675–81.

13. Migliorati Ca, Schubert MM, Peterson DE, Seneda LM. Bisphos- phonate-associated osteonecrosis of the mandibular and maxillary

LETTERS 3721