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 :: Case
 :: Discussion
 :: Introduction
 ::  References
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  Table of Contents     
ADVERSE DRUG REACTION [ADR] REPORT
Year : 2016  |  Volume : 62  |  Issue : 2  |  Page : 126-128

Possible alendronate-induced polyarticular synovitis


1 Department of Orthopaedics and Trauma, Antalya Memorial Hospital, Antalya, Turkey
2 Department of Endocrinolgy and Metabolism Disease, Antalya Memorial Hospital, Antalya, Turkey
3 Department of Radiodiagnostic, Antalya Memorial Hospital, Antalya, Turkey
4 Department of Physical Therapy and Rehabilitation, Zirve University, Gaziantep, Turkey

Date of Submission17-Apr-2015
Date of Decision04-Jun-2015
Date of Acceptance21-Jun-2015
Date of Web Publication15-Apr-2016

Correspondence Address:
K Gökkus
Department of Orthopaedics and Trauma, Antalya Memorial Hospital, Antalya
Turkey
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0022-3859.174160

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 :: Abstract 

We present a case of polyarticular synovitis following alendronate treatment for osteoporosis.
The patient had no evidence of rheumatoid arthritis, pyrophosphate arthropathy, or seronegative/seropositive arthritis. Our main aim in this study is to highlight the potential adverse effects of alendronate and to warn orthopedic surgeons about the possibility of such a side effect that might lead orthopedic surgeons to administer wrong and unnecessary treatments like arthrocentesis. The withdrawal of alendronate is found to be the treatment of choice. Alendronate should be considered as a possible cause of synovitis or polyarthritis in patients treated with this agent in the absence of any other pathology. An association between alendronate and synovitis has rarely been described in the literature. We present a patient who developed polyarticular synovitis after treatment with alendronate and responded to its withdrawal.


Keywords: Adverse event, alendronate, drug adverse effect, osteoporosis, polyarthritis, synovitis


How to cite this article:
Gökkus K, Yazicioglu G, Sagtas E, Uyan A, Aydin A T. Possible alendronate-induced polyarticular synovitis. J Postgrad Med 2016;62:126-8

How to cite this URL:
Gökkus K, Yazicioglu G, Sagtas E, Uyan A, Aydin A T. Possible alendronate-induced polyarticular synovitis. J Postgrad Med [serial online] 2016 [cited 2021 Feb 28];62:126-8. Available from: https://www.jpgmonline.com/text.asp?2016/62/2/126/174160



 :: Introduction Top


Bisphosphonates are a widely used drug class for diseases associated with bone resorption. They can be used in the treatment of osteoporosis and skeletal complications in patients with osteoporosis, Paget's disease of bone, multiple myeloma, hypercalcemia of malignancy, and bone metastases. [1],[2] Despite reports of osteonecrosis of the jaw following the use of nitrogen containing bisphosphonates in the oncology setting, they continue to be used as benefits outweigh risks. [3],[4],[5]

An association between alendronate and synovitis was first reported by the Uppsala monitoring centre in 2003 based on 8 cases enlisted in their database. [6]

We present in this paper a case of possible alendronate induced synovitis for its rarity and its potential to be overlooked by orthopedicians.


 :: Case Top


A 57 year old post menopausal woman came to the endocrinology department for a routine examination. When a DEXA scan showed osteoporosis, she was advised to take 70 mg/week of alendronate. She developed pain and swelling of the right wrist joint on Day 2 and the symptoms continued through Day 7. She took the next dose on Day 8 and she now developed right shoulder pain apart from the right wrist joint pain. On Day 11, she undrwent investigations for polyarthritis [ESR 87 mm, elevated C-reactive protein 50.8 mg/L]. HLA B27, uric acid and anti-nuclear antibodu were within normal limits and the rheumatoid factor was negative. She was started on diclofenac sodium and received the third dose of alendronate on Day 15 following which she developed right knee joint swelling. The pain was severe and there was generalized malaise. She herself noticed the association between drug administration and the joint pains.

Physical examination revealed pain and limitation of movement in the right shoulder and right knee with prominent effusion in the suprapatellar pouch. Plain radiographs (antero-posterior (AP) and lateral view) of the knee and shoulder revealed soft tissue effusion. Magnetic resonance imaging (MRI) scans of the knee demonstrated a suprapatellar pouch effusion and synovial tissue thickening in the joint [Figure 1]. Alendronate was now considered as the potential causative agent and was dsicontinued. She had a full recovery (she showed good progression and arthritic complaints were resolved in 3-4 days after the discontinuation) and ESR and C-reactive protein levels decreased to normal after discontinuation of alendronate (1 week after discontinuation).
Figure 1: MRI scans of the right knee. Notice the suprapatellar pouch effusion (yellow arrows) and synovial thickening (red arrows)

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 :: Discussion Top


Amino-containing BPs such as alendronate (4-amino-1-hydroxybutylidene-bisphosphonate) have proinflammatory properties and can cause an acute phase response. [7],[8] The basis for these pharmacological properties is unclear. [7],[8]

An acute phase response (ESR and CRP levels were elevated) was noted in our case. After discontinuation of alendronic acid, ESR and CRP levels became normal. These findings in our case suggested alendronate-induced polyarticular synovitis.

IV administration of BPs (e.g., pamidronate, ibandronate, zoledronate) generally produces more adverse effects than oral administration. These adverse effects are considered to depend on the route of administration. Symptoms such as myalgia, arthralgia, and bone pain with or without flu-like symptoms [systemic acute phase reactions with fever and general fatigue and with a number of well-delineated biochemical changes in C-reactive protein (CRP), lymphocyte count, and serum zinc concentration] are generally associated with IV administration of BPs. [5],[9] These adverse effects, which appear within 24 h after the first dose administration, may persist for a couple of days. Like all pharmacologic agents, these adverse effects are dose dependent (within the therapeutic range), most of the time, and they are not seen in future administrations. [5],[9]

According to the recently published data from major clinical studies about oral alendronate and risedronate [in accordance with evidence-based medicine (EBM)-based guidelines, which state that this drug group is most widely used in osteoporosis treatment], musculoskeletal adverse effects are seen less frequently than IV of BPs. [2],[10],[11]

Since once-a-week dosing regimens have shown a reduction in the incidence of upper gastrointestinal adverse effects [2],[9],[12] and improvement in the patients' overall convenience, compliance, and adherence to oral BPs, [2],[7],[12] most patients with osteoporosis are currently treated with alendronate (70 mg/oral) or risendronate (35 mg/oral). [2],[11]

The patients reported more musculoskeletal adverse effects following weekly, single-dose oral administration of alendronate and risedronate in clinical practice. [2]

An association between alendronate has been described by a few authors in literature. [8],[13],[14],[15]

The present report adds to the existing body of evidence and will help warn orthopedic surgeons of this rare possibility. The withdrawal of alendronate is the treatment of choice in those cases. Alendronate should be considered as a possible cause of synovitis or polyarthritis in patients treated with this agent in the absence of any other pathology.

Our study is limited by lack of dechallenge for ethical reasons and lack of measurement of drug concentrations in the synovial fluid and inherent weaknesses of the Naranjo scale. [16] Nonetheless, we do feel that this report would orthopedicians to this possibility and prevent unnecessary treatments and invasive procedures.

Acknowledgment

The authors would like to thank Antalya Memorial Hospital's Chief of Medicine, Dr. Sevim Suekinci for providing the necessary setting for the study and our English editor Taylan Alpaslan for his work. The junior authors also would like to thank our senior author, Ahmet Turan Aydin for his leadership and devotion.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
 :: References Top

1.
Fleisch H. Bisphosphonates in Bone Disease: From the Laboratory to the Patient, 4 th edn, Academic Press 2000: San Diego, CA.  Back to cited text no. 1
    
2.
Bock O, Boerst H, Thomasius FE, Degner C, Stephan-Oelkers M, Valentine SM, et al. Common musculoskeletal adverse effects of oral treatment with once weekly alendronate and risedronate in patients with osteoporosis and ways for their prevention. J Musculoskelet Neuronal Interact 2007;7:144-8.  Back to cited text no. 2
    
3.
Marx RE. Pamidronate (Aredia) and zoledronate (Zometa) induced avascular necrosis of the jaws: A growing epidemic. J Oral Maxillofac Surg 2003;61:1115-7.  Back to cited text no. 3
[PUBMED]    
4.
Zojer N, Keck AV, Pecherstorfer M. Comparative tolerability of drug therapies for hypercalcaemia of malignancy. Drug Saf 1999; 21:389-406.  Back to cited text no. 4
    
5.
Conte P, Guarneri V. Safety of intravenous and oral bisphosphonates and compliance with dosing regimens. Oncologist 2004;9(Suppl 4): 28-37.  Back to cited text no. 5
    
6.
The Uppsala Monitoring Centre. Alendronic Acid and Synovitis. Signal, March 2003. (Restricted Document). Contact the Uppsala Monitoring Centre for Details. e-mail: [email protected]  Back to cited text no. 6
    
7.
Merck Sharpe and Dohme (New Zealand) Limited. Fosamax (Alendronate) Data Sheet; 17 th October 2005. Available from: http://www.medsafe.govt.nz/profs/datasheet/f/fosamaxtab.htm. [Last accessed on 2007 Dec 06].  Back to cited text no. 7
    
8.
Makkonen N, Salminen A, Rogers MJ, Frith JC, Urtti A, Azhayeva E, et al. Contrasting effects of alendronate and clodronate on RAW 264 macrophages: The role of a bisphosphonate metabolite. Eur J Pharm Sci 1999;8:109-18.  Back to cited text no. 8
    
9.
Gerster JH. Acute polyarthritis related to once-weekly alendronate in a woman with osteoporosis. J Rheumatol 2004;31:829-30.  Back to cited text no. 9
[PUBMED]    
10.
Emkey R. Alendronate and risedronate for the treatment of postmenopausal osteoporosis: Clinical profiles of the once-weekly and once-daily dosing formulations. Med Gen Med 2004;6:6.  Back to cited text no. 10
    
11.
Emkey RD, Ettinger M. Improving compliance and persistence with bisphosphonate therapy for osteoporosis. Am J Med 2006;119 (Suppl 1):S18-24.  Back to cited text no. 11
    
12.
Baker DE. Alendronate and risedronate: What you need to know about their upper gastrointestinal tract toxicity. Rev Gastroenterol Disord 2002;2:20-33.  Back to cited text no. 12
    
13.
Gwynne Jones DP, Savage RL, Highton J. Alendronate-induced synovitis. J Rheumatol 2008;35:537-8.   Back to cited text no. 13
    
14.
Frederiksen L, Junker P, Brixen KT. Persistent polyarticular synovitis after treatment with alendronate. Ugeskr Laeger 2007;169:1583-4.   Back to cited text no. 14
    
15.
Jones DG, Savage R, Highton J. Synovitis induced by alendronic acid can present as acute carpal tunnel syndrome. BMJ 2005;330:74.  Back to cited text no. 15
    
16.
Naranjo CA, Busto U, Sellers EM, Sandor P, Ruiz I, Roberts EA, Janecek E, et al. A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981;30:239-45.  Back to cited text no. 16
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